Human-Nonhuman Chimeras, Ontology, and Dignity: A Constructivist Approach to the Ethics of Conducting Research on Cross-Species Hybrids

Developments in biological technology in the last few decades highlight the surprising and ever-expanding practical benefits of stem cells. With this progress, the possibility of combining human and nonhuman organisms is a reality, with ethical boundaries that are not readily obvious. These inter-species hybrids are of a larger class of biological entities called “chimeras.” As the concept of a human-nonhuman creature is conjured in our minds, either incredulous wonder or grotesque horror is likely to follow. This paper seeks to mitigate those worries and demotivate reasonable concerns raised against chimera research, all the while pressing current ethical positions toward their plausible conclusions. In service of this overall aim, first, I intend to show that chimeras are far less foreign and fantastic in light of recent research in the lab; second, I intend to show that anti-realist (so-called “constructivist”) commitments regarding species ontology render the species distinction (i.e., the divide between human and nonhuman) superfluous as a basis for ethical practice; and third, I discuss some prevailing dignity accounts regarding the practical ethics of the creation, research, and treatment of chimeras. Consequently I intend to show that the adoption of this particular set of views (constructivist ontology, capacity-based ethics) in conjunction with recent research ought to justify a parallel with what we accord to humans persons, and that trajectory allows for cases of moral permissibility

The Use of Simulation in Pre-doctoral Medical Emergencies Training

poster abstractObjective: This purpose of this study was to determine the level and method of teaching medical emergencies management in U.S. pre-doctoral programs, particularly the extent to which patient simulation techniques are employed for instruction and /or assessment. Methods: In the fall of 2013, a 22- item survey instrument was developed, piloted with a small cohort of oral and maxillofacial surgery faculty, and modified based on feedback. Survey items assessed curriculum content and teaching methods used for medical emergencies training, and program demographics. A link to the survey was sent to the institutional email of the Academic Dean and Oral and Maxillofacial Surgery Department Chair at each U.S. dental school. The internet-based survey platform Qualtrics was used to record responses and track non-responders. Two follow-up reminders were sent via email to non-responders. Response data were de-identified and statistical analyses were conducted. Results: Completed surveys were returned by respondents from 40 schools (62.5% response rate). Of responding schools, 95% (38) offered medical emergencies training; teaching methods included lecture, seminar, and small group learning. Median instruction time was 12 hours. Of responding schools, 12 reported providing management of medical emergencies instruction via high fidelity patient simulation (HFPS), 16 used role playing, 5 employed computer-based programs, and 6 utilized standardized patients. While 6 schools reported employing HFPS for 3-5 yrs., no school reported using it for > 5 yrs.; however, 4 schools reported utilizing role-playing for > 5 yrs. While class size was not significantly associated with use of HFPS, cost was significantly associated with non-use of HFPS (p=0.0274). Conclusions: Although the vast majority of pre-doctoral dental programs educate students in the management of medical emergencies, few programs utilize simulation as an instructional method

Minimum disparity estimators for discrete and continuous models

summary:Disparities of discrete distributions are introduced as a natural and useful extension of the information-theoretic divergences. The minimum disparity point estimators are studied in regular discrete models with i.i.d. observations and their asymptotic efficiency of the first order, in the sense of Rao, is proved. These estimators are applied to continuous models with i.i.d. observations when the observation space is quantized by fixed points, or at random, by the sample quantiles of fixed orders. It is shown that the random quantization leads to estimators which are robust in the sense of Lindsay [9], and which can achieve the efficiency in the underlying continuous models provided these are regular enough

Analysis of Binding Site Hot Spots on the Surface of Ras GTPase

We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the “off” and “on” allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond the active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target

Encounter complexes and dimensionality reduction in protein-protein association

An outstanding challenge has been to understand the mechanism whereby proteins associate. We report here the results of exhaustively sampling the conformational space in protein–protein association using a physics-based energy function. The agreement between experimental intermolecular paramagnetic relaxation enhancement (PRE) data and the PRE profiles calculated from the docked structures shows that the method captures both specific and non-specific encounter complexes. To explore the energy landscape in the vicinity of the native structure, the nonlinear manifold describing the relative orientation of two solid bodies is projected onto a Euclidean space in which the shape of low energy regions is studied by principal component analysis. Results show that the energy surface is canyon-like, with a smooth funnel within a two dimensional subspace capturing over 75% of the total motion. Thus, proteins tend to associate along preferred pathways, similar to sliding of a protein along DNA in the process of protein-DNA recognition

Thermal regimes of HTS cylinders operating in devices for fault current limitation

We reveal obstacles related to the application of HTS cylinders in current limiting devices based on the superconducting - normal state transition. It is shown that, at the critical current density achieved presently in bulk materials, and especially in BSCCO-2212, the required thickness of the cylinder wall in a full-scale inductive device achieves several centimeters. A simple mathematical model of the operation of an inductive fault current limiter (FCL) is used to show that such cylinders cannot be cooled in admissible time after a fault clearing and, hence, the inductive FCLs and current-limiting transformers employing BSCCO cylinders do not return to the normal operation in the time required. For the recovery even with a non-current pause in the circuit, the cylinders are needed with the critical current density by an order higher than the existed ones.Comment: 15 pages, 5 figure

X-ray remote sensing and in-situ spectroscopy for planetary exploration missions and gamma-ray remote sensing and in-situ spectroscopy for planetary exploration missions

Detectors that will be used for planetary missions must have their responses calibrated in a reproducible manner. A calibration facility is being constructed at Schlumberger-Doll Research for gamma and x ray detectors. With this facility the detector response can be determined in an invariant and reproducible fashion. Initial use of the facility is expected for the MARS94 detectors. Work is continuing to better understand the rare earth oxyorthosilicates and to define their characteristics. This will allow a better use of these scintillators for planetary missions. In a survey of scintillating materials two scintillators were identified as promising candidates besides GSO, LSO, and YSO. These are CdWO4 and CsI(Tl). It will be investigated if a detector with a better overall performance can be assembled with various photon converters. Considerable progress was achieved in photomultiplier design. The length of an 1 inch diameter PMT could be reduced from 4.2 to 2.5 inches without performance degradation. This technology is being employed in the gamma ray detector for the NEAR project. A further weight and size reduction of the detector package can be achieved with miniaturized integrated power supplies

The outcomes of pregnancy in women with untreated epilepsy

Purpose: To determine the outcomes in regards to seizure control and foetal malformation in pregnant women with epilepsy not treated with antiepileptic drugs (AEDs). Method: Analysis of data from the Australian Register of AEDs in Pregnancy on 148 women with epilepsy who were not receiving AEDs before and during at least the first trimester of pregnancy. Results: Seizure control was less likely to be maintained in AED-untreated pregnancies. Whether AED therapy had been ceased in preparation for pregnancy, or had not been employed for long periods before pregnancy, made no statistically significant difference to seizure control outcomes, but those who ceased therapy in preparation for pregnancy were more likely to again be taking AED therapy by term. Foetal malformation rates were reasonably similar in untreated pregnancies, and in treated pregnancies if pregnancies exposed to known AED teratogens (valproate and probably topiramate) were excluded from consideration. Conclusion: Leaving epilepsy untreated during pregnancy appears disadvantageous from the standpoint of seizure control: it also does not reduce the hazard of foetal malformation unless it avoids valproate or topiramate intake during pregnancy