Multimode bolometer development for the PIXIE instrument

The Primordial Inflation Explorer (PIXIE) is an Explorer-class mission concept designed to measure the polarization and absolute intensity of the cosmic microwave background. In the following, we report on the design, fabrication, and performance of the multimode polarization-sensitive bolometers for PIXIE, which are based on silicon thermistors. In particular we focus on several recent advances in the detector design, including the implementation of a scheme to greatly raise the frequencies of the internal vibrational modes of the large-area, low-mass optical absorber structure consisting of a grid of micromachined, ion-implanted silicon wires. With $\sim30$ times the absorbing area of the spider-web bolometers used by Planck, the tensioning scheme enables the PIXIE bolometers to be robust in the vibrational and acoustic environment at launch of the space mission. More generally, it could be used to reduce microphonic sensitivity in other types of low temperature detectors. We also report on the performance of the PIXIE bolometers in a dark cryogenic environment.Comment: 10 pages, 7 figure

Targeting the folate receptor: Improving efficacy in inorganic medicinal chemistry

The discovery of the high-affinity, high-specificity folate receptor in mamalian kidney cells, coupled with the ability of folate to enter cells by folate receptor-mediated endocytosis and the subsequent elucidation of the folate receptor’s overexpression in specific cancer cell types; heralded the arrival of the area of chemotherapeutic folate targeting. The application of purely organic folate-based small-molecule drug conjugates that selectively target the folate receptor, which is over expressed in several diseases such as cancer, is well established. The application of inorganic folate-targeted drugs offers significant potential to expand and enhance this therapeutic approach. From the data made available to date, it is apparent that this aspect of inorganic medicinal chemistry is in its youth but has the capability to contribute greatly to cancer research, both in therapy and diagnosis. The union of folate-receptor targeting and inorganic medicine may also lead to the development of treatments for disorders such as chronic-inflammation, tuberculosis, neurodegenerative disease and leishmaniasis. In this review, we summarize what is known about the coordination chemistry of folic acid and the therapeutic potential of such complexes. We also describe approaches adopted to conjugate platinum drugs to folate- or folate-carrier- systems and their prospective ability to overcome problems associated with unwanted side-effects and resistance by improving their delivery and/or selectivity. The literature pertaining to non-platinum metal complex conjugates with folic acid is also reviewed revealing that this is an area that offers significant potential to develop targeted therapeutic approaches in areas such as chemotherapy and molecular imaging for diagnostics

Copper mediated, heterogeneous, enantioselective intramolecular Buchner reactions of a-diazoketones using continuous flow processing

Enantioselective intramolecular Buchner reactions of α-diazoketones can be effected using heterogeneous copper−bis(oxazoline) catalysts in batch or using continuous flow processing in up to 83% ee. The catalyst can be reused up to 7 times without loss of activity. For α-diazoketones 3 and 4, the enantioselection achieved in flow with the immobilized catalyst was comparable with the standard homogeneous catalyzed process

Multimode Bolometer Development for the PIXIE Instrument

The Primordial Inflation Explorer (PIXIE) is an Explorer-class mission concept designed to measure the polarization and absolute intensity of the cosmic microwave background. In the following, we report on the design, fabrication, and performance of the multimode polarization-sensitive bolometers for PIXIE, which are based on silicon thermistors. In particular we focus on several recent advances in the detector design, including the implementation of a scheme to greatly raise the frequencies of the internal vibrational modes of the large-area, low-mass optical absorber structure consisting of a grid of micromachined, ion-implanted silicon wires. With approximately 30 times the absorbing area of the spider-web bolometers used by Planck, the tensioning scheme enables the PIXIE bolometers to be robust in the vibrational and acoustic environment at launch of the space mission. More generally, it could be used to reduce microphonic sensitivity in other types of low temperature detectors. We also report on the performance of the PIXIE bolometers in a dark cryogenic environment

Safety culture in a major accredited Irish university teaching hospital: a mixed methods study using the safety attitudes questionnaire.

Background: The measurement of safety culture, the way in which members of an organisation think about and prioritise safety, in a hospital can provide valuable insight and inform quality improvement strategies. Aims: The aim of this study is to describe the safety culture of a university teaching hospital in the Republic of Ireland. Methods: This is a mixed methods survey study using the Safety Attitudes Questionnaire (SAQ). The SAQ was distributed to all staff in the study hospital. Staff attitudes towards six domains of patient safety culture were assessed over 32 Likert-scaled items. Thematic analysis was performed on qualitative data. Results: A total of 768 staff members completed and returned a copy of the SAQ. The hospital scored above the international benchmark in five out of six domains, indicating a positive safety culture, but scored below the international benchmark in the domain 'Working Conditions'. This positive safety culture was not mirrored in the qualitative data, from which five themes emerged; three major-Staffing Issues, Patient-Focused Care and Hospital Environment-and two minor-Safe Reporting Culture and Training and Education. Conclusions: In this study, a mixed methods approach was successfully used to investigate the safety culture in a large Irish hospital. Although the SAQ results indicated a positive safety culture, the qualitative data revealed a number of issues that the hospital staff felt impacted negatively on patient safety. The results of this study will inform future work on the design of an intervention to improve patient safety in the hospital

Taming tosyl azide: the development of a scalable continuous diazo transfer process

