The Relativistic Proton Spectrometer: A Review of Sensor Performance, Applications, and Science.

The Relativistic Proton Spectrometer (RPS) on the Van Allen Probes spacecraft was a particle spectrometer designed to measure the flux, angular distribution, and energy spectrum of protons from ∼ 60 MeV to ∼ 2000 MeV . RPS provided new information about the inner Van Allen belt: a nearby region of space that had been relatively unexplored because of the difficulties of making charged particle measurements there and the associated hazards to satellite operations. We met the primary mission objective of providing accurate data for the AP9 radiation specification model at the high energies where there were little to no data prior to the Van Allen Probes mission. Along the way, we were able to demonstrate the long-term stability of parts of the Inner Belt by comparison with short-lived space science missions that operated decades prior to Van Allen Probes. The most significant surprises were the agreement between RPS and some of those historical measurements and the discovery of a trapped population of > 30 MeV leptons at the outer edge of the inner belt. This end-of-mission paper summarizes the instrument performance, calibration, data products, and specific science and engineering results, and includes suggestions for future investigations of intense radiation fields like those found within the inner belt.

The Magnetic Electron Ion Spectrometer: A Review of On-Orbit Sensor Performance, Data, Operations, and Science.

Measurements from NASA's Van Allen Probes have transformed our understanding of the dynamics of Earth's geomagnetically-trapped, charged particle radiation. The Van Allen Probes were equipped with the Magnetic Electron Ion Spectrometers (MagEIS) that measured energetic and relativistic electrons, along with energetic ions, in the radiation belts. Accurate and routine measurement of these particles was of fundamental importance towards achieving the scientific goals of the mission. We provide a comprehensive review of the MagEIS suite's on-orbit performance, operation, and data products, along with a summary of scientific results. The purpose of this review is to serve as a complement to the MagEIS instrument paper, which was largely completed before flight and thus focused on pre-flight design and performance characteristics. As is the case with all space-borne instrumentation, the anticipated sensor performance was found to be different once on orbit. Our intention is to provide sufficient detail on the MagEIS instruments so that future generations of researchers can understand the subtleties of the sensors, profit from these unique measurements, and continue to unlock the mysteries of the near-Earth space radiation environment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11214-021-00855-2.

Empirically Estimated Electron Lifetimes in the Earth's Radiation Belts: Van Allen Probe Observations.

We use measurements from NASA's Van Allen Probes to calculate the decay time constants for electrons over a wide range of energies (30 keV to 4 MeV) and L values ( L = 1.3-6.0) in the Earth's radiation belts. Using an automated routine to identify flux decay events, we construct a large database of lifetimes for near-equatorially mirroring electrons over a 5-year interval. We provide the first accurate estimates of the long decay timescales in the inner zone ( ∼ 100 days), which are highly resolved in energy and free from proton contamination. In the slot region and outer zone, we compare our lifetime calculations with prior empirical estimates and find good quantitative agreement (lifetimes ∼ 1-20 days). The comparisons suggest that some prior estimates may overestimate electron lifetimes between L ≈ 2.5-4.5 due to instrumental effects and/or background contamination. Previously reported two-stage decays are explicitly demonstrated to be a consequence of using integral fluxes.

Empirically Estimated Electron Lifetimes in the Earth's Radiation Belts: Comparison With Theory.

We compute quasilinear diffusion rates due to pitch angle scattering by various mechanisms in the Earth's electron radiation belts. The calculated theoretical lifetimes are compared with observed decay rates, and we find excellent qualitative agreement between the two. The overall structure of the observed lifetime profiles as a function of energy and L is largely due to plasmaspheric hiss and Coulomb scattering. The results also reveal a local minimum in lifetimes in the inner zone at lower energy ( ∼ 50 keV), attributed to enhanced scattering via ground-based very low frequency transmitters, and a reduction in lifetimes at higher L and energy ( > 1 MeV), attributed to enhanced electromagnetic ion cyclotron wave scattering. In addition, we find significant quantitative disagreement at L < 3 . 5 , where the theoretical lifetimes are typically a factor of ∼ 10 larger than the observed, pointing to an additional loss process that is missing from current models. We discuss potential factors that could contribute to this disagreement.

