Astronaut Rescue Air Pack (ARAP) and Emergency Egress Air Pack (EEAP)

Two designs for a lightweight, low profile, mobile rescue apparatus providing a 15-minute air supply and self-contained two-way communications assembly are described. Units are designed for astronaut use in hazardous environments

A Method for the Study of Human Factors in Aircraft Operations

A method for the study of human factors in the aviation environment is described. A conceptual framework is provided within which pilot and other human errors in aircraft operations may be studied with the intent of finding out how, and why, they occurred. An information processing model of human behavior serves as the basis for the acquisition and interpretation of information relating to occurrences which involve human error. A systematic method of collecting such data is presented and discussed. The classification of the data is outlined

Pursuit of purity: Measurement of chelation binding affinities for NOTA, DOTA, and desferal with applications to effective specific activity

Introduction The effective specific activity of a radioisotope is an indirect and highly useful way to describe a radioactive sample’s purity. A high effective specific activity combines the concept of an isotopically pure product with suitability via selectivity of a particular chelating body. The primary goals of this work are twofold: 1) To determine which metallic impurities have the largest impact on the effective specific activity for a given chelator, and 2) to form a model based on the binding affinities of each metal for to calculate a ‘theoretical effective specific activ-ity’ from broad band trace metal analysis. If successful, this information can be used to guide the production of high specific activity products through the systematic elimination of high-impact metallic impurities. Material and Methods Phosphor plate thin layer chromatography (TLC) was used to measure the effective specific activ-ity of 64Cu by NOTA and DOTA, and 89Zr by des-feral (DF). Typical measured effective specific activities are 2–5 Ci/μmol for 64Cu and 1–2 Ci/μmol for 89Zr. Samples were created containing increasing cod competitive burdens (X) of CuCl2, ZnCl2, FeCl2, NiCl2, CrCl3, CoCl2, MnCl2, and YCl3. Standard concentrations were measured by microwave plasma atomic emission spectrometry. 50 pmol of NOTA, DOTA, or DF were added following the activity aliquots of 64Cu or 89Zr. Labeling efficien-cies (64Cu-NOTA, 64Cu-DOTA, 89Zr-DF) were measured using TLC’s, and were fit by linear regression to the form f(X) = b/(1 − AX), where A is the chelation affinity (inverse of dissociation constant) and X is the molar ratio of the metallic impurity to the amount of chelator. Results and Conclusion Affinity of Zr for DF was assumed to be unity, while the affinities of Cu for NOTA and DOTA were explicitly measured and were found to be 0.93 ± 0.13 and 5.2 ± 3.2 respectively. It was found that Cu had the highest affinity for NOTA by a factor of 266, and that Zr had the highest affinity for DF by a factor of 40. • In order of decreasing affinity to NOTA: Cu, Zn, Fe, Co, Cr, Y, and Ni • In order of decreasing affinity to DOTA: Cu, Y, Zn, Co, Ni, Cr, and Fe • In order of decreasing affinity to DF: Zr, Y, Cu, Zn, Ni, Fe, Co, Cr These results suggest that aside from the carrier element it is most important to remove zinc from 64Cu products prior to chelation with NOTA and yttrium from 64Cu and 89Zr products prior to chelation with DOTA and DF, respectively. Therefore, it is logical to believe that 89Zr effective specific activities could be greatly improved by secondary separations with the goal of re-moving additional yttrium target material. Chelation affinities of NOTA, DOTA, and DF for several common metals have successfully been investigated. These values will guide our future attempts to provide high effective specific activity 64¬Cu and 89Zr. Furthermore, a preliminary model has been formed to calculate effective specific activity from the quantitative broad band analysis of trace metals. Future work will include chelator affinity measurements for other likely contaminants, such as scandium, titanium, zirconium, molybdenum, niobium, gold, gallium, and germanium. Details will be presented

Mild recessive epidermolytic hyperkeratosis associated with a novel keratin 10 donor splice-site mutation in a family of Norfolk terrier dogs

