902 research outputs found

    Molecular simulations of ion permeation in potassium channels.

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    Assessing Human Error Against a Benchmark of Perfection

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    An increasing number of domains are providing us with detailed trace data on human decisions in settings where we can evaluate the quality of these decisions via an algorithm. Motivated by this development, an emerging line of work has begun to consider whether we can characterize and predict the kinds of decisions where people are likely to make errors. To investigate what a general framework for human error prediction might look like, we focus on a model system with a rich history in the behavioral sciences: the decisions made by chess players as they select moves in a game. We carry out our analysis at a large scale, employing datasets with several million recorded games, and using chess tablebases to acquire a form of ground truth for a subset of chess positions that have been completely solved by computers but remain challenging even for the best players in the world. We organize our analysis around three categories of features that we argue are present in most settings where the analysis of human error is applicable: the skill of the decision-maker, the time available to make the decision, and the inherent difficulty of the decision. We identify rich structure in all three of these categories of features, and find strong evidence that in our domain, features describing the inherent difficulty of an instance are significantly more powerful than features based on skill or time.Comment: KDD 2016; 10 page

    The conduction pathway of potassium channels is water free under physiological conditions.

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    Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a "water-mediated" knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a "direct" knock-on mechanism where ions are in direct contact. Using solid-state nuclear magnetic resonance techniques tailored to characterize the interaction between water molecules and the ion channel, we show here that the selectivity filter of a potassium channel is free of water under physiological conditions. Our results are fully consistent with the direct knock-on mechanism of ion conduction but contradict the previously proposed water-mediated knock-on mechanism

    Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation

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    The changes in synaptic morphology and receptor content that underlie neural plasticity are poorly understood. Here, we use a pH-sensitive green fluorescent protein to tag recombinant glutamate receptors and monitor their dynamics onto dendritic spine surfaces. We show that chemically induced long-term potentiation (chemLTP) drives robust exocytosis of AMPA receptors. In contrast, the same stimulus produces a small reduction of NMDA receptors from the spine surface. chemLTP produces similar modification of small and large spines. Interestingly, during chemLTP induction, spines increase in volume before accumulation of AMPA receptors on their surface, indicating that distinct mechanisms underlie changes in morphology and receptor content

    The effects of Tween-80 on the integrity of solutions of capsaicin: useful information for performing tussigenic challenges

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    ABSTRACT: BACKGROUND: Because variable results of capsaicin challenges may be due to the incomplete solubility of capsaicin, we sought to determine if the use of Tween-80 in solutions of capsaicin improves actual concentrations of freshly prepared and stored solutions. METHODS: Capsaicin solutions ranging from 0.5-128 muM were mixed with and without Tween-80. Samples of various concentrations were then stored under 4 environmental conditions: 4 degrees C, protected from light; room temperature, protected from light; room temperature, exposed to light; -20 degrees C. All samples were analyzed initially, and at 2 and 4 months. RESULTS: While freshly prepared solutions with Tween-80 had consistently higher concentrations than those prepared without Tween-80 (83% vs. 69%), Tween-80 does not facilitate complete solubility. For solutions stored at 4 degrees C and protected from light, there was a significant decrease after 2 months in low concentration solutions of both the Tween-80 and non-Tween-80 solutions. Both Tween-80 and non-Tween-80 containing solutions significantly decreased in concentration after 2 months when stored at room temperature and protected from light, room temperature and exposed to light, and -20 degrees C. Concentrations of solutions made of 4 muM or higher are stable when stored at 4 degrees C and protected from light for 4 months. CONCLUSION: While the inherent difficulty of forcing capsaicin into solution cannot be eliminated, it can be improved with Tween-80. However, the addition of Tween-80 does not prevent the breakdown of stored capsaicin solutions. We recommend preparing and storing capsaicin solutions according to the methods and results of this study

    Corporate Culture and Its Connection with External and Internal Public Relations

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    The main aim of this article is to present the influence of corporate culture on company's stakeholders. This paper signalises the tendency in corporate communication with its internal and external publics. It is focused on two issues: corporate social responsibility and employer branding. Those two categories are consequences of corporate culture model.Głównym celem artykułu jest zaprezentowanie wpływu jaki wywiera charakter kultury korporacyjnej na związanych z przedsiębiorstwem interesariuszy (stakeholders). W artykule zasygnalizowane zostały główne tendencje wyznaczające charakter komunikacji między organizacją a jej wewnętrznym i zewnętrznym otoczeniem. Tekst koncentruje się na dwóch kwestiach: społecznej odpowiedzialności przedsiębiorstwa (corporate social responsibilty) i budowanie wizerunku pracodawcy (employer branding), które zaprezentowane zostały jako efekty określonego modelu kultury organizacyjnej

    Direct detection of bound ammonium ions in the selectivity filter of ion channels by solid-state NMR.

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    The flow of ions across cell membranes facilitated by ion channels is an important function for all living cells. Despite the huge amount of structural data provided by crystallography, elucidating the exact interactions between the selectivity filter atoms and bound ions is challenging. Here, we detect bound 15 N-labeled ammonium ions as a mimic for potassium ions in ion channels using solid-state NMR under near-native conditions. The non-selective ion channel NaK showed two ammonium peaks corresponding to its two ion binding sites, while its potassium-selective mutant NaK2K that has a signature potassium- selective selectivity filter with four ion binding sites gave rise to four ammonium peaks. Ions bound in specific ion binding sites were identified based on magnetization transfer between the ions and carbon atoms in the selectivity filters. Magnetization transfer between bound ions and water molecules revealed that only one out of four ions in the selectivity filter of NaK2K is in close contact with water, which is in agreement with the direct knock-on ion conduction mechanism where ions are conducted through the channel by means of direct interactions without water molecules in between. Interestingly, the potassium-selective ion channels investigated here (NaK2K and, additionally, KcsA-Kv1.3) showed remarkably different chemical shifts for their bound ions, despite having identical amino acid sequences and crystal structures of their selectivity filters. Molecular dynamics simulations show similar ion binding and conduction behavior between ammonium and potassium ions and identify the origin of the differences between the investigated potassium channel

    Structural plasticity of the selectivity filter in a nonselective ion channel

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    The sodium potassium ion channel (NaK) is a nonselective ion channel that conducts both sodium and potassium across the cellular membrane. A new crystallographic structure of NaK reveals conformational differences in the residues that make up the selectivity filter between the four subunits that form the ion channel and the inner helix of the ion channel. The crystallographic structure also identifies a side-entry, ion-conduction pathway for Na+ permeation that is unique to NaK. NMR studies and molecular dynamics simulations confirmed the dynamical nature of the top part of the selectivity filter and the inner helix in NaK as also observed in the crystal structure. Taken together, these results indicate that the structural plasticity of the selectivity filter combined with the dynamics of the inner helix of NaK are vital for the efficient conduction of different ions through the non-selective ion channel of NaK

    First-order transitions and triple point on a random p-spin interaction model

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    The effects of competing quadrupolar- and spin-glass orderings are investigated on a spin-1 Ising model with infinite-range random pp-spin interactions. The model is studied through the replica approach and a phase diagram is obtained in the limit pp\to\infty. The phase diagram, obtained within replica-symmetry breaking, exhibits a very unusual feature in magnetic models: three first-order transition lines meeting at a commom triple point, where all phases of the model coexist.Comment: 9 pages, 2 ps figures include
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