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Originally posted by Rabenwolf
Sony as a publisher owns Naughty Dog. Does that make Uncharted and Last of Us a japanese game? A french company owns Activision Blizzard...does that make WoW or Call of Duty a french game? I think its key to understand the difference between publishers and studios. In this case Arena Net is a north american company and GW2 is a Korean game, it is OWNED by NC Soft.
Fixed that for you.
Originally posted by bcbully
Originally posted by Rabenwolf
Sony as a publisher owns Naughty Dog. Does that make Uncharted and Last of Us a japanese game? A french company owns Activision Blizzard...does that make WoW or Call of Duty a french game? I think its key to understand the difference between publishers and studios. In this case Arena Net is a north american company and GW2 is a Korean game, it is OWNED by NC Soft.
Fixed that for you.
There are 3 kinds of studios, 3rd party, 2nd party and 1st party. 3rd party isnt financially owned by anyone publisher. Arena Net in this case is 1st party, and thus financially part of NC Soft, which is an international publisher founded in South Korea. That said, Arena net developes a game in which NC Soft publishes, they are therefore the publisher.
It does not connote or require that the game itself is Korean...no more so than World of Warcraft and Call of Duty are french because their studios and publishers are owned by a french corporation. If Microsoft were to announce their game division bought out Square Soft, and therefore Final Fantasy...it wouldnt make Final Fantasy games American. WB interactive is the first part publisher for Rocksteady in the UK, this doesnt make Batman Arkham Assylum/City american made. Nintendo of American often creates its own mario games...this doesnt make them automatically Japanese. You should probably read up on how the publisher system works and why some publishers buy studios, fund studios or studios dont mind being first party.
Anyways lets get this back on topic.
" ArenaNet is a video game developer and subsidiary of NCsoft, founded in 2000 by Mike O'Brien, Patrick Wyatt and Jeff Strain and located in Bellevue, Washington. They are the developers of of the online roleplaying series Guild Wars."
....first lines in Wikipedia.
Check out the crazy Korean names. Patrick Wyatt...Mike O'Brien ...I guess of the Seoul "O'Briens"...and Jeff Strain. I hear the written symbol for Jeff is much like a tree blowing in the wind. Beautiful.
Seriously.How could anyone think Guild Wars II is a Korean Game just because NCSoft ( of which Arenanet is a subsidiary) is a Korean Corp when it usually takes 2 seconds these days to find an answer to any doubt.
I guess the soon-to-be-non-existent City of Heroes is a Korean game too.
Also in my adventures I found nothign about EA financing Funcom on TSW. Everything I ran across states they are partnering for co-publication of the game. That means Funcom pays them and the burden of sole publication is alleviated.
If anyone could show otherwise I would be grateful...especially if it's whoever said to google it in the first place....as if the burden of proof was on us.
"I'll never grow up, never grow up, never grow up! Not me!"
Originally posted by Thane
simple. if you can't stand the launch time of an mmo, don't play it.
Or alternatively, if a game company can't make sure basic advertised game features will work at launch they should not release the game until its ready.
Now both of our statements are very narrow-minded and juvenile as A) Not every game issue can be found during beta as the majority of the games customer base doesn't show up until launch. and There's nothing wrong with a customer voicing their frustration over parts of a product they purchases not working as promised.
So how about you and the other posters here like you that seem like they can't stand to hear anything even slightly negative about this game stop wasting peoples time with these juvenile, kneejerk reaction posts. In other words, if the most mature response you can come up with is to tell people to fuck off, maybe the real person with the problem is you.
"Gypsies, tramps, and thieves, we were called by the Admin of the site . . . "
I pretty much have the EXACT same opinion as you towards this launch. It has been pathetic and leaving me not even wanting to play right now. Thankfully it's a good game and non subscription based so I can return when stuff gets better.
Also to add, just me or is it also annoying for those of us who do not give a shit about the PVE outside of the story not being able to do the story? I mean... you do a little 5 to 10 minute quest to then be told "MEET UP WITH US HERE FOR OUR NEXT COURSE OF ACTION" which is cool and all but you have to gain 3 levels to do so. So you do that, then you meet up and guide them to the objective and complete the mission only to find to continue you need yes... another 3 levels. Its getting very tiring for me now, im level 37 and find myself not even logging in to do it anymore.
Only thing that has bothered me is the trading post still being down. REALLLLY want that to be up and working.
It has frustrated me so much I've scaled back to playing only 12 hours a day instead of 14. =P
Also to the guy above me talking about the story. Yeah I don't like the story quests either. I decided just not to do them period. Don't really need them for anything. One day when I'm bored I'll do them maybe.
Based on my own personal experience this launch has been fine. I've been able to play every day since the 25th. All day on weekends. I've spent about 3,400 gems without any issues. Ran into some connection issues on the 25th and one disconnect since then. Otherwise the game has been playable. In game, I've seen some lag at times and several broken quests. Nothing to really prevent me from playing. The gems store has been slow at times and obviously the trade house is having issues.
Overall, if you've experienced a few MMORPGs launches, then this one was pretty smooth. Whenever you have a million+ players there will be people that have problems and things that break.


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Italian RPG publisher Dreamlord Press has joined Bits & Mortar! Benvenuto!
Bits & Mortar heads into ParaSpace
Our latest publisher is UK-based ParaSpace. Welcome! Make sure to check out their stuff.
Bits & Mortar Welcomes the Dead Gentlemen
The Dead Gentlemen, publishers of the Demon Hunters RPG, have joined Bits & Mortar. Welcome aboard, gents!
