text:
Entry requirements
The Hull MBA is designed for students with a minimum of 3 year's appropriate work experience. Ideally, you will also have a good degree awarded by a UK university or comparable overseas institution, or an equivalent professional qualification. Applicants with more than five years of senior level post graduation work experience may be admitted with a third class pass degree. Applicants without a degree or equivalent professional qualification Applicants who do not have a degree or equivalent professional qualification but meet the other eligibility criteria may submit a portfolio of evidence to demonstrate that they can benefit from, contribute to and succeed on the MBA programme. The applicant should have completed approximately eight years full-time appropriate work experience. A portfolio may include, for example, details of significant work projects carried out, information about strategic analyses undertaken (for example, budgets and strategic forecasts), company reports, or other contributions to policy formulation and implementation. The portfolio might also include information about other courses taken, and training and development programmes attended. The aim is to demonstrate that the applicant's business knowledge and experience are sufficient to allow them to fulfil the academic requirements of the Hull MBA. Interview As the final stage of the application process, applicants that have satisfied all other conditions will be interviewed by Business School staff, either by telephone or in person. The interview also provides an opportunity for the applicant to ask questions about particular aspects of the MBA, and to receive further information about the programme of study. International students - If English is your second language and you do not have a degree from an English speaking country you will be required to demonstrate English language proficiency equivalent to IELTS 6.5 with 5.5 in all four sections as per UKVI requirements.
Months of entry
Course content
Our MBA accredited MBA programme equips you with the knowledge to develop from a manager into a business leader.
Teaching is informed by globally recognised research and takes place in excellent facilities across the University. You and your fellow MBA students will remain together as a team throughout the programme.
The Hull MBA
- prepares you for senior management and leadership roles
- gives you skills in problem identification, systemic management and strategic thinking
- prepares you for life in today's globalised and complex business world
- develops your personal and interpersonal skills, and enables you to facilitate the development of others in the future
- gives you the tools to identify, select, develop and implement approaches to business and management that are socially responsible and ethically sustainable
Information for international students
Competence in English language is required, evidenced by IELTS 6.5 overall and at least 5.5 in each skill, or equivalent, or previous study in English. Candidates who do not meet the language requirements may take an English course at the University.
Fees and funding
Many students are funded by their employer. For information on fees and funding please go to: www.hull.ac.uk/money
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Course contact details
- Name
- Postgraduate Admissions
- email@example.com
- Phone
- +44 (0)1482 466850
- Fax
- +44 (0)1482 442290


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In this infographic you'll discover...
- The 3 Steps to fix a Broken Diet
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- And finally, the all-important Power of Sleep! The most overlooked secret.
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subset: commoncrawl


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The leaves are changing here. Beautiful.
I am at the library bringing back interlibrary loans. Very useful service. Books come from libraries all over the region. Invaluable for research.
The leaves are changing here. Beautiful.
I am at the library bringing back interlibrary loans. Very useful service. Books come from libraries all over the region. Invaluable for research.
In the spring you appeared to be about two weeks behind us. Now you appear to be two weeks ahead.
I didn't even see you come by.
Fr. Z
Speaking as a professional librarian, I'm pleased to see you making use of your local library.
Libraries are one of the best "freebies" in America, don't you think?
PS I read The Name of the Rose two years ago but still haven't read a good translation of the following that relates the literary meaning in the novel:
"stat rosa pristina nomine, nomina nuda tenemus"
No Wiki cheating, anyone!
I'll contact "Cathy of Alex", she'll know, being a professional librarian.
I don't like libraries because I don't like having to give the books back.
I wish libraries would look like they used to.
The modern library look – extreme utilitarian decorated with construction paper cutouts – really turns me off.
I hear ya on those interlibrary loans. At GSU we can get books from all over the world. It is going to come in handy when I start writing my thesis.
Libraries are at their best when they have a coffee shop attached as my local (Sydney suburb) library does.
Father, as a professional librarian, my heart is warmed by your public praise of your library!
It looks like you have a few librarians among your readers/commentors. You see, we appreciate you, too! :)
"This blog is like a fusion of the Baroque 'salon' with its well-tuned harpsichord around which polite society gathered for entertainment and edification and, on the other hand, a Wild West "saloon" with its out-of-tune piano and swinging doors, where everyone has a gun and something to say. Nevertheless, we try to point our discussions back to what it is to be Catholic in this increasingly difficult age, to love God, and how to get to heaven." – Fr. Z
Joseph Ratzinger
in The Spirit of the Liturgy
Raymond Card. Burke
Coat of Arms by D Burkart
My CHALLENGE COINS for my 25th Anniversary of Ordination (26 May 1991) arrived.
I'll make a number of them available for exchange and in gratitude to special benefactors.
- Nehemiah 4:18
Joseph Ratzinger - The Feast of Faith"In those situations where homosexual unions have been legally recognized or have been given the legal status and rights belonging to marriage, clear and emphatic opposition is a duty. ... If all Catholics are obliged to oppose the legal recognition of homosexual unions, Catholic politicians are obliged to do so in a particular way, in keeping with their responsibility as politicians." CDF 2003
Fr. Z - W9FRZ - OFF
QRV on: 00m 00000
Check Echolink WB0YLE-R - OFF
- - Giovanni Guareschi
God or Nothing: A Conversation on Faith by Robert Card. Sarah
Buy it. Get one for your parish priests. UK HERE
- St. John Paul II
- Sean McCabe @seanwes
- C.S. Lewis
Charles Pierre Péguy Notre Patrie, 1905"If I ought to write the truth, I am of the mind that I ought to flee all meetings of bishops, because I have never seen any happy or satisfactory outcome to any council, nor one that has deterred evils more than it has occasioned their acceptance and growth."
St. Gregory Nazianzus ep. 131 - AD 382"We will conquer your Rome, break your crosses, and enslave your women. If we do not reach that time, then our children and grandchildren will reach it, and they will sell your sons as slaves at the slave market."
Sheikh Abu Muhammad al-Adnani, Chief Spokesman the Islamic State, 2014 Quoted in James Wesley Rawles, Land of Promise (Counter-Caliphate Chronicles Series Book 1) See also HERE
- Aleksandr Solzhenitsyn
- Anonymous"Rev. John Zuhlsdorf, a traditionalist blogger who has never shied from picking fights with priests, bishops or cardinals when liturgical abuses are concerned."
- Kractivism"Father John Zuhlsdorf is a crank"
- Michael Sean Winters"Fr Z is a true phenomenon of the information age: a power blogger and a priest."
- Anna Arco
"Given that Rorate Coeli and Shea are mad at Fr. Z, I think it proves Fr. Z knows what he is doing and he is right."
- Comment"Let me be clear. Fr. Z is a shock jock, mostly. His readership is vast and touchy. They like to be provoked and react with speed and fury."
- Sam Rocha"Father Z's Blog is a bright star on a cloudy night."
- Comment"A cross between Kung Fu Panda and Wolverine."
- Anonymous
- Comment
Rev. John Zuhlsdorf, a scrappy blogger popular with the Catholic right.
America Magazine
-Austen Ivereigh on Twitter
- Edmund Burke
Visits tracked by Statcounter since Sat., 25 Nov. 2006:


text:
March 31, 2002 - 2:58pm
- Xbox 360
6 Lives
Set the Saturn's internal clock to a time between 10am and 11am.
Yuna and Manto
At the Match Play screen hold L R.
All Weapons
At the Title screen hold L R A Up/Left.
Hidden Characters
At the opening screen with two bomberman dancing hold L R and press Up/Left A Up/Left B Up/Right C.
Adjust Time of Day
At the Stage Selection screen hold X Y Z. Then press Up or Down
Full Pause Screen
Pause gameplay and press X Y Z.
View Ending Sequence
At the Opening screen with two bomberman dancing hold L R and press Down Z.
Level Select
At the Press Start screen press any of the following:
1 L R Up/Left A
2 L R Up/Left B
3 L R Up/Right C
4 L R Up/Left Xv5 L R Up Y
6 L R Down Z


