Laser Spectroscopy for Atmospheric and Environmental Sensing

Lasers and laser spectroscopic techniques have been extensively used in several applications since their advent, and the subject has been reviewed extensively in the last several decades. This review is focused on three areas of laser spectroscopic applications in atmospheric and environmental sensing; namely laser-induced fluorescence (LIF), cavity ring-down spectroscopy (CRDS), and photoluminescence (PL) techniques used in the detection of solids, liquids, aerosols, trace gases, and volatile organic compounds (VOCs)

Functional polarity is introduced by Dicer processing of short substrate RNAs

Synthetic RNA duplexes that are substrates for Dicer are potent triggers of RNA interference (RNAi). Blunt 27mer duplexes can be up to 100-fold more potent than traditional 21mer duplexes (1). Not all 27mer duplexes show increased potency. Evaluation of the products of in vitro dicing reactions using electrospray ionization mass spectrometry reveals that a variety of products can be produced by Dicer cleavage. Use of asymmetric duplexes having a single 2-base 3′-overhang restricts the heterogeneity that results from dicing. Inclusion of DNA residues at the ends of blunt duplexes also limits heterogeneity. Combination of asymmetric 2-base 3′-overhang with 3′-DNA residues on the blunt end result in a duplex form which directs dicing to predictably yield a single primary cleavage product. It is therefore possible to design a 27mer duplex which is processed by Dicer to yield a specific, desired 21mer species. Using this strategy, two different 27mers can be designed that result in the same 21mer after dicing, one where the 3′-overhang resides on the antisense (AS) strand and dicing proceeds to the ‘right’ (‘R’) and one where the 3′-overhang resides on the sense (S) strand and dicing proceeds to the ‘left’ (‘L’). Interestingly, the ‘R’ version of the asymmetric 27mer is generally more potent in reducing target gene levels than the ‘L’ version 27mer. Strand targeting experiments show asymmetric strand utilization between the two different 27mer forms, with the ‘R’ form favoring S strand and the ‘L’ form favoring AS strand silencing. Thus, Dicer processing confers functional polarity within the RNAi pathway

A role for the Dicer helicase domain in the processing of thermodynamically unstable hairpin RNAs

In humans a single species of the RNAseIII enzyme Dicer processes both microRNA precursors into miRNAs and long double-stranded RNAs into small interfering RNAs (siRNAs). An interesting but poorly understood domain of the mammalian Dicer protein is the N-terminal helicase-like domain that possesses a signature DExH motif. Cummins et al. created a human Dicer mutant cell line by inserting an AAV targeting cassette into the helicase domain of both Dicer alleles in HCT116 cells generating an in-frame 43-amino-acid insertion immediately adjacent to the DExH box. This insertion creates a Dicer mutant protein with defects in the processing of most, but not all, endogenous pre-miRNAs into mature miRNA. Using both biochemical and computational approaches, we provide evidence that the Dicer helicase mutant is sensitive to the thermodynamic properties of the stems in microRNAs and short-hairpin RNAs, with thermodynamically unstable stems resulting in poor processing and a reduction in the levels of functional mi/siRNAs. Paradoxically, this mutant exhibits enhanced processing efficiency and concomitant RNA interference when thermodynamically stable, long-hairpin RNAs are used. These results suggest an important function for the Dicer helicase domain in the processing of thermodynamically unstable hairpin structures

Dbf2–Mob1 drives relocalization of protein phosphatase Cdc14 to the cytoplasm during exit from mitosis

Exit from mitosis is characterized by a precipitous decline in cyclin-dependent kinase (Cdk) activity, dissolution of mitotic structures, and cytokinesis. In Saccharomyces cerevisiae, mitotic exit is driven by a protein phosphatase, Cdc14, which is in part responsible for counteracting Cdk activity. Throughout interphase, Cdc14 is sequestered in the nucleolus, but successful anaphase activates the mitotic exit network (MEN), which triggers dispersal of Cdc14 throughout the cell by a mechanism that has remained unknown. In this study, we show that a MEN component, protein kinase Dbf2–Mob1, promotes transfer of Cdc14 to the cytoplasm and consequent exit from mitosis by direct phosphorylation of Cdc14 on serine and threonine residues adjacent to a nuclear localization signal (NLS), thereby abrogating its NLS activity. Our results define a mechanism by which the MEN promotes exit from mitosis

Giving ecological meaning to satellite-derived fire severity metrics across North American forests

Satellite-derived spectral indices such as the relativized burn ratio (RBR) allow fire severity maps to be produced in a relatively straightforward manner across multiple fires and broad spatial extents. These indices often have strong relationships with field-based measurements of fire severity, thereby justifying their widespread use in management and science. However, satellite-derived spectral indices have been criticized because their non-standardized units render them difficult to interpret relative to on-the-ground fire effects. In this study, we built a Random Forest model describing a field-based measure of fire severity, the composite burn index (CBI), as a function of multiple spectral indices, a variable representing spatial variability in climate, and latitude. CBI data primarily representing forested vegetation from 263 fires (8075 plots) across the United States and Canada were used to build the model. Overall, the model performed well, with a cross-validated R2 of 0.72, though there was spatial variability in model performance. The model we produced allows for the direct mapping of CBI, which is more interpretable compared to spectral indices. Moreover, because the model and all spectral explanatory variables were produced in Google Earth Engine, predicting and mapping of CBI can realistically be undertaken on hundreds to thousands of fires. We provide all necessary code to execute the model and produce maps of CBI in Earth Engine. This study and its products will be extremely useful to managers and scientists in North America who wish to map fire effects over large landscapes or regions

Empathetic Understanding and Deliberative Democracy

Epistemic democracy is standardly characterized in terms of “aiming at truth”. This presupposes a veritistic conception of epistemic value, according to which truth is the fundamental epistemic goal. I will raise an objection to the standard (veritistic) account of epistemic democracy, focusing specifically on deliberative democracy. I then propose a version of deliberative democracy that is grounded in non‐veritistic epistemic goals. In particular, I argue that deliberation is valuable because it facilitates empathetic understanding. I claim that empathetic understanding is an epistemic good that doesn't have truth as its primary goal

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

What is (accounting) history?

I am grateful for the invitation to present this paper to you today. I have had a long association with Victoria University and as an undergraduate here I was introduced to the fathers of history - Herodotus and Thucydides. Unfortunately, although I had to read their main works, at the time I remained oblivious to their full significance, namely, that they represent two extremes of historiography that have remained throughout the history of history - two approaches to how history is created and written. These themes are the background for this paper. However, before I go any further I want to make a clarification - Philip was keen that my presentation remain consistent with the theme of the conference - history and the state. This is not difficult as the great majority of written history has been about the state . Both Herodotus and Thucydides were, of course, writing histories of the state , namely Athens. And, of course, if we are considering theories of history we can recall that Plato pointed out, any theory of man (sic), implicit or explicit, will be reflected in a theory of the state (cf Rist, 2002, pp 228 - 229)