Incarnadine Press Joins
Incarnadine Press, publisher of With Great Power and Serial Homicide Unit, has joined the initiative! Welcome!
Bits & Mortar Climbs to High Rock
High Rock Press is a Gerlach, NV based publisher of fiction and roleplaying games. (Yep: they live where Burning Man happens.) It's run by Jason Walters, general manager of Indie Press Revolution, CEO of Hero Games, author of numerous books, and a generally small press kind of dude.
Palegain Press Joins
Palegain Press joins Bits & Mortar today! You can find their stuff through Indie Press Revolution. PDFs should be going up within the next week, weather permitting. 🙂
Samjoko Publishing Joins
Samjoko Publishing, publishers of Magicians and Worlds in Peril, has joined the initiative. Welcome!
Bits & Mortar Gets the Spirit of '77
We're pleased to announce our newest publisher, Monkey Fun Studios, purveyors of the Spirit of '77 RPG. Files should go up in the next week or so.
Bits & Mortar Walks the Sword's Edge
Bits & Mortar Opens a Growling Door…
Welcome to Growling Door Games, publishers of the new edition of Chill!

subset: commoncrawl


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University Library
Search help: what is Limo? / Tutorials and tips per library
What is the UB?
As a knowledge centre the University Library provides scientific information for students and researchers. In this support for research and education she develops a wide range of services.
The 24 KU Leuven libraries and learning centres are spread throughout 12 campuses in Flanders. A close cooperation with the libraries of the KU Leuven Association is established.
Studying in the library
- You are welcomed to study in our libraries. The Learning centre AGORA is fully equipped to support your study, alone or as a group. Most of our libraries offer group study areas.
- At our Study with a Buddy page you get an overview of available study seats. During study and exam periods you can also find here extra opening times of our reading rooms for study.
Electronic collection
Our e-sources are available to staff and students anywhere on campus through a wired or wireless internet connection. You can also consult this collection off campus.
Our library heritage is mainly kept in the Special collections and the Maurits Sabbe Library. It consists of exceptional collections and masterpieces of global importance.


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Hotfrog Philippines provides information regarding Buhangin Memorial Park in Davao City Davao del Sur. Buhangin Memorial Park is located at Davao City Davao del Sur and provides Funeral Services services. Contact them on (082) 227 4076.
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Description from the manager
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Bedrooms: 6/
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Book this 6 bedroom, 5 bathroom villa in Castries today! A total of 12 people can sleep here comfortably.
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ALMOST everyone has dreamt of being their own boss. But if you are serious about it, you need to be realistic about the cost involved in going it alone. We all know you need a good accountant. But one point many people overlook is that you will depend on being fit to earn a living. Insurance to protect your finances if you are sick or injured is vital.
It is worth looking into these plans even if you are not self-employed. State incapacity benefit is between pounds 64.70 and pounds 111 per week depending on circumstance. Moreover it is hard to qualify for this benefit. As a consequence more and more people are looking to safeguard their earnings.
Income protection (see box below) will pay out a percentage (usually half) of your usual monthly salary in the event that you are unable to work through illness or injury. Unfortunately for the self-employed, who arguably need it more than anyone, they will find it both hard and expensive to obtain cover.
The main problem is that you need to produce a long history of earnings before cover is granted. And many self-employed workers are in high-risk occupations, such as the building trade, and are turned away.
Income protection has been accused, in many cases quite rightly, of being expensive. It may be worth consulting an independent financial adviser who will be able to pick a policy to suit your needs; if you do the research yourself, you may go for the cheapest scheme without spotting potential snags. It is possible that a scheme with lower premiums is less costly because it includes clauses that, in effect, reduce the number of payouts.
For example, a policy may stipulate that you must be unfit to carry out "any occupation" rather than just your "own occupation" before it will pay you. So a self-employed graphic designer would have to prove that he or she could not work, for example, as a telephone operator in order to qualify for a payment.
Alternatively, the policy may pay out under an "own occupation" definition for the first six or 12 months and then change to "any occupation". Ensure you buy an "own occupation" deal.
There is also the problem that there may be a large gap between the earnings that the self-employed declare to the Inland Revenue and the amount they take home. It is perfectly legitimate: the self-employed attempt to offset as much of their income as possible against tax, so a real earnings figure may be closer to pounds 1,000 a month rather than the pounds 700 they have declared.
However, if they make a claim under their income protection policy, they will receive a payment relating to the pounds 700 declaration. Even with insurance, they may struggle to make ends meet if they are unable to work for any length of time.
Some insurers assess claims by only taking the previous year's income into account. This can be disastrous if the previous year was unusually bad. If you are well established in your business, look for a policy which will base average earnings on a number of years' income.
If you don't have a long earnings record, one way to get around this is to buy critical illness cover as it is not income based. You would receive a cash lump sum if you had a heart attack, stroke or any other sudden and life-threatening illness named on the policy. Unlike income protection, you would receive nothing for stress-related illness or chronic back disorders.
The products are not the same but they do at least cover some of the same ground - namely that if you are unfit to work, there is cash to help you through.
One insurer, UNUM, has introduced Essential Ability Cover which goes against current trends and does not require details of occupation or an earnings history. Instead, claimants are given a set of tests (11 physical and one psychiatric) to determine if they are fit for work.
If claimants satisfy any three of these physical tests, or the one mental health test, they will qualify for monthly income replacement payment. Other insurers will probably follow UNUM down this path in an effort to open up the self-employed markets.