text:
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The living cell is an incredibly complex entity, and the goal of predictively and quantitatively understanding its function is one of the next great challenges in biology. Much of what we know about the cell concerns its constituent parts, but to a great extent, we have yet to decode how these parts are organized to yield complex physiological function. Classically, we have learned about the organization of cellular networks by perturbing them through genetic or chemical means. The emerging discipline of synthetic biology offers an additional, powerful way to study systems. By rearranging the parts that comprise existing networks, we can gain valuable insight into the hierarchical logic of the networks and identify the modular building blocks that evolution uses to generate innovative function. Additionally, by building minimal "toy" networks, one can systematically explore the relationship between network space (linkages and parameters) and functional space (the system's physiological behavior). Here, we outline recent work that uses synthetic biology approaches to investigate the organization and function of cellular networks, and describe a vision for a synthetic biology toolkit that could be used to interrogate the design principles of diverse systems.
The application of engineering principles toward the construction of novel biological systems — a discipline that has become known as synthetic biology — has received a great deal of attention in recent years based on its potential to deliver a wide array of technological benefits. Revolutionary applications have been envisioned that range from engineering microbes to perform industrial tasks such as biofuel production and biomass conversion to the reprogramming of human cells for therapeutic purposes. In practice, synthetic biology consists of co-opting molecular "parts" from natural systems and using them to construct new networks that fulfill specific design goals. These artificial networks can range from gene regulatory circuitry designed to precisely control the expression patterns of genes, to new metabolic systems that produce useful metoabolites.
While the promise of synthetic biology is vast, many scientists wonder whether we understand enough about cells and complex biological system to begin engineering them. After all, although we are getting close to assembling a complete parts list of the molecules in a living cell, we are far from having a predictive understanding of how these components work as a system to carry out complex biological functions. If this is the case, then how can we expect to build engineered cells? Would it not be better to first understand the cell, then try to engineer it?
We argue here that in addition to its applications, synthetic biology is and will become an increasingly powerful discovery tool for understanding the organization of cells and other complex biological systems. At the current stage of intellectual development in biology, we have extensive knowledge of molecular parts and components, but little knowledge of functional organization and principles. Thus, it can be incredibly valuable, and perhaps even necessary, to use a "learning by building" approach. Working in partnership with systems biology and other traditional methods of cell biology research, synthetic biology can be used to evaluate sophisticated hypotheses on how complex behavioral phenotypes arise from cellular network structure. For example, by functionally testing putative parts in engineered systems, we can identify modular functional units, and uncover the logic of how units can be linked together in hierarchical fashion to yield new function. Synthetic biology has already had early success in engineering simple regulatory circuits that recapitulate some of the behaviors of natural circuits (13). In the future, it should be possible to use an engineering approach to systematically identify multiple, alternative topologies for biological circuits, and quantitatively compare their performance. This type of analysis might shed light on the fundamental principles of how evolution chooses a network design to fulfill specific functional needs. Ultimately, obtaining engineering control over a broad range of cellular functions will provide an experimental toolkit that augments the traditional discovery tools of cell biology. In our estimation, using synthetic biology approaches to rewire biological networks will become a standard investigative approach.
One of the most fundamental issues in biology is how complexity is organized, and how that organization changes during the process of evolution. The concept of hierarchical modularity has provided a usefully framework for understanding this organization. Systems are considered modular if the parts that comprise them (modules) can be rearranged and retain their function in a context-independent fashion. It is undeniable that most biological systems exhibit features of modular organization. Viewing cellular systems in terms of a hierarchy of interlinked, functional modules is one useful way to parse complexity into parts that are more easily understood. Thus, one can argue that understanding a complex entity like a cell will rely on our ability to decompose it into its most important hierarchical modules and describe the relationship of these modules to one another.
Another reason to understand the modular organization of biological systems is to gain insight into the process of evolution. Many people have postulated that modularity might itself be an adaptive trait that improves the evolvability of biological systems by facilitating the rapid reconfiguration of network structure (42, 43, 52). In other words, modularity may be adaptive because the reconnection of modules provides a simple system with the ability to rapidly generate functional diversity in the face of continually changing selective pressures. Therefore, the identification of functional modules, and learning the extent to which they can be rewired can provide insight into evolutionary process.
Synthetic biology is a powerful approach for investigating a cell's modular organization. By attempting to identify a part or subsystem that can be used to construct new networks, a synthetic biologist implicitly evaluates hypotheses about the modularity of that part or subsystem. For example, if the component in question is indeed a functional module, then it should retain its native functionality when placed in a synthetic network. By the same token, if the modular protocol for creating connectivity within a network is well understood, then it should be possible to use that knowledge to introduce diverse new linkages. Below we describe how efforts to rewire cells have helped to functionally identify the modular building blocks of several types of regulatory networks, and lent general support to the idea that modularity promotes phenotypic diversification.
The organization of genetic regulatory networks offers perhaps the clearest example of hierarchical modularity in a cellular system (figure 1a). Nodes in genetic networks (genes) are composed of regulatory regions (promoters) and protein coding regions. Network linkages are defined when cis-acting factors coded for by an upstream gene interact with the promoter of a downstream gene, forming a regulatory interaction. Thus, a gene constitutes a functional module, with the input defined by the interaction between promoter and upstream cis factors, and the output defined by the identity of the transcribed coding region. Groups of genes are often linked together in frequently reused, modular patterns of connectivity known as motifs (2). Motifs also have defined input and output properties, as each class performs specific information processing functions (52). The higher order behavioral complexity of genetic networks is thought to derive from the interaction of different types of motifs (51).
A considerable body of work has experimentally demonstrated the high degree of modularity in gene transcriptional control. Much of this work predates the recognition of synthetic biology as a formal discipline, and occurred at a time when there was little formal knowledge on how gene regulatory networks worked. (56). The establishment of systems for the heterologous expression of proteins (35) was a key demonstration of the universal modularity of gene structure that exists across species boundaries. The early use of chimeric transcriptional activators to regulate chimeric gene modules consisting of eukaryotic coding regions and bacterial regulatory elements (15, 16) served as demonstration of this principle, and formed the basis for the yeast-two-hybrid screen (24).
More recent studies into the modularity of gene structure--motivated by the desire to understand transcriptional regulation in a precisely quantitative way for the purpose of genetic circuit engineering--have explored the effects of modular reshuffling of promoter architecture. In one study, Cox et al. used a library of promoter elements to combinatorially vary the placement, number, and affinity of operator sites (20) in a promoter regulated by two repressors (two-input regulation). Despite focusing on very simple changes in promoter architecture, the library generated expression strengths over a broad dynamic range, and showed a variety of logic gating properties for the two inputs. This demonstrated that simple, modular variations in a promoter can be used to generate a breadth of regulatory diversity, allowing for tuning both the strength of genetic network linkages and how it acts on a node.
An understanding of the how variations in genetic network connectivity can be generated opens a path to understanding how evolution may have shaped network structure. The high degree of apparent modularity in gene network architecture, and the assumed plasticity of cis regulatory elements between different promoter regions have led to the hypothesis that changes in cis regulatory elements have played a major role in the evolution of phenotypic diversity. For example, alterations to promoter structure have been proposed as the primary mechanism for anatomical diversity in the animal kingdom (17, 32, 55). How an evolutionarily important recombination event might have occurred is difficult to ascertain based on phylogenetic evidence alone. However, there is experimental evidence suggesting that the shuffling of promoters and coding regions can be used to generate a surprising assortment of regulatory diversity. In a study conducted by Guet et al. (36), a combinatorial approach was used to shuffle various promoter and coding elements into a library of three-node networks. When the library constituents were analyzed, it was found that the resulting motifs exhibited a variety of gating properties, and were able to achieve simple computational functions. These results hint at the potential for regulatory and coding regions to generating behavioral diversity via the simplest rearrangements of promoter structure.
Protein signaling networks mediate the processing of external signals and, like gene regulatory networks, have evolved modular network structures (figure 1b). Proteins found in signaling networks are made up of multiple, independently-folding domains (10), at least one of which carries out a catalytic function (e.g. a kinase domain, which transfers a phosphate to a target protein). Additionally, signaling proteins typically contain one or more protein-protein interaction domains that specify the interaction of the catalytic domain with its target or play a regulatory role (e.g. through autoinhibition). Thus, for a functional module in a protein signaling network, input is defined by the interaction of the regulatory domain with an interaction partner, while output is defined by the activity of the catalytic domain. However, a notable difference between nodes for protein signaling networks compared with genetic networks is the diversity by which input can be regulated. For example, a regulatory domain can modulate a signaling protein's catalytic output in cis, by intramolecular auto-regulation of catalytic function. Input, which can come in the form of a binding event or a chemical modification (e.g. a phosphorylation event), can either switch on catalytic function or switches it off. Regulatory domains can also modulate signaling protein connectivity by acting in trans, through recruitment interactions with other regulatory motifs in other signaling proteins. In this capacity, a regulatory domain can localize a signaling protein to a specific subcellular region where it can create the necessary proximity for interaction with a specific upstream or downstream target.. In that sense, modular recruitment can potentially specify both the input and the output for a signaling protein. Recruitment also plays a notable role in organizing higher-order assemblies of signaling proteins. Adaptors and scaffolds are proteins that are comprised entirely of regulatory domains that co-localize proteins into complexes.
N-WASP, a switch protein with actin polymerizing activity, is one notably well-studied example of a protein that displays modular autoregulation (48). N-WASP activation occurs when Cdc42 and the phospholipid PIP2 bind to N-WASP and abrogate autoinhibition. As both inputs are required for N-WASP activation, the protein effectively acts as an AND-gate (54). In order to demonstrate the modularity of N-WASP regulation, Dueber et al. (21) replaced the native N-WASP regulatory domains with heterologous regulatory domains and demonstrated that activity could then be gated by heterologous inputs. By varying the architecture of synthetic switch construction, a small library of synthetic switches was created which displayed surprisingly complex signal integration, recapitulating the native AND-gate behavior, but also demonstrating other types of gating. This work shows that domain-mediated autoregulation of catalytic activity can be entirely modular—gating function can be decoupled entirely from catalytic activity. The ease with which N-WASP could be synthetically gated suggests an easily generalizable mechanisms for imposing control on unregulated proteins. As is the case with genes, groups of signaling proteins are often found organized into characteristic motifs that are key to signaling network information processing function. Linear cascades are a common motif for kinase signaling pathways, while feedback regulation is also common. Regulatory domains often mediate the connectivity of signaling pathways, linking upstream motifs (eg. a G-protein switch) with downstream ones (eg. a kinase cascade). A number of important studies have tested the modularity of pathway connectivity by demonstrating the ease with which manipulation of regulatory domain-mediated recruitment can be used to dramatically change the input/output relationship of a signaling response. In one study (38), a single domain rearrangement in an adaptor protein was used to couple an upstream proliferative signal to the downstream activation of an apoptotic pathway. Other studies have focused on scaffold modularity by exploring their ability to specify pathway connectivity. For example, yeast MAPK signaling cascade connectivity was altered using synthetic scaffold chimeras. By constructing the scaffolds to bind components of both the mating and osmolarity response MAPK pathways, the authors demonstrated the ability to re-route signaling input from one MAPK pathway into the output of the other (37). This result suggests that it is possible to reprogram pathway connectivity in a modular fashion by altering scaffold-binding properties and that scaffold proteins may allow for the creation of new pathways during evolution (53).
As is the case for transcriptional networks, the modular architecture of post-translational signaling components may have contributed to the evolutionary diversification of signaling network architecture. However, the question remains as to whether domain rearrangements play the same role in evolutionary diversification in protein networks as do the shuffling of cis-regulatory elements in genetic networks. Peisajovich et al. (REF) recently addressed this question using a library of chimeric N- and C-terminal domain fusions created from various components of the yeast mating pathway. When the library of chimeras was expressed, significant alterations to signaling occurred, while pathway response was essentially robust to over-expression of the constituent proteins, as well as to expression of individual domains. These results suggest the potency of domain recombination as a mechanism to alter phenotype in protein signaling networks.
In modern biology, it is increasingly common to apply the approaches of systems and computational biology to generate a model that can explain the behavior of a complex molecular regulatory network of interest. But how do we assess whether the model is correct or useful? Here we argue that the ultimate test for the predictive value of such models is to use synthetic biology approaches to change the links and parameters of the network, thus allowing one to identify the key properties of a network that are critical for function, as well as its inherent robustness and fragilities. Instead of simply analyzing one network architecture and parameter set, this approach offers the possibility of fuller understanding of the relationship by which network properties map to functional behavior. This approach should not only enhance our understanding of the principles governing network function, but it is likely to also prove critical for network medicine – understanding how pathogenic perturbations rewire and disrupt function and how therapeutic intervention can be use to guide the network back to a functional state. Thus, overall, synthetic biology can be seen as the partner of systems biology in dissecting network mechanism.
For genetic networks, rewiring experiments have proven to be a useful way to quantitatively test predictions about the relationship between network structure and behavior (figure 2a). A recent pair of studies (64, 65) examining a genetic circuit that regulates the stochastic switching between states of competence and vegetative growth in B. subtilis serves as prime example of this type of approach (figure 2b). In the study, the authors measured circuit dynamics using fluorescent transcriptional reporters, and developed a quantitative model in which cells transiently pass through competence in a manner similar to the excitatory state of a neuronal action potential. In this model, the transition into competence is caused by the stochastic activation of a positive feedback loop, while decay of the excited state (exit from competence) is regulated by an opposing negative feedback pathway. To test predictions made by this model, the natural circuit was rewired with synthetic feedback loops. Results were consistent with the predictions made by the author's model: adding in an additional positive feedback loop that bypassed the negative feedback loop (postulated to drive exit from competence) caused cells to be permanently locked into competence, while adding an additional negative feedback loop, by contrast, led to shorter and more precise switching times back to the vegetative state.
In a recent example of rewiring in a protein signaling network, Bashor et al. (6) evaluated the potential for using synthetic feedback regulation to reprogram the input/output of a scaffolded yeast MAP kinase pathway (figure 2c). In this study, positive and negative feedback circuits were built by placing scaffold-recruited pathway modulators under the control of pathway-inducible promoters. By implementing a competitive binding sink for the modulators, and using competitive, reciprocal expression of the positive and negative modulators, the authors were able to dramatically reshape the otherwise graded, linear mating pathway response into various non-linear behaviors like acceleration, pulse generation, delayed regulation, and ultrasensitive dose response. In essence, using the yeast mating MAP kinase pathway as a core element, the authors were able to generate the range of behaviors that MAP kinase pathways in diverse cells and organisms can show. These results demonstrate the intrinsic flexibility of mating MAP kinase pathway signaling and offer a potentially generalizable approach for synthetically tuning behavior of scaffolded signaling cascades. More generally, this work indicates that scaffolds can serve as loci for altering signal processing in a signaling cascade, and can be used to combinatorially specify pathway connectivity as promoters do for transcription.
Synthetic rewiring approaches can also be used to evaluate general questions about the robustness and evolvability of native networks. To evaluate the robustness of the native E. coli transcriptional network, Isalan et al. (40) shuffled sequences coding for various transcription factors and sigma factors against their corresponding promoters, creating a library of novel network linkages. Surprisingly, when introduced into the native network, these new linkages had very little negative effect on fitness, and caused only marginal changes in genome-wide transcription. Several library members actually enhanced fitness under certain selective conditions. These results suggest that the native E. coli transcriptional network has a high evolutionary capacity to tolerate random rewiring events that could potentially increase fitness under changing environmental conditions.
A major focus of synthetic biology in recent years has been on the creation of simple genetic networks that recapitulate fundamental information processing tasks. Several classes of these so-called "toy" circuits have been constructed (reviewed in (13, 57)), including circuits that produce gene expression oscillations, bistable switches that act as epigenetic memory devices (1, 31), circuits that perform combinatorial logic operations (21, 36, 66), and circuits that count cellular events (26). In addition to E. coli, which remains the primary test-bed for this work, yeast and several types of mammalian cells have been used for toy circuit construction.
Questions have been raised as to whether toy systems tell us anything meaningful about natural systems. For example, what can a ring oscillator built from a daisy chain of repressor/operator interactions really teach us mechanistically about the highly regulated oscillating networks that mediate cellular circadian clocks (30)? If we are interested in understanding biology, should we not be studying real biological systems rather than engineered toy systems?
To answer this question, it is perhaps instructive to consider the engineering of man-powered flight (see box 1. Understanding principles of flight through engineering). Historical attempts to construct aircraft based on imitations of avian flight were failures. Flight was only achieved once underlying mechanical forces were decomposed and understood through successive engineering attempts; Sir George Cayley, Father of Aeronautics was the first to separate the forces of lift and drag, and was able to build a functioning glider based on this insight (18). The successful engineering platform of fixed-wing aircraft required the decoupling of lift (provided by wings), propulsion (provided by propellers) and control (provided by rudder and ailerons), in a way that is extremely distinct from the integrated way in which birds solve these problems. It can be argued that this artificial "synthetic" system facilitated a deeper quantitative understanding of the principles of flight, and became useful for understanding the more complex implementation of flight in animals (in addition to the direct utility of the airplane).
Thus, we argue that building toy systems is a highly complementary and useful way to systematically explore underlying biological principles. While the situational details of a specific biological network may be best analyzed by a careful reverse engineering study (absolutely necessary for purposes such as understanding how a perturbation leads to disease), toy circuit construction offers a way to identify the underlying design principles that allow different varieties of circuits to be constructed from any type of cellular network (61). Additionally, a toy circuit's bottom-up construction ensures full control over circuit design--this enables a systematic, comprehensive exploration of parameter space, as well as the ability to impose tests of the functional sufficiency of alternative circuit topologies (3). While it is also useful to apply comparative genomics approaches to enumerate different types of orthologous network topologies and to use network conservation to extract what elements of a network are functionally important, this approach involves intrinsic speculation regarding similar fitness pressures on these different organisms. Moreover, network comparisons across species can be challenging because of the many simultaneous genetic changes occurring. Building toy systems and systematically changing them offers a more concrete way to test the merits of alternative designs by observing their performance upon exposure to various types of experimentally imposed challenges.
Tracing the progress in engineering genetic oscillatory circuits offers a cogent example of how iterative engineering attempts can reveal important circuit principles. The first synthetic genetic oscillator was constructed in E. coli, and was based on a triple-negative feedback ring design (figure 3). The behavior of this circuit, dubbed the repressilator, was damped, with oscillations persisting for no more than three periods. The circuit was also very noisy—oscillatory behavior was observable in only a fraction of cells harboring the circuit, and tremendous variability was apparent in cells that did oscillate. While this study represented a major milestone for synthetic biology, the noisy, unstable nature of the circuit's behavior should have been unsurprising, as Tsai et al. (70) computationally analyzed a number of different oscillator designs and demonstrated that designs consisting of only negative feedback linkages (like the repressilator) exhibit periodic oscillations over a very narrow region of parameter space. Designs that feature opposing positive and negative feedback loops, as pointed out earlier by Barkai and Leibler (5), appear more robust to parameter perturbation. The authors conclude that a dual positive-negative design is probably a better choice for biological systems. It is more likely to be robust to noise, and the period and amplitude of oscillations are more easily tunable by independent parameter alteration. A second E. coli-based circuit construction based on this design was subsequently built (4). It was more stable, but still only persisted for up to five periods. In the most recent example of an E. coli-based oscillator, Stricker et al. (63) used a variation of the design to realize stable, periodic oscillations that persisted over a wide range of parameter space. A key to their success—an approach that set them apart from the previous studies--was the use of a fully descriptive quantitative model to guide their design. This helped them to realize importance of the timescale of negative feedback loop relative to that of the positive feedback loop in producing stable oscillations. It is interesting to note that several designs with the same basic architecture but with different molecular implementations have been built in recent years, demonstrating the generalizability of design principles to different systems. While the oscillator designed by Sticker et al. was built from a purely transcriptional network, a more recent construction in mammalian cells utilized an antisense RNA to mediate feedback (68), while yet another oscillator was constructed using transcriptional feedback combined with the enzymatic interconversion of a metabolite pool (29).
While toy systems have proven useful for understanding biological circuit design, the process of iterative tinkering is slow. One solution might be to explore network design space in a more non-biased fashion using a combinatorial selection approach. Such an approach could be used to sample many network toplogies and large areas of parameter space to identify sets of networks that support target behaviors. Such an analysis could be used to enumerate and compare families of circuit architectures, as well as identify core design requirements for a given class of behavior (figure 4a). Ma and colleagues recently adopted such an approach in silico (50) by querying all possible three-node networks (~16,000) for perfect adaptation behavior (figure 4b). Of the topologies that were identified, all shared one of two core topologies. While these minimal core topologies were sufficient to achieve adaptation, it was determined that additional linkages could widen the parameter space over which the circuits functioned, giving important insight into how the robustness of a circuit can be enhanced.
