MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.

The subthreshold, voltage-gated potassium channel of skeletal muscle is shown to contain MinK-related peptide 2 (MiRP2) and the pore-forming subunit Kv3.4. MiRP2-Kv3.4 channels differ from Kv3.4 channels in unitary conductance, voltage-dependent activation, recovery from inactivation, steady-state open probability, and block by a peptide toxin. Thus, MiRP2-Kv3.4 channels set resting membrane potential (RMP) and do not produce afterhyperpolarization or cumulative inactivation to limit action potential frequency. A missense mutation is identified in the gene for MiRP2 (KCNE3) in two families with periodic paralysis and found to segregate with the disease. Mutant MiRP2-Kv3.4 complexes exhibit reduced current density and diminished capacity to set RMP. Thus, MiRP2 operates with a classical potassium channel subunit to govern skeletal muscle function and pathophysiology

Lateral vegetation growth rates exert control on coastal foredune hummockiness and coalescing time

Coastal foredunes form along sandy, low-sloped coastlines and range in shape from continuous dune ridges to hummocky features, which are characterized by alongshore-variable dune crest elevations. Initially scattered dune-building plants and species that grow slowly in the lateral direction have been implicated as a cause of foredune hummockiness . Our goal in this work is to explore how the initial configuration of vegetation and vegetation growth characteristics control the development of hummocky coastal dunes including the maximum hummockiness of a given dune field. We find that given sufficient time and absent external forcing, hummocky foredunes coalesce to form continuous dune ridges. Model results yield a predictive rule for the timescale of coalescing and the height of the coalesced dune that depends on initial plant dispersal and two parameters that control the lateral and vertical growth of vegetation, respectively. Our findings agree with previous observational and conceptual work - whether or not hummockiness will be maintained depends on the timescale of coalescing relative to the recurrence interval of high-water events that reset dune building in low areas between hummocks. Additionally, our model reproduces the observed tendency for foredunes to be hummocky along the southeast coast of the US where lateral vegetation growth rates are slower and thus coalescing times are likely longer

Comprehensive transcriptomic analysis of cell lines as models of primary tumors across 22 tumor types.

Cancer cell lines are a cornerstone of cancer research but previous studies have shown that not all cell lines are equal in their ability to model primary tumors. Here we present a comprehensive pan-cancer analysis utilizing transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia to evaluate cell lines as models of primary tumors across 22 tumor types. We perform correlation analysis and gene set enrichment analysis to understand the differences between cell lines and primary tumors. Additionally, we classify cell lines into tumor subtypes in 9 tumor types. We present our pancreatic cancer results as a case study and find that the commonly used cell line MIA PaCa-2 is transcriptionally unrepresentative of primary pancreatic adenocarcinomas. Lastly, we propose a new cell line panel, the TCGA-110-CL, for pan-cancer studies. This study provides a resource to help researchers select more representative cell line models

Bayesian Conditioning, the Reflection Principle, and Quantum Decoherence

The probabilities a Bayesian agent assigns to a set of events typically change with time, for instance when the agent updates them in the light of new data. In this paper we address the question of how an agent's probabilities at different times are constrained by Dutch-book coherence. We review and attempt to clarify the argument that, although an agent is not forced by coherence to use the usual Bayesian conditioning rule to update his probabilities, coherence does require the agent's probabilities to satisfy van Fraassen's [1984] reflection principle (which entails a related constraint pointed out by Goldstein [1983]). We then exhibit the specialized assumption needed to recover Bayesian conditioning from an analogous reflection-style consideration. Bringing the argument to the context of quantum measurement theory, we show that "quantum decoherence" can be understood in purely personalist terms---quantum decoherence (as supposed in a von Neumann chain) is not a physical process at all, but an application of the reflection principle. From this point of view, the decoherence theory of Zeh, Zurek, and others as a story of quantum measurement has the plot turned exactly backward.Comment: 14 pages, written in memory of Itamar Pitowsk

Non-supersymmetric Extremal RN-AdS Black Holes in N=2 Gauged Supergravity

We investigate extremal Reissner-Nordstrom-AdS black holes in four-dimensional N=2 abelian gauged supergravity. We find a new attractor equation which is not reduced to the one in the asymptotically flat spacetime. Focusing on so-called the T^3-model with a single neutral vector multiplet, we obtain non-supersymmetric extremal Reissner-Nordstrom-AdS black hole solutions with regular event horizon in the D0-D4 and the D2-D6 charge configurations. The negative cosmological constant emerges even without the Fayet-Iliopoulos parameters. Furthermore, we also argue the formal description of the non-supersymmetric black hole solutions of the T^3-model and the STU-model in generic configurations.Comment: 23 pages, accepted version in JHE

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

Use of an Anaerobic Chamber Environment for the Assay of Endogenous Cellular Protein-Tyrosine Phosphatase Activities

Protein-tyrosine phosphatases (PTPases) have a catalytic cysteine residue whose reduced state is integral to the reaction mechanism. Since exposure to air can artifactually oxidize this highly reactive thiol, PTPase assays have typically used potent reducing agents to reactivate the enzymes present; however, this approach does not allow for the measurement of the endogenous PTPase activity directly isolated from the in vivo cellular environment. Here we provide a method for using an anaerobic chamber to preserve the activity of the total PTPase complement in a tissue lysate or of an immunoprecipitated PTPase homolog to characterize their endogenous activation state. Comparison with a sample treated with biochemical reducing agents allows the determination of the activatable (reducible) fraction of the endogenous PTPase pool