Robust Hypothesis Tests for Detecting Statistical Evidence of 2D and 3D Interactions in Single-Molecule Measurements

A variety of experimental techniques have improved the 2D and 3D spatial resolution that can be extracted from \emph{in vivo} single-molecule measurements. This enables researchers to quantitatively infer the magnitude and directionality of forces experienced by biomolecules in their native cellular environments. Situations where such forces are biologically relevant range from mitosis to directed transport of protein cargo along cytoskeletal structures. Models commonly applied to quantify single-molecule dynamics assume that effective forces and velocity in the $x,y$ (or $x,y,z$) directions are statistically independent, but this assumption is physically unrealistic in many situations. We present a hypothesis testing approach capable of determining if there is evidence of statistical dependence between positional coordinates in experimentally measured trajectories; if the hypothesis of independence between spatial coordinates is rejected, then a new model accounting for 2D (3D) interactions should be considered to more faithfully represent the underlying experimental kinetics. The technique is robust in the sense that 2D (3D) interactions can be detected via statistical hypothesis testing even if there is substantial inconsistency between the physical particle's actual noise sources and the simplified model's assumed noise structure. For example, 2D (3D) interactions can be reliably detected even if the researcher assumes normal diffusion, but the experimental data experiences "anomalous diffusion" and/or is subjected to a measurement noise characterized by a distribution differing from that assumed by the fitted model. The approach is demonstrated on control simulations and on experimental data (IFT88 directed transport in the primary cilium).Comment: 7 pages, 6 figure

The Assessment of Impacts and Risks of Climate Change on Agriculture (AIRCCA) model:a tool for the rapid global risk assessment for crop yields at a spatially explicit scale

A main channel through which climate change is expected to affect the economy is the agricultural sector. Large spatial variability in these impacts and high levels of uncertainty in climate change projections create methodological challenges for assessing the consequences this sector could face. Crop emulators based on econometric fixed-effects models that can closely reproduce biophysical models are estimated. With these reduced form crop emulators, we develop AIRCCA, a user-friendly software for the assessment of impacts and risks of climate change on agriculture, that allows stakeholders to make a rapid global assessment of the effects of climate change on maize, wheat and rice yields. AIRCCA produces spatially explicit probabilistic impact scenarios and user-defined risk metrics for the main four Intergovernmental Panel on Climate Change’s (IPCC) emissions scenarios

The roles of Bcl-x(L )in modulating apoptosis during development of Xenopus laevis

BACKGROUND: Apoptosis is a common and essential aspect of development. It is particularly prevalent in the central nervous system and during remodelling processes such as formation of the digits and in amphibian metamorphosis. Apoptosis, which is dependent upon a balance between pro- and anti-apoptotic factors, also enables the embryo to rid itself of cells damaged by gamma irradiation. In this study, the roles of the anti-apoptotic factor Bcl-x(L )in protecting cells from apoptosis were examined in Xenopus laevis embryos using transgenesis to overexpress the XR11 gene, which encodes Bcl-x(L). The effects on developmental, thyroid hormone-induced and γ-radiation-induced apoptosis in embryos were examined in these transgenic animals. RESULTS: Apoptosis was abrogated in XR11 transgenic embryos. However, the transgene did not prevent the apoptotic response of tadpoles to thyroid hormone during metamorphosis. Post-metamorphic XR11 frogs were reared to sexual maturity, thus allowing us to produce second-generation embryos and enabling us to distinguish between the maternal and zygotic contributions of Bcl-x(L )to the γ-radiation apoptotic response. Wild-type embryos irradiated before the mid-blastula transition (MBT) underwent normal cell division until reaching the MBT, after which they underwent massive, catastrophic apoptosis. Over-expression of Bcl-x(L )derived from XR11 females, but not males, provided partial protection from apoptosis. Maternal expression of XR11 was also sufficient to abrogate apoptosis triggered by post-MBT γ-radiation. Tolerance to post-MBT γ-radiation from zygotically-derived XR11 was acquired gradually after the MBT in spite of abundant XR11 protein synthesis. CONCLUSION: Our data suggest that Bcl-x(L )is an effective counterbalance to proapoptotic factors during embryonic development but has no apparent effect on the thyroid hormone-induced apoptosis that occurs during metamorphosis. Furthermore, post-MBT apoptosis triggered by irradiation before the MBT could only be restrained by maternal expression of Bcl-x(L). Although maternal expression of XR11 was sufficient to abrogate apoptosis triggered by post-MBT γ-radiation, radiation tolerance from zygotically-derived XR11 was acquired gradually, indicating that synthesis of XR11 protein is not sufficient to prevent apoptosis. Thus, repression of radiation-induced apoptosis by overexpression of Bcl-x(L )during embryonic development depends upon the timing of its expression and post-translational events that enable the protein to become effective

Capillarity in pressure infiltration: improvements in characterization of high-temperature systems

In the pressure infiltration of metal matrix composites, molten metal is injected under external pressure into a porous preform of the reinforcing material. Equilibrium capillary parameters characterizing wetting for this process are summarized in plots of metal saturation versus applied pressure, also known as drainage curves. Such curves can be measured in our laboratory during a single experiment with an infiltration apparatus designed to track the rate of metal penetration into porous preforms under conditions characteristic of metal matrix composite processing (temperatures in excess of 1000°C and pressures in the order of 10MPa). For such measurements to be valid, infiltration of the preform with molten metal must be mechanically quasi-static, i.e., the metal must flow at a rate sufficiently low for the metal pressure to be essentially uniform across the preform at all times. We examine this requirement quantitatively, using a finite-difference model that simulates the unsaturated unidirectional ingress of molten metal into a ceramic particle preform of finite width. We furthermore present improvements in the experimental apparatus developed in our laboratory to measure the entire drainage curve in a single experiment. We compare numerical results with new experimental data for the copper/alumina system to show (i) that pressurization rates sufficiently low for quasi-static infiltration can be produced with this apparatus, and (ii) that taking the relative permeability equal to the saturation yields better agreement with experiment than does the expression originally proposed by Brooks and Core

The first direct measurement of ¹²C (¹²C,n) ²³Mg at stellar energies

Neutrons produced by the carbon fusion reaction ¹²C(¹²C,n)²³Mg play an important role in stellar nucleosynthesis. However, past studies have shown large discrepancies between experimental data and theory, leading to an uncertain cross section extrapolation at astrophysical energies. We present the first direct measurement that extends deep into the astrophysical energy range along with a new and improved extrapolation technique based on experimental data from the mirror reaction ¹²C(¹²C,p)²³Na. The new reaction rate has been determined with a well-defined uncertainty that exceeds the precision required by astrophysics models. Using our constrained rate, we find that ¹²C(¹²C,n)²³Mg is crucial to the production of Na and Al in Pop-III Pair Instability Supernovae. It also plays a non-negligible role in the production of weak s-process elements as well as in the production of the important galacti