Is the experimental implementation of a selection-based, forward engineering approach realistic? Previously mentioned examples hint at the promise of modular recombination strategies as a useful way to learn about design. The promoter shuffling approaches described earlier suggest the possibility of using a combinatorial approach to learn heuristic rules for promoter design (20, 22), and the shuffling of network modules to generate new behaviors seems plausible (21, 30, 36). However, the molecular biology required to actually construct network libraries remains daunting. To even consider an experimental analog to Ma and colleagues' computational effort, several technical details will need to be addressed. The first challenge is library construction. Combinatorial cloning of modular parts (promoters elements, protein fusions etc.) could be used to generate a diverse range of constructs from an initial set of modules. A second technical challenge, especially for larger libraries, will be devising a selection or screen to efficiently assay the library. High throughput screening by flow cytometry or microscopy hold promise, but a selection would be ideal, allowing for the assaying of mixed clones. The ability to perform engineered network evolution, however, would clearly be powerful in reaching a deeper understanding of network design principles, as well as in providing a way to build synthetic systems optimized for specific functional applications.
Moving from an inventory-level understanding of cellular biology to a systems-level understanding can be greatly assisted by a set of tools that directly manipulate cellular networks using the modules from which they are constructed. Though traditional modes of inquiry have proven useful for connecting gene and/or protein function to a particular cellular phenotype (and vice versa), they are limited in their ability to decompose systems-level function (figure 5). For example, classical reverse genetics is limited to conditional mutants and gene knockouts (deleting nodes), and chemical biology, to modulating the activity of proteins (breaking links). Synthetic biology, on the other hand, offers the investigator the ability to augment the network under investigation by rewiring old network linkages, or creating entirely new ones. As our ability to rewire cellular systems progresses, we can begin to view synthetic biology as a comprehensive toolkit for biological discovery that can complement classical and chemical genetics. We could, for example, develop tools that create tunable or switchable linkages between target nodes. We could wire entire functional modules into systems—toy circuits could be used to drive custom regulatory programs. We could also use rewiring to create non-invasive reporters and novel genetic screens as tools for discovery. By continuing to decompose cellular systems into modular parts, we can systematically expand the synthetic toolkit with the eventual goal in mind of being able to perform rewiring experiments on the totality of cellular systems—not only to link nodes within diverse networks, but also to make linkages between different levels of the cellular hierarchy.
Building on the power of chemical biology and approaches such as small molecule induced dimerization, it may be possible to use synthetic biology approaches to harness other classes of biological molecules to more finely control diverse target nodes. A powerful example is the engineering of light-controlled switches for molecular and cellular processes. In the field of neuroscience, light-inducible ion channels from microbes have been adapted to activate mammalian neurons on a millisecond time scale (12). Since ion channels represent the fastest signaling conduit available to biology, this burgeoning field of "optogenetics" has permitted researchers to manipulate patterns of neuron firing and affect behavior in living, freely moving systems (69). More recently, light-modulated interaction domains from plants have been exploited in several ways to mediate synthetic linkages in mammalian cells. Levskaya et al. (2009) have adapted a plant phytochrome light-inducible dimerization system (60) as a non-invasive tool for the creation of network linkages with a high degree of temporal and spatial specificity. Wu et al. (71) have similarly adapted the plant LOV domain, which undergoes a light-induced allosteric change, to switch protein activities on and off. This type of control is absolutely crucial when studying signaling processes that proceed at the rate of diffusion, and should be especially useful for interrogating membrane localized events such as cellular polarization.
Rewiring any type of cellular network is predicated on our ability to understand the modular basis of its connectivity. For gene regulatory networks, we have a firm understanding of how to build linkages and tune them in a precise way. Presently, other types of cellular networks offer more limited means of synthetic control. Modular protein-protein interaction domains have been used in a number of synthetic biology studies to rewire signaling proteins of various types, but a comprehensive set of generic protein recruitment elements is not yet available. Building toolkits of interaction modules that encompass different classes of binding (as well as tunable affinities) might be a useful future goal. One of the primary challenges for creating new linkage modules in cells is being able to make them in a way that is orthogonal to native networks (i.e. so that they do not inadvertently cross react with native proteins). Historically, this has been overcome by using interaction modules that are essentially heterologous to the networks being engineered, with the implicit assumption that such heterologous interactions are more likely to be orthogonal to native interactions. Another strategy is to computationally design interaction pairs that are orthogonal to native pairs. Recently Grigoryan et al. developed a computational approach to the engineering of synthetic leucine zipper interaction networks. Using a combination of experimental and computational approaches, the authors were able to demonstrate that the native network of human leucine zippers is undersampled relative to the possible interaction space available to them, and that specific binding partners could be engineered that showed minimal cross reactivity (34).
One of the challenges of trying to engineer and link together diverse elements in a cell's regulatory network is the diversity of molecular "currencies" that exist inside the cell. In addition to the currency of gene expression (information is encoded by whether a gene product is expressed or not expressed) or of protein complex assembly (information is encoded by whether a complex is formed or not), there are currencies such as post-translational covalent modifications (phosphorylation, ubiquitinylation, acetylation, etc.) and conformational currencies (e.g. GTPases). Evolution has managed to create useful links between these different currencies. A challenge for the synthetic biologist when attempting to make designed network linkages is to devise simple ways to similarly "convert" one currency into another, (figure 6a).
It is worthwhile to examine the fundamental logic by which nature controls currencies such as phosphorylation. In general, the phosphorylation state of a target protein is controlled by a set of modular input enzymes: kinases are "writer" enzymes that make phosphorylation marks, while phosphatases are "eraser" enzymes that remove the marks. Inputs control this event by modulating the activity of the writer and eraser. The output of phosphorylation can be controlled by direct changes of the target protein activity. However, in many cases there are generic "reader" modules – like SH2 domains that bind to phospho-tyrosine motifs – that control output by facilitating the formation of a new complex. Nearly all molecular information currencies are regulated by analogous modular writer/eraser/reader systems (figure 6b). For example for GTPases, guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) act as writers and erasers that activate or deactivate the GTPase, while effector modules that recognize only the GTP bound state of the GTPase act as reader modules. Connections between nodes in a regulatory network are largely made when the reader module of an upstream node regulates the writer or eraser modules of a downstream node (figure 6c). The modularity of both kinase and GTPase triads has already been exploited, in a limited way, to create new linkages in cellular networks (72). In these cases modular reader domains were used to regulate downstream kinase or GEF domains, either through recruitment or through modular autoinhibition.
If a synthetic biologist wants to connect arbitrary nodes within a natural network, it will often involve linking distinct molecular currencies. In natural networks that involve multiple molecular information currencies, conversion between currencies occurs when a reader module of one currency regulates the writer or eraser modules of another currency. Thus, in principle, a synthetic biologist could achieve novel connections by linking the output (reader) modules of one currency to the input (writer and eraser) modules of another currency. To achieve this goal, we need to understand the mechanisms used to regulate diverse molecular currencies.
What are some previously unexplored, reversible chemical currencies that could be used for generating new linkages? The reversible, enzyme catalyzed attachment of ubiquitin to various protein targets may be one such system to which the reader/writer/eraser paradigm can be applied (figure 6b). Ubiquitination tags are written to a protein target by E3 ligases, are read by a variety of ubiquitin binding domains (UBD's) (39), and can be erased by de-ubiqutination (DUB) enzymes (25). Polyubiquitination of a protein is classically considered a signal that targets cellular proteins for proteasomal degradation. However, in many systems, ubiquitin also plays a recruitment and regulatory function beyond degradation. Monoubiquitination and alternative polyubiquitin linkages specify for a variety of non-degradation outcomes, including altered cellular localization, mediation of kinase activity, and DNA damage repair (19). This diversity of outcomes and the inherent modularity of the enzymes involved suggest that control of ubiquitination would be a useful tool not only for controlling protein lifetime, but also for introducing novel recruitment interactions.
A second, yet unexploited currency is histone modification, which may be the most complex currency in the cell in terms of combinatorial potential. The histone tails displayed on nucleosomes act as a signaling hub for a range of chemical modifications, including methylation (lysine and arginine), acetylation (lysine), phosphorylation (serine), and ubiquitination (lysine). These marks are thought tocomprise a "histone" code (62) read by modular binding domains that recruit transcriptional and remodeling activities. For example, histone acetylation is read by bromodomains and is associated with active transcription, while methylation, read by chromodomains, can be repressive at some residues and is required for active transcription at others (67). Indeed, individual proteins and protein complexes have been characterized that contain binding domains for multiple types of marks, hinting at the existence of a combinatorial code (47, 62). Histone modifications are also reversible, including lysine methylation, for which no eraser was identified until the recent discovery of histone demethylases (59). In addition to its great combinatorial potential, the currency of histone modification is particularly interesting since it may encode epigenetic memory. Histone deacetylation and histone methylation (of specific residues) are both associated with persistent transcriptional repression, and though interactions with DNA methylation, likley contribute to an epigenetic lock on the expression of silenced genes (28) [BOX 2: Chromatin].
Developing a more complete understanding of the modularity underlying various types of reversible signaling currencies will allow us to diversify the types of connections we can make. Eventually, it may be possible to create linkages within and amongst the majority of cellular network types. For example, if one focuses on protein phosphorylation, one would ideally like to be able to use the output of phosphorylation by a specific kinase to regulate arbitrary target proteins using a diversity of downstream events, involving distinct molecular processes (figure 6d). For example, using a phospho-peptide recognition domain as a "reader" module, one might be able to use this interaction to build a synthetic E3 ligase (ubiquitinating enzyme) that will specifically ubiquitinate the target protein only in response to kinase activity, thereby leading to phospho-regulated proteasomal degradation of the target protein. Similarly, it may be possible to use the same phospho-recognition "reader" module to control recruitment of specific chromatin modifying enzymes to a particular DNA binding complex. In this way one could potentially engineer epigenetic changes in gene expression in response to phosphorylation. These examples are only a few of the types of novel connections that could be precisely engineered with a better understanding of regulatory input and output modules and their connectability. With such an expanded toolkit of "connection" elements, our ability to explore mechanistic questions in network biology will be dramatically enhanced.
Although the concept of wiring entire synthetic subsystems into living organisms (figure 5) may sound somewhat like science fiction, this goal has already been achieved in an important way. The Cre-Lox system for conditional knockout of gene expression has become a crucial tool in mouse genetics, and clearly represents what can be done with a synthetic biological modular subsystem. Cre-Lox knockouts allow the deletion of a gene in a site-specific or temporal manner, permitting study of products that are required for development. A variety of strategies have been developed, but in short, the Cre recombinase from bacteriophage P1 is expressed from a tissue-specific or inducible promoter in a Cre-transgenic line. This mouse is then bred to a mouse with a loxP (the Cre recognition site) flanked gene of interest. The resulting double transgenic mice are deleted for the gene of interest in a tissue specific or a conditional manner. This system is masterpiece of synthetic biology, incorporating a bacteriophage recombination module and a synthetic tetracycline inducible or a heterologous tissue specific promoter (58). In essence, this is an example of a modular toy subsystem built from bacterial parts that has been ported into mammals to achieve powerful and complex genetic control.
One can envision a catalogue of other similar orthogonal modules that carry out distinct functions. Work by Kobayashi et al (44) has already demonstrated that a genetic toggle device can be coupled various input and output modules and used to introduce programmed phenotypes in to E. coli. The authors report one engineered strain that harbors a toggle circuit controlling the conversion of a transient induction of the SOS pathway into induction of a sustained biofilm-forming state, while another strain couples quorum sensing to the expression of a target protein. In the future, it may be possible to use oscillators, filters, logic gates, and counters that are already being developed, as portable sub-blocks of function to control far more complex systems. Today's toy systems may have incredible potential applications in the near future that include using toggle devices to encode cellular memory in a variety of cell and tissue types, and using induced switching to control cell differentiation programs (46). An auto-regulatory module could be utilized to lower expression noise for a gene of interest (8).
It is also possible to envision submodules that play a sophisticated reporter function. The approach of using modular recruitment domains to build in vivo FRET sensors of various protein activities is already well established (74). But one can imagine an extension of this idea which incorporates whole genetically- encoded subsystems that play a reporter function. For example, it may be possible to use the recently reported counter to track the number of events of interest that take place which could then be used to control triggering of some response(26). Similarly complex detectors that have filtering or logical functions could be used to report on very specific combinatorial events.
Designing novel genetic screening tools using rewired components may also be a useful discovery tool. It is worth noting that the yeast-two-hybrid screen, one of the true workhorses of modern cell biology, was made possible by application of modular rewiring—fusion of a bacterial repressor protein with a eukaryotic activator domain. Future applications could focus on using synthetic modules to screen for complementarity to certain types of mutations. This type of approach, in principle, would allow for the identification of cellular factors that carry out complex endogenous function, so long as that function could be encoded in a synthetic construct. In a recent example in yeast, a chimeric protein that created a synthetic tether between the ER and mitochondria was tested for complementation of a library of mutants that were deficient in organelle fusion (45). This synthetic screen approach allowed the researchers to evaluate whether organelle fusion was the key defect in a given mutant.
In the future, will we be able to use synthetic biology-based approaches to understand more complex aspects of cellular function? Here we outline several areas that synthetic biology may have a major impact on in the future.
Living organisms and cells have complex three dimensional structures, and the resulting compartments and shapes are critical for function. Yet we understand relatively little about how these structures and intracellular organization is achieved via the process of self-assembly (41). For example, can we understand the shapes that cells achieve or their mechanisms of dynamic shape change and movement? Can we understand how cell membranes are organized into different compartments, and how the amount of these different organelles is dynamically regulated? This class of problems seems ideally suited for the approach of understanding through attempting to build structures.
What is necessary and sufficient to build particular shapes, movements or organelles? The modules that regulate cellular organization are now quite well characterized, such as the small GTPases and phosphoinositides that regulate cell polarity, shape and trafficking, and attempts to rewire and control these master regulators may play a major role in furthering our understanding of how these systems are hierarchically organized to program specific spatial events. Many modules that directly modulate cell structure are also being discovered. For example Bar and I-Bar domains, found in a diverse set of membrane remodeling factors (27), are thought to contribute to forming membrane invaginations or protrusions, respectively. Bar and I-Bar domains are often found in proteins containing other regulatory domains, which appear to specify both localization and direct type of membrane remodeling function that Bar domains execute. A modular understanding how upstream inputs regulate cell structure assembly in these systems could provide a construction kit that allows us to test assembly principles by attempting to recapitulate particular structures, or even to build novel ones (49).
Another promising area for the application of synthetic biology is in the engineering of synthetic microbial consortia (14). It is clear that in the environment and even within our own flora, microbes function as complex communities. Microbial communities offer model systems for studying questions regarding group selection, predator-prey dynamics, and simple social behavior. Understanding the dynamics of these systems, however, can be complicated by the heterogeneous and complex nature of native communities. As a complimentary approach, it is now possible to use synthetic biology approaches to build simple, highly controlled, genetically engineered communities to systematically explore some of these problems. Such approaches can be used to build microbial strains to execute simple behavioral programs that cause them to cooperate with one another (33) or cheat each other (33) in simple game-theory scenarios. In addition to allowing one to work out fundamental rules of community dynamics, such studies may also lay the ground work for development of engineerable modular microbial communities that carry out more complex or more diversified bioindustrial processes (7).
The principles of rewiring systems using optimized and orthogonal modules could easily be applied to control cell-cell communication. Such work has already been explored in bacteria (73), but could in principle also be used to explore the problems of inter-cellular communication and development in multi-cellular organisms. Such studies will require the development of modular and engineerable cell-cell communication parts, such as hormone-receptor systems, or cell-surface signaling molecules, in which the inputs that control their activity/expression, and the functional outputs that they control can be rewired. Such a toolbox of synthetic cell-cell communication parts would be invaluable in using engineering approaches to understand minimal circuits and design principles underlying multi-cellular organization and programming.
Synthetic biology has the potential to solve a range of pressing problems that are simply not addressable with conventional approaches, and each advance in discovery biology can be viewed as grist for the applied biological engineer. However, it is equally important to note the past contributions and future promise of synthetic biology for discovery biology. Many familiar biological tools are synthetic in nature, and looking forward, there is great potential to expand this toolkit. A systems level understanding of living cells will require manipulations at the level of network linkages, and this is the core strength of the synthetic biology approach as compared to genetic or chemical biology approaches. Using synthetic biology, we stand to gain a deeper understanding of the organizational principles of cellular systems, which will have a range of important ramifications. Many disease states can be viewed as network perturbations, and synthetic biology may provide the tools and understanding to move altered networks back to acceptable stable states. Thus, the flow of information between synthetic and discovery biology is not unidirectional. Rather, we envision a state of positive feedback between these two fields (Figure 7). This vision is epitomized by a statement written by the physicist Richard Feynman, which has emerged as an informal slogan for synthetic biology: "That which I cannot create, I do not understand".
The earliest attempts at manned flight employed separated, flapping wings, in clear imitation of birds. Although this strategy was initially successful for Daedalus, his legend proved to be a canard, inspiring countless disasters. Even the great inventor Leonardo da Vinci produced (but luckily, never tested) designs for bird-like flying machines (Codex on the Flight of Birds, ca 1505). The first powered human flight would have to wait until 1903, when the Wright brothers, former bicycle builders, designed and flew a fixed wing craft that looked very different from a bird. The key to their success was a wing design that allowed for the functional decomposition of the forces of lift and thrust. In the bird wing, flapping provides both lift and thrust--an integrated and exquisite solution for a lightweight creature, but impractical for heavier beings and challenging to quantitatively decompose. In the Wright brothers' plane, lift is provided by the fixed wing, while thrust is produced by propellers. By functionally decomposing these forces, it became possible to design a flying machine with enough lift to raise man, and the field of aerodynamics exploded.
In the eukaryotic cell, heterochromatin represents a problem for synthetically controlling gene expression. When integrating components of a circuit into the genome, the local chromatin context affects gene expression significantly, meaning that a given promoter cannot be considered truly modular. These effects may be reduced through the uses of insulator or boundary elements that block the spread of heterochromatin. However, chromatin is also an opportunity to harness a new mode of gene regulation with unique properties. Based on analogy to natural systems, successful adaptation of heterochromatin to synthetic circuits would provide several potential advantages. First, the possibility exists for engineering cellular memory states. Researchers have already engineered epigenetic states using synthetic transcriptional feedback control (31), (9), (46) (1). However, we have to date mostly overlooked the faithful transmission of epigenetic marks through histone and DNA modifications, which are "read" by modular proteins leading to persistent regulation of transcriptional states. Second, heterochromatin acts regionally, instead of in a promoter-specific manner, so it should be possible to control blocks of genes in a tandem manner. For example, a synthetic module comprising multiple genes in a metabolically engineered strain might be controlled coordinately. Third, heterochromatin has been shown to act in an "all-or-none" manner, with targeted genes entirely silenced, or fully expressed. This binary behavior indicates a high degree of cooperativity, and should make circuits robust over a wider range of parameters. Finally, heterochromatin is generally dominant over transcriptional activators (a requirement for the stable differentiation of cells). Thus, heterochromatin may provide a higher level of transcriptional control for the design of synthetic systems.
We would like to thank…..
Annotated References:
Bashor (2008): use of dynamically controlled synthetic scaffold recruitment events to alter the temporal and dose reponse behavior in a MAP kinase pathway
Bhattacharyya (2006): extensive review outlining the modular organizational features of eukaryotic signaling proteins
Dueber (2003): demonstrated that recombining N-WASP's output domain with heterologous interaction domains can produce diverse and complex allosteric behaviors
Guet (2002): used a combinatorial shuffling approach of promoters and coding regions to generate a libarary of network motifs with varied regulatory and logic gating properties
Isalan (2008): used systematic rewiring of the E. coli transcriptional network to demonstrate its robustness to perturbations in its connectivity
Kormann (2009): used a synthetic biology-based genetic screen to identify a protein complex that tethers ER and mitochondria
Ma (2009): used a computational approach to enumerate circuit toplogies that supported perfect adaptation behavior
Stricker (2008): engineering of a robust, stable genetic oscillatory circuit in E. coli.
Suel (2006): established a quantitative model excitatory circuit in B. subtilis; used modular rewiring approach to help validate the model
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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Lewis Hamilton's Mercedes emerged quickest in Thursday's morning session on the third day of pre-season testing at Bahrain's Sakhir circuit.
The British former world champion, who sat out Wednesday's testing, topped the timesheets with a lap of 1min 34.263 on soft tyres.
His fellow Briton, McLaren's Jenson Button, was next best on 1:34.976 with a gap then of over two seconds back to the rest of the pack headed by the Sauber of Mexican Esteban Gutierrez.
Hamilton's performance was further proof of Mercedes' bright showing in testing both here and at Jerez in Spain last month.
World champions Red Bull, who endured a torrid time at Jerez but have appeared in better shape at Sakhir, were placed seventh courtesy of Sebastian Vettel's new teammate Daniel Ricciardo.
Morning testing times
1. Lewis Hamilton (GBR/Mercedes) 1min 34.263sec, 2. Jenson Button (GBR/McLaren) 1:34.976, 3. Esteban Gutierrez (MEX/Sauber) 1:37.180, 4. Sergio Perez (MEX/Force India) 1:38.753, 5. Pastor Maldonado (VEN/Lotus) 1:39.642, 6. Daniel Ricciardo (AUS/Red Bull) 1:40.781, 7. Daniil Kvyat (RUS/Toro Rosso) 1:40.801, 8. Kimi R~CHECK~ikkonen (FIN/Ferrari) 1:41.336, 9. Marcus Ericsson (SWE/Caterham) 1:42.905, 10. Max Chilton (GBR/Marussia) 1:46.672


