Feasibility study of the solar scientific instruments for Spacelab/Orbiter

The feasibility and economics of mounting and operating a set of solar scientific instruments in the backup Skylab Apollo Telescope Mount (ATM) hardware was evaluated. The instruments used as the study test payload and integrated into the ATM were: the Solar EUV Telescope/Spectrometer; the Solar Active Region Observing Telescope; and the Lyman Alpha White Light Coronagraph. The backup ATM hardware consists of a central cruciform structure, called the "SPAR', a "Sun End Canister' and a "Multiple Docking Adapter End Canister'. Basically, the ATM hardware and software provides a structural interface for the instruments; a closely controlled thermal environment; and a very accurate attitude and pointing control capability. The hardware is an identical set to the hardware that flow on Skylab

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

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

Geodetic Constraints on the 2014 M 6.0 South Napa Earthquake

On 24 August 2014, the M 6.0 South Napa earthquake shook much of the San Francisco Bay area, leading to significant damage in the Napa Valley. The earthquake occurred in the vicinity of the West Napa fault (122.313° W, 38.22° N, 11.3 km), a mapped structure located between the Rodger’s Creek and Green Valley faults, with nearly pure right‐lateral strike‐slip motion (strike 157°, dip 77°, rake –169°; http://comcat.cr.usgs.gov/earthquakes/eventpage/nc72282711#summary, last accessed December 2014) (Fig. 1). The West Napa fault previously experienced an M 5 strike‐slip event in 2000 but otherwise exhibited no previous definitive evidence of historic earthquake rupture (Rodgers et al., 2008; Wesling and Hanson, 2008). Evans et al. (2012) found slip rates of ∼9.5  mm/yr along the West Napa fault, with most slip rate models for the Bay area placing higher slip rates and greater earthquake potential on the Rodger’s Creek and Green Valley faults, respectively (e.g., Savage et al., 1999; d’Alessio et al., 2005; Funning et al., 2007)

A flexible and efficient template format for circular consensus sequencing and SNP detection

A novel template design for single-molecule sequencing is introduced, a structure we refer to as a SMRTbell™ template. This structure consists of a double-stranded portion, containing the insert of interest, and a single-stranded hairpin loop on either end, which provides a site for primer binding. Structurally, this format resembles a linear double-stranded molecule, and yet it is topologically circular. When placed into a single-molecule sequencing reaction, the SMRTbell template format enables a consensus sequence to be obtained from multiple passes on a single molecule. Furthermore, this consensus sequence is obtained from both the sense and antisense strands of the insert region. In this article, we present a universal method for constructing these templates, as well as an application of their use. We demonstrate the generation of high-quality consensus accuracy from single molecules, as well as the use of SMRTbell templates in the identification of rare sequence variants