Ethics, space, and somatic sensibilities: comparing relationships between scientific researchers and their human and animal experimental subjects

Drawing on geographies of affect and nature-society relations, we propose a radical rethinking of how scientists, social scientists, and regulatory agencies conceptualise human and animal participants in scientif ic research. The scientific rationale for using animal bodies to simulate what could be done in human bodies emphasises shared somatic capacities that generate comparable responses to clinical interventions. At the same time, regulatory guidelines and care practices stress the differences between human and animal subjects. In this paper we consider the implications of this differentiation between human and animal bodies in ethical and welfare protocols and practices. We show how the bioethical debates around the use of human subjects tend to focus on issues of consent and language, while recent work in animal welfare reflects an increasing focus on the affectual dimensions of ethical practice. We argue that this attention to the more-than-representational dimensions of ethics and welfare might be equally important for human subjects. We assert that paying attention to these somatic sensibilities can offer insights into how experimental environments can both facilitate and restrict the development of more care-full and response-able relations between researchers and their experimental subjects. <br/

An Instrument For Investigation of the Cosmic Microwave Background Radiation at Intermediate Angular Scales

We describe an off-axis microwave telescope for observations of the anisotropy in the cosmic microwave background (CMB) radiation on angular scales between 0.5 deg and 3 deg. The receiver utilizes cryogenic high-electron-mobility transistor (HEMT) amplifiers and detects the total power in multiple 3 GHz wide channels. Both frequency and polarization information are recorded allowing discrimination between CMB radiation and potential foreground sources and allowing checks for systematic effects. The instrumental radiometric offset is small (~1 mK). Data are taken by rapidly sampling while sweeping the beam many beamwidths across the sky. After detection, a spatio-temporal filter is formed in software which optimizes the sensitivity in a multipole band in the presence of atmospheric fluctuations. Observations were made from Saskatoon, Saskatchewan (SK), Canada during the winter of 1993 with six channels between 27.6 and 34.0 GHz, in 1994 with twelve channels between 27.6 and 44.1 GHz, and in 1995 with six channels between 38.2 and 44.1 GHz. The performance of the instrument and assessment of the atmospheric noise at this site are discussed.Comment: latex file is called inst.tex. 30 pages with 14 Postscript figures. Uses aas2pp4.sty (included). Submitted to Ap

Electron exchange model potential: Application to positronium-helium scattering

The formulation of a suitable nonlocal model potential for electron exchange is presented, checked with electron-hydrogen and electron-helium scattering, and applied to the study of elastic and inelastic scattering and ionization of ortho positronium (Ps) by helium. The elastic scattering and the $n = 2$ excitations of Ps are investigated using a three-Ps-state close-coupling approximation. The higher ($n\ge 3$) excitations and ionization of Ps atom are treated in the framework of Born approximation with present exchange. Calculations are reported of phase shifts, and elastic, Ps-excitation, and total cross sections. The present target elastic total cross section agrees well with experimental results at thermal to medium energies.Comment: 16 latex pages, 7 postscript figure

Polypyrrole-Fe2O3 nanohybrid materials for electrochemical storage

We report on the synthesis and electrochemical characterization of nanohybrid polypyrrole (PPy) (PPy/Fe2O3) materials for electrochemical storage applications. We have shown that the incorporation of nanoparticles inside the PPy notably increases the charge storage capability in comparison to the “pure” conducting polymer. Incorporation of large anions, i.e., paratoluenesulfonate, allows a further improvement in the capacity. These charge storage modifications have been attributed to the morphology of the composite in which the particle sizes and the specific surface area are modified with the incorporation of nanoparticles. High capacity and stability have been obtained in PC/NEt4BF4 (at 20 mV/s), i.e., 47 mAh/g, with only a 3% charge loss after one thousand cyles. The kinetics of charge–discharge is also improved by the hybrid nanocomposite morphology modifications, which increase the rate of insertion–expulsion of counter anions in the bulk of the film. A room temperature ionic liquid such as imidazolium trifluoromethanesulfonimide seems to be a promising electrolyte because it further increases the capacity up to 53 mAh/g with a high stability during charge–discharge processes

The PARP inhibitor AZD2461 provides insights into the role of PARP3 inhibition for both synthetic lethality and tolerability with chemotherapy in preclinical models

The PARP inhibitor AZD2461 was developed as a next-generation agent following olaparib, the first PARP inhibitor approved for cancer therapy. In BRCA1-deficient mouse models, olaparib resistance predominantly involves overexpression of P-glycoprotein,so AZD2461 was developed as a poor substrate for drug transporters. Here we demonstrate the efficacy of this compound against olaparib-resistant tumors that overexpress P-glycoprotein. In addition, AZD2461 was better tolerated in combination with chemotherapy than olaparib in mice, which suggests that AZD2461 could have significant advantages over olaparib in the clinic. However, this superior toxicity profile did not extend to rats. Investigations of this difference revealed a differential PARP3 inhibitory activity for each compound and a higher level of PARP3 expression in bone marrow cells from mice as compared with rats and humans. Our findings have implications for the use of mouse models to assess bone marrow toxicity for DNA-damaging agents and inhibitors of the DNA damage response. Finally, structural modeling of the PARP3-active site with different PARP inhibitors also highlights the potential to develop compounds with different PARP family member specificity profiles for optimal antitumor activity and tolerability

Genetically encoded sender-receiver system in 3D mammalian cell culture

Engineering spatial patterning in mammalian cells, employing entirely genetically encoded components, requires solving several problems. These include how to code secreted activator or inhibitor molecules and how to send concentration-dependent signals to neighboring cells, to control gene expression. The Madin-Darby Canine Kidney (MDCK) cell line is a potential engineering scaffold as it forms hollow spheres (cysts) in 3D culture and tubulates in response to extracellular hepatocyte growth factor (HGF). We first aimed to graft a synthetic patterning system onto single developing MDCK cysts. We therefore developed a new localized transfection method to engineer distinct sender and receiver regions. A stable reporter line enabled reversible EGFP activation by HGF and modulation by a secreted repressor (a truncated HGF variant, NK4). By expanding the scale to wide fields of cysts, we generated morphogen diffusion gradients, controlling reporter gene expression. Together, these components provide a toolkit for engineering cell-cell communication networks in 3D cell culture.Facultad de Ciencias Exacta