Background  Epidermolytic hyperkeratosis in humans is caused by dominant-negative mutations in suprabasal epidermal keratins 1 and 10. However, spontaneous keratin mutations have not been confirmed in a species other than human. Objectives  To describe an autosomal recessive, mild, nonpalmar/plantar epidermolytic ichthyosis segregating in an extended pedigree of Norfolk terrier dogs due to a splice-site mutation in the gene encoding keratin 10 (KRT10). Methods  Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Genomic DNA samples and cDNA from skin RNA were sequenced and defined a mutation in KRT10. Consequences of the mutation were evaluated by assessing protein expression with immunohistochemistry and Western blotting and gene expression with real-time RT-PCR (reverse transcriptase-polymerase chain reaction). Results  Adult dogs with the disease had generalized, pigmented hyperkeratosis with epidermal fragility. Light microscopic examination defined epidermolysis with hyperkeratosis; ultrastructural changes included a decrease in tonofilaments and abnormal filament aggregation in upper spinous and granular layer keratinocytes. Affected dogs were homozygous for a single base GT→TT change in the consensus donor splice site of intron 5 in KRT10. Keratin 10 protein was not detected with immunoblotting in affected dogs. Heterozygous dogs were normal based on clinical and histological appearance and keratin 10 protein expression. The mutation caused activation of at least three cryptic or alternative splice sites. Use of the cryptic sites resulted in transcripts containing premature termination codons. One transcript could result in shortening of the proximal portion of the 2B domain before the stutter region. Quantitative real-time PCR indicated a significant decrease in KRT10 mRNA levels in affected dogs compared with wild-type dogs. Conclusions  This disease is the first confirmed spontaneous keratin mutation in a nonhuman species and is the first reported recessive form of epidermolytic hyperkeratosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74670/1/j.1365-2133.2005.06735.x.pd

Runout model evaluation based on back-calculation of building damage

We evaluated the ability of three debris-flow runout models (RAMMS, FLO2D and D-Claw) to predict the number of damaged buildings in simulations of the 9 January 2019 Montecito, California, debrisflow event. Observations of building damage after the event were combined with OpenStreetMap building footprints to construct a database of all potentially impacted buildings. At the estimated event volume, all models overpredict the number of damaged buildings by a factor of 1.5–3

Production and novel radiochemical separation of 194Au from Pt for use in multi-modality nanoparticles: Production and novel radiochemical separation of 194Au from Pt for use in multi-modality nanoparticles

Introduction Gold nanoparticles (AuNPs) have demonstrated their incredible versatility in applications such as in vitro and in vivo imaging, cancer therapy, and drug delivery.[1-3] These AuNPs come in many shapes including nanospheres, nanorods, nanoshells, and nanocages. Their versatility stems from the ability to construct or label a single AuNP with many functions. Many types of AuNPs are inherently flourescent, allowing for ex vivo utilization as well as small animal fluorescence imaging.[4] High atomic number and physical density allow for the possibility of using AuNPs as computed tomography (CT) contrast agents, especially in dual energy applications.[5] Some attempts have been made to bring AuNPs into the realm of nuclear medicine, mostly involving the extrinsic labeling of chelated radio-metals. Although these strategies have brought some success, an intrinsic labeling strategy could reduce concerns of in vivo instability, and changes in pharmacokinetic behavior.[6] Intrinsic radiolabeling strategies involve synthesizing the nanoparticles in the presence of a gold radioisotope, which is thereby structurally incorporated. The isotope of choice for this technique has typically been 198Au (t½ = 2.7 d, Eγ = 411.8 keV) as it is reactor produced and commercially available. However with such a high energy gamma ray, SPECT aquisition is far from optimal. Motivated by the shortcomings of previous intrinsic labeling techniques, we have sought to develop 194Au (t½ = 1.48 d, β+ = 1.73 %) as a potential PET isotope for labeling AuNPs. Although this nuclide has a weak positron branching ratio, it also has prominent gamma ray energies of 328 and 294 keV which are closer to the optimal SPECT energy window, allowing for the ability to image with both PET and SPECT. Material and Methods 194Au was produced by natPt(p,x) using 16 MeV protons. Target construction consisted of a water jet cooled platinum disc. Following irradiation, targets were etched by fresh concentrated aqua regia at 80 °C for four hours. The resulting solution was diluted by a factor of four and loaded onto a 50 mg UTEVA (Eichrom extraction resin) column equilibrated by 1 M HNO3. The column was rinsed with 10 mL 1 M HNO3, and the product was eluted using concentrated HNO3 in less than 1 mL. Results and Conclusion End of bombardment (EOB) yield for 194Au was measured to be 0.134 mCi/μAh by high purity germanium analysis. The half life was measured to be 38.5 ± 2.8 hours, which agrees well with the true half life of 37.92 hours. In addition to the production of 194Au, the production of 190–193Au and 196Au was observed. Most notably, the EOB yield for 193Au (t½ = 17.7 h) was 0.189 mCi/μAh. Target dissolution was slow and incomplete after four hours of etching. Alternative dissolution strategies i.e. electrolytic dissolution may be needed moving forward. The separation of 194Au from bulk Pt via the UTEVA extraction resin was robust and efficient, with an average separation efficiency of 96 %. An extensive literature review revealed no other Au/Pt separation from solutions containing aqua regia. Future goals include synthesis of ultrasmall 194Au incorporated AuNPs using a facile thermal reduction method.PET, CT and fluorescence imaging will also be carried out in vivo to establish the multimodal capabilities of the intrinsically radio-labeled nanoplatforms. To conclude, a novel separation technique has been developed to separate 194Au from Pt for use in intrinsically radiolabeled multi-modal AuNPs