Electron Microburst Size Distribution Derived With AeroCube-6.

Microbursts are an impulsive increase of electrons from the radiation belts into the atmosphere and have been directly observed in low Earth orbit and the upper atmosphere. Prior work has estimated that microbursts are capable of rapidly depleting the radiation belt electrons on the order of a day; hence, their role to radiation belt electron losses must be considered. Losses due to microbursts are not well constrained, and more work is necessary to accurately quantify their contribution as a loss process. To address this question, we present a statistical study of > 35 keV microburst sizes using the pair of AeroCube-6 CubeSats. The microburst size distribution in low Earth orbit and the magnetic equator was derived using both spacecraft. In low Earth orbit, the majority of microbursts were observed, while the AeroCube-6 separation was less than a few tens of kilometers, mostly in latitude. To account for the statistical effects of random microburst locations and sizes, Monte Carlo and analytic models were developed to test hypothesized microburst size distributions. A family of microburst size distributions were tested, and a Markov chain Monte Carlo sampler was used to estimate the optimal distribution of model parameters. Finally, a majority of observed microbursts map to sizes less than 200 km at the magnetic equator. Since microbursts are widely believed to be generated by scattering of radiation belt electrons by whistler mode waves, the observed microburst size distribution was compared to whistler mode chorus size distributions derived in prior literature.

Statistical Properties of Electron Curtain Precipitation Estimated With AeroCube-6.

Curtain precipitation is a recently discovered stationary, persistent, and latitudinally narrow electron precipitation phenomenon in low Earth orbit. Curtains are observed over consecutive passes of the dual AeroCube-6 CubeSats while their in-track lag varied from a fraction of a second to 65 s, with dosimeters that are sensitive to >35-keV electrons. This study uses the AeroCube-6 mission to quantify the statistical properties of 1,634 curtains observed over 3 years. We found that many curtains are narrower than 10 km in the latitudinal direction with 90% narrower than 20 km. We examined the geographic, magnetic local time, and geomagnetic dependence of curtains. We found that curtains are observed in the late-morning and premidnight magnetic local times, with a higher occurrence rate at premidnight, and curtains are observed more often during times of enhanced Auroral Electrojet. We found a few curtains in the bounce loss cone region above the North Atlantic, whose electrons were continuously scattered for at least 6 s. Such observations suggest that continuous curtain precipitation may be a significant loss of >35-keV electrons from the magnetosphere into the atmosphere. We hypothesize that the curtains observed in the bounce loss cone were accelerated by parallel electric fields, and we show that this mechanism is consistent with the observations.

A Revised Look at Relativistic Electrons in the Earth's Inner Radiation Zone and Slot Region.

We describe a new, more accurate procedure for estimating and removing inner zone background contamination from Van Allen Probes Magnetic Electron Ion Spectrometer (MagEIS) radiation belt measurements. This new procedure is based on the underlying assumption that the primary source of background contamination in the electron measurements at L shells less than three, energetic inner belt protons, is relatively stable. Since a magnetic spectrometer can readily distinguish between foreground electrons and background signals, we are able to exploit the proton stability to construct a model of the background contamination in each MagEIS detector by only considering times when the measurements are known to be background dominated. We demonstrate, for relativistic electron measurements in the inner zone, that the new technique is a significant improvement upon the routine background corrections that are used in the standard MagEIS data processing, which can "overcorrect" and therefore remove real (but small) electron fluxes. As an example, we show that the previously reported 1-MeV injection into the inner zone that occurred in June of 2015 was distributed more broadly in L and persisted in the inner zone longer than suggested by previous estimates. Such differences can have important implications for both scientific studies and spacecraft engineering applications that make use of MagEIS electron data in the inner zone at relativistic energies. We compare these new results with prior work and present more recent observations that also show a 1-MeV electron injection into the inner zone following the September 2017 interplanetary shock passage.

Szt2, a novel gene for seizure threshold in mice.