Heat and shock sensitive tosyl azide was generated and used on demand in a telescoped diazo transfer process. Small quantities of tosyl azide were accessed in a 'one pot' batch procedure using shelf stable, readily available reagents. For large scale diazo transfer reactions tosyl azide was generated and used in a telescoped flow process, to mitigate the risks associated with handling potentially explosive reagents on scale. The in situ formed tosyl azide was used to rapidly perform diazo transfer to a range of acceptors, including beta-ketoesters, beta-ketoamides, malonate esters and beta-ketosulfones. An effective in-line quench of sulfonyl azides was also developed, whereby a sacrificial acceptor molecule ensured complete consumption of any residual hazardous diazo transfer reagent. The telescoped diazo transfer process with in-line quenching was used to safely prepare over 21 g of an alpha-diazocarbonyl in > 98% purity without any column chromatography

Exploiting continuous processing for challenging diazo transfer and telescoped copper-catalyzed asymmetric transformations

Generation and use of triflyl azide in flow enables efficient synthesis of a range of α-diazocarbonyl compounds, including α-diazoketones, α-diazoamides, and an α-diazosulfonyl ester, via both Regitz-type diazo transfer and deacylative/debenzoylative diazo-transfer processes with excellent yields and offers versatility in the solvent employed, in addition to addressing the hazards associated with handling of this highly reactive sulfonyl azide. Telescoping the generation of triflyl azide and diazo-transfer process with highly enantioselective copper-mediated intramolecular aromatic addition and C–H insertion processes demonstrates that the reaction stream containing the α-diazocarbonyl compound can be obtained in sufficient purity to pass directly over the immobilized copper bis(oxazoline) catalyst without detrimentally impacting the catalyst enantioselectivity

Zebrafish brd2a and brd2b are paralogous members of the bromodomain-ET (BET) family of transcriptional coregulators that show structural and expression divergence

<p>Abstract</p> <p>Background</p> <p>Brd2 belongs to the bromodomain-extraterminal domain (BET) family of transcriptional co-regulators, and functions as a pivotal histone-directed recruitment scaffold in chromatin modification complexes affecting signal-dependent transcription. Brd2 facilitates expression of genes promoting proliferation and is implicated in apoptosis and in egg maturation and meiotic competence in mammals; it is also a susceptibility gene for juvenile myoclonic epilepsy (JME) in humans. The <it>brd2 </it>ortholog in <it>Drosophila </it>is a maternal effect, embryonic lethal gene that regulates several homeotic loci, including Ultrabithorax. Despite its importance, there are few systematic studies of <it>Brd2 </it>developmental expression in any organism. To help elucidate both conserved and novel gene functions, we cloned and characterized expression of <it>brd2 </it>cDNAs in zebrafish, a vertebrate system useful for genetic analysis of development and disease, and for study of the evolution of gene families and functional diversity in chordates.</p> <p>Results</p> <p>We identify cDNAs representing two paralogous <it>brd2 </it>loci in zebrafish, <it>brd2a </it>on chromosome 19 and <it>brd2b </it>on chromosome 16. By sequence similarity, syntenic and phylogenetic analyses, we present evidence for structural divergence of <it>brd2 </it>after gene duplication in fishes. <it>brd2 </it>paralogs show potential for modular domain combinations, and exhibit distinct RNA expression patterns throughout development. RNA <it>in situ </it>hybridizations in oocytes and embryos implicate <it>brd2a </it>and <it>brd2b </it>as maternal effect genes involved in egg polarity and egg to embryo transition, and as zygotic genes important for development of the vertebrate nervous system and for morphogenesis and differentiation of the digestive tract. Patterns of <it>brd2 </it>developmental expression in zebrafish are consistent with its proposed role in <it>Homeobox </it>gene regulation.</p> <p>Conclusion</p> <p>Expression profiles of zebrafish <it>brd2 </it>paralogs support a role in vertebrate developmental patterning and morphogenesis. Our study uncovers both maternal and zygotic contributions of <it>brd2</it>, the analysis of which may provide insight into the earliest events in vertebrate development, and the etiology of some forms of epilepsy, for which zebrafish is an important model. Knockdowns of <it>brd2 </it>paralogs in zebrafish may now test proposed function and interaction with homeotic loci in vertebrates, and help reveal the extent to which functional novelty or partitioning has occurred after gene duplication.</p

Ongoing Laboratory Performance Study on Chemical Analysis of Hydrophobic and Hydrophilic Compounds in Three Aquatic Passive Samplers

The quality of chemical analysis is an important aspect of passive sampling-based environmental assessments. The present study reports on a proficiency testing program for the chemical analysis of hydrophobic organic compounds in silicone and low-density polyethylene (LDPE) passive samplers and hydrophilic compounds in polar organic chemical integrative samplers. The median between-laboratory coefficients of variation (CVs) of hydrophobic compound concentrations in the polymer phase were 33% (silicone) and 38% (LDPE), similar to the CVs obtained in four earlier rounds of this program. The median CV over all rounds was 32%. Much higher variabilities were observed for hydrophilic compound concentrations in the sorbent: 50% for the untransformed data and a factor of 1.6 after log transformation. Limiting the data to the best performing laboratories did not result in less variability. Data quality for hydrophilic compounds was only weakly related to the use of structurally identical internal standards and was unrelated to the choice of extraction solvent and extraction time. Standard deviations of the aqueous concentration estimates for hydrophobic compound sampling by the best performing laboratories were 0.21 log units for silicone and 0.27 log units for LDPE (factors of 1.6 to 1.9). The implications are that proficiency testing programs may give more realistic estimates of uncertainties in chemical analysis than within-laboratory quality control programs and that these high uncertainties should be taken into account in environmental assessments