Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3

The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry. During infection of intestinal epithelial cells, SipA was found to be responsible for the early activation of caspase-3, an enzyme that is required for SipA cleavage at a specific recognition motif that divided the protein into its two functional domains and activated SipA in a manner necessary for pathogenicity. Other caspase-3 cleavage sites identified in S. Typhimurium appeared to be restricted to secreted effector proteins, which indicates that this may be a general strategy used by this pathogen for processing of its secreted effectors

Probing the N=14N = 14 subshell closure: gg factor of the 26^{26}Mg(21+^+_1) state

The first-excited state $g$~factor of $^{26}$Mg has been measured relative to the $g$ factor of the $^{24}$Mg($2^+_1$) state using the high-velocity transient-field technique, giving $g=+0.86\pm0.10$. This new measurement is in strong disagreement with the currently adopted value, but in agreement with the $sd$-shell model using the USDB interaction. The newly measured $g$ factor, along with $E(2^+_1)$ and $B(E2)$ systematics, signal the closure of the $\nu d_{5/2}$ subshell at $N=14$. The possibility that precise $g$-factor measurements may indicate the onset of neutron $pf$ admixtures in first-excited state even-even magnesium isotopes below $^{32}$Mg is discussed and the importance of precise excited-state $g$-factor measurements on $sd$~shell nuclei with $N\neq Z$ to test shell-model wavefunctions is noted.Comment: 8 pages, 5 figure

Surface Mining and Reclamation Effects on Flood Response of Watersheds in the Central Appalachian Plateau Region

Surface mining of coal and subsequent reclamation represent the dominant land use change in the central Appalachian Plateau (CAP) region of the United States. Hydrologic impacts of surface mining have been studied at the plot scale, but effects at broader scales have not been explored adequately. Broad-scale classification of reclaimed sites is difficult because standing vegetation makes them nearly indistinguishable from alternate land uses. We used a land cover data set that accurately maps surface mines for a 187-km2 watershed within the CAP. These land cover data, as well as plot-level data from within the watershed, are used with HSPF (Hydrologic Simulation Program-Fortran) to estimate changes in flood response as a function of increased mining. Results show that the rate at which flood magnitude increases due to increased mining is linear, with greater rates observed for less frequent return intervals. These findings indicate that mine reclamation leaves the landscape in a condition more similar to urban areas rather than does simple deforestation, and call into question the effectiveness of reclamation in terms of returning mined areas to the hydrological state that existed before mining

Extracting non-linear integrate-and-fire models from experimental data using dynamic I–V curves

The dynamic I–V curve method was recently introduced for the efficient experimental generation of reduced neuron models. The method extracts the response properties of a neuron while it is subject to a naturalistic stimulus that mimics in vivo-like fluctuating synaptic drive. The resulting history-dependent, transmembrane current is then projected onto a one-dimensional current–voltage relation that provides the basis for a tractable non-linear integrate-and-fire model. An attractive feature of the method is that it can be used in spike-triggered mode to quantify the distinct patterns of post-spike refractoriness seen in different classes of cortical neuron. The method is first illustrated using a conductance-based model and is then applied experimentally to generate reduced models of cortical layer-5 pyramidal cells and interneurons, in injected-current and injected- conductance protocols. The resulting low-dimensional neuron models—of the refractory exponential integrate-and-fire type—provide highly accurate predictions for spike-times. The method therefore provides a useful tool for the construction of tractable models and rapid experimental classification of cortical neurons

Optimizing end-labeled free-solution electrophoresis by increasing the hydrodynamic friction of the drag-tag

We study the electrophoretic separation of polyelectrolytes of varying lengths by means of end-labeled free-solution electrophoresis (ELFSE). A coarse-grained molecular dynamics simulation model, using full electrostatic interactions and a mesoscopic Lattice Boltzmann fluid to account for hydrodynamic interactions, is used to characterize the drag coefficients of different label types: linear and branched polymeric labels, as well as transiently bound micelles. It is specifically shown that the label's drag coefficient is determined by its hydrodynamic size, and that the drag per label monomer is largest for linear labels. However, the addition of side chains to a linear label offers the possibility to increase the hydrodynamic size, and therefore the label efficiency, without having to increase the linear length of the label, thereby simplifying synthesis. The third class of labels investigated, transiently bound micelles, seems very promising for the usage in ELFSE, as they provide a significant higher hydrodynamic drag than the other label types. The results are compared to theoretical predictions, and we investigate how the efficiency of the ELFSE method can be improved by using smartly designed drag-tags.Comment: 32 pages, 11 figures, submitted to Macromolecule

Staying true with the help of others: doxastic self-control through interpersonal commitment

I explore the possibility and rationality of interpersonal mechanisms of doxastic self-control, that is, ways in which individuals can make use of other people in order to get themselves to stick to their beliefs. I look, in particular, at two ways in which people can make interpersonal epistemic commitments, and thereby willingly undertake accountability to others, in order to get themselves to maintain their beliefs in the face of anticipated “epistemic temptations”. The first way is through the avowal of belief, and the second is through the establishment of collective belief. I argue that both of these forms of interpersonal epistemic commitment can function as effective tools for doxastic self-control, and, moreover, that the control they facilitate should not be dismissed as irrational from an epistemic perspective

A dynamical approach to the spatiotemporal aspects of the Portevin-Le Chatelier effect: Chaos,turbulence and band propagation

Experimental time series obtained from single and poly-crystals subjected to a constant strain rate tests report an intriguing dynamical crossover from a low dimensional chaotic state at medium strain rates to an infinite dimensional power law state of stress drops at high strain rates. We present results of an extensive study of all aspects of the PLC effect within the context a model that reproduces this crossover. A study of the distribution of the Lyapunov exponents as a function of strain rate shows that it changes from a small set of positive exponents in the chaotic regime to a dense set of null exponents in the scaling regime. As the latter feature is similar to the GOY shell model for turbulence, we compare our results with the GOY model. Interestingly, the null exponents in our model themselves obey a power law. The configuration of dislocations is visualized through the slow manifold analysis. This shows that while a large proportion of dislocations are in the pinned state in the chaotic regime, most of them are at the threshold of unpinning in the scaling regime. The model qualitatively reproduces the different types of deformation bands seen in experiments. At high strain rates where propagating bands are seen, the model equations are reduced to the Fisher-Kolmogorov equation for propagative fronts. This shows that the velocity of the bands varies linearly with the strain rate and inversely with the dislocation density, consistent with the known experimental results. Thus, this simple dynamical model captures the complex spatio-temporal features of the PLC effect.Comment: 17 pages, 18 figure

The HPS electromagnetic calorimeter

The Heavy Photon Search experiment (HPS) is searching for a new gauge boson, the so-called “heavy photon.” Through its kinetic mixing with the Standard Model photon, this particle could decay into an electron-positron pair. It would then be detectable as a narrow peak in the invariant mass spectrum of such pairs, or, depending on its lifetime, by a decay downstream of the production target. The HPS experiment is installed in Hall-B of Jefferson Lab. This article presents the design and performance of one of the two detectors of the experiment, the electromagnetic calorimeter, during the runs performed in 2015–2016. The calorimeter's main purpose is to provide a fast trigger and reduce the copious background from electromagnetic processes through matching with a tracking detector. The detector is a homogeneous calorimeter, made of 442 lead-tungstate (PbWO4) scintillating crystals, each read out by an avalanche photodiode coupled to a custom trans-impedance amplifier