In a chemical mutagenesis screen we identified Szt2 (seizure threshold 2) as a gene that confers low seizure threshold to mice and may also enhance epileptogenesis. The semidominant phenotype was mapped to Chromosome 4 and narrowed further to a critical interval of approximately 650 kb. A novel large (> 10 kb) transcript in the critical interval was found to have fourfold increased steady-state expression at the RNA level in Szt2 homozygous mutant brain. The corresponding 72 exon gene encodes a 378-kD protein with no significant or suggestive sequence similarities to any other protein. The mutant allele of Szt2 contains a splice donor mutation after exon 32, predicting transcriptional read-through, translational frameshift and premature stop. A second Szt2 allele, containing a gene-trap mutation in exon 21, also conferred a low seizure threshold and increased RNA expression, but unlike the original allele, some gene-trap homozygotes died embryonically. Szt2 is transcribed in many tissues, with the highest expression in brain, and it is also expressed during embryonic development. Szt2 is highly conserved in evolution, with a clear, single orthologue found in all land vertebrates and in many invertebrates. Interestingly, in mammals the Szt2 gene resides in a highly conserved head-to-head configuration with Med8 (which encodes a Mediator complex subunit), separated by only 91 nt. While the biological function of Szt2 remains unknown, its high conservation, unique structure and effect on seizure threshold suggest that it serves an important role in the central nervous system.

Corneal tattoo with tea infusion.

Except in animal models of cataractogenesis, the literature on the effects of tea infusion on ocular tissue is scant. In our patient, prolonged exposure to tea infusion may have led to a hypesthetic cornea with secondary limbal stem cell loss. In turn, the eye developed keratinization and corneal neovascularization.

Surgical feasibility study of a novel polytetrafluoroethylene graft design for the treatment of peripheral arterial disease.

Disturbed flow patterns, material mismatch, and surgical injury are often cited as being significant contributors to failure at the distal end of femoropopliteal bypass grafts. The objective of this research is to propose a novel bypass graft design concept which seeks to reduce the incidence of disturbed flow in the bypass junction and to establish the surgical feasibility of the proposed device. A preliminary evaluation of the hemodynamic benefit associated with the proposed device was made using computational fluid dynamics. A prototype of the device was then constructed from commercially available materials, and it was prepared for implantation into the aorta of a pig. The computational model of the proposed device showed that significant flow correction was occurring in the in vitro model due to the geometric configuration of the design. The magnitude of the peak wall shear stress in the recirculation region was noted to decrease by 78%. Surgical feasibility of the proposed device was verified by successful implantation into the aorta of the pig. The pig was sacrificed after 7 weeks, the graft and host artery were excised, and histological examination downstream from the distal junction showed that intimal hyperplasia had developed in the host artery. The proposed device is surgically feasible and may offer a significant hemodynamic advantage over current graft designs.

Emerging guidelines for use of NSAID therapy to optimize cataract surgery patient care.

This analysis provides guidelines for the proper use of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs), discusses their effect on inflammation, and their role in the prevention of cystoid macular edema (CME). A novel treatment strategy is presented for recommended topical ophthalmic NSAID dosing in patient populations based on risk factors for CME. The article reviews current topical ophthalmic NSAIDs, as well as a newest generation of pro-drug NSAIDs. In addition, combination therapy of NSAIDs and corticosteroids are discussed, along with a general review of therapeutic guidelines for dosing regimens, and benefits and risks of therapy. The goal of this analysis is to provide a suggested therapeutic regimen with topical NSAIDs to assist in achieving optimal clinical and functional outcomes.

The role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea.

OBJECTIVE: To investigate the potential role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea. METHODS: Twenty-one corneal buttons from patients with Fuchs dystrophy and 15 control corneas were studied. Apoptosis was assessed by the in situ end-labeling of double-stranded DNA breaks, and by immunohistochemical characterization of cellular markers associated with apoptosis (Fas, FasL, Bcl-2, and Bax). Expression of Bcl-2 and Bax mRNA in the corneal stroma and endothelium was separately analyzed by a semiquantitative reverse transcriptase polymerase chain reaction. Furthermore, cultivated keratocytes generated from diseased corneal buttons and donor rims were exposed to camptothecin, an apoptotic inducer, for 6 and 24 hours. They were then examined for protein and messenger RNA (mRNA) expression of apoptotic regulatory molecules. RESULTS: DNA fragmentation was seen in the epithelium, stroma, and endothelium in 6 of 7 corneas with Fuchs dystrophy. A statistically significant difference was identified in the expression of Bax and its mRNA in the stroma, but not in the endothelium of Fuchs dystrophy corneas. Following exposure to camptothecin, keratocytes from patients with Fuchs dystrophy responded with an increased level of Bax and a low level of Bcl-2. This trend was distinctively different from the response of normal keratocytes. CONCLUSIONS: The evidence in this study points to a disease-related disturbance in the regulation of apoptosis in Fuchs dystrophy. Our findings suggest that excessive apoptosis may be an important mechanism in the pathogenesis of Fuchs dystrophy.

