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I love this view of the Conways but Gary, I think your memory is starting to go or you're pulling our collective legs when you say "Rolls Royce Conways purring along over Greenland". The Rolls Royce Conways did anything but purr, THEY ROARED and if you were in the last few rows, you could here the inner window liner crackle from the roaring vibrations. Damn, that sweet noise put me to sleep like a baby every time after meal service.
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- Research
- Open Access
Reduction of calcium release site models via optimized state aggregation
- Yan Hao1Email author
© Hao. 2016
- Received: 25 January 2016
- Accepted: 17 May 2016
- Published: 4 June 2016
Markov chain models of calcium release sites in living cells exhibit stochastic dynamics reminiscent of the experimentally observed phenomenon of calcium puffs and sparks. Such models often take the form of stochastic automata networks in which the transition probabilities for each of a large number of intercellular channel models depend on the local calcium concentration and thus the state of nearby channels. The state-space size in such compositionally defined calcium release site models increases exponentially as the number of channels increases, which is referred to as "state-space explosion".
In order to overcome the state-space explosion problem, we utilized the idea of "coarse graining" and implemented an automated procedure that reduces the state space by aggregating and lumping states of the full release site model. For a given state aggregation scheme, the transition rates between reduced states are chosen consistent with the conditional probability distribution among states within each group. A genetic algorithm-based approach is then applied to select the state aggregation schemes that lead to reduced models that approximate the observable behaviors of the full model.
The genetic algorithm-based approach is implemented in Matlab®; and applied to two different release site models. The approach found reduced models that approximate the full model in the number of open channels, spark statistics, and the jump probability matrix as a function of time.
A novel automated genetic algorithm-based searching technique is implemented to find reduced calcium release site models that approximate observable behaviors of the full Markov chain models that possess intractable state-spaces. As compared to the full model, the reduced models produce quantitatively similar results using significantly less computational resources.
- State space explosion
- Genetic algorithms
- Calcium signaling
- Stochastic automata network
- Set partition
- Coarse graining strategies
Coarse-graining methods as a model reduction strategy
Increasingly over the years, mathematical models and computer simulation have been used in the natural sciences and the social sciences. As more and more scientific discoveries from experiments are included, models and simulation approaches have been developed to be more and more accurate. Unfortunately, the corresponding computational cost also gets higher. When a problem to be modeled is large in scale or possesses multiple scales, the complexity and dimensionality of the model may increase to unmanageable levels of storage and computational capacity. How to reduce the computational cost without losing important properties of mathematical/computational models is therefore an important scientific question. Molecular dynamics (MD) simulation for example, is a type of N-body simulation that allows atoms and molecules to interact for a fixed period of time [1]. While the trajectories of atoms and molecules can be quite accurately determined by numerically solving Newton's equations of motion for a system of interacting particles, the computations are highly expensive [2]. To reduce the computational cost for MD simulations, the field of coarse-grained modeling and simulation has been rapidly expanding. Instead of explicitly representing every atom of a system, one partitions the system into a number of groups of atoms, and then uses "pseudo-atoms" to represent each group. The coarse-grained modeling significantly reduces the time and computational storage requirement of MD simulations. Simulations of soft matter systems, polymer dynamics, protein folding and many other physical or biological systems that feature the spatiotemporal coupling between scales thus become possible [3, 4].
As another example, continuous time Markov chains have become an important modeling approach over the past a few decades. Because it well describes the systems that undergoes transitions from one state to another, it was used extensively in modeling ion channels in cell membranes [5, 6]. However, when the collaborative behavior of a cluster of these ion channels are of interest, the state space of the cluster model increases exponentially as the number of channels increases. This combinatorial state-space explosion causes some modeling approaches to become intractable. In this paper, we present a novel approach to reduce large Markov chain models that shares the spirit of coarse-graining methods: the state-space of the Markov chain model is partitioned into groups, then each group is represented by a "mega-state" so that the full model is compressed into a tractable size. The partition scheme is selected by a genetic algorithm-based approach to preserve selected features of the full model.
Markov chain models of Ca2+ signaling
As a second messenger, calcium ions (Ca2+) play an important role in many physiological activities. Signaling occurs when the cell is stimulated to release calcium ions (Ca2+) from the endoplasmic/sarcoplasmic reticulum (ER/SR), the intracellular Ca2+ reservoir, or when Ca2+ enters the cell through plasma membrane ion channels [7]. The intracellular Ca2+ release which causes localized Ca2+ elevations known as puffs and sparks arises from concerted gating of clusters of inositol 1,4,5-trisphosphate receptors (IP3Rs) or ryanodine receptors (RyRs) on the surface of ER/SR [8–10]. For example, in cardiac myocyte excitation-contraction coupling (ECC), the cell membrane depolarizes causing L-type Ca2+ channels to open and the Ca2+ influx further activates RyRs located on the SR, known as Ca2+-induced Ca2+ release (CICR) [11].
The spatial organization of IP3Rs and RyRs has been shown to be the basis of intracellular Ca2+ signaling activities that are observed via confocal microfluorimetry in cardiomyocytes, oocytes, and other cell types [10, 12, 13]. The spacing of receptor clusters was identified as a decisive parameter for the occurrence of collective behaviors [14, 15].
From the literature, the behavior of single IP3R/RyR channel gating is often modeled by continuous-time discrete-state Markov chains (CTMCs) [16, 17]. When Markov chain models of these channels are coupled via a Ca2+ microdomain in which the transition rates between the states of each channel become dependent on the states of other channels, the simulated Ca2+ channel clusters (release sites) may exhibit stochastic excitability that is reminiscent of Ca2+ puff/sparks [6, 14, 18]. However, the number of states possessed by these compositionally defined Ca2+ release site models increases exponentially as the number of channels increases. This combinatorial state-space explosion causes some modeling approaches to become intractable.
While the dynamics of any individual Ca2+ release site can theoretically be obtained by Monte Carlo simulation regardless of model complexity, in practice these simulations are prohibitively computationally intensive due to the large state spaces. Moreover, because cells usually possess a large number of release sites, compositionally defined Ca2+ release site models have often been excluded from multiscale whole cell simulations. On the other hand, many recently developed approaches that accelerate whole cell simulations, such as probability density and moment closure approaches [19, 20], require release site models to be as compact as possible while retaining the physiological realism of collective channel gating.
For these reasons, we developed several automated approaches based on fast/slow analysis [21]. To reduce Markov chain Ca2+ release site models where the rate constants in release site models are categorized as either fast or slow, groups of states that are connected by fast transitions are lumped so that the full model is compressed into a tractable size while the physiological gating and interaction properties of the channels are preserved. However, when the time scale separation between transition rates that is necessary for fast/slow analysis is absent, the manner in which the full model states should be partitioned and aggregated for optimal reduction is difficult to determine a priori. Naively enumerating all partitions for a Markov chain Ca2+ release site model and choosing the one with the smallest error is not possible because the number of valid partitions is too large. Actually, finding out how many ways one can divide a graph that possesses n vertices into k smaller components is know to be an NP-hard problem [22]. For example, a release site model composed of merely five three-state Ca2+ channels (15 states) can be partitioned in approximately 1010 distinct ways. In this paper we discuss the implementation of a genetic algorithm that is able to automatically and rapidly select partition schemes that reduce the corresponding Markov chain model to a tractable size while keeping the reduction error in control.
Genetic algorithms
Developed in the 1970s by John Holland [23], genetic algorithms are widely used as computational schemes to find exact or approximate solutions for optimization and search problems. Genetic algorithms have been applied to various aspects of biological research, such as the profiling of gene expression in bacteria [24, 25] and phylogenetic analysis of proteins [26]. More recently, it has been used to identify parameters for cell-specific electrophysiology models [27]. Nevertheless, the application of genetic algorithms in the context of the automated reduction of Ca2+ release site models is novel. In our implementation, each individual in a population corresponds to a potential scheme for state aggregation. The program "evolves" the population by selecting the partitions that lead to reduced models that approximate the full model behavior.
Unlike the fast/slow analysis that assumes fixed ER/SR [ Ca2+] and instantaneous coupling between the channels [21], we motivate a whole cell homeostasis formulation that takes both local and global Ca2+ signaling into consideration. Consequently the reduced models selected by the genetic algorithm must generate small errors for a wide range of ER/SR [ Ca2+]. In the implementation of the genetic algorithm, a population of set partitions is randomly generated, where each partition corresponds to a potential scheme for state aggregation. The states of the full model is aggregated and reduced following each individual set partition scheme. Then the difference between the full model and the corresponding reduced model on the behaviors of interest, spark statistics for example, are measured and called the "error" of the reduced model. The error is used as the key factor for deciding the fitness of each individual partition scheme. Since partition schemes that produce low errors are preferred, the fitness is chosen to be a decreasing function of error. The program selects survivors from the current population in a manner that favors better fitness (i.e. low error), then each survivor will generate one child (a new set partition scheme) by mutation. The set partition population thus evolves toward the partitions that have better fitness and lead to reduced models that better approximate the full model.
