Characterization of the PCMBS-dependent modification of KCa3.1 channel gating.

Intermediate conductance, calcium-activated potassium channels are gated by the binding of intracellular Ca(2+) to calmodulin, a Ca(2+)-binding protein that is constitutively associated with the C terminus of the channel. Although previous studies indicated that the pore-lining residues along the C-terminal portion of S6 contribute to the activation mechanism, little is known about whether the nonluminal face of S6 contributes to this process. Here we demonstrate that the sulfhydral reagent, parachloromercuribenze sulfonate (PCMBS), modifies an endogenous cysteine residue predicted to have a nonluminal orientation (Cys(276)) along the sixth transmembrane segment (S6). Modification of Cys(276) manipulates the steady-state and kinetic behavior of the channel by shifting the gating equilibrium toward the open state, resulting in a left shift in apparent Ca(2+) affinity and a slowing in the deactivation process. Using a six-state gating scheme, our analysis shows that PCMBS slows the transition between the open state back to the third closed state. Interpreting this result in the context of the steady-state and kinetic data suggests that PCMBS functions to shift the gating equilibrium toward the open state by disrupting channel closing. In an attempt to understand whether the nonluminal face of S6 participates in the activation mechanism, we conducted a partial tryptophan scan of this region. Substituting a tryptophan for Leu(281) recapitulated the effect on the steady-state and kinetic behavior observed with PCMBS. Considering the predicted nonluminal orientation of Cys(276) and Leu(281), a simple physical interpretation of these results is that the nonluminal face of S6 forms a critical interaction surface mediating the transition into the closed conformation, suggesting the nonluminal C-terminal portion of S6 is allosterically coupled to the activation gate

A Computational Model of Protein Induced Membrane Morphology with Geodesic Curvature Driven Protein-Membrane Interface

Continuum or hybrid modeling of bilayer membrane morphological dynamics induced by embedded proteins necessitates the identification of protein-membrane interfaces and coupling of deformations of two surfaces. In this article we developed (i) a minimal total geodesic curvature model to describe these interfaces, and (ii) a numerical one-one mapping between two surface through a conformal mapping of each surface to the common middle annulus. Our work provides the first computational tractable approach for determining the interfaces between bilayer and embedded proteins. The one-one mapping allows a convenient coupling of the morphology of two surfaces. We integrated these two new developments into the energetic model of protein-membrane interactions, and developed the full set of numerical methods for the coupled system. Numerical examples are presented to demonstrate (1) the efficiency and robustness of our methods in locating the curves with minimal total geodesic curvature on highly complicated protein surfaces, (2) the usefulness of these interfaces as interior boundaries for membrane deformation, and (3) the rich morphology of bilayer surfaces for different protein-membrane interfaces

Presence and television.

Film and a number of emerging entertainment technologies offer media consumers an illusion of nonmediation known as presence. To investigate the possibility that television can evoke presence, 65 undergraduate students were shown brief examples of rapid point-of-view movement from commercially available videotapes on a television with either a small screen (12 inches [30.5 cm], measured diagonally) or a large screen (46 inches [116.8 cm]). Participants\u27 responses were measured via a questionnaire and a computer-based recording of arousal (electrodermal activity). Viewers of both televisions reported an enjoyable sense of physical movement, excitement, involvement, and a sense of participation. Furthermore, as predicted, participants who watched the large screen television thought the movement in the scenes was faster, experienced a greater sense of physical movement, enjoyed the movement to a greater extent, found the viewing experience more exciting, and were more physiologically aroused. Practical and theoretical implications are discussed

Biophysics at the coffee shop: lessons learned working with George Oster

Over the past 50 years, the use of mathematical models, derived from physical reasoning, to describe molecular and cellular systems has evolved from an art of the few to a cornerstone of biological inquiry. George Oster stood out as a pioneer of this paradigm shift from descriptive to quantitative biology not only through his numerous research accomplishments, but also through the many students and postdocs he mentored over his long career. Those of us fortunate enough to have worked with George agree that his sharp intellect, physical intuition and passion for scientific inquiry not only inspired us as scientists but also greatly influenced the way we conduct research. We would like to share a few important lessons we learned from George in honor of his memory and with the hope that they may inspire future generations of scientists.Comment: 22 pages, 3 figures, accepted in Molecular Biology of the Cel

Cascading the use of Web 2.0 technology in secondary schools in the United Kingdom: identifying the barriers beyond pre-service training

This paper reports on research that took place at Nottingham Trent University and Sheffield Hallam University, United Kingdom, over two years. The research focuses on the use of Web 2.0 technology, specifically web logs, with pre-service teachers, both during their university programme and the first year of teaching as full-time newly qualified teachers (NQTs). The purpose of this research was to add a developing body of knowledge by identifying whether technology used by pre-service teachers during their training course can be cascaded into their practice once qualified. Key findings identify a number of enablers and barriers to cascading technology in the classroom; these include curriculum time, pupil skills and support. The research concludes that early professional support and development should be on-going and assumptions about new teachers as champions of cascading innovative use of Web 2 technologies into their practice as NQTs may be over optimisti

Modeling and control of UAV bearing formations with bilateral high-level steering

