The production of mosaic mutations in Neurospora crassa

The production of mosaic mutations in Neurospora crass

Can Modal Skepticism Defeat Humean Skepticism?

My topic is moderate modal skepticism in the spirit of Peter van Inwagen. Here understood, this is a conservative version of modal empiricism that severely limits the extent to which an ordinary agent can reasonably believe “exotic” possibility claims. I offer a novel argument in support of this brand of skepticism: modal skepticism grounds an attractive (and novel) reply to Humean skepticism. Thus, I propose that modal skepticism be accepted on the basis of its theoretical utility as a tool for dissolving philosophical paradox

Empirically-Informed Modal Rationalism

In this chapter, it is suggested that our epistemic access to metaphysical modality generally involves rationalist, a priori elements. However, these a priori elements are much more subtle than ‘traditional’ modal rationalism assumes. In fact, some might even question the ‘apriority’ of these elements, but I should stress that I consider a priori and a posteriori elements especially in our modal inquiry to be so deeply intertwined that it is not easy to tell them apart. Supposed metaphysically necessary identity statements involving natural kind terms are a good example: the fact that empirical input is crucial in establishing their necessity has clouded the role and content of the a priori input, as I have previously argued (Tahko forthcoming). For instance, the supposed metaphysically necessary identity statement involving water and its microstructure can only be established with the help of a controversial a priori principle concerning the determination of chemical properties by microstructure. The Kripke-Putnam framework of modal epistemology fails precisely because it is unclear whether the required a priori element is present. My positive proposal builds on E. J. Lowe’s work. Lowe holds that our knowledge of metaphysical modality is based on our knowledge of essence. Lowe’s account strives to offer a uniform picture of modal epistemology: essence is the basis of all our modal knowledge. This is the basis of Lowe’s modal rationalism. I believe that Lowe’s proposal is on the right lines in the case of abstract objects, but I doubt that it can be successfully applied to the case of natural kinds. Accordingly, the case of natural kinds will be my main focus and I will suggest that modal rationalism, at least as it is traditionally understood, falls short of explaining modal knowledge concerning natural kinds. Yet, I think that Lowe has identified something of crucial importance for modal epistemology, namely the essentialist, a priori elements present in our modal inquiry. The upshot is that rather than moving all the way from modal rationalism to modal empiricism, a type of hybrid approach, ‘empirically-informed modal rationalism’, can be developed.Peer reviewe

What do young adolescents think about taking part in longitudinal self-harm research?: findings from a school-based study

Background: Research about self-harm in adolescence is important given the high incidence in youth, and strong links to suicide and other poor outcomes. Clarifying the impact of involvement in school based self-harm studies on young adolescents is an ethical priority given heightened risk at this developmental stage. Methods: Here, 594 school-based students aged mainly 13-14 years completed a survey on self-harm at baseline and again 12-weeks later. Change in mood following completion of each survey, ratings and thoughts about participation, and responses to a mood-mitigation activity were analysed using a multi-method approach. Results: Baseline participation had no overall impact on mood. However, boys and girls reacted differently to the survey depending on self-harm status. Having a history of self-harm had a negative impact on mood for girls, but a positive impact on mood for boys. In addition, participants rated the survey in mainly positive/neutral terms, and cited benefits including personal insight and altruism. At follow-up, there was a negative impact on mood following participation, but no significant effect of gender or self-harm status. Ratings at follow-up were mainly positive/neutral. Those who had self-harmed reported more positive and fewer negative ratings than at baseline: the opposite pattern of response was found for those who had not self-harmed. Mood mitigation activities were endorsed. Conclusions: Self-harm research with youth is feasible in school settings. Most young people are happy to take part and cite important benefits. However, the impact of participation in research appears to vary according to gender, self-harm risk and method/time of assessment. The impact of repeated assessment requires clarification. Simple mood-elevation techniques may usefully help to mitigate distress

An empirical evaluation of the impact of missing data on treatment effect

Objectives Missing data represent a potential source of bias in randomized clinical trials (RCTs). A simple approach that makes use of the responses subsequently obtained via reminder is proposed to assess the validity of the inferences from a missing at random (MAR)-based primary analysis of incomplete RCTs. Methods We explored mechanism behind the reminder responses in two pragmatic RCTs - the TATE and STarT Back trials - by utilizing the fact that data that are recovered through reminders would otherwise have been missing. The present approach considered two data scenarios: (i) with the actual dataset and (ii) with a modified dataset, where outcome responses obtained after a certain number of reminders were treated as missing. The impact of the reminder responses was assessed by comparing the estimates from MAR-based analyses between the two data scenarios. Results In the TATE trial, the reminder approach showed that an MAR-based analysis was likely to yield biased estimates of treatment effect. Therefore, further sensitivity analyses were required under a range of plausible missing not at random (MNAR) assumptions. However, in the STarT Back trial, this approach showed that an MAR-based analysis was likely to yield an unbiased estimate of treatment effect. Conclusion The proposed reminder approach can be used to assess the robustness of the MAR assumption by checking expected consistency in MAR-based estimates. If the results deviate, then MAR-based estimates are likely to be biased, and analyses incorporating a range of plausible MNAR assumptions are advisable at least as sensitivity tests for the evaluation of treatment effect

A comparison of high-level waste form characteristics

There are currently about 1055 million curies of high-level waste with a thermal output of about 2950 kilowatts (KW) at four sites in the United States: West Valley Demonstration Project (WVDP), Savannah River Site (SRS), Hanford Site (HANF), and Idaho National Engineering Laboratory (INEL). These quantities are expected to increase to about 1200 million curies and 3570 kw by the end of year 2020. Under the Nuclear Waste Policy Act, this high-level waste must ultimately be disposed of in a geologic repository. Accordingly, canisters of high-level waste immobilized in borosilicate glass or glass-ceramic mixtures are to be produced at the four sites and stored there until a repository becomes available. Data on the estimated production schedules and on the physical, chemical, and radiological characteristics of the canisters of immobilized high-level waste have been collected in OCRWM's Waste Characteristics Data Base, including recent updates an revisions. Comparisons of some of these data for the four sites are presented in this report. 14 refs., 3 tabs

Microbe sample from Escherichia coli

BioSample: SAMN11037806; Sample name: C41 delta ompF delta acrB; SRA: SRS442251

Improving the purification of membrane proteins from Escherichia coli C41(DE3)

The overexpression and purification of membrane proteins to high purity and homogeneity is a challenging task. Over time, several strains have been developed that decrease the toxic side-effects and thus result in higher bio mass and protein yield. However, two major contaminants have been identified in membrane protein preparations from E. coli: the outer membrane porin OmpF and AcrB, which is part of a tripartite efflux pump. Both proteins crystallise from low concentrations and diverse conditions, which make them a major problem, especially in membrane protein crystallography. In this study, we present a C41(DE3)-derived expression strains that is depleted of these two proteins