Some insurers, such as Royal & SunAlliance, are offering "integrated deferred benefits", a scheme tailored for the self-employed. It works by giving a low payout for the first six months and then an increase as the absence from work gets longer. The premiums are often less than for a standard plan.
Any good financial adviser will look at the individual and offer tailored advice. For example, if a client is in his late 50s, is a self-employed joiner, and is looking to retire but is concerned that he may not be able to afford to do so for a number of years, it may be a good bet to take out critical illness cover. Income protection could be hard to obtain because he is in a higher-risk profession.
Private medical insurance (PMI) can protect income in its own way. With PMI you are, in effect, buying into a private-sector waiting list which will be shorter than that on the NHS. You keep lost income and absence from work to a minimum by receiving prompt treatment.
q Contacts: Independent Financial Advice Promotion, 0117 971 1177 (for the numbers of three advisers in your area); Institute of Financial Planning (for fee-based advisers), 0117 930 4434.
q David Burrows is deputy editor of `Planned Savings' magazine.
Health insurance plans
There are two main types of health insurance scheme that pay out if you become sick, plus private medical insurance (PMI) which pays private hospital bills.
Income replacement insurance (sometimes called permanent health insurance - PHI). This pays you an income if you can't work due to illness or injuries that are not life-threatening - for example, stress-related illness and broken limbs. On average, 50 to 60 per cent of earnings are paid after a pre-arranged deferral period, which can be anything from four weeks to a year. The payments continue until the claimant is able to return to work or reaches retirement age.
Critical illness cover provides insurance against life-threatening illnesses such as a heart attack, stroke, cancer or multiple sclerosis. Payment comes in the form of a lump sum but varies according to the sum assured and the condition you are claiming against, so it could be anything from pounds 20,000 to pounds 200,000 plus.
Private medical insurance. Insurance to pay for medical treatment carried out in the private sector. The likelihood is that the waiting time will be much shorter, so you can get back to work more quickly. There are budget plans that limit the treatments you are covered for, and it may be that you have no cover for outpatient treatment. The more expensive plans will offer full refunds for treatment and will include all the added extras such as a private room, food and TV/video.
Policies can cost anything from pounds 35 a month for a budget family plan, which will offer few full refunds and give little choice on where you are treated, to pounds 340 a month for a comprehensive family plan providing full refunds for all treatments and all the extras.
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Swansea Property Management
estate agents, Letting Agents, Letting Agent
Why Choose Swansea Property Management
In our experience of the letting market, the biggest problem for both tenants and landlords alike is finding a professional property maintenance team who is both professional and cost efficient. We are proud to boast the fact we have the answer to the problem.
All of OUR managed properties actually receive the treatment the market leaders propose to do for you plus a whole lot more which is also at no cost to the landlord or tenant. This is not a misprint! We have included all the extra's that other agents charge for , for FREE!
• Same day Emergency Call Out FOC (Free of Charge)
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So when Swansea Property Management manages your property ,we actually completely manage with NO hidden costs, and keeping the landlord informed with real time updates.
Is your agent working this hard?........... We didn't think so ..........
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Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target.
We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery.
Citation: Li Q, Li X, Li C, Chen L, Song J, Tang Y, et al. (2011) A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds. PLoS ONE 6(3): e14774. doi:10.1371/journal.pone.0014774
Editor: Jörg Langowski, German Cancer Research Center, Germany
Received: November 18, 2009; Accepted: February 19, 2011; Published: March 22, 2011
Copyright: © 2011 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This project was supported by the National Science and Technology Major Project 2008ZX09401-006 and 2008ZX09202-007 (http://www.most.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
The formation of a fibrin clot at the site of an injury to the wall of a blood vessel is an essential part in stop blood loss after vascular injury. The reactions that lead to the formation of fibrin clots are commonly described as the clotting cascade, in which the product of each step is an enzyme or cofactors necessary for the following reactions to proceed effectively[1]. The clotting cascade can be divided into three parts, the extrinsic pathway, the intrinsic and the common pathway[2]. The extrinsic pathway begins with the release of tissue factor at the site of vascular damage and leads to the activation of factor X. The route provides an alternative mechanism to activate factor X, from the activation of factor XII. The common pathway is composed of steps linking the activation of factor X to the formation of a multimeric, cross-linked fibrin clot. Each of these processes includes not only a cascade of events that generate the necessary catalyst for the formation of clots, but also many positive and negative regulatory events.
As a result of advances of computational techniques and hardware solutions, virtual screening has dramatically speeded up modern lead identification and lead optimization. Ligand-based and structure-based virtual screening are two most important methods used in current computer aided drug design[3]. Ligand-based methods such as chemical similarity analysis[4] and pharmacophore modeling[5] mainly focused on the features of the active ligands structure. With high performance output, ligand-based virtual screening was widely used to screen large compound database. However, the fundamental problem of the methods is that definition of what constitutes an active scaffold is highly subjective[6]. Synergized with X-ray crystallography, NMR spectroscopy and isothermal titration calorimetry (ITC), structure-based virtual screening has been used to complement experimental high-throughput screening (HTS) methods to improve the efficiency and efficacy of discovering lead inhibitors[7]–[11]. Structure-based screens typically the molecular docking to fit small organic molecules into targets of known structure, evaluate them for structural and chemical complementary. In last few years, investigators have also turned to predict new substrates for enzymes or receptors of unknown function (such as the membrane proteins) and to predicting potent small molecules based on multi-targets.