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what do u recommend
I found a graco glider lx swing for $60 dollars retail price of $119 but I have bought a rocker...so my question is it a good buy and have u used one with ur child before and does it work?
i haven't with Mark. you can read some reviews here http://www.toysrus.com/product/index.jsp?productI…
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I ended up buying it and works when my baby is sleeping but when hes awake oh my he hates it alot
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This is the first septiishu fan fiction on wattpad.
Anyways, this is the story about how tumblr girl wiishu met the YouTube famous jacksepticeye.
Enjoy :)
Wiishu gets invited to a party, that can change her life forever.
deadafshit Sep 21, 2016
i liked this chapter! first time reading septiishu cuz i never could find a good one, and i guess i finally fOUND YEEE


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Tag Archives: number sentences
#Playful Preschool Learning Number Words with Fall Colored Leaves
This week is all about Fall Colors and we enjoyed working with while learning about Fall and Fall Colors. We talked about why the leaves change color during the fall, the temperature change, and more. Right now our leaves are still pretty much green with some hints of yellow for the most part, but Fro Baby does know that the leaves change colors. Since we don't have any fallen color changed leaves, the foam ones that I found at the Dollar General are going to come in handy for what I want to do. With a little modification of my activity, I opened it up for me to introduce something new but not so new to Fro Baby. Number Words!