The remainder of this paper is organized as follows. In the 'Model' section we motivate the network reduction process by partitioning a minimal whole cell model of Ca2+ homeostasis where both localized (subcellular) and global (cellular) aspects of Ca2+ signaling are modeled. In the 'Methods' section we introduce genetic algorithms and detail their implementation in the context of reducing a minimal whole cell model of Ca2+ homeostasis that features bidirectional local and global Ca2+ signaling. In the 'Results' section, we demonstrate that the reduced model approximates the full model with regard to several important steady-state responses observed in the minimal whole cell environment. To show that the reduction technique is applicable to more realistic Ca2+ release site models, we also present Ca2+ release site reduction results using a single channel model that includes both cytosolic and luminal Ca2+ regulation.
A minimal whole cell model
Steady-state of domain concentration
where ν rel is the maximum release rate through a release site, c cyt and c e r/s r are the bulk cytosolic and ER/SR concentrations, and γ n =n/N is the fraction of open channels at an N-channel per release site. The rate constants ν cyt and ν e r/s r determine the time required for the decay and refilling of the cytosolic and luminal microdomains, respectively [32, 33].
Notice that for a release site with N channels, the number of open channels takes integer values from 0 to N. Consequently, there are N+1 pairs of cytosolic and luminal domain [ Ca2+] values for any given value of the bulk concentration (c cyt and c e r/s r ).
Concentration balance equations for the bulk cytosol and ER
where k pm is chosen large enough so that the bulk cytosolic [ Ca2+] is "clamped" to the extracellular bath (c ext =0.1μ M).
where f n is the fraction of release sites with n open channels.
The Markov chain model of single channel gating
where i≠j and the diamonds (◇) on the diagonal entries are negative values leading to row sums of zero.
where e is a commensurate column vector of ones.
Compositionally defined Ca 2+ release site models
Reduction technique
Our basic strategy of reducing a Ca2+ release site model to a smaller model with pre-determined size \(\hat {b}\) includes three major steps: Step 1 Partition the full model into \(\hat {b}\) groups. Step 2 Lump the states within each group. Step 3 Calculate proper transition rates between groups.
In previous work [21], S t e p 1 was achieved automatically based on the separation of time scales, where states that are connected by fast transitions were aggregated. In this paper, we employ a genetic algorithm to search for partition schemes that generate small reduction errors for general Ca2+ release site models, especially those without time scale difference. In the future, a partition that divides the states of a release site model into \(\hat {b}\) groups will be referred to as a "\(\hat {b}\) -partition". S t e p 2 and S t e p 3 in this reduction technique are carried on from [21].
Theoretically, this genetic algorithm-based technique can be used to reduce any Ca2+ release site models of size β(N,M) to any pre-determined size \(\hat {b}\) (\(\hat {b} < \beta ({N,M})\)). Furthermore, the partition scheme can be restricted by certain rules, such as "each group must be connected on the transition diagram" or "all states in each group must present the same number of open channels", etc. Hereafter, we will demonstrate the implementation of the genetic algorithm using a minimal example where the 6-state release site model illustrated in Fig. 2 b is partitioned into 3 groups with the constraint "states in each group must be connected". Results from reducing a release site that is composed of 10 three-state channels will be presented in the 'Results' section. Other partition restrictions can be implemented by restricting the reproduction procedure or modifying the objective function.
Genetic algorithms
The program starts with initialization, where a number of "individuals" (solution candidates) are randomly generated to form an initial "population". The size N p of the population is usually kept constant throughout the entire searching procedure. After initialization, this population goes through the evaluation procedure, where each individual is evaluated by the objective function and its fitness is assigned according to the objective function value. The program then checks whether the termination criteria are satisfied; usually either the desired objective function value is attained or a predetermined number of generations is reached. If none of the termination criteria is satisfied, the program will move on to the selection process, which is usually stochastic and designed so that the individuals with better fitness have a higher probability to be selected as compared to those who are less fit. Only a fraction of the current population (N s individuals, where N s <N p ) can survive and enter the reproduction process as the "parent" solutions. To generate each "child" (a new solution candidate), one or more parents are selected, recombined (crossover) and/or varied (mutate). The reproduction process continues till N p individuals are generated and thus a new generation of population is formed. The new generation will then go through an evaluation process to have its fitness evaluated and the entire program continues until one or more of the termination criteria are satisfied.
In the initialization process, N p distinct three-partitions are randomly generated.
In the evaluation process each of the N p individuals (partition schemes) must be applied to the full model and have its corresponding reduced model compared to the full model. The fitness of each individual is then assigned in a manner that favors those that produce less error.
and e i are the commensurate column vectors of ones.
\(\hat {\boldsymbol {E}}(t)\) is a b×b matrix and is cumbersome to use for evaluation. Consequently, we define \(E_{\max }(t) = \underset {ij}\max \left | \hat {\boldsymbol {E}}_{ij} (t)\right |\), the element of \(\hat {\boldsymbol {E}}(t)\) with largest absolute value at time t. Note that E max is a function of both time and c e r/s r because the transition rates of the full Ca2+ release site model are functions of the luminal [ Ca2+]. Figure 5 a shows E max(t;c e r/s r ) for the 6-state Ca2+ release site model (Fig. 2 b) reduced to a three-state model following the partition scheme given by \(\mathcal {I}_{1}\). As validated in [21], the reduced model better approximates the full model as E max gets smaller. The maximum transition error decreased significantly as the luminal [ Ca2+] is dropped from 1100 μM (dashed line) to 100 μM (dot-dash-dot line), indicating reductions following partition scheme \(\mathcal {I}_{1}\) make better approximations of the full model at relatively low levels of luminal [ Ca2+].
the area under each curve in Fig. 5 a. Then, for any partition scheme \(\mathcal {I}\), the integrated error \(\mathcal {E}\) can be calculated as a function of c e r/s r , and the maximum \(\mathcal {E}(c_{er/sr})\) is selected as the global reduction error of scheme \(\mathcal {I}\). In Fig. 5 b the dashed and solid lines show the integrated error \(\mathcal {E}\) associated with \(\mathcal {I}_{1}\) and \(\mathcal {I}_{2}\), respectively, as a function of c e r/s r (100−2000 μM).
As shown in Fig. 5 b, when the full model is partitioned and lumped following \(\mathcal {I}_{1}\) (dashed line), the maximum possible error (star) generated by the reduced model \(\mathcal {E}_{1}\) is approximately 210 times larger than the maximum error (dot) generated by using \(\mathcal {I}_{2}\). The fitness of \(\mathcal {I}_{1}\) is consequently 210 times less than the fitness of \(\mathcal {I}_{2}\).
Selection and reproduction
This section introduces how the genetic algorithm implementation forms the "next generation" from the current population. The conventional reproduction process in genetic algorithms usually consists of selection, crossover and mutation.
that is, the probabilities of selection are proportional to the fitness, \(\mathcal {F}_{i}\). To generate each child, we start by randomly selecting a pair of parents, one at a time, from the current population following the corresponding PMF. For example, the probability of \(\mathcal {I}_{1}\) being selected is 210 times smaller than the probability that \(\mathcal {I}_{2}\) is selected.
where k=1,2,3,… and p=0.8.
Note that the reproduction process generates one child at a time and continues until the number of children reaches N p . These children then forms a new generation of individuals and are sent to the evaluation process, starting a new iteration in the genetic algorithm. The genetic algorithm is executed until either a set partition has a fitness \(\mathcal {F} \geq 1000\) (reduction error \(\mathcal {E}\) less than 0.1 % for all luminal [ Ca2+] values) is found, or the maximum number of allowed iterations (2000) is reached.
In this section we first validate the genetic algorithm implemented in the previous section by showing that the algorithm converges and produces set partition schemes that generate small reduction errors. To demonstrate that the genetic algorithm can be applied to general Ca2+ channels, we use this approach to reduce a release site that is composed of several four-state channels (Fig. 7) under the constraint that each group of states must be connected in the state transition diagram. This four-state model features activation by cytosolic Ca2+ and luminal [ Ca2+] regulation of the activation affinity. The reduced Ca2+ release site model is integrated into the whole cell model, and simulation results from the reduced and the full model are compared.