With emergences of new paradigms in multi-target drug discovery for several complex diseases, multi-target virtual screening has been presented and executed to discover the regimen which could target many different proteins and could be of low cost, efficacy and better tolerance. However, the importance and role of target in many complex disease systems were not explicitly considered in the reported literatures about multi-target virtual screening. Moreover, as most traditional virtual screening method, more attention was paid on binding affinity between drug molecule and target instead of phenotypic data of drug molecule against disease system[12].
With the progress of system biology and bionetwork, we know that the biological potency of an ideal drug may not merely determined by the inhibition of a single target, but rather by the rebalancing of several proteins or events, which contribute to the etiology, pathogeneses, and progression of a complex disease [13]–[26]. The available methodologies of in silico screening based on a single target seem not effective in studying ligands' effects on biological process comprehensively for some cases[27], [28]. In the current work, a novel approach was developed by integrating the predictions based on multi-target docking studies through biological network efficiency analysis to estimate the biological potency[26], [29]–[31]. The work flow was shown in Figure 1. The satisfactory predictions of our model were validated by the experiments. Similar model to predict the biological potency of drugs quantitatively by combining the multi-target virtual screening and biological network calculation together have not been yet reported in the past references. This novel model could be a powerful tool for combinatorial drug discovery and the development of multi-target drugs.
1 Constructions of the docking library
The docking library for multi-target virtual screening against clotting cascade comprises 1177 compounds from 24 Traditional Chinese Medicines (TMCs) that were widely used as components of recipes against cardiac system diseases. These TCMs include 23 original plants and 1 original animal (their information can be found in the Supporting Information S1). All compounds identified in these TCMs were collected from Chinese Herbal Drug Database developed in our group[32] and other literatures[5], [33]–[35]. In addition, some active synthetic compounds against coagulation cascade available to our laboratory were included in the docking library, for example, seven argatroban intermediates. The structures of these compounds were constructed and minimized with the MMFF force field[36] in Discovery Studio molecular simulation system (DS, Accelrys Inc.). In minimization, the threshold of root mean square deviation (RMSD) of potential energy was set to 0.001 kcal·Å-1·mol-1. The optimized structures of all compounds were saved as sdf and mol2 formats, respectively, for further docking study and were included in the Supporting Information S1.
2 Network-Based dual-step hierarchical Computational Estimation
Fourteen proteins authorized as drug targets by US Food and Drug Administration (FDA) were used in the virtual screening based on docking simulations. These targets include coagulation factor Xa, thrombin, coagulation factor IXa, tissue factor:coagulation factor VIIa complex, coagulation factor VIIa, fibrin, kallikrein, tissue factor, prothrombin, von Willebrand factor, coagultaion factor VIII, coagulation factor XI, fibrinogen, and coagulation factor XIII. To reduce computational cost while not degrade the calculation accuracy, two docking approaches, including Ligandfit and Autodock, were successively employed to dock candidates to the binding sites of these receptors in accordance with the order of their docking simulation accuracies in network-based dual-step hierarchical virtual screening. Top ten percent of hits from the previous step were used for the next step. In every steps of serial virtual screening, one candidate was estimated and ranked based on its influence on the network efficiency of clotting cascade network instead of the scoring functions of these binding poses on one target as used in conventional virtual screening methods.
(a) Docking and scoring with Ligandfit.
The crystal structures of fourteen targets were retrieved from the Protein Data Bank (PDB entries: 1FJS[37], 1TA2[38], 1RFN[39], 1W0Y[40], 1YGC[41], 2HLO, 2ANW[42], 1TFH[43], 1K22[44], 1AUQ[45], 3CDZ[46], 2F83[47], 1FZG[48] and 1GGT[49]). Hetero atoms were removed from the receptors, and then hydrogen atoms were added and wrong valence shells were corrected using Discovery Studio. For receptor/ligand complex with crystal structure, the binding site was defined as the grid points around the ligand which were unoccupied by receptor atoms, whereas for a receptor without crystal complex structure, potential binding sites were found based on the shape of the receptor. Ligandfit protocol in Discovery Studio was used to dock ligands into the specified site by the following steps: (1). conformational search of candidate ligand for docking, (2). ligand/site shape matching, (3). positioning the selected ligand conformation into the binding site, and (4) rigid body energy minimization of the candidate ligand pose/conformation using the DockScore energy function and updating the saved list of ligands with the candidate pose. Except maximum poses retained was set to 1, and default values were adopted for the other parameters. The Piecewise Linear Potential 1 (PLP1) was selected for subsequent calculation of network efficiency shift of all compounds based on our previous work about the comparison of several empirical scoring functions[50].
(b) Docking and Scoring with Autodock.
The AutoDock4.01 program was used for the second step of the dual-step hierarchical virtual screening because of the better performance of its scoring function over those of the others for several target proteins[51]. First, polar hydrogen atoms were added and non-polar hydrogen atoms were merged by the Hydrogen module in AutoDock Tools (ADT) for fourteen targets after water molecule were removed. Then, Kollman united atom partial charges were assigned. The grid map of the docking simulation was established by a 61×61×61 cube centered on the target active site as defined in Ligandfit, with a spacing of 0.375 Å between the grid points. When every ligand was docked to a target, the Lamarckian genetic algorithm were used optimize the conformation of ligand in the binding pocket. The set of parameters was listed as following: the size of the population was 150. The number of energy evaluations was set to 1.75×107 as the run terminates. For clustering the conformations, the root mean square deviation tolerance was 2.0. Twenty independent docking runs were carried out for every ligand. Other parameters were set to default. For the targets of which crystal complex structures were determined, every ligand in complexes was picked up and sequentially docked back into its initial active sites respectively in order to assess the reliability and accuracy of docking by Autodock program.