In this paper we address the problem of controlling the motion of a group of unmanned aerial vehicles (UAVs) bound to keep a formation defined in terms of only relative angles (i.e. a bearing formation). This problem can naturally arise within the context of several multi-robot applications such as, e.g. exploration, coverage, and surveillance. First, we introduce and thoroughly analyze the concept and properties of bearing formations, and provide a class of minimally linear sets of bearings sufficient to uniquely define such formations. We then propose a bearing-only formation controller requiring only bearing measurements, converging almost globally, and maintaining bounded inter-agent distances despite the lack of direct metric information.The controller still leaves the possibility of imposing group motions tangent to the current bearing formation. These can be either autonomously chosen by the robots because of any additional task (e.g. exploration), or exploited by an assisting human co-operator. For this latter 'human-in-the-loop' case, we propose a multi-master/multi-slave bilateral shared control system providing the co-operator with some suitable force cues informative of the UAV performance. The proposed theoretical framework is extensively validated by means of simulations and experiments with quadrotor UAVs equipped with onboard cameras. Practical limitations, e.g. limited field-of-view, are also considered. © The Author(s) 2012

Simulations of the Alternating Access Mechanism of the Sodium Symporter Mhp1

AbstractSodium coupled cotransporters of the five-helix inverted repeat (5HIR) superfamily use an alternating access mechanism to transport a myriad of small molecules across the cell membrane. One of the primary steps in this mechanism is the conformational transition from a state poised to bind extracellular substrates to a state that is competent to deliver substrate to the cytoplasm. Here, we construct a coarse-grained model of the 5HIR benzylhydantoin transporter Mhp1 that incorporates experimental structures of the outward- and inward-open states to investigate the mechanism of this conformational change. Using the weighted ensemble path-sampling method, we rigorously sample the outward- to inward-facing transition path ensemble. The transition path ensemble reveals a heterogeneous set of pathways connecting the two states and identifies two modes of transport: one consistent with a strict alternating access mechanism and another where decoupling of the inner and outer gates causes the transient formation of a continuous permeation pathway through the transporter. We also show that the conformational switch between the outward- and inward-open states results from rigid body motions of the hash motif relative to the substrate bundle, supporting the rocking bundle hypothesis. Finally, our methodology provides the groundwork for more chemically detailed investigations of the alternating mechanism

Satellite Remote Sensing of Atmospheric SO_2: Volcanic Eruptions and Anthropogenic Emissions

In this article, we present satellite data analysis of atmospheric Sulfur Dioxide (SO_2) from volcanic eruptions and anthropogenic activities. Data from Global Ozone Monitoring Experiment (GOME) on board ERS-2 for the years 1996 to 2002 is analyzed using a DOAS based algorithm with the aim of retrieving SO_2 Slant Column Densities (SCDs). Difficulties in the retrieval of SO_2 SCDs due to instrumental effects are investigated in detail and significantly improved. The retrieved SCDs can be used to identify and monitor several volcanic eruptions. A brief introduction of different volcanic eruptions around the globe is presented Also informations about the anthropogenic SO_2 emissions can be easily achieved from the retrieved data set. A time series of anthropogenic SO_2 emissions over Eastern Europe is presented in this study. The time series showed high SO_2 SCDs over Eastern Europe during the winter months. The results demonstrate a high sensitivity of GOME instrument towards SO_2 emissions

A telephone- and text-message based telemedical care concept for patients with mental health disorders - study protocol for a randomized, controlled study design

<p>Abstract</p> <p>Background</p> <p>As in other countries worldwide, the prevalence of mental disorders in Germany is high. Although numerically a dense network of in- and outpatient psychiatric health services exists, the availability in rural and remote regions is insufficient.</p> <p>In rural regions, telemedical concepts can be a chance to unburden and complement the existing healthcare system. Telemedical concepts consisting of video or telephone consulting show first positive results, but there are only a few studies with a randomized controlled design.</p> <p>To improve the treatment of patients with mental disorders in rural regions, we developed a telemedical care concept based on telephone contacts and text-messages. The primary objective of this study is to evaluate the effects of the telemedical interventions on psychopathological outcomes, e. g. anxiety, depressive symptoms, and somatisation. Secondary objective of the study is the analysis of intervention effects on the frequency of medical contacts with healthcare services. Furthermore, the frequency of patients' crises and the frequency and kind of interventions, initiated by the project nurses will be evaluated. We will also evaluate the acceptance of the telemedical care concept by the patients.</p> <p>Methods/Design</p> <p>In this paper we describe a three-armed, randomized, controlled study. All participants are recruited from psychiatric day hospitals. The inclusion criteria are a specialist-diagnosed depression, anxiety disorder, adjustment disorder or a somatoform disorder and eligibility to participate in the study. Exclusion criteria are ongoing outpatient psychotherapy, planned interval treatment at the day clinic and expected recurrent suicidality and self-injuring behaviour.</p> <p>The interventions consist of regular patient-individual telephone consultations or telephone consultations with complementing text-messages on the patients' mobile phone. The interventions will be conducted during a time period of 6 months.</p> <p>Trial registration</p> <p>This study is registered in the German Clinical Trials Register (DRKS00000662).</p

Chinese L2 learners’ depth of vocabulary knowledge and its role in reading comprehension

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Using a Chinese Word Associates Test (WAT-C), this study examined the vocabulary depth of second language learners of Chinese and its contribution to the learners’ reading comprehension. Results showed no significant effects of word frequency, word class (i.e., adjectives vs. verbs), and type of association relationships (i.e., paradigmatic vs. syntagmatic) on learners’ WAT-C performance. More important, vocabulary depth was found to be a significant and unique predictor of reading comprehension over and above vocabulary size. On the other hand, the relative contributions of vocabulary depth and size depended on what types of texts were read and what comprehension skills were assessed. Specifically, for the long passage comprehension task with questions testing literal comprehension, vocabulary size was a more important predictor, whereas for the short passage comprehension task with questions testing inferencing, vocabulary depth was a more important predictor. These findings were discussed in light of the different levels of lexical complexity between the short and long passages and the different cognitive processing demands the questions of the two comprehension tasks placed on learners