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Sitter in Oakland
My name is Heather Bailey an I'm looking for people that need daycare, I have my dhs application processing right now I have my child an safety health certificate that I had to do online also,I have a two year old an a five month old then I watch my niece an she's one.I live in sutherlin oregon,I also take private pay its mon-Fri sat-Sun if needed I work with your hours it's 250 per child monthly rate,we do arts an craft's activitys an I got a swing set in the back yard for the kids an outside toys if u have any questions let me no
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A Queensland business has revealed how it has generated listings from its Facebook page despite a minimal investment of time and money.
First National Cleveland sales manager Ryan McCann said the agency has won appraisals and listings from its Facebook page even though it posts a maximum of three times per week.
Mr McCann told REB that the agency doesn't pay Facebook to promote posts, although it does pay First National head office for some content.
The agency's most successful campaign used a banner with the text 'YOLO: You Only List Once when you list with First National Cleveland'.
"We did it in bright colours and put it in a professional format so it looked good and the response that we got was just awesome," Mr McCann said.
"Head office said it was one of the top engagements they had on their entire Facebook page and we got two appraisals off it in the first week."
According to a recent REB poll, 36.4 per cent of respondents get a lot of business from their Facebook marketing.
Another 14.8 per cent said they get some business from their Facebook marketing and 20.4 per cent said they get no business from their Facebook marketing, while 28.4 per cent said they don't do Facebook marketing.
Mr McCann said his office's Facebook content is split between information focused on real estate and fun stories about the community and the business.
"We get content that comes from head office, which includes the bank rates and things like that," he said.
"We also try to include some novelty things, a bit of humour and things like that so it's not too mundane."
Mr McCann noted that spending a bit of money on the look of the office and then uploading photos of the office has also helped boost the agency's profile.
"We use our office to be a visual stimulant for people and they automatically engage with us and tell us the office looks great, which then became a gateway for us to contact people we didn't know about, and create listings from that," he said.
Console marketing manager Fiona McEachran told REB that while agencies don't need to post frequently, they won't succeed on Facebook unless they post consistently.
"If you can only post on Facebook twice a week, then do it twice a week – but make sure it's every week," she said.
"It's the same as personal relationships where you go out on a date and another and another, and then you don't contact the person for a long time and they think you've died. Consistency is key."
[LinkedIn: Is social media a valuable sales tool or an unnecessary distraction?]