In vitro susceptibilities of bacterial ocular isolates to fluoroquinolones.

PURPOSE: To evaluate and compare the in vitro antimicrobial activity of levofloxacin versus ciprofloxacin and ofloxacin against ocular isolates from patients with bacterial conjunctivitis. METHODS: The in vitro antimicrobial susceptibilities of ocular isolates to levofloxacin, ofloxacin, and ciprofloxacin were determined using both the agar disk diffusion and broth dilution methods. RESULTS: Disk diffusion susceptibility testing disclosed that 99% (100 of 101 isolates) of gram-negative isolates and 98% (127 of 129 isolates) of gram-positive isolates were susceptible to levofloxacin; 96% (97 of 101 isolates) of gram-negative isolates and 78% (100 of 129 isolates) of gram-positive isolates were susceptible to ofloxacin; and 94% (95 of 101 isolates) of gram-negative isolates and 61% (79 of 129 isolates) of gram-positive isolates were susceptible to ciprofloxacin. Broth dilution testing disclosed that 99% (72 of 73 isolates) of gram-negative isolates and 98% (111 of 113 isolates) of gram-positive isolates were susceptible to levofloxacin; 96% (70 of 73 isolates) of gram-negative isolates and 92% (104 of 113 isolates) of gram-positive isolates were susceptible to ofloxacin; and 95% (69 of 73 isolates) of gram-negative isolates and 82% (93 of 113 isolates) of gram-positive isolates were susceptible to ciprofloxacin. CONCLUSIONS: In this study, levofloxacin demonstrated superior in vitro activity against human bacterial conjunctival isolates compared with either ofloxacin or ciprofloxacin (levofloxacin > ofloxacin > ciprofloxacin).

The role of matrix metalloproteinases in ulcerative keratolysis associated with perioperative diclofenac use.

OBJECTIVE: To investigate the role of matrix metalloproteinases (MMPs) in the pathogenesis of ulcerative keratolysis associated with topical use of generic diclofenac preoperatively and postoperatively. To characterize the inflammatory response of the cornea in this case of ulcerative keratolysis. DESIGN: Case report with clinicopathologic correlation. MAIN OUTCOME MEASURES: Corneal culture for microbial growth. Clinical and histopathologic examinations including routine histolopathologic, immunofluorescent, and immunohistochemical studies. RESULTS: Microscopic examination of the corneal button disclosed fibrinous material with neutrophils and mononuclear inflammatory cells. The corneal epithelial basement membrane was irregularly thickened and patchy. Immunohistochemical staining detected weak staining of MMP-1 and a strong presence of MMP-8 in the epithelium. MMP-8 and 9 were also present in areas of leukocytic infiltration. MMP-2 appeared in a few stromal cells. Macrophages and leukocytes were the predominant infiltrating cells. CONCLUSIONS: A nonspecific inflammatory response occurred in this case of ulcerative keratolysis. Corneal epithelial cells are capable of secreting MMP-1 and 8 and may participate in the stromal degradation and repair process of the ulcerative keratolysis associated with topical nonsteroidol antiinflammatory use.

Molecular and functional mapping of the piebald deletion complex on mouse chromosome 14.