Production and isolation of 72As from proton irradiation of enriched 72GeO2 for the development of targeted PET/MRI agents

Introduction Two current major research topics in nuclear medicine are in the development of long-lived positron-emitting nuclides for imaging tracers with long biological half-lives and in theranostics, imaging nuclides which have a chemically analogous therapy isotope. As shown in TABLE 1, the radioisotopes of arsenic (As) are well suited for both of these tasks with several imaging and therapy isotopes of a variety of biologically relevant half-lives accessible through the use of small medical cyclotrons. The five naturally abundant isotopes of germanium are both a boon and challenge for the medical nuclear chemist. They are beneficial in that they facilitate a wide array of producible radioarsenic isotopes. They are a challenge as monoisotopic radioarsenic production requires isotopically-enriched targets that are expensive and of limited availability. This makes it highly desirable that the germanium target material is reclaimed from arsenic isolation chemistry. One major factor which has limited the development of radioarsenic has been difficulties in its incorporation into biologically relevant targeting vectors. Previous studies have labeled antibodies and polymers through covalent bonding of arsenite (As(III)) with the sulfydryl group1,2,3. Recent work in our group has shown the facile synthesis and utility of superparamagnetic iron oxide nanoparticle- (SPION-)bound radioarsenic as a dual modality positron emission tomography (PET)/magnetic resonance imaging (MRI) agent4. Presently, we have built upon previous studies producing, isolating, and labeling untargeted SPION with radioarsenic4,5. We have incorp-rated the use of isotopically-enriched 72GeO2 for the production of radioisotopically pure 72As. The bulk of the 72GeO2 target material was re-claimed from the arsenic isolation chemical procedure for reuse in future irradiations. The 72As was used for ongoing development toward the synthesis of targeted, As-SPION-based, dual-modality PET/MRI agents. Material and Methods Targets of ~100 mg of isotopically-enriched 72GeO2 (96.6% 72Ge, 2.86% 73Ge, 0.35% 70Ge, 0.2% 74Ge, 0.01% 76Ge, Isoflex USA) were pressed into a niobium beam stop at 225 MPa, covered with a 25 µm HAVAR containment foil, attached to a water-cooling target port, and irradiated with 3 µA of 16.1 MeV protons for 2–3 hours using a GE PETtrace cyclotron. After irradiation, the target and beam stop were assembled into a PTFE dissolution apparatus, where the 72GeO2 target material was dissolved with the addition of 2 mL of 4 M NaOH and subsequent stirring. After dissolution was completed, the clear, colorless solution was transferred to a fritted glass column and the bulk 72GeO2 was reprecipitated by neutralizing the solution with the addition of 630 µL [HCl]conc, filtered, and rinsed with 1 mL [HCl]conc. To the combined 72As-containing filtrates, 100 µL 30% H2O2 was added to ensure that 72As was in the nonvolatile As(V) oxidation state. The ~3 mL solution was then evaporated at 115 ˚C while the vessel was purged with argon, followed by a second addition of 100 µL H2O2 after the volume was reduced to 1 mL. When the filtrate volume was ~0.3 mL, the vessel was removed from heat, allowed to cool with argon flow, and the arsenic reconstituted in 1 mL [HCl]conc and loaded onto a 1.5 mL bed volume Bio-Rad AG 1×8, 200–400 mesh anion exchange column preconditioned with 10 M HCl. The radioarsenic was eluted in 10 M HCl in the next ~10 mL, with 90% of the activity eluting in a 4 mL