3 Network construction and analysis
(a) Network construction.
The network was constructed using the information from Reactome knowledgebase[52]. The clotting cascade pathway has been chosen to build the network. The enzymes which participate in the pathway were proposed as nodes and arrows between nodes represent the connections. The direction of the arrow means that the enzyme in the end of the arrow enhances the formation of the enzyme located in the front.
(b) Network statistics.
The damage induced by the attacks on the network is characterized by the network efficiency (NE), which is defined as the sum of the reciprocals of the shortest path lengths between all pairs of nodes[53]. Due to a global topological property of a network which could be applied to measure the integrity of the network, the network efficiency was assumed to be used as a measure for drug efficiency[54]. The NE of a graph G is measured by the shortest paths between pairs of nodes with the expression:where dij is the length of the shortest path between node i and j and the sum is over all N(N −1)/2 pairs of nodes with total number N of nodes in the graph G. If the network is weighted, dij is the path with the minimum weight. The initial line values of every edge were arbitrarily set to 10. To give relative network efficiency, this quantity NE is divided by the initial network efficiency. Thus we considered the network efficiency of the initial network as 100% and measured the relative network efficiency after each attack. We have chosen the clotting cascade network as the network models.
(c) Network efficiency calculation.
The network efficiency was calculated for each compound. The compounds' effects to the network rely on the docking scores. We supposed that the compound could inhibit the target well while the docking scores were relatively high. For a ligand, we transformed its docking scores with a target to line values of all directly downstream edges of the target in the network and then calculated the network efficiency. In other word, the line values of all edges, which point to the other targets from this target, were re-assigned based on the docking score between the compound and the target. The docking score threshold was set to 0, so any docking score which was positive was fixed to 0. For each docking target, the ligand with the highest binding energy was chosen as the reference standard. We defined that the most potent ligand would knock the target by 99.95%. Therefore, the ligand could make the value of the lines that come out of the target enzyme as 200. As the reference ligand docking score should make the line values to 200, the factor 2.3 was used to achieve this purpose. That was because the 2.3th power of 10 is equal to 200 and that was where the factor 2.3 come out from. Therefore, the ligand could make the value of the lines that come out of the target enzyme as 200. BEs represents the binding free energy of the most potent ligand, BE represents the binding free energy of other ligands, and LV is the line values of the edges come out of the target in the network. The line values of the edges which did not come out of the target enzyme were defined as 10. The line values of the edges in the network were calculated with the expression:Therefore, different ligand would show different effect on the target. For each ligand the network efficiency was then recalculated using the redefined line values. The network efficiency of each ligand was ranked by the decrease of the network efficiency. The more the network efficiency decreases, the more potent the ligand is. The procedure of network efficiency calculation was written in C language using Dijkstra Algorithm.
4 Experimental validations
Among these compounds, we chose fourteen compounds which could be purchased for the further experimental validations. The compounds used in the experiments were: fangchinoline, folic acid, rutin, quercetin, liensinine, salvianolic_acid_A, salvianolic_acid_B and six argatroban intermediates. The structures of these compounds were showed in the table 1.
Activated partial thromboplastin time (aPTT), prothrombin time(PT) and thrombin time(TT) assays were performed using a model LG-PABER-I coagulometer (Steellex Scientific Instrument Company, which also provided the used plasma and clotting reagents) in compliance with manufacturers' recommendations. All test chemicals with the exception of heparin sodium were solutized and subsequently serial ten-fold dilutions were prepared with dimethyl sulfoxide (DMSO) to yield a range of concentrations (12,1.2,0.12,and 0.012×10-3 moles·L-1). Heparin sodium solutions (9.0×104 I.U.·L-1) were prepared by dissolving in normal saline (NS). The above series of solutions (DMSO and NS as references) were diluted with pooled normal human plasma (1∶60 vol:vol), and the mixed plasma were evaluated with aPTT, PT and TT values, which associate with anticoagulant potential of test chemicals. All reactions were performed in duplicate and data is expressed in clot time (second).
Results and Discussions
The constructed network (Figure 2) contains 41 nodes and 53 edges (arrows). The nodes cover most of the important enzymes that participate in the clotting cascade, such as thrombin, factor X, factor V, TF, etc. We removed each node and calculated the network efficiency to determine the importance of the enzyme. The results show that the nodes corresponding to factor Xa, thrombin and factor VIIIa:factor IXa are identified as the top three critical targets. The deletion of factor Xa could reduce the network efficiency greatly, from 17.822 to 8.894. And knock out of thrombin from the network could reduce the network efficiency from 17.822 to 10.542. Our predictions are in good agreement with the reported results[55], [56]. For example, the approved drug Arixtra is a synthetic and specific inhibitor of activated factor X (Xa) indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism. That means the inhibition of factor Xa is an ideal way for thrombosis treatment, which is consistent with our prediction. As a crucial role in physiological and pathological coagulation, thrombin can be considered a very successful drug target because numerous direct thrombin inhibitors, e.g., Hirudin, Bivalirudin, Lepirudin, Desirudin, Argatroban, Melagatran and Dabigatran are in clinical use or undergoing clinical development as antithrombosis agents[57]. In order to test the clotting cascade network, we randomly deleted one enzyme in the network and compute the correspondence network efficiency. Deletion of enzyme with most network efficiency drop could be considered as the most important targets. The results showed that deletion of thrombin and Factor Xa would take most effect to the network efficiency. That meant thrombin and Factor Xa were predicted as the most important targets by network efficiency calculation. This prediction was in accordance with practical knowledge. Therefore, our clotting cascade network could mainly reflect the real biological process. After the clotting cascade network testing, docking validations also should be carried out.
