Simulating rare events using a Weighted Ensemble-based string method

We introduce an extension to the Weighted Ensemble (WE) path sampling method to restrict sampling to a one dimensional path through a high dimensional phase space. Our method, which is based on the finite-temperature string method, permits efficient sampling of both equilibrium and non-equilibrium systems. Sampling obtained from the WE method guides the adaptive refinement of a Voronoi tessellation of order parameter space, whose generating points, upon convergence, coincide with the principle reaction pathway. We demonstrate the application of this method to several simple, two-dimensional models of driven Brownian motion and to the conformational change of the nitrogen regulatory protein C receiver domain using an elastic network model. The simplicity of the two-dimensional models allows us to directly compare the efficiency of the WE method to conventional brute force simulations and other path sampling algorithms, while the example of protein conformational change demonstrates how the method can be used to efficiently study transitions in the space of many collective variables

Ventilation of double facades

This paper deals with the development and thetesting of a simulation algorithm for the temperaturebehaviour and the flow characteristics of doublefaçades. It has been developed in order to obtain atool which enables the energy consultant to makequick design decisions without being required to usefairly complicated CFD tools.In order to determine the degree of accuracy of thealgorithm, a double façade has been monitored undercontrolled conditions and the results have beencompared against the predicted values for severaldesign situations. The resulting inaccuracy in somecases can be traced back to how the flow resistanceof various geometries are modelled. This paper deals with the development and thetesting of a simulation algorithm for the temperaturebehaviour and the flow characteristics of doublefaçades. It has been developed in order to obtain atool which enables the energy consultant to makequick design decisions without being required to usefairly complicated CFD tools.In order to determine the degree of accuracy of thealgorithm, a double façade has been monitored undercontrolled conditions and the results have beencompared against the predicted values for severaldesign situations. The resulting inaccuracy in somecases can be traced back to how the flow resistanceof various geometries are modelled

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

Organisatoriese reelings vir fisiese beplanning

Policies for physical planning take shape, among other things, the government-created institutions to achieve certain physical planning goals. This article will cover the institutions created for this purpose, namely the Department of Environmental Planning and Energy; the Planning Advisory Board; the Economic Advisory Council; the Scientific Advisory Board and the Council on the Environment. Furthermore, the contribution ofeach of these institutions is shown to the formulation of physical planning policy.*This article is written in Afrikaans

Fluency in reading—Thirty-five years later

Paul Nation’s talents and interests extend well beyond vocabulary to include research on speaking, writing, classroom learning and teaching, reading, and fluency. In keeping with Nation’s interests in fluency, extensive reading, and reading instruction, I outline current perspectives on reading fluency and its role as a key component of reading comprehension abilities. This discussion will include the rapidly increasing importance being given to reading fluency, extensive reading, and reading speed training in English as a first language (L1) contexts in the past decade. While this extraordinary growth in fluency research in English L1 contexts might not be well known to many second language (L2) practitioners, it offers many implications for L2 reading research and instruction (and Nation is one of very few L2 researchers to have been out ahead of this curve). The article will also address reasons why fluency research studies often do not demonstrate extraordinary gains in reading comprehension outcomes, pointing to the incremental nature of both fluency and reading comprehension development. Finally, the article will connect messages consistently advocated for by Nation over the past 35 years with current views on reading fluency

Structural and functional analysis of the Drosphila antennal lobe

The antennal lobe (AL) of the vinegar fly Drosophila melanogaster ranks among the best investigated structures in neuroscience. Increasing knowledge of its detailed morphological properties is paralleled by an enlarging number of studies on precise chemosensory functions and their related ecology. These meanings, like hard-wired aversion to geosmin or attraction to cis-vaccenyl acetate, are often assigned to be coded by a single subunit of the AL, glomerulus, each. Despite their functional heterogeneity, glomeruli are usually thought to be uniform. Only exception is the macroglomerular complex, a cluster of enlarged glomeruli located at the sensory entrance of the AL in most insects, known to be responsible for pheromone perception. The aim of this thesis was to show if glomeruli are actually uniform regarding their anatomy and if their putative morphological variability allows a functional prediction. Therefore we generated the first ever in vivo atlas of the Drosophila AL from a novel transgenic fly line (END1-2), providing a least artificial anatomical foundation for the succeeding projects. Based on the in vivo atlas we characterized each glomerulus regarding its number of afferent olfactory sensory neurons, in vivo volume and efferent projection neurons as well as integrated an external data set on the local interneuron innervation patterns (Chou et al. 2010). In parallel we carried out two studies on the functional specificity of glomeruli regarding their connectivity between each other as well as their stereotypic neuronal output in higher brain centers. We could show that increased functional specificity of the AL glomeruli in Drosophila is accompanied by morphological specialization. This allows predicting the functional significance of a glomerulus from its anatomy

Why We Should Lower The Voting Age to Sixteen

America’s lackluster democratic tendencies are widely recognized as problematic. Through encouraging civic involvement from a young age, voter turnout and overall civic engagement can be bolstered. Drawing on public polling data, NGO reports, academic journals, and informant interviews including Montana and Oregon state legislators, this white paper advocates the societal benefits from lowering the voting age to sixteen in presidential, state, and local elections. Youth have the passion to enact positive change in the world they will inherit. Two recent examples are Greta Thunberg, the 15-year old phenom, who took her global campaign against climate change all the way to the United Nations; and the Parkland, Florida teens who led the nationwide #NeverAgain movement against gun violence after the Marjory Stoneman Douglas High School shooting. While further assessment is needed to more comprehensively determine the potential effects of extending voting rights to 16- and 17-year olds, research does exist, from this country and others, to suggest that potential negative consequences are minimal and that lowering the voting age improves voter participation and overall civic engagement. Similar to how Vietnam War protests sparked the movement to lower the voting age to eighteen, youth today face existential crises such as climate change in which their say in political matters is imperative. Through my research I explore whether extending voting rights to 16- and 17-year olds will fundamentally improve the political processes and dialogue in the United States