The piebald deletion complex is a set of overlapping chromosomal deficiencies surrounding the endothelin receptor B locus collected during the Oak Ridge specific-locus-test mutagenesis screen. These chromosomal deletions represent an important resource for genetic studies to dissect the functional content of a genomic region, and several developmental defects have been associated with mice homozygous for distinct piebald deletion alleles. We have used molecular markers to order the breakpoints for 20 deletion alleles that span a 15.7-18-cM region of distal mouse chromosome 14. Large deletions covering as much as 11 cM have been identified that will be useful for regionally directed mutagenesis screens to reveal recessive mutations that disrupt development. Deletions identified as having breakpoints positioned within previously described critical regions have been used in complementation studies to further define the functional intervals associated with the developmental defects. This has focused our efforts to isolate genes required for newborn respiration and survival, skeletal patterning and morphogenesis, and central nervous system development.

Perioperative microbiologic profile of the conjunctiva in photorefractive keratectomy.

PURPOSE: Therapeutic soft contact lenses are used commonly as an adjunctive treatment after photorefractive keratectomy (PRK) to decrease postoperative pain caused by the movement of lids over the corneal epithelial defect and to facilitate epithelial healing. We assessed the microbiological profile of the conjunctiva of patients undergoing PRK for myopia, before and after the concurrent use of a therapeutic soft contact lens, and compared the effect on ocular bacterial colonization of prophylactic administration of topical tobramycin 0.3% versus ofloxacin 0.3%. METHODS: Forty-three consecutive eyes from 37 patients underwent PRK for myopia or myopic astigmatism. Eyes were assigned randomly to prophylactic antibacterial treatment with either topical ofloxacin 0.3% or tobramycin 0.3%, applied prior to surgery and three times daily after surgery until therapeutic soft contact lens removal. Material from the conjunctival sac was obtained for bacteriologic cultures prior to surgery. Clinical evaluation of all eyes was conducted prospectively. Three days after PRK, the therapeutic soft contact lenses were removed and cultured. Cultures from the conjunctival sac were then repeated. RESULTS: No statistically significant differences were observed in culture positivity between the two groups of eyes, in spite of some positive preoperative and postoperative cultures. Only one out of 43 eyes (assigned to the ofloxacin group) developed a peripheral corneal infiltrate. The corneal infiltrate healed completely without sequelae using antibiotic and corticosteroid therapy. CONCLUSIONS: The use of therapeutic soft contact lenses after PRK with either topical tobramycin 0.3% or ofloxacin 0.3% were well tolerated. However, perioperative positive conjunctival cultures were relatively frequent and prophylactic antibiotics should be used in the setting of an epithelial defect and therapeutic soft contact lens following PRK.

Long-term survival of allogeneic donor cell-derived corneal epithelium in limbal deficient rabbits.

PURPOSE: To investigate the capability of cultivated allogeneic epithelial stem cells to restore a functional ocular surface in a limbal deficient cornea; to verify the long term survival of epithelial allograft; and to examine the host immune response to heterologous cell transplant in a rabbit model. METHODS: Limbal deficiency was established by performing limbectomy on rabbits (n = 100). Corneal epithelial stem cells were obtained from the limbus and replicated in vitro without a supporting layer. The cell (3 x 10(5)) suspension was then transplanted via topical application as eye drops. Animals were divided into allograft, autograft, and control groups. Females were used as recipients and males as donors for the allograft. Corneas were collected at 7, 14, 21, 40 days as well as 2, 3, 7 and 8 months after cell transplantation. Experimental corneas were evaluated by histology, immunofluorescence, immunohistochemistry and Y chromosome analysis. RESULTS: A well-differentiated corneal epithelium was recognized at 14 to 40 days after cell transfer overlying an infiltrated corneal stroma. Corneal re-epitheliazation was confirmed in 31 of 36 allograft corneas. No significant immune rejection was noted. Stromal abnormality caused by previous limbal deficiency was mostly resolved three months after the regeneration of corneal epithelium. CONCLUSIONS: Transplanted corneal epithelial stem cells were able to differentiate into normal corneal epithelium in vivo without the use of membrane scaffolding. This non-autologous donor cell-derived corneal epithelium survived up to 8 months without immunosuppression and was able to reverse the stromal scarring. Thus, cultivated epithelial stem cells have great potential as an alternative to multiple-surgical procedures in the treatment of limbal deficiency states.