fraction. The column was then eluted with 5 mL 1 M HCl. The 72As-rich 10 M HCl fraction was reduced to As(III) with the addition of ~100 mg CuCl, and heating to 60 ˚C for 1 hour. The resulting AsCl3 was then extracted twice into 4 mL cyclohexane, which were combined and back extracted into 500 µL of water as As(OH)3. This solution of 72As in H2O was then used directly to label SPION and for subsequent experiments conjugating 72As-SPION with TRC105, an angiogenesis-marking monoclonal antibody (MAb) targeting endoglin/CD105. Several methods were initially attempted involving directly conjugating the surface-modified SPION to the MAb through a polyethylene glycol (PEG) linker. More recent studies have investigated the radioarsenic labeling of SPION encapsulated in hollow mesoporous silica nanoparticles (SPION@HMSN) and its subsequent conjugation to TRC105. Results and Conclusion Irradiation of pressed, isotopically-enriched 72GeO2 resulted in a production yield for 72As of 17 ± 2 mCi/(µA·hr·g) and for 71As of 0.37 ± 0.04 mCi/(µA·hr·g), which are 64 % and 33 %, of those predicted from literature6, respectively. However, these production yields are in agreement with those scaled from observed production yields using analagous natGeO2 targets. The end-of-bombardment 72As radionuclidic purity can be improved by minimizing the 72Ge(p,2n)71As reaction by degrading the beam energy. A 125 µm Nb containment foil would degrade impinging protons to 14.1 MeV and is predicted to reduce 71As yield by a factor of three, while only reducing 72As yield by 1 %6, improving end-of-bombardment radionuclidic purity from 98 % to greater than 99 %. Overall decay-corrected radiochemical yield of the 72As isolation procedure from 72GeO2 were 51 ± 2 % (n = 3) in agreement with those observed with natGeO2 57 ± 7 % (n = 14). The beam current was limited to 3 µA as higher cur-rents 4–5 µA exhibited inconsistent dissolution and reprecipitation steps, resulting in an overall yield of 44 ± 21 % (n = 6). Dissolution time also played an important role in overall yield with at least one hour necessary to minimize losses in these first two steps. The separation procedure effectively removed all radiochemical contaminants and resulted in 72As(OH)3 isolated in a small volume, pH~4.5 water solution. Over the course of minutes to hours after back extraction, rapid auto-oxidation to 72AsO4H3 was observed. The bulk 72GeO2 target material, which was reclaimed from the isolation procedure, is being collected for future use. The synthesis of a targeted PET/MRI agent based on the functionalization of 72As-SPION has proved to be a difficult task. Experiments conjugating 72As-SPION to TRC105 through a PEG linker were unsuccessful, despite the investigation of a variety bioconjugation procedures. Current work is investigating the use of SPION@HMSN, which have a similar affinity for 72As as unencapsulated SPION. This new class of 72As-labeled SPION@HMSN has a hollow cavity for potential anti-cancer drug loading, as well as the mesoporous silica surface, which may facilitate the efficient conjugation of TRC105 using a well-developed bioconjugation technique. In summary, radioarsenic holds potential in the field of diagnostic and therapeutic nuclear medicine. However, this potential remains locked behind challenges related to its production and useful in vivo targeting. The present work strives to address several of these challenges through the use of enriched 72GeO2 target material, a chemical isolation procedure that reclaims the bulk of the target material, and the investigation of new targeted nanoparticle-based PET/MRI agents