Reducing Ca2+ release site models that are composed of three-state channels
Reducing Ca2+ release site models that are composed of four-state channels with luminal regulation
The four-state Ca2+ channel model is assumed to have a regular or "unsensitized" mode (states C u ,O u ) in which the activation dissociation constant (\(K_{a} = \sqrt {k_{a}^{-}/k_{a}^{+}}\)) is higher than the activation dissociation constant (\(K_{d} = \sqrt {k_{d}^{-}/k_{d}^{+}}\)) of the "sensitized" mode (C s ,O s ). We also assume that the channel is more likely to be in the "sensitized" mode when the ER/SR [ Ca2+] is high. \(k_{i}^{+}\left (c_{cyt}^{d}\right)^{2}\), \(k_{j}^{+}c_{er/sr}^{d}\) and \(k_{i}^{-}\), for i,j∈{a,...,e}, are transition rates with units of reciprocal time. \(k_{i}^{+}\) is an association rate constant with units of conc −η time −1, where η is the cooperativity of Ca2+ binding while \(c_{cyt}^{d}\) and \(c_{er/sr}^{d}\) are the domain [ Ca2+] experienced by the release site on the cytosol and ER/SR side respectively. Notice that we assume that the Ca2+ binding cooperativity (η=1) of the channel sensitization (luminal regulation) process is different from the binding cooperativity of the activation process (η=2).
An important motivation in using this four-state model is that luminal regulation of RyRs is observed in many experiments [37, 38] but the detailed mechanism is yet not clear. In this paper, we are interested in how the "sensitization" of the activation of each individual Ca2+ channel affects the cooperative gating of the Ca2+ release site. Consequently we experiment on different sensitized activation rates as well as the dissociation constant \(K_{c} = k_{c}^{-}/k_{c}^{+}\) (Fig. 7) of the sensitization process. On the other hand, the parameters of the regular or "unsensitized" Ca2+ activation were chosen to be consistent with the parameters in [28], where many puff/spark statistics of a group of 10 two-state Ca2+-activated channels were studied.
where γ n =n/N, \(c_{cyt}^{d,\,n}\) and \(c_{er/sr}^{d,\,n}\) are given by Eqs. 5, 6 and 7, and π n is the probability that a randomly sampled release site has n open channels, which can be found from π=(π 0,π 1,⋯,π N ) by integrating Eq. 18.
from which the presence or absence of puff/spark can be assessed. This measure ranges between 0 and 1, and values that are larger than 0.2 indicate the presence of robust Ca2+ puffs/sparks. Figure 8 c, shows the Scores of the full model and the reduced model as a function of K C . The reduced model Scores give a close approximation to the full model results.
Notice that the Score values are above 0.35 for all K C values, indicating robust Ca2+ puffs/sparks present in both the full and reduced model. We further studied the mean duration of spontaneous Ca2+ puffs/sparks occurring as a function of K C in the whole cell formulation, shown in Fig. 8 d. We assume that a transition from N O =4 to N O =5 is considered to initialize a puff/spark and a transition from N O =1 to N O =0 (all channels closed) terminates the puffs/spark. The mean puffs/spark duration was calculated using the matrix analytic method described in [39]. As K C decreases, the channels are more likely to be sensitized, the puff/spark duration increases, indicating that the luminal regulation of the channel might lead to longer puffs/sparks, which is consistant with experimental observations [38, 40]. Compared to the Ca2+ release site model composed of 10 two-state channels (filled circle), the average puff/spark duration of a release site composed of the same number of four-state channels can be up to four times (when K C =1) longer. While in prior work [21], similar comparisons to a Ca2+ release site composed of Keizer-Levine model [41] and its corresponding reduced model gave good agreement, in this new study the reduced model tends to slightly underestimate the puff/spark durations.
Conclusions and discussion
A brief summary
We have implemented and validated a novel genetic algorithm-based searching technique to find reduced models that produce moderate errors for Ca2+ release site models that are compositionally defined from single channel Markov models. Given a full model and the designated size of the reduced model, this algorithm samples and evolves a population of set partitions, each corresponding to a potential scheme for state aggregation, that leads to the partitions that lead to reduced models which approximate the full model on the behaviors of interest. A Ca2+ release site composed of 10 four-state channels that are activated by the cytosolic Ca2+ and regulated by luminal Ca2+ is reduced by this technique and the steady state responses of the reduced model well approximate the full model in the minimal whole cell homeostasis environment (Fig. 8).
When a Ca2+ release site model is reduced, the resulting models are designated to have significantly fewer states, which is inevitably accompanied by losing some transition information. Different state aggregation schemes may preserve different information. A main benefit from using genetic algorithms is that the evaluation function is flexible enough to pick state aggregation schemes that maximize any information that is of specific interest to the user. In this report, for example, we are interested in how luminal regulation affects the spark behavior of the Ca2+ release site, and the evaluation function is consequently designed to assign higher fitness to the partitions which generate small errors in a wide range of ER/SR [ Ca2+]. As another example, if the spark frequency is crucial in some study, we can conveniently edit the e v a l u a t i o n function to calculate the spark frequency of each reduced model generated from partition \(\mathcal {I}\) and assign higher fitness to the ones that better approximate the full model spark frequency. When focusing on a single release site, behaviors of interest that could be implemented include, but not limited to: the number of open channels, transition probabilities among specific states, puff/spark amplitude, puff/spark durations, and inter-puff/spark-intervals. When considering Ca2+ diffusion and homeostasis, hybrid stochastic and deterministic simulations as used by Rückl and colleagues [42, 43] can be implemented in the e v a l u a t i o n function such that reduced models approximate the [ Ca2+] wave and oscillation statistics of the full model.
Comparison to previous work
As compared to the fast/slow reduction technique [21], the genetic algorithm-based approach does not require time scale differences and allows users to choose the size of the reduced model freely. More importantly, the genetic algorithm-based approach often finds partition schemes that produce less error than the fast/slow technique. It is also important to note that this procedure performs better on models whose parameters are of the same scale. When time scale differences are present, like in the Keizer-Levine model and the De Young-Keizer model, because for every \(Individual\ \mathcal {I}\), we must reduce the full model following the aggregation scheme, calculating the reduction error by computing matrix exponentials. Thus, it is recommended to fine tune the genetic algorithm parameters to achieve faster convergence. The choice of crossover and/or mutation probabilities, selection techniques, and even population size per generation could affect the performance of genetic algorithms [44]. For example, when reducing a full model consisting of 10 four-state channels, if using 10 as the population size and 2000 generations are generated until the program terminates, the total time consumed is approximately 2000 times that of the fast/slow procedure. If the population size was increased to 200 individuals per generation, the genetic algorithm can find equally good reductions approximately 10 times faster. Fortunately, for any specific objective assigned, the reduction procedures need to execute very few times and the reduced release site models are potentially able to save significantly more time in the whole cell simulations. Furthermore, this genetic algorithm-based reduction technique can be hybridized with other stochastic optimization methods. For example, we implemented one version of the genetic algorithm with a simulated annealing twist, where the crossover procedure was skipped and every individual that survived selection would generate a child through mutation. This version converges faster as compared to the traditional genetic algorithm when applied to some release site models.
Future work
As discussed in the 'Background' section, how to control computational cost of large mathematical/computational models has become an increasingly important research topic. The recent work by Cao and colleagues [45] that proposed a deterministic model of IP3Rs that qualitatively predicts some stochastic Ca2+ oscillation properties is very encouraging. This two-state model was constructed by reducing a 6-state stochastic IP3R model [46], where the six states were partitioned into two groups assuming time scale differences and the experimentally observed "two mode" property. Then each group was lumped to a single state according to the steady state probability distribution of the full model. Not only can this deterministic model quantitatively reproduce Ca2+ puffs and stochastic oscillations, but their model is also approximately 10 times faster than the comparable stochastic simulations. It would be very beneficial if we can find simple deterministic models that can replace other stochastic calcium channel models under certain circumstances. Since not all models possess time scale differences, we can potentially use the genetic algorithm approach to search for partition schemes of stochastic IP3R or RyR models that allow the reduced deterministic models to well approximate the stochastic behaviors of these channels.
Another important project for the near future is to search for common features in the partition schemes that produce small errors. Should the aggregated states in the reduction follow certain topological pattern or possess similar functional feature (having similar number of open/refractory channels for example) the model reduction approach can be significantly accelerated by using a biased initial population. So far, an interesting phenomenon observed while reducing Ca2+ release site models using the genetic algorithm based approach is that the state aggregation schemes which result in small reduction errors tend to be "heavy headed". That is, these low-error partitions usually feature one large group that contains more than 50 % of the states while other groups contain significantly fewer (sometimes only one or two) states. Moreover, the states aggregated in the small groups are highly likely to be the states that are less often visited in the full model, and this phenomenon exists in all Ca2+ release site reduction procedures. This observation is a good explanation for the fact that the generator matrices associated with the reduced model \(\hat {\boldsymbol {Q}}\) tend to be ill-conditioned. This observation suggests that it may be possible to generate a biased initial population to accelerate the evolution procedure.