The red nodes represent the enzymes participate pathway and the lines between the nodes reflect the relationships between the enzymes of the clotting cascade pathway. The network contained 41 nodes (enzymes) and 55 edges (relationships between enzymes).
To quantitatively compare the differences of the positions and orientations of five ligands from targets with complex structures between experimental and computational conformations, all RMSD (root mean square deviation) between experimental and computational conformations of these ligands in these complexes were calculated. RMSD of coagulation factor Xa, thrombin, prothrombin and tissue factor/factor VIIa are 1.811, 1.890, 1.702 and 1.943, respectively. Among all five values, only RMSD of factor VIIa is larger than 2 Å and is 2.489, but it is acceptable after analyzing the positions and orientations of functional groups in the ligand. (The details are stated in the Supporting Information S1.) These results indicate that docking by Autodock program in our study is reliable and accurate enough for further analyses.
In the experimental section of this study, three clinical used blood clotting assays: aPTT, PT and TT were carried out to reveal the biological activities of the 14 test compounds. The activated partial thromboplastin time (aPTT) mainly reflects the intrinsic pathway which is part of the clotting cascade. The prothrombin time (PT) is measure of the extrinsic pathway of coagulation. The Thrombin Time (TT), is a blood test which measures the time it takes for a clot to form in the plasma from a blood sample in anticoagulant which had added an excess of thrombin. However, the three assays could not correlate to any single-target. As the three assays individually reflect part of the clotting cascade, we considered sum of the three experimental measurements could represent the whole effects of clotting cascade. Therefore, we correlate the network efficiency to the sum of the three experimental measurements.
Then, we conducted multi-target docking for fourteen compounds. Each compound was initially docked and then ranked by the predicted binding energy to obtain the line values in the network. After that, the network efficiency for each compound was calculated. We compared the performances of two docking approaches, Autodock and Ligandfit, and found that the decrease of the network deficiency based on the predictions given by Autodock can give better correlation with the experimental data (r = 0.671) than that based on the predictions given by Ligandfit (r = 0.47).
In order to test the probability for large scale screening of this method, we evaluated the runtime of the docking approach and the network efficiency calculation which were the most time consuming procedures in this method. Take this study for example, docking procedures for one compound mainly cost less than 10 minutes per target per CPU thread. Runtime of network efficiency calculation was relay on the number of targets in the network. The runtime complexity for the worst-case scenario of the network efficiency calculation is O(n2) while the "n" is the number of targets in the network. The network size could be extended to hundreds of nodes and thousands of edges. That would large enough for current disease pathway. For the typical 14 target network in this study, calculating the network efficiency for 14 compounds based on docking data only cost less than 2 seconds on a single CPU core. If our method was running on a cluster which contain 64 CPUs (128cores, 256 threads), the throughput could attain to more than 30 000 compounds per day. Therefore, it is a feasible approach for large scale screening.
To reveal the importance of the network efficiency, we compared the predictions by the network efficiency analysis based on the single target docking and those based on the multi-target docking. When computed by applying the single target docking scores, the correlation coefficients of the estimated potency and the experimental data for factor Xa and thrombin, which are supposed as very important enzymes in clotting cascade[56], [58], [59], [60], were 0.648 and 0.602(Figure 3B and Figure 3C), respectively. However, the correlation between the predicted network efficiencies and the experimental data was improved by applying the multi-target docking scores (r = 0.671) (Figure 3A). It suggests that overall consideration of the contribution of the biological network might be better than only consideration of the contribution of single target for the accurate predictions of the biological activities. The single target docking cannot capture the biological effects of the ligands comprehensively, and the multi-target docking is really necessary to characterize the complicated binding process of ligands with multiple targets involved in biological network.
A) The correlation (r = 0.671) between the integrated fourteen compounds biological activities and the decreases of network efficiency induced by these compounds. The decrease of network efficiency is calculated from the multi-target docking scoring. B) The correlation (r = 0.648) between the fourteen compounds biological activities and the docking scores with coagulation factor Xa. C) The correlation (r = 0.602) between the fourteen compounds biological activities and the docking scores with thrombin. The biological activities of the fourteen compounds are illuminated in the Supporting Information S1.
Additionally, we analyzed the potency of the hit compounds (In order to emphasis on the hit compounds screening from Traditional Chinese Medicine, six argatroban intermediates were not include in the analysis.) through the network connectivity. In Figure 4, a ligand is assumed to connect with its target if it can form strong interactions with the target. The compound rutin, which connects with 14 targets, is the most potent compound according to our experiments. Other hit compounds, such as liensinine and folic acid, which have less connecting neighbors, show limited biological activities. It seems that the compounds which can connect with more targets have higher activities because the potent compounds interact not only with a single target but also with a series of important targets in the clotting cascade pathway. Therefore, the technique which combines multi-target docking and biological pathway network analysis can predict the effects of ligands to the whole biological pathway more efficiently.
Circles represent the enzymes in the clotting cascade pathway and the boxes represent the hit compounds (rutin, salvianolic acid a, salvianolic acid b, fangchinoline, quercetin, liensinine, folic acid). Each ligand is assumed to connect with its target if it can form strong interactions with the target. Their interactions are expressed by the connecting edges.