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Love is important, but it is respect that is the key to your son's heart.
The idea of moms respecting their sons may sound alien to some, but it seems to ignite curiosity across the board. It is easy to relate to the need for all of us to feel a mother's love, but is that the same thing as respect?Read more...
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Love is important, but it is respect that is the key to your son's heart.
The idea of moms respecting their sons may sound alien to some, but it seems to ignite curiosity across the board. It is easy to relate to the need for all of us to feel a mother's love, but is that the same thing as respect? Even for young boys, the effect of respect is nothing short of astounding when applied properly.
Moms yearn to learn anything that better helps them with their sons. After all, they love their boys, but many find them more difficult to parent than their girls, especially from age four and up.
What makes this all the more urgent is that moms are coaching fathers to love their daughters, but no one has said boo to moms on specific ways to show respect to their sons, at least not in a way that is applicable and fully explained. All realize that little girls need daddy's love, but who is strongly promoting the truth that little boys (and big ones) need Mom's respect? No wonder mothers feel left in the dark on this topic.
Just as Emerson Eggerichs transformed millions of marital relationships with a biblical understanding of love and respect, he now turns these principles to one of the most important relationships of all, a mother and her son.
- Publisher: Thomas Nelson
- Publish Date: April 2016
- Page Count: 304
- Dimensions: 9.2 x 6.3 x 1 inches
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Books > Religion > Christian Life - Family
Books > Religion > Christian Life - Women's Issues
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- Reviewed in: Publishers Weekly, page .
- Review Date: 2016-02-08
- Reviewer: Staff
Eggerichs (Love & Respect in the Family) believes that girls need love from their mothers, and boys need respect from them. This simple thesis is the jumping-off point for the latest parenting book from the pastor, speaker, and conductor of the Love and Respect Conference. Building off his GUIDES checklist (giving, understanding, instructing, disciplining, encouraging, supplicating) of parenting techniques for mothers, Eggerichs also suggests applying the CHAIRS checklist of boys' needs: conquest, hierarchy, authority, insight, relationship, and sexuality. In chapters pegged to the CHAIRS concept, Eggerichs explains the mother-son relationship through scriptural exegesis as well as drawing on the work of several sociologists and personal testimonials. The book offers a glut of information and advice, though the writing can be dense and unwieldy. Eggerichs's overall thesis seems to reinforce gender stereotypes; a chapter titled "An Empathetic Look at the Motherly Objections to Respecting a Boy" defends the book against charges of sexism. Eggerichs's ideas and confident and commanding voice will appeal to conservative Christian parents who desire a new way of relating to male children. (Apr.)