This material is based upon the work supported by the National Science Foundation under Grant No. 0443843 and the provost office of Hobart and William Smith Colleges. The author would like to thank Prof. Gregory D. Smith for setting this project up. His advice and valuable suggestions have greatly shaped the frame of this work. The author also thank Associate Prof. Matthew S. Haner for proofreading and editing part of this paper. The author acknowledges stimulating discussions with H. Drew LaMar and Ryan Carpenter and the support from SciClone Computing Complex.
licensee Springer on behalf of EPJ. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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subset: commoncrawl


text:
The effects of rising fuel costs, increased energy demands and environmental considerations have pushed the issue of renewable fuel sources in the past decade. Amid this turmoil the world of synthetic fuel production has flourished and continues to evolve.
That has been great news for one of Louisiana's newest establishments, Dynamic Fuels, LLC, a Geismar-based business which was a 50/50 joint venture between Arkansas conglomerate Tyson Foods, Inc., and Syntroleum Corporation out of Tulsa, Oklahoma.
The two parties forged a partnership to build upon the growing area of renewable synthetic fuels that aims to produce energy in a manner that reduces life cycle greenhouse gas emissions, while building forwards-compatible renewable fuels infrastructure and the site currently being built will represent North America's first renewable, synthetic fuels plant.
Synthetic fuels are one of the few economically viable and industrially scalable alternatives to petroleum capable of providing a major source of the liquid transportation fuels required to run the economy, and the only known non-petroleum source of aviation fuel.
However, change was in the air and in June of 2014, Renewable Energy Group, Inc. (NASDAQ: REGI) announced that its wholly-owned subsidiary, REG Synthetic Fuels, LLC, had completed its acquisition of the remaining 50 per cent ownership interest in Dynamic Fuels, LLC, previously owned by Tyson Foods, Inc. (NYSE: TSN).
REG has now taken full ownership of Dynamic Fuels' 75 million gallon nameplate capacity renewable diesel biorefinery in Geismar, Louisiana.
Tyson and Syntroleum formed Dynamic Fuels in 2007 as a 50/50 joint venture. Completed in 2010, the facility is the first large-scale renewable diesel biorefinery built in the U.S. and will now be known as REG Geismar, LLC.
"Closing these transactions enables our entry into the renewable diesel market in a significant way," said Daniel J. Oh, Renewable Energy Group, Inc. President and Chief Executive Officer. "We are excited about the opportunity to offer new products to our customers, while building on our core competencies in research, engineering, production, and distribution of advanced biofuels. We look forward to bringing the Geismar biorefinery online and work to do so has begun."
REG paid Tyson approximately $16.5 million in cash at closing and retired approximately $13.5 million of Dynamic Fuels' indebtedness to Tyson. REG has also agreed to make up to $35 million in future payments to Tyson tied to product volumes at the Geismar biorefinery over a period of up to eleven and a half years. REG intends to use proceeds from its recent $143,750,000 convertible senior notes offering to either replace the letter of credit that Tyson Foods obtained to support the biorefinery's $100 million in Gulf Opportunity Zone Bonds, issued through the Louisiana Public Facilities Authority, or to redeem these bonds.
Renewable Energy Group, Inc. is a leading North American advanced biofuels producer and developer of renewable chemicals. REG utilizes a nationwide production, distribution and logistics system as part of an integrated value chain model to focus on converting natural fats, oils and greases into advanced biofuels and converting diverse feedstocks into renewable chemicals. With 10 active biorefineries across the country, research and development capabilities, and a diverse and growing intellectual property portfolio, REG is committed to being a long-term leader in bio-based fuels and chemicals.
At the time the transaction was announced, most of the employees at the former Dynamic Fuels, LLC were expected to join the company as part of the renamed REG Geismar, LLC.
And it is a skilled workforce, with so many ethanol plants and refineries located in this area of the Mississippi, the company was able to hire a team of experts with most individuals bringing at least 10 years of petrochemical knowledge to the fledgling operation.
Developing the fuel is a 3-step process, requiring lots of hydrogen, which is conveniently close to hand at nearby Praxair – indeed proximity to suppliers was a primary consideration in the joint venture selecting Geismar as the base for its $158 million project.
"We use a mixture of low-cost feedstocks delivered to the plant by a combination of rail and truck and react it with hydrogen to restructure the molecule; the second step is to produce a normal paroffin and to then convert this into an isoparaffin," Plant Manager Doug Duga explained back in 2009.
"The primary product is diesel fuel which can be sold as blend for refineries or can be used neat, but we also produce naphtha and Liquid Petroleum Gas (LPG). As non-fossil fuels, our products are so much cleaner burning fuels and contain less than one-part-per-million sulphur. Our fuel generates 74 per cent less greenhouse gas than burning a gallon of petroleum-based diesel."
"The pioneering technology we use was devised by Syntroleum and is known as Bio-Synfining™; a couple of years ago they were talking to suppliers of animal fats as they commercialized their technology and Tyson (who already had a renewable division) decided they would rather be partners than just a supplier."
With the environment high on everyone's agenda in the 21st Century, REG Geismar LLC is well placed to play a significant role in producing cleaner energies.


text:
La Crosse Technology WD-3209 User Manual
Version 1.4 - 9/26/2008
Owner's Manual
Presented by La Crosse Technology®
La Crosse Technology, Ltd.
2809 Losey Blvd. S.
La Crosse, WI 54601
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Table of Contents
Table of Contents ............................................................................................................................
Quality Forecasts.............................................................................................................................
Weather Direct® is Green ...............................................................................................................
Included in the Box ..........................................................................................................................
915 MHz Wireless Sensor Technology ...........................................................................................
What You Need to Get Started:.......................................................................................................
Set Up your
Hardware Installation.......................................................................................................................
Wireless Outdoor Sensor Installation Options ............................................................................
To Surface Mount the Outdoor Sensor:..................................................................................
To Wall Mount the Outdoor Sensor: .......................................................................................
Gateway Installation ........................................................................................................................
Online Resources ............................................................................................................................
Time Setting on Wireless Display..................................................................................................
Wireless Outdoor Sensor ..............................................................................................................
Wireless Display Operation ...........................................................................................................
"MODE" Key ..............................................................................................................................
"ALARM" Key ............................................................................................................................
Turn Alarm ON/OFF..............................................................................................................
Set Alarm Time .....................................................................................................................
"SNOOZE" Key..........................................................................................................................
Alarm Snooze .......................................................................................................................
Change the Display Mode.....................................................................................................
View Outdoor Temperature...................................................................................................
"+" Key.......................................................................................................................................
Toggle Between Time, Date & Temperature ........................................................................
View Outdoor Temperature...................................................................................................
Manually Request a Weather Direct® Data Update .............................................................
"SET" Key..................................................................................................................................
When ADD 4 LOCATIONS Expansion Option is Active .......................................................
Changing Settings on Your Wireless Display .......................................................................
Set Mode 1 – Set LCD Contrast
Set Mode 2 – Enable Acoustic Weather Warnings (ON/OFF) .........................................
Set Mode 3 - Set Text Scrolling Speed
Set Mode 4 - View Device ID............................................................................................
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Factory Reset of Wireless Display.................................................................................................
FREE Trial of Expansion Options for 14 Days ..............................................................................
Four Additional Forecast Locations...........................................................................................
Severe Weather Alerts ..................................................................................................................
Types of Severe Weather Alerts:..........................................................................................
Forecast Icons Explained ..............................................................................................................
Care and Maintenance ..................................................................................................................
Battery Replacement .....................................................................................................................
Temperature Range..............................................................................................................
Battery Life............................................................................................................................
Dimensions ...........................................................................................................................
Weather Direct® Update Rate ..............................................................................................
Weather Direct® Wireless Range.........................................................................................
Power Requirements .....................................................................................................................
Liability Disclaimer.........................................................................................................................
FCC Statements ............................................................................................................................
Warranty Information .....................................................................................................................
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You have just purchased the world's first
Weather Direct® uses the power of the Internet to deliver weather data and other important information tailored to you, because you are in control of the information it delivers.
We understand that no one likes having to read a manual, so we've tried to make this a fun and rewarding read. After all, Weather Direct® is all about you. It's like having your own personal assistant to tell you the weather how, when and where you want it. Knowing how Weather Direct® works will allow you to get the most out of this innovative new system.
Weather Direct® - Not Just Another Weather Station. Weather Direct® is the complete weather experience.
Quality Forecasts
Weather Direct® provides the most accurate forecast information available, customized to your exact location! Our forecasts go beyond backyard measurements by using
National Weather Service instrumentation and local weather reporting stations widely distributed throughout North America.
The same quality weather information used by meteorologists to deliver the local forecast plus additional weather data unique to the Weather Direct® network is available to you 24 hours a day! We provide the most detailed, customized, up-
Weather Direct® is Green
We are doing our part to keep our planet healthy by eliminating our paper manuals, saving trees in the process. Not only are we reducing the amount of paper, but we are also trying to help you save space in your desk drawer, file cabinet or box in the basement where all these pesky manuals end up. Now you can print only the pages from this manual that you need… or not print any at all if you find what you are looking for online.