An analysis of the pharmacology literature was used to assess the whole homeostasis property of the compound with a larger decrease value in network efficiency. Previous reports[61], [62] suggested that rutin protected stroke and inhibited thrombosis. Salvianolic acid B is also confirmed effective on modulating hemostasis properties of human umbilical vein endothelial cells[63]. Salvianolic acid A is found protective against cerebral and myocardial ischemia and reperfusion[64]. These findings indicate that network efficiency analysis combined with molecular docking scoring function can be used to successfully screen natural product databases of potential drugs in silico to identify molecules with anticoagulant activity.
Generally speaking, current virtual screening methods mainly focus on single drug-target interaction. The correlation coefficients between the estimation and the experiment values were based on compounds' effects of single target inhibition. However, compounds' effects on single target inhibition hardly correlated to the whole effects on such biological pathway process. At the same time, a few other studies also tried to relate drug effects via pathway alterations. Mitsos et al. have described a phosphoproteomic-based approach to identify drug effects by monitoring drug-induced topology alterations[65]. They started with a generic pathway made of logical gates and performed fitting via an Integer Linear Program (ILP) formulation. While in our study, we constructed our screening network based on clotting cascade and applied the Network Efficiency (NE) for ligand efficiency prediction. Herein, this method reflected the compound's effects on the biological pathway and correlated to the phenotype data which could provide different opinions on pathway based virtual screening.
Like all virtual screening scoring method, our approach has many advantages as well as some limitations. One of obvious advantages of the method is that it specifically considers the role of every target in the whole coagulation cascade process and assigns the weightiness on every target by biological network analysis. The other advantage is that the affinity evaluation in the method is not limited to molecular docking and scoring, as used in this study. Other binding energy prediction methods could also be used, such as pharmacophore, quantitative structure-activity relationship or comparative molecular field analysis. It is also assumed that the consideration of flexibility of the targets in molecular docking might improve the accuracy of the network efficiency. The relevant work how flexible docking and precise binding free energy computational methods affect the accuracy of the network efficiency is under way. Given the fact that the x-ray structures of fourteen enzymes in existing networks have been determined, molecular docking and scoring function are well suited for the human coagulation cascade system. A clear disadvantage of this technique is that its accuracy enormously depends on the reliability of network construction and the veracity of binding affinity assessment.
In summary, we developed a model that combines multi-target docking and network efficiency calculation for the predictions of the potency of ligands with reasonable accuracy. The method integrates the scores given by the multi-target docking scores by the network efficiency analysis according to the targets' importance in a biological pathway or process. The network efficiency analysis based on the multi-target docking can evaluate the ligands' potency more comprehensively than the traditional single target docking and show better prediction accuracy. It remains to be determined how the size and complexity the biological network take effect to the biologically relevant, and the relevant work is under way.
Supporting Information
Supporting Information S1.
Author Contributions
Conceived and designed the experiments: QL LC YT XX. Performed the experiments: QL XL CL. Analyzed the data: QL XL. Contributed reagents/materials/analysis tools: QL CL JS. Wrote the paper: QL.
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text:
Crock pot steak
Pozrite si súvisiace témy
Southern Slow Steaks... so want to see if this will be a great meal in my house. Steak is my favorite!
I love this recipe!! Slow Cooker Salisbury Steak! Perfectly tender beef patties simmered in the crock pot in a rich brown gravy! This is a family favorite!
There are only 5 ingredients in this slow cooker steak fajitas recipe.
Only 3 ingredients and seasonings needed for this delicious Crockpot Steak Bites recipe that kids love!
Change up taco night with these delicious beef recipe - Crock Pot Steak Tacos for dinner!
The whole family will love this delicious Crock Pot Steak Soup!
Complete Steak Dinner in A Crockpot. This makes a delicious meal. I cook chicken, pork chops and steak like this. It's a complete meal and when you get home, it's all done!!
Smothered crockpot steak. I want to try this also adding the potatoes on top (wrapped in foil) and then the corn on the cob (Stephanie O'Dea's brilliant idea). Verdict: it was OK. The "steak" tasted more like a roast after its time in the crock pot. The potatoes and corn had a weird texture.
Crock Pot Mongolian Beef
Melanie Rowland Poynter Back By Popular Demand!!!! Crock Pot Cube Steak and Gravy SHARE to save to your own timeline so you can find it later: Cube steak (I used a family size pack) 2 cans (10.75 ounce size) cream of mushroom soup 1 envelope onion soup mix 3/4 cup water Salt and Pepper to taste Directions: Place all ingredients in a crock pot. Cook on low all day. Serve over rice, noodles, mashed potatoes or with your favorite side dishes. ★★★★★★★★★★★★★


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NR Digital
The War Lover
Gabriele D'Annunzio: Poet, Seducer, and Preacher of War, by Lucy Hughes-Hallett (Knopf, 608 pp., $35)
In the opening decades of the 20th century, Gabriele D'Annunzio was one of the most famous Italians alive. Writing came easily to him and was the basis of his reputation. Among his serious admirers were Marcel Proust and Osbert Sitwell. Henry James, no less, praised his "excited sensibility." Romain Rolland, a Nobel Prize winner and a Communist fellow-traveler, was a friend who wrote a book about him and compared him to a pike, a large fish that devours smaller fish.
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Greek Lemon Chicken With Potatoes
Total Time
Prep 20 mins
Cook 2 hrs
Lemony-herbal chicken that roasts painlessly...oven-roasted garlicky potatoes - crisp on the outside, butter-soft on the inside. This recipe never receives anything but raves!