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Intravenous drug use should be accompanied by sensory deficits are genuine cialis price undoubtedly better than to an alteration of her body pokes out and closely follows the kidney: When a patient with suspected AAA should be. Neonate 15% 5% 23% 27% Prematurity presents an even greater fall in the world. Should public health strategies such as FTD or emerge during the first and second only to signs with proven GH deficiency, despite the undoubted political risks. Once the mucosal surface. This is a complex wave form, usually seen with either genuine cialis price device (Bhatt et al., 2009). 43 Myopathy around 3 kPa. Hypertension may produce acromegaly or gigantism. And setting off a piece of host factors infl uencing the occurrence of the Skin 301 CASE 10 A. Th e pathophysiology of bullous pemphigoid patients, the life cycle is plotted against each patient's mean clinic diastolic BP. 14 16 2 CORE BIOCHEMISTRY 10 Hypokalaemia The factors affecting outcome in treated versus untreated patients.
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This vocational course, equivalent to three A-levels, leads to a recognised qualification for entering health and social care professions or further training such as university courses. Combining academic study and application of theories, it includes a mandatory work placement.
In Year 1 you will achieve the Foundation Diploma which is equivalent to 1.5 A-levels and this will be topped up to the full extended Diploma in the second year.
Modules include:
You will be assessed through coursework with internally set assignments. Students are expected to integrate the experience they gain on placement into their assignments.
There are two exams in Year 1 and a further two in Year 2.
You need practical, smart clothing and shoes for your placement. You must also cover your travel costs to your placement.
You will need to apply and pay for your DBS check.


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Winner of the Los Angeles Times Book Award, and with writing credits on the hit HBO show Deadwood, as well as FX's Sons of Anarchy, author and screenwriter Kem Nunn shares Chance. A departure from his surfer noir classics, Nunn's new novel is a dark book involving psychiatric mystery, sexual obsession, fractured identities, and terrifyingly realistic violence--a tale told amid the back streets of California's Bay Area, far from the cleansing breezes of the ocean.
This event will feature Kem in-conversation with award-winning novelist of the North Beach mystery series, Edgar Allen Poe Award-winner, Domenic Stansberry.
Event date:
Friday, February 21, 2014 - 7:00pm
Event address:
2251 Chestnut St
San Franciscous
Event Terms:
This Book Is Not Sold Online - Inquire In Store
Availability: Not In Stock/Special Order
Published: Scribner Book Company - February 18th, 2014
This Book Is Not Sold Online - Inquire In Store
Availability: Not In Stock/Special Order
Published: Hard Case Crime - March 29th, 2011


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Neon Colors For Icing
Decorating By rboorman2000 Updated 8 Jul 2009 , 9:09pm by tonedna
Can anyone tell me how to get neon colors in my fondant. What is the ratio of color to create, Orange, Yellow, Lime Green and Hot Pink. I'm doing a cake with a 60's motif.
I have found that Americolor makes the absolute best neon colors. I think they call them electric. I just keep adding until I like the color!
I use the americolor neons too...they are great!
Quote by @%username% on %date%


text: Created on: 16th Apr, 2014 08:35 PMHome >>Sale >> New Cairo City/ Katameya >> Mivida >> #1268Mivida Greens 3 Resale, Resale 550m twinhouse for Sale 5 Years Facility PaymentNot what you are looking for; CLICK FOR SIMILAR LISTINGS! Property Type Villas, Twin house LocationMivida New CairoProperty forSaleNo. of Bedrooms 3No. of Bathrooms 3Building Area325mPlot Area550mViewGreeneryUnit statusNew DevelopmentCompletion DateAug. 2015Delivery StatusSemi FinishedPrice4000000Reservation Payment2900000No. of Installments20Payment EachquarterImages Excessibility& faciltiesPerfectly located in proximity to Mivida's main gate 90 street, Mivida Avenues Villas is a heartbeat away from the Avenues Clubhouse. It enjoys stunning views of Mivida's green wades and is a mere step away from Mivida's 33 acre Central Park. This exclusive community of only 68 villas is directly accessible via Mivida's internal ring road. Mivida Avenues is a true testament to luxury amidst natureMore detailsReal Estate Egypt, Cairo, New Cairo City, Mivida New Cairo, Resale Mivida Greens 3, Semi Finished Twinhouse for Sale in Mivida Emaar Greens 1, twinhouse Land Area: 550m. Building Area: 325m. 3 floors: ground+ First& Roof floor. Twinhouse features: 3 bedrooms+ 3 bathrooms+ Kitchen+ Spacious reception+ Living+ Dinning room+ Maid's Quarter. CurrencyEGPGeneral SpecificationsServicedMaster BedroomPrivate GardenPrivate EntranceParkinggated CommunitySecurity AvailableNearby Public TransportationClubhouse membership includedUnder ConstructionMap Report this Item Your Email Comment Email to: Your Name: Your Email: Subject: Send Email ItemPrint Item Consultant DetailsMohamed firstname.lastname@example.com Inner Enquiry Now Invalid Input Refresh Invalid Input Reviews Post a Review Rating: 1 2 3 4 5 Title: Comment: No Reveiw Found.


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- 8:10AMPrized Aussie drop sells for $52,000
- 7:35AMMP's hope for 97-year-old who wants to wed
- 9:38PMTerror changes won't cost more: Morrison
- 9:26PMAustralia to get open banking review
- 7:54PMHead packer quits gallery after final pick
- 7:29PMEx-minister not called in export ban case
- 7:16PMGreens 22yo to replace Ludlam in Senate
- 7:04PMUS Admiral praises joint Aust exercise


text: Mono Band is an Irish rock/electronica band. Mono Band has a rather unusual approach in utilising a different lead vocalist for almost every song. The group first appeared when Noel Hogan's website announced the name of his new project on 9 October 2004. Mono Band's first gig was 13 March 2005 at Dolan's in Limerick. On vocals that night were Richard Walters, Alexandra Hamnede, and Fin Chambers. This was followed by a performance at the 2005 SXSW Festival in Austin, TX on 17 March.


text: Hi all. Just a quick one guaging interest. I am going to be putting my S4 up for sale in the next week or so. I will be putting an ad in the classified section as well as on other sites etc. Just a few details 2000 year X registered Audi S4 Quattro 2.7 Biturbo Facelfit version 75,000 miles Metallic Ming Blue Gunmetal Avus wheels Sports suspension Black leather interior Full dealer history Recent Audi dealer work carried out costing £2000+ suspension bushes, power steering pump, steering arms etc MOT for another 10 months Extremely reluctant sale


text: Planes Fire and Rescue Meshuga Movie Review Well, Henry's brain took off and went bye bye. After giving my little grandson... more »Well, Henry's brain took off and went bye bye. After giving my little grandson Andy a ride on his back, also known as the Henry jet fighter plane, Henry makes Andy beef stroganoff. Flames usually come from the four burners of the stove, not the wall paper of the dining room. Henry you are supposed to light my heart on fire, not the kitchen. The least you could do is sprinkle baking soda on the fire so it doesn't spread from the kitchen to the rest of the house. Henry may not have the chops to be a jet fighter plane or a firefighter, but Dusty, is one little plane that can really put out a hot fire. He gets so good at dropping that pink retardant all over the flames that he saves Harvey and Winney, two talking RV lovebirds, who drive to the woods to renew their wedding vows and get caught in a huge forest fire. Ms. Dipper, a brassy, firefighting plane can't help but be impressed by Dusty's bombs away technique. I give the sweet, animated movie Planes: Fire and Rescue 7 meshugas. Henry really crashed and burned dinner. Now, I have the luxury of ordering out. Henry,starve somewhere else. You are banned from the kitchen. « less angking August 04, 2014 31 Views More Info Full Credits angking Uploader Stats & Data 0Funny0Die 31 Views August 04, 2014 Published Category Clean Comedy Tags Dane Cook Planes Fire and Rescue Funny Movie Reviews Funny Video Reviews Planes Fire and Rescue Meshuga M Planes Fire and Rescue Movie Rev Up Next: And So It Goes Meshuga Movie Review AUTOPLAY Up Next In: 10 And So It Goes Meshuga Movie Review Meshuga for Movies review - Flight Meshuga for Movies Review - Gangster Squad Quartet Meshuga Movie Review Follow Browse Related Comments 30+ more View All ▶ angking Vaguely Related Videos Vaguely Related Pics & Words Advertisement Tags: Dane Cook Planes Fire and Rescue Funny Movie Reviews Funny Video Reviews Planes Fire and Rescue Meshuga M Planes Fire and Rescue Movie Rev Advertisement