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The Gateway uses only 1 watt of power with a two year battery life on the
Wireless Display and Temperature sensor. Since the Weather Direct® system works even when your computer is off, you save money on electricity.
Included in the Box
Direct® system that includes:
•Wireless Gateway + Mounting Plate – Powers your Weather Direct®
System with weather data and other customizable feeds from the Internet. Sends data your Wireless Display with a wireless range of up to 330 feet (open air).
Measures the outdoor temperature where you are and sends temperature data to your Wireless Display with a wireless range of up to 330 feet (open air).
•(4) Screws and drywall anchors for mounting the Wireless Outdoor Temperature Sensor and the Wireless Gateway
•Quick Set Up Card
•Weather Club Information Card
•LAN cable to connect the Gateway to a network router
•AC adapter for Gateway
915 MHz Wireless Sensor Technology
This product offers:
INSTANT TRANSMISSION is the
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What You Need to Get Started:
Internet service will work.
•Router or broadband modem with
•If you have any questions about routers, or you would like a recommendation on a great router for use with Weather Direct®, see - www.weatherdirect.com/router
•2 "AA" Alkaline batteries for the Wireless Outdoor Sensor
NOTE: Rechargeable batteries are not recommended due to the wide variation in performance between brands and types. Please use only fresh Alkaline batteries.
•2 "C" Alkaline batteries for the Wireless Display
NOTE: Rechargeable batteries are not recommended due to the wide variation in performance between brands and types. Please use only fresh Alkaline batteries.
•Visit www.weatherdirect.com and click "Register" to Start
•After you have registered and selected a forecast location and Time Zone for your Wireless Display, the forecast data will show up on the display within 60 seconds.
•A reasonably current Windows, Macintosh, or Linux PC with internet
browser installed is required for initial set up and configuration changes1.
1 Any internet use involves computer security maintenance. It is your responsibility to maintain current operating system and internet security patches to protect your PC resources. Contact your operating system vendor or ISP for maintenance details. The following reference may also be helpful:http://www.cert.org/tech_tips/home_networks.html
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Please DO NOT insert batteries into the Wireless Display or the Outdoor Sensor until instructed to do so.
Connect the Gateway to an available LAN port on your network router with the
LAN cable (included) and then power up the Gateway with the AC Adapter (included).
Set Up your
NOTE: TheQuick
Open www.weatherdirect.com in a web browser and click "REGISTER" at the top of the page. Our Online Registration Wizard will guide you through the complete registration process.
Hardware Installation
NOTE: Hardware installation is only intended to be performed after you have registered your Gateway and Wireless Display, inserted batteries into the Wireless Outdoor Temperature Sensor, and have confirmed successful reception of weather data.
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Wireless Outdoor Sensor Installation Options
NOTE: Move the Wireless Outdoor Sensor into its intended location and wait for 10 minutes to make sure the outdoor temperature is still being received by the Wireless Display. Press the "SNOOZE" Key on your Wireless Display to show the outdoor temperature. If the display shows -
DO NOT mount the Wireless Outdoor Sensor in a permanent fashion until you are sure the signal is being received by the Wireless Display.
To Surface Mount the Outdoor Sensor:
We have provided a mounting plate that you can attach to a surface with the supplied screws. The Sensor can be positioned on a flat surface by securing the stand to the bottom by gently pushing the bottom of the Sensor onto the holding pegs of the stand until they click into place in the grooves on the Sensor.
To Wall Mount the Outdoor Sensor:
The Outdoor Sensor is weather resistant, but not water proof. To
ensure maximum Sensor life, mount it in a covered place out of the
elements like under the eaves. Placement on the North side of your
home will provide the most accurate readings. Mount it about 18"
down from the eaves for optimum performance. This ensures that the weather data collected by the Outdoor Sensor will not be affected by
the temperature of the air leaving the attic.
We have provided a mounting plate that you can attach to the wall with the supplied screws. Gently snap the Sensor onto the holding pegs on the mounting plate after the plate is screwed to the wall. When the holding pegs are securely locked into the slots on the Sensor, you will hear a "Click".
Gateway Installation
The Gateway should be installed indoors in an
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If you require a longer LAN cable to mount the Gateway in a desired location, any standard Category 5 network cable will work, but a crossover cable may not work. Crossover cables designed to connect two computers without networking hardware may not work with your Gateway.
NOTE: Network cables usually have length limitations. The same length limitations will apply that apply to computers on your home network.
Online Resources
These links can help to enrich your Weather Direct® experience:
•Help – www.weatherdirect.com/help
•FREE Membership Included to the Weather Club, at www.theweatherclub.com featuring:
1.Online weather forecasts by Meteorologist Paul Douglas
2.Radar maps
3.Video and photo uploads
4.And Much more!
•For a list of places to choose from as forecast locations - www.weatherdirect.com/places
•Free Forecasts for Over 40,000 Locations in the United States and Canada, Including Your Hometown, Golf Courses, Parks Sports Venues and More.
•Automatically Updates Itself via the Gateway
•4 Day Forecast with Daily Sky Condition Icons
•Specific Forecast for Morning, Afternoon, Evening and Night and Full Day
•Lower LCD Line Scrolls City Name, Forecast, Outdoor Temperature,
Sun Rise/Set
•Lower LCD Line Scrolling Speed Adjustment
•LCD Contrast Setting
•Daily HI / LOW Temperature Forecast
•Indoor Temperature (°F/°C)
•Wireless Outdoor Temperature (°F/°C)
•Monitor Your Outdoor Temperature From Anywhere in the World on a Free Membership to the Online Weather Club. For more details, please visit www.theweatherclub.com
•Time Alarm with Snooze
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•Time and Date Set Automatically
•Low Battery Indicator on the LCD and the web site for the Wireless Display and Outdoor Sensors
•Expansion Options:
1.View Up To Five Forecast Locations on the Wireless Display
2.Receive Severe Weather Alerts
Time Setting on Wireless Display
The Time Zone you select on www.weatherdirect.com for your Wireless Display is intended to set the time for your physical location so the clock on your Wireless
Display is accurate. This time is independent of your selected forecast locations. The Wireless Display will ONLY display the time from the "Time Zone for Wireless
Display Clock" set on the web site, NOT the time at the forecast locations.
There is only one Time
Zone available per Wireless
The Daylight Saving Time (DST) checkbox on your Wireless Display settings at www.weatherdirect.com is selected by default because most locations observe
DST. If you are in a location that does not observe DST, please make sure to uncheck this box.
Wireless Outdoor Sensor
The Wireless Outdoor Sensor sends temperature data to your Wireless Display, accurate to within a tenth of one degree.
The Outdoor Temperature Sensor uses 2 x "AA",
Alkaline batteries. To install and replace the batteries, please follow the steps below:
1. Remove the battery compartment cover on the back of the sensor.
Page 10 of 25
Version 1.4 - 9/26/2008
2.Insert the batteries, observing the correct polarity (see marking).
3.Replace the battery compartment cover on the unit.
Press the "SNOOZE" Key on your Wireless Display to show the outdoor temperature at any time. The outdoor temperature will scroll on the bottom of the LCD.
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Wireless Display Operation
This section will teach you how to use your Wireless Display once you have completed online registration. There are 5 control Keys located on the back of the Wireless Display: "SET", "+", "SNOOZE", "ALARM" and "MODE". The following information is divided into sections based on the function of each Key.
"MODE" Key
Specific Forecasts help you prepare for different weather conditions during the day by providing weather information for Morning, Afternoon, Evening and Night.
You'll know if the weather during the morning commute will be different from the weather during the rest of the day.
You'll know to bring your umbrella to work on a deceptively beautiful sunny morning, because Micro Forecasts will inform you that it will rain in the afternoon on your way home.
Going to the game today? The Afternoon and Evening forecasts are a lifesaver! Micro Forecasts help to make sure that you pack a blanket or a rain coat if needed.
Work 2nd or 3rd shift? Receive detailed forecast information tailored to specific times of the day when you are the most active.
You can change the Micro Forecast reading on your Wireless Display by pressing the "MODE" Key to toggle between the available options.
Press the "MODE" Key to cycle through the Micro Forecast options:
Forecast from 6:00 AM - 11:59 AM with Daily HI/LO Temperature
Forecast from 12:00 PM - 5:59 PM with Daily HI/LO Temperature
Forecast from 6:00 PM - 11:59 PM with Daily HI/LO Temperature
Forecast from 12:00 AM – 5:59 AM with Daily HI/LO Temperature
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Rotates between the four Micro Forecasts and the Daily Forecast
Shows the forecast for the next six hour period so you can be prepared for the upcoming weather. If it was morning now, it would show the afternoon forecast. If it was evening now, it would show the night forecast, etc.
Shows only the Daily forecast when you are only interested in the weather for the day rather than forecasts for morning, afternoon, evening or night.
"ALARM" Key
Turn Alarm ON/OFF
•Press the "ALARM" Key to turn the alarm ON. The Alarm icon "((•))" will appear on the LCD.
•Press the "ALARM" Key again to turn the alarm OFF. The Alarm icon
"((•))" will disappear from the LCD.
•Press the "ALARM" Key when the alarm is sounding to stop the alarm for 24 Hours.
Set Alarm Time
•Press and Hold the "ALARM" Key until the hours digit flashes to set the alarm time. Alarm will sound once every 24 hours while active.
•Press the "+" Key to change the hour. "PM" will indicate a PM time, while no icon next to the time means AM time.
•Press the "ALARM" key again and the minutes digit will flash.
•Press the "+" key to change minutes.
•Press the "ALARM" key once more to return to normal display
"SNOOZE" Key
Alarm Snooze
•Press the "SNOOZE" Key to temporarily silence the alarm for 5 minutes. The Alarm icon "((•))" will flash on the LCD while the Snooze function is active. Press any Key to cancel Snooze and turn the Alarm off until tomorrow.
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Change the Display Mode
•Press the "SNOOZE" Key to cycle through the type of detailed weather information that will display below the forecast icons:
1.Sunshine Forecast
2.% Chance of Rain/Snow
3.Amount of Rain/Snow
4.Relative Barometric Pressure with Tendency Arrow
5.Wind Gust Speed and Direction
6.Wind Speed and Direction
View Outdoor Temperature
•Press the "SNOOZE" Key to view the current outdoor temperature from your synchronized wireless outdoor sensor. Pressing the "SNOOZE"
Key will also change the display mode.
"+" Key
Toggle Between Time, Date & Temperature
•The "+" Key cycles through the date, seconds and indoor temperature on the top segment of the LCD
View Outdoor Temperature
•Press the "+" Key to view the current outdoor temperature from your synchronized wireless outdoor sensor. Pressing the "+" Key will also cycle through the date, seconds and indoor temperature on the top segment of the LCD.
Manually Request a Weather Direct® Data Update
•When you register your Wireless Display, the weather data is updated within a few minutes. Every 6 hours after that, your Gateway will send weather data to update your Wireless Display.
•After changing the forecast location or other setting on the web site, it can be up to six hours for your next scheduled automatic update.
•After adding an Expansion Option to your Wireless Display, it can be up to six hours for your next scheduled automatic update.
•If you do not want to wait for your Wireless Display to update automatically, Press and Hold the "+" Key for 3 seconds until your Wireless Display beeps once. A second beep within a few seconds will signify that the Wireless Display has received the data.
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"SET" Key
When ADD 4 LOCATIONS Expansion Option is Active
Press the "SET" Key to toggle between the forecast locations on the Wireless Display when the ADD 4 LOCATIONS Expansion Option is active. The name of the location will appear briefly on the bottom of the LCD when it is selected.
Weather data for up to 5 locations can be viewed on your Wireless Display.
Changing Settings on Your Wireless Display
Press and hold the "SET" Key until the Wireless Display beeps to enter the SET mode. Press the "SET" Key to toggle through the four SET modes. If you wait for
5 seconds without pressing a key, the Wireless Display will exit the SET mode and return to normal operation.
The Four SET modes are:
Set Mode 1 – Set LCD Contrast
1.Press and Hold the "SET" Key until the Wireless Display beeps to enter the SET mode
2."LCD" and number
3.Press the "+" Key to update the LCD Contrast settings.
Lightest Contrast = "0", Darkest Contrast = "7"
4.Press the "SET" Key to save the current settings and advance to the next option
Set Mode 2 – Enable Acoustic Weather Warnings (ON/OFF)
NOTE: This SET mode is only available when the Severe Weather Alerts Expansion Option is active. In addition to the scrolling text of the Severe Weather Alerts, an Acoustic Weather Warning provides a beep to notify you of a weather condition. You can turn this beep off to silence this warning so only the text of the warning is displayed. To change the setting, follow the instructions below:
5. Press the "SET" Key until "AAL ON" or "AAL OFF" flashes at the top and "ENABLE ACOUSTIC WEATHER WARNINGS" scrolls across the bottom
6.Press the "+" Key to turn AAL "ON" or "OFF"
7.Press the "SET" Key to save the current settings and advance to the next option
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NOTE: You can silence an Acoustic Weather Warning by pressing any Key.
Set Mode 3 - Set Text Scrolling Speed
8.Press the "SET" Key until "Scr" flashes at the top and "SET SCROLL SPEED" scrolls across the bottom
9.The standard speed is set to "2"
10.There are four speeds available – "1" is the slowest and "4" is the fastest
11.Press the "+" Key to change the scroll speed.
12.Press the "SET" Key to save the current settings and advance to the next option
Set Mode 4 - View Device ID
NOTE: Device ID is a reference item for customer service only. You may press the "SET" Key again to exit SET mode if you are not asked to provide this number by customer service.
13.Press the "SET" Key until "SEC 1" appears at the top
14.The first part of the Device ID will appear at the bottom
15.Press the '+" Key to view second part of the Device ID under
16.Press the "SET" Key to exit SET mode
Factory Reset of Wireless Display
NOTE: It is not possible to
NOTE: Expansion Options that are Lifetime Upgrades are still active on your Wireless Display even if you delete it from your user account onwww.weatherdirect.com or perform a Factory Reset. The selection of locations and other custom settings will need to be performed again if the Wireless Display is
WARNING: The Factory Reset procedure will erase any registration and setup information from your Wireless Display. You must register the Wireless Display again withwww.weatherdirect.com to use it after a Factory Reset.
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WARNING: Deleting the Wireless Display from a user account onwww.weatherdirect.com will erase the weather and other setup information such as forecast locations from the Wireless Display.
If you have trouble registering your Wireless Display after multiple attempts, you can try a Factory Reset.
If you wish to give your Wireless Display to someone else or simply to register it under a different user account, you must perform the Factory Reset to clear the registration information from the memory of the Wireless Display and delete the device from the user account on www.weatherdirect.com
Additional diagnostic and reset information, including how to reset the gateway (if necessary), is contained at www.weatherdirect.com/help
Hold both the "SET" and "ALARM" Keys down together for about 6 seconds; you will hear a double beep. This resets the Wireless Display to the original factory state.
FREE Trial of Expansion Options for 14 Days
When you register your Wireless Display and have the included forecast location selected, you will be given the opportunity to try our most popular Expansion
Options FREE for 14 Days! NO CREDIT CARD OR PAYMENT REQUIRED!
14 Days of FREE Expansion Options, including:
1.4 Additional Forecast Locations on your Wireless Display
Four Additional Forecast Locations
The standard Weather Direct® Wireless Display includes weather information for one location. - But what about the weather happening in other places that are important to you?
In addition to your standard location, the Four Additional Locations Expansion Option allows you to monitor four more forecast locations on your Wireless
Display, for a total of five.
Press the "SET" Key on your Wireless Display to display the weather data for another forecast location. You can have up to five locations on your Wireless
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Version 1.4 - 9/26/2008
Display. Every press of the "SET" Key rotates through the list of available locations.
Now you can keep an eye on the weather where your daughter goes to school, your favorite vacation spot, your parents' house and more.
Severe Weather Alerts
Keep your family safe with Severe Weather Alerts issued by the National Weather Service. This valuable information will help you prepare for upcoming weather events. Choose which types of severe weather events you want to receive. Even be alerted via
Severe Weather Alerts are available for either 1 year or 3 year periods that cover one forecast location. You can add up to 5 total alert locations if you also have the Add 4 Locations Expansion Option active.
Severe Weather Alerts are available for any of our 40,000 places to choose from.
Weather Direct® is not liable for any incidents that may occur as a result of any National Weather Service alert. This alert service is provided as a convenience to make you aware of a potential situation, not as a replacement for local severe weather warning systems.
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Version 1.4 - 9/26/2008
Types of Severe Weather Alerts:
Heavy Rainfall
Severe Thunderstorm
Coastal Flood
Heavy Snow
Severe Wind
Excessive Heat
Heavy Snowfall
Small Craft
Flash Flood
High Wind
Special Marine
Hurricane Force
Ice Storm
Lake Effect Snow
Lake Snow
Wind Chill
Heavy Rain
River Flood
Winter Storm
Coastal Flood
Lake Effect Snow
Excessive Heat
Lake Snow
Flash Flood
High Wind
River Flood
Advisories and Statements
Blowing Dust
Tropical Storm
Blowing Snow
Heavy Snow
Urban And Small Stream
Dense Fog
Hurricane Statement
Urban Flood
Freezing Drizzle
Lake Effect Snow
Freezing Fog
Small Stream Flood
Wind Chill
Freezing Rain
Winter Weather
Snow And Blowing Snow
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Version 1.4 - 9/26/2008
Forecast Icons Explained
There are two sets of icons presented on your Wireless Display, one for day and one for night. A sun appears on many of the day icons while a moon appears on many of the night icons. Night icons only available with the Micro Forecast Expansion Option.