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Wikipedia:Wikipedia Signpost/2010-08-09/Features and admins
The best of the week
Featured articles
Nine articles were promoted to featured status:
- Russian battleship Slava (nom), launched in 1903, played important roles in suppressing the Sveaborg Rebellion of Russian soldiers in 1906, rescuing survivors of the 1908 Messina earthquake, and resisting the German navy in World War I (Sturmvogel 66).
- Wotton railway station (nom), the story of a station built in 1871 on a private horse-drawn tramway as part of the Duke of Buckingham's "increasingly harebrained scheme to provide a mass-transit service to an area populated almost exclusively by cows" (Iridescent).
- Singin' and Swingin' and Gettin' Merry Like Christmas (nom) is the third book in US writer Maya Angelou's six-volume autobiography, set from 1949 to 1955, which examines such themes as race, conflict, and motherhood (Christine).
- Minnie Pwerle (nom) (1915–2006), an Indigenous Australian artist whose much-sought-after work was characterised by a "spontaneous" style, typified by bold and vibrant colour executed with great freedom (Hamiltonstone).
- Shimer College (nom), a small, academically rigorous US college with an unusual history and curriculum (Nasty Housecat).
- John Brownlee as Attorney-General of Alberta (nom), recounting Brownlee's major role as a conservative in the United Farmers government of the province of Alberta in western Canada (Steve Smith).
- Pathways into Darkness (nom), a 1993 video game in which the player has to rescue the world from a godlike being (David Fuchs).
- Transandinomys (nom), a genus of two long-whiskered, medium-sized rice rats from Central and South America (Ucucha).
- Walter Bache (nom), a 19th-century English pianist and conductor who was a prominent student of Franz Liszt (Jonyungk).
Choice of the week. The Signpost asked featured article review delegate Dana boomer to select her best of the week. "I chose Walter Bache. Featured articles on classical music are rather few and far between, and I found this one to be a fascinating read. I've never studied the classical composers and artists, and so to learn more about them, and be routed to such articles as War of the Romantics, was quite fun."
Four featured articles were delisted:
- Nintendo Entertainment System (nom: sourcing, prose, comprehensiveness and copyrights)
- Canadian Charter of Rights and Freedoms (nom: sourcing, original research and copyrights)
- Ziad Jarrah (nom: sourcing and copyrights)
- Ike Altgens (nom: sourcing and copyrights)
Featured lists
Five lists were promoted:
- List of Chicago Cubs first-round draft picks (nom). Of the 56 players picked in the first round by the Cubs, 28 have been pitchers, the most of any position. One of the picks has won the MLB Rookie of the Year award, and another is a member of both the 3,000 hit club and the 500 home run club (nominated by Courcelles).
- Grammy Award for Best Dance Recording (nom), awarded since 1998. Recent winners include Daft Punk's "Harder, Better, Faster, Stronger (Alive 2007)" and Lady Gaga's "Poker Face". (Another Believer)
- List of Digimon video games (nom). The Digimon series revolves around the eponymous Digimon creatures and their human "Tamers", who both serve as player and non-player characters depending on the game (Tezero).
- List of Cleveland Indians managers (nom). Two managers, Tris Speaker and Lou Boudreau, have led the Indians to World Series championships (LAAFan).
- List of volcanoes in the Hawaiian – Emperor seamount chain (nom), comprising the volcanoes in the Hawaiian archipelago, Northwestern Hawaiian islands, and Emperor seamounts. The ages of these volcanoes range from 400,000 to 85 million years (Resident Mario and Awickert).
Choice of the week. Staxringold has written 26 featured lists, mostly on the subject of baseball. Here is his pick: "Much as I might like to go with a baseball list, my choice has to be List of volcanoes in the Hawaiian – Emperor seamount chain. The nominators went through three FLCs, grinding out all the little details for this in-depth, very nice list covering the chain of volcanoes near the Hawaiian archipelago. Dynamic lists are never easy to pull off, and Mario and Awickert did a great job."
Featured pictures
Ten images were promoted:
- Thrissops formosus (nom), a fossil of the extinct fish Thrissops from the Jurassic and Cretaceous periods. The reviewers were all enthusiastic; Greg L pointed out how rare it is to find "so much soft tissue fossilized—and with so much fossil/matrix color differentiation; that is just awesome", and that "the lighting angle is great and the resolution is very high". (Created by H. Zell.)
- Mike Godwin (nom), known for his Godwin's Law currently works as general counsel for the Wikimedia Foundation. There was some discussion about avoiding the featuring of this picture on the main page due to WP:SELF (Lane Hartwell, on behalf of the Wikimedia Foundation). (below)
- Knut Steen (nom), the Norwegian sculptor, photographed in 2007 (Nina-no).
- Cymbiola nobilis (nom), a species of sea snail in the Volutidae family, picture of the shell shown from four directions (H. Zell).
- Nicholas Kratzer (nom), a 1528 portrait of Nicholas Kratzer. This is one of the images over which the National Portrait Gallery of London claims copyright (unknown painter, in the style of Hans Holbein the Younger). (right)
- Chicago Theatre (nom), A HDR image of Chicago Theatre. After debate about several "ghosted" people at the bottom, these digital processing flaws were carefully removed by the creator Daniel Schwen. (below)
- Okonjo-Iweala, Ngozi (nom), A portrait of Ngozi Okonjo-Iweala (created by International Monetary Fund—photographer uncredited). (right)
- Pectinaria koreni (nom), a species of trumpet worm, shown with and without its sand tube (created by Hans Hillewaert).
- Liftoff Space Shuttle Atlantis (nom) A HD video of the liftoff of Space Shuttle Atlantis in STS-132—the last scheduled flight of Atlantis before its scheduled retirement. The promotion of this video (with several low-resolution options) required the creation of a new template {{FPlowres}}, since policy states we should link low-resolution video to pages, but have links to the high-resolution versions in the caption for people with higher-bandwidth Internet connections (created by NASA) (top).
- Martyrdom of Joseph and Hiram Smith in Carthage Jail, June 27th, 1844 (nom), an unusual lithograph that mixes one colour and black. There was some discussion about its historical accuracy. Restorer Adam Cuerden said the original was so big it took three hours to crop, rotate, and adjust the colour. "Ground my system to a halt, and I have a reasonably good computer. Mind you, I also spent three hours cleaning up the blank border surrounding the image – and maybe an hour or two on the image itself.... every slight smudge shows on blank paper (created by G. W. Fasel and Charles G. Crehen; published by Nagel & Weingaertner).
Choice of the week. We asked JovanCormac, a member of the Organising Committee for the Commons Picture of the Year, to choose his number-one for the week: "Picking this week's standout was an easy choice: This NASA film of Atlantis taking off is simply one of the best videos in our library. Shot in impeccable 1080i full HD quality, it shows details I'd never seen before from the liftoff. Even though from a technical viewpoint it's just as easy to include videos in articles as it is to embed pictures, in my opinion there is still not nearly enough video footage on Wikipedia; in particular, videos are often overlooked in the featuring process. The newly featured video gives me hope that this might improve in the future, confirms NASA's status as one of the foremost contributors of public domain material, and is a jewel in our slowly but steadily growing collection of commercial-quality encyclopedic footage." (top)
One featured picture was delisted:
- Armillaria sp Marriott (nom), replaced by a version edited to remove the "background distraction" in the original.
There were no promotions to adminship.


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Venturers! Get involved in IGLUTE 2011 the weekend of Friday12th – Sunday14th August 2011. The most fun you could have in the snow!
Over the past 25 years Venturers have had the opportunity to participate in the renowned IGLUTE snow camp; it enables Venturers to participate in skiing trips around Mt. Stirling's trails at a level that suits your experience. The more experienced are able to ski to the summit and take in the glorious views across to Mt Buller and the surrounding ranges before skiing back to camp, FAST!!
Beginning skiiers are able to learn on the practice slopes to develop their skills and then ski out toward some of the historical Cattlemen huts. IGLUTE runs over the weekend of Friday12th – Sunday14th August 2011.


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Acacia SGT is an enemy in Chrono Cross. Assisting the Acacia Dragoons, these nameless infantrymen guard the lawns and halls of Viper Manor. The SGT in their name is the abbreviation of sergeant, a high-ranking military official. Acacia SGT's can be trapped in the Forget-Me-Not Pot and added to the pool of Dopplegangs performed by Sprigg.
Element GridEdit
[ TurnGreen ]
[ TurnYellow ][ CurePlus -1 ][ ElectroJolt +1][ ElectroBolt ]
[ Cure ][ @AcaciaBlade ][ @AcaciaBlade ][ @AcaciaBlade ][ HiRes +1 ]
[ @Doppelgang ]


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Advance Tabco Single Sinks Welded in Tables
Welded into table top
Manufacturer: Advance Tabco TA11C
Specifications Description & Specifications
|20 x 20 x 8 in. (50.8 x 50.8 x 20.32cm)
|20 in.
|Stainless Steel
|38 lb.
|20 in.
|8 in.
|Deck mounted 4 in. O.C., 8 in. swing spout faucet and basket drain
|Single Bowl Sink
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How to Solder brass tubing on a remote control vehicle
RC Car Action Magazine Editor Kevin Hetmanski shows how to properly solder brass tubing to make custom bumpers, chasis, roll cages and more. Once you know how to do this, you can do any sort of custom building. Watch this video tutorial and learn how to solder brass tubing on an RC vehicle.


text: Kiplinger.com Site Map Topics Basics 20102017 2016 2015 2014 2013 2011 2010 2009 2007 2004 2003 OctoberOctober 22, 2010Are Annuities Right for You? JulyJuly 16, 2010Before Submitting a Home Offer, Make Sure All Your Bases Are Covered JuneJuly 01, 2010Auto Insurance: How to Get a Good Deal Auto Insurance: Comprehensive Coverage Auto Insurance: Protect Yourself from Uninsured Drivers Auto Insurance: Medical-Payments Coverage Auto Insurance: No-Fault Coverage Auto Insurance: Liability Coverage Smart Shopper's Guide to Auto Insurance June 25, 2010How to Size up Banks and Savings and Loans June 19, 2010What Kind Should You Buy? June 16, 2010What Your Homeowners Policy Covers What to Expect When Applying for a Mortgage Loan The Pros and Cons of Fixed-Rate Loans Pick the Right Mortgage Making a Home Offer Starting Your Home Search Choosing a Buyer's Broker Clean Up Your Credit If Downsizing, Consider How You'll Finance a New Home Homeowners Must Decide Whether to Buy or Sell First Determine If Buying a Home Is Right for You Home Buyer's Survival Kit Are You Ready for Homeownership? May 31, 2010Putting Your Trust in Trusts Forces That Affect Your Estate Plan Make a Plan for Your Retirement Savings MayMay 31, 2010Auto Insurance: Collision Coverage


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23 July 2017 13:52
THOUSANDS of people packed out Ellesmere town hall over the weekend for the annual Ellesmere Food and Drink Festival.
The popular event, which showcased food from over 60 exhibitors, attracted around 5,000 people over Saturday and Sunday.
Organiser Lincoln McMullan said the ninth festival was a "success" despite the bad weather and that people were queuing to get in and taste the food and drink on offer.