NOTE: Trace precipitation will not display droplets on the icon and "MEDIUM" conditions generally use the "HEAVY" icons to communicate weather events that are likely to affect your plans for the day.
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This past week, WhyCauseICan.com had a chance to team up with the lovely Amber Jaii to do an exclusive interview with clothing company D.R.U.G.S. (Do Right U Gain Success) and their new artist Bambie.
In the interview, we had a chance to find out where D.R.U.G.S. all began, Who is the father?, and what hip-hop artist Bambie has coming up in the music industry.
Previous Posts:
- Video: Drake Announces Jordan Brand Partnership (www.whycauseican.com)
- Listen: Alicia Keys "I'd Die Without You" (www.whycauseican.com)
- Listen: M.I.A. "Trouble Again" (www.whycauseican.com)
- Kelis' New "Feast" Sauce Line Well Bring Everyone To The Yard (www.whycauseican.com)
- Video: Lorde "Team" (www.whycauseican.com)


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If you want to know what America's shadow government has in store for Argentina, look no further than Detroit. Argentina has been in the sights of RAND Corporation for some time now but recently there has been an increased urgency for bankrupting Argentina.
2001 was quite the year for the world, 2001 is the year that the U.S. Government was replaced with a shadow government run by think tanks. After the December 12, 2000 Supreme Court coup that installed the George W. Bush Administration, there was a purge of federal judges in the United States.
The Bush Administration installed, in its place, the most highly ideological judges and Supreme Court members he could scrape up from Reagan's Administration and the Christian law school, Regent University.
"You can't look at the Roberts court and say that they've done anything other than systematically unravel voting rights, women's rights, workers' rights [and] environmental progress," Lithwick tells Moyers.
Greenhouse adds: "I think it's hard for anybody looking at this court objectively to come away not thinking that it's a court in pursuit of an agenda."
It is hard to remember America before December 12, 2000. In the spring of 2001, RAND Corporation's Frank Carlucci, Robert Hunter, and Zalmay Khalilzad prepared "A Global Agenda for the U.S. President".
By Frank Carlucci, Robert Hunter, and Zalmay Khalilzad
The authors co-chaired Transition 2001, a panel of 54 American leaders in foreign and defense policy who were convened by RAND to forge a bipartisan agreement on the central tenets of U.S. national security policy and to offer bipartisan recommendations to the new U.S. president.
Frank Carlucci, a RAND trustee, was secretary of defense from 1987 to 1989. Robert Hunter, a senior advisor at RAND, was ambassador to NATO from 1993 to 1998. Zalmay Khalilzad, corporate chair for international security studies at RAND, was assistant deputy undersecretary of defense for policy planning from 1991 through 1992 and director of President George W. Bush's Department of Defense Transition Team in December 2000 and January 2001. The conclusions of the panel are summarized below.
Now, isn't that nice? One thing is for sure, when RAND offers a "global plan for the new president" you'd better be listening.
The array of new global challenges and opportunities will significantly increase the demand for U.S. diplomacy and other nonmilitary involvement abroad. Therefore, nonmilitary spending on foreign policy and national security should increase substantially as well.
Thus, Mr. President, we urge that you ask Congress for a 20 percent hike in spending for the U.S. Department of State, for payment of U.N. dues, and for other critical nonmilitary requirements of foreign policy. We also recommend that you seek about a 10 percent increase in defense spending, or about $30 billion more for procurement plus another $5-$10 billion for property maintenance, recruitment, targeted pay raises, retirement, and medical care.
When George W. Bush took office in 2001, there was a peace dividend, a budget surplus and prosperity was spread across the United States and thus the world. So it's quite fortuitous that RAND would have the foresight to bulk up military spending in spring of 2001. Part of RAND's road map for the president were short term objectives, such as missile defense system.
Mr. President, we believe that you will need to address three critical issues right away, involving (1) national missile defense, (2) a modernized defense program, and (3) Arab-Israeli peacemaking.
Yeah, I'll be RAND wanted that missile defense shield right away. That missile shield boondoggle is worth a shitload of money for RAND. Remember all those missile tests that failed? Think those days are over with the Obama Administration? Not so, check out this April 2014 article from Mark Strauss at io9.com:
Last month, the U.S. Government Accountability Office issued a scathing report: the system to defend the U.S. from ballistic missiles doesn't work, and probably never will. But it gets worse. Congress then voted to expand the broken system, allocating money for a new, sub-par missile defense site. How did this happen?
It's the latest iteration of federally-funded cognitive dissonance that has been going on for years. In theory, the U.S. Ground-Based Midcourse Defense (GMD) system—which is overseen by the Missile Defense Agency —should be capable of launching missile interceptors, each tipped with a "kill vehicle" that detaches, detects and destroys the incoming threat. In the real world, ground-based missile defense has failed all three of its flight tests since 2010.
Yep, doesn't work and never will. So while public pension funds are decimated and our military is left sick and wounded from all the wars that have been fought for a war based economy, our congress is shoveling billions more into a missile system that will never work.
So RAND had 3 short-term goals for the G.W. Administration, missile defense shield, modernize military and Israeli Arab peace. Sounds like a great big goose egg for the United States, but a huge cash cow for RAND.
So why the heated rush to destroy Argentina? This from Counterpoint.com:
Preparing the Beggar's Banquet
The Ukraine is being prepped, like an ingénue for a beggar's ball, for mass immiseration. How frankly the terms are discussed in the mainstream, such is the pervasive nature of groupthink (a tautology, perhaps). The blandly discussed facts tumble forth—a 50 percent increase in gas prices, property tax hikes, reduced pensions (pensioners not consulted), and efforts to hollow out regulatory bodies…
Have a glance at this image, of a hushed exchange between the central puppets in the Ukrainian debacle. First, the PM of the 'people's putsch', Arseny Yatseniuk or, affectionately, "Yats" to coup director Victoria Nuland, Secretary of State John Kerry's hitman, or hitperson, as it were…
Bribe the leaders. Fill their coffers with cash. Promise them protection. Embrace them in public. Then watch them slip the keys to the kingdom into your pocket. For every Nestor Kirchner there are a dozen Yatseniuks. And for every Kirchner that succeeds there's a dead Allende, an isolated Castro, an exiled Aristide, or a hanged Hussein.
(Kirchner threw the IMF out of a bankrupt Argentina and helped rebuild the Argentine economy.)
That's right, Argentina threw out the corrupt IMF and has been coming out of bankruptcy and building up their economy since. Argentina has been pissing off RAND Corporation, the IMF, Victoria Nuland, Joe Biden and John Kerry with their support of Russia's annexation of Crimea, and their defiance of the austerity that caused their bankruptcy.
and their defiance of the austerity that caused their bankruptcy.
So it wasn't any surprise when a corrupt New York court declared that Argentina is not allowed to pay off its creditors that were willing to work with them, until they pay shake down money to America's think tank financial vultures. From New York Times:
The hedge fund firm of billionaire Paul E. Singer has about 300 employees, yet it has managed to force Argentina, a nation of 41 million people, into a position where it now has to contemplate a humbling surrender.
Argentina on Wednesday failed to make scheduled payments on its government bonds. The country has the money to pay the bonds. But a federal court in Manhattan has ruled that unless Argentina settles its debt dispute with Mr. Singer's firm, Elliott Management, it is barred from paying its main bondholders.
Now what kind of judge forces a country, with cash on deposit to pay their creditors, to default on their loan obligations? I suspect a crooked one installed by a rogue government.
After more than five hours of meetings on Wednesday, the sides failed to reach an agreement and the court-appointed mediator said that Argentina would "imminently be in default." Because a $539 million interest payment was not made, the ratings agency Standard & Poor's said that Argentina was in default on those bonds.
So not only is a crooked N.Y. judge presiding over Argentina's dispute with venture capitalist firm, Elliott Management, but the COURT has APPOINTED a mediator. What a racket 1) crooked judge issues court order blocking Argentina from making it's agreed interest payments to its creditors; 2) payments to creditors won't be released by court until Argentina pays off vulture capitalists and 3) crooked rating agency, Standard and Poor's downgrades Argentina's credit rating for missing payment to creditors.
Man, what some crooks.
The government of Argentina now faces a stark choice: Try to restart negotiations with investors it has repeatedly called "vultures," who have insisted on full repayment. Or it can remain ensnared in a default that could weigh on the country's fragile economy and unsettle global markets.
After the talks collapsed, the economy minister of Argentina, Axel Kicillof, characterized the negotiations as extortion.
"We're not going to sign any deal which compromises the future of Argentines," he said at a news conference in Manhattan.
Damn straight its extortion, but that's the world of think tank mafias. This is the new world order baby.
While Mr. Singer's firm has yet to collect any money from Argentina, some debt market experts say that the battle may already have shifted the balance of power toward creditors in the enormous debt markets that countries regularly tap to fund their deficits. Countries in crisis may now find it harder to gain relief from creditors after defaulting on their debt, they assert.
No shit it's going to be a boondoggle for vulture capitalists with practically no capital at stake and huge profits for the very top. It's like taking candy from a baby.
As a hedge fund, Elliott's pursuit of Argentina is motivated by a desire to make money. Having bought its Argentine bonds for well below their original value, the firm stands to make a killing if Argentina pays the bonds in full. Legal filings indicate that the face value of its Argentine government bonds was around $170 million, but the firm most likely acquired many of them for much less than that. Elliott and other investors are now seeking more than $1.5 billion, which includes years of unpaid interest.
Life is good for vultures in RAND's America. So can Argentina get a "new" court appointed mediator, since the current one obviously is not an independent arbitrator?
From New York Times:
A lawyer for Argentina told a federal judge on Friday that the nation had lost faith in the mediator appointed to work with a group of hedge funds that hold the country's bonds.
The lawyer, Jonathan Blackman, pointed to a statement issued by the mediator, Daniel Pollack, on Wednesday that said Argentina was in "imminent default."
That statement, Mr. Blackman said, was "harmful and prejudicial," and he asked that Mr. Pollack be replaced…
The statement is more than "harmful and prejudicial", it's more akin to pouring blood into shark infested waters.
On Wednesday, Argentina slipped into its second default in 13 years after missing a regular bond payment. The news sent Argentina's bonds and stocks into turmoil on Thursday and Friday.
Yes, the first default for Argentina since 2001. So Argentina was forced to default because of their "court appointed" mediator. Reminds me of Detroit and their "court appointed" emergency manager, Kevyn Orr. From Black Agenda Report:
The Siege of Detroit: A War of Black Urban Removal
Like the rapist who insists his victim "wanted it," Detroit emergency manager Kevyn Orr claims city retirees were expressing "strong support for the city's plan to adjust its debts" when they voted to accept a 4.5 percent cut in their meager pensions. Corporate media echoed the state appointee's interpretation of the court-ordered ballot, in which about half the 32,000 eligible workers and retirees participated. In reality, Detroit's pensioners were violated in broad daylight, stripped of retirement protections and forced to choose whether to die in poverty or an even more extreme destitution.
Earlier this year, as part of the Shock and Awe of state-imposed bankruptcy, Orr threatened to cut pensions by 26 percent, in defiance of Michigan state constitutional protections. He was backed by federal bankruptcy court judge Steven Rhodes, who has brushed aside every objection from lesser, non-corporate beings. Rather than risk the loss of one-quarter of an already meager $20,000 a year pension, 73 percent of retirees and workers accepted the lesser cut, plus an end to cost-of-living increases. This was not an election, but the cruelest coercion – a rape of the elderly, who were forced not only to acquiesce to their own further impoverishment, but to give up the right to challenge the process in court…
Boy, Detroit has RAND Corp's fingerprints all over it with "shock and awe" state-imposed bankruptcy. And, once again a crooked federal bankruptcy judge tilts the scale toward creditors.
Detroit's elected officials cannot pass laws, and collect a salary at the pleasure of dictator Kevyn Orr, who is answerable only to the ruling class, as directly represented by the Fortune 500 clients of the law firm that spawned him, Jones Day. (Orr's nominal boss, Gov. Rick Snyder, answers to the same people.) The state-imposed emergency manager is authorized to usurp the powers of the city – to act as a dictator – but he is not the city in any but the most technical, legalistic sense.
The 82 percent Black metropolis is under siege, in the Medieval sense of the term. Just as ancient armies deprived towns under siege of food and water, to starve and thirst them into submission, so Kevin Orr has caused the Detroit Water and Sewage Department to cut off tens of thousands of residents, in an escalating trajectory of systematically inflicted mass punishment and pain designed to make life in the city unbearable for a huge proportion of the population.
So Argentina, if you want to know what America's shadow government has in store for you, look no further than Detroit, government by think tank mafias.
By: Patricia Baeten


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The male teacher who was allegedly sexually abused by two twerking women says he has been hit with a vicious backlash online after reporting the abuse.
CCTV footage taken on October 7 shows two women harassing the man, who does not want to be named, while he is waiting by a shop counter in Washington, D.C.
In the video, two women grind against his crotch, twerk and grab his privates as he speaks to someone on the phone.
"They were all over my chest and grabbing me. If I would have done that obviously I would have been arrested, thrown to the ground, probably 20 years in prison, no out. You know, it's not the same thing," the victim told news channel WTTG-TV.
He said he had seen online vitriol directed towards him after he filed a police report against the twerkers.
Answering social media critics, the man says he didn't push either women away from his body because he believed a group of men, who he thought were the women's pimps, were watching the scene unfold from outside the store.
"I thought they would have a pimp who was pushing them to be prostitutes who could have been outside with one of the gentlemen that were out there watching and witnessing, could have been with guns to come and shoot me," the victim explained. "I did not want to be shot that day."
The victim left the convenience store. He says the two female suspects flashed him as he called police.
One woman has since been arrested for twerking without his consent, and faces charges of third degree sexual abuse.
DC police are still looking for the second woman, whose identity remains unknown.
© Nine Digital Pty Ltd 2019


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Fish Eye
While playing press C-Left, C-Right, C-Left, C-Right, C-Left, C-Right, C-Left, C-Right.
Open Portals
During gameplay, pause the game by pressing START. Now enter the following code: C-Up, C-Right, C-Right, C-Down, C-left, C-Down, C-Up, C-Right. All games will now be open.
Play as Froggy
While playing, press Start and enter this code: Up-C, Right-C, Down-C, Right-C, Up-C, Left-C, Left-C, Up-C. You will turn into a frog and gain a life every time you eat a bug.
Player Codes
When you start the game, if you head to the left you will see a bird on a swing. If you go to him and press the ball search button (A) you will hear an aasortment of sounds. When you press start you will notice when you press the "C" buttons, the same sounds are made. Simply copy the sounds you hear for a code (some can be played backwards for a different effect). Every time you give a new ball to the monkey in the hill a new code will be given!


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Harmonised unemployment rates define the unemployed as people of working age who are without work, are available for work, and have taken specific steps to find work. The uniform application of this definition results in estimates of unemployment rates that are more internationally comparable than estimates based on national definitions of unemployment. This indicator is measured in numbers of unemployed people as a percentage of the labour force and it is seasonally adjusted. The labour force is defined as the total number of unemployed people plus those in civilian employment.
Unemployment rate is the number of unemployed people as a percentage of the labour force, where the latter consists of the unemployed plus those in paid or self-employment. Unemployed people are those who report that they are without work, that they are available for work and that they have taken active steps to find work in the last four weeks. When unemployment is high, some people become discouraged and stop looking for work; they are then excluded from the labour force. This implies that the unemployment rate may fall, or stop rising, even though there has been no underlying improvement in the labour market.
This indicator shows the unemployment rates of people according to their education levels: below upper secondary, upper secondary non-tertiary, or tertiary. The unemployed are defined as people without work but actively seeking employment and currently available to start work. This indicator measures the percentage of unemployed 25-64 year-olds among 25-64 year-olds in the labour force.
Long-term unemployment refers to people who have been unemployed for 12 months or more. The long-term unemployment rate shows the proportion of these long-term unemployed among all unemployed. Unemployment is usually measured by national labour force surveys and refers to people reporting that they have worked in gainful employment for less than one hour in the previous week, who are available for work and who have sought employment in the past four weeks. Long-term unemployment causes significant mental and material stress for those affected and their families. It is also of particular concern for policy makers, as high rates of long-term unemployment indicate that labour markets are operating inefficiently. This indicator is measured as a percentage of unemployed.
Those in unemployment are people aged 15 and over who were without work during the reference week, available for work and actively seeking work during the previous four weeks including the reference week. Without work refers to those not in paid employment or self-employment during the reference week. Available for work refers to those who were available for paid employment or self-employment during the reference week or four weeks after the reference week in the case of EU countries. Seeking work refers those who took specific steps to actively seek paid employment or self-employment during a specified recent period operationalised as previous four weeks including the survey reference week.
English French
Keywords: unemployment
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Graph of the day
I like it
also explains why the "kid" in Polar Express was so icky.
Also, according to the graph Uncanny Valley also has an excellent moustache
You appreciate this concept even more if you replace 'zombie' with 'real doll'.
It also applies to the comfortableness of technical music amongst Indies as well. Oasis at the bottom. Weezer following. Foals edging up the hill. Mastodon approaching the top. Blue Note Jazz on the cusp. Then it goes too far into Dream Theater country, before rising majestically into the high arts of classical composition - which many people like to hear, but don't fully (need to) understand.
Are Dream Theater at the place represented by zombies on the above graph? I thought you LOVED That shit. Along with Seinfeld.
arrrrrrrrrrgh euuuuuuuuuuuurrgh
ahhhhhhhh :-(