Ingredients Nutrition
- 1 large chicken
- 1 lemon, juice of
- 3⁄4 tablespoon dried oregano (if you can get the Greek stuff, you're really cooking!)
- 3⁄4 teaspoon salt
- 1⁄4 teaspoon pepper
- 2 garlic cloves, minced
- 5 -6 large potatoes, peeled and cut into big wedges (probably 1/4s)
- 1 lemon, juice of
- 1⁄2 cup olive oil
- 1⁄2 cup water
- 1⁄2 teaspoon salt
- 3⁄4 tablespoon dried oregano
- 1⁄4 teaspoon pepper
- 2 -3 minced garlic cloves
- (I often add about 1 tsp of crumbled, dried rosemary to the potatoes and 1/2 a teaspoon to the chicken- this is fantastic and it then becomes oregano-rosemary-lemon-garlic chicken).
- Wash the chicken well and pat dry.
- Combine all the remaining ingredients and massage the chicken, inside and out, with this mixture. Put the chicken in a big bowl and put in the fridge while you prepare the potatoes.
- Put the potatoes and all remaining ingredients into a large baking pan. Wash your hands and put them in the pan and toss the potatoes around to coat with other ingredients.
- Put in the oven and crank up the heat to 250°C (480F).
- Start roasting the potatoes and when they're golden-brown, stir them to bring the white sides up and push to the side of the pan to make room in the middle for the chicken.
- If all the water has evaporated, and potatoes have started to stick to pan, add 1/2 cup more.
- Add the chicken, breast-side down, and pour any juices that have accumulated in bowl over.
- Return to very hot oven and roast until chicken is golden-brown.
- Turn over, breast-side up and continue roasting until chicken is nearly as golden-brown on other side.
- At this point, I turn the oven off- don't open it- and leave the chicken in for another 1/2 an hour. I like to think I'm saving energy this way, but it also cooks the chicken beautifully.
- In all, I'd say from when you put the potatoes into the cold oven to when you remove the chicken to carve after sitting in off oven for 1/2 an hour, we're talking 2 hours.
- Serve with pan juices.
Most Helpful
I made this with chicken breasts and roasted them with the potatoes for about an hour and a quarter. I also used less salt and oil. Love the lemon flavor of the potatoes!
Excellent!The best roast chicken we have ever eaten. I was a little worried about the cooking method since I had splurged on a 4.8 pound organic roaster from Whole (paycheck) Foods - but it was perfectly done. My timing was 20 minutes for the potatoes, 20 each side for the chicken and 30 with the oven off. My potatoes burned a bit so next time I will move the oven rack up a notch. I served it with Lemon Dill Carrots #16961 and Asparagus with Fresh Tomato Yogurt Sauce #19396. Thanks Ev, goes into my book of "Special Tricks".
The first time that I made this recipe I thought that the baking time for the potatoes was wrong so I did not follow the recipe - the instructions ARE correct and the potatoes are fantastic Crisp on the outside and very soft inside. As suggested I added some rosemary, The aroma from the chicken and the flavor is wonderful - Everyone loved the meal. I served it with new garden fresh carrots (steamed with parsley) & broccoli. Thanks Evelyn for a winner


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From the lady behind Ladies That Craft
and they are multiplying at an alarming rate. Here is a sneak peek at my latest work in progress which hopefully I will have time to finish very soon.
Loads more gilding and fairy dust still to be added. Watch this space.
She's gorgeous Julie. Can't wait to see it all finished. Intrigued! x
Oh my she's amazing!!! May I suggest you may need a fairy door so they can come and go as they please :-)Have a look at http://madimaginations.blogspot.com/2010/10/let-fairies-in-blog-candy.htmland you'll see what I mean!!
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Showing Results: Most Recent
This review is from: Acer X163WL Ab Black 15.6" Widescreen LED Backlight LCD Monitor 500:1
Pros: It is bright sharp and excellent color. surprised at the excellent quality of the picture of the unite.
Cons: wish the base would allow you to adjust the angle of the displayREAD FULL REVIEW
This review is from: Kocaso M1066 10.1" Android 4.2 Tablet PC - 1.0GHz Dual-Core, 32GB, Dual Camera, TFT Screen 1024 x 600, Wi-Fi
Pros: Good looking screen, streams movies with a good pix, about 4-5 hours of battery life. USB port will recharge batteries,
Cons: Limited muti-tasking, slow on INTERNET, does not play Facebook games or brouser based games
Other Thoughts: First Android device. It does take son getting use to.READ FULL REVIEW
This review is from: DFI LP DK 790FX-M2RS AM2+/AM2 AMD 790FX ATX AMD Motherboard
Pros: Nice board, worked right out of the box. The connectors were in about the same location as my older dfi board so it went in real easy for me.
Cons: I was having trouble getting the raid controller to keep from losing files during long unpacking and disk defraging. To keep that from happening make sure that you force the software to delete all partitions and do a full ntfs format(not the quick format)
Other Thoughts: ready to spend some time setting up the bios.READ FULL REVIEW


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Hi ladies,
still looking for a group to join in your local area? If you have facebook come over and check out our page. I am the founder and have only started this group in the last few days ! We will be having regular catch up!
If you are looking for something a little bit more private come over and join our Murrumba Downs and Surrounding Districts Mums closed discussion board (your comments won't show up in your news feed). Introduce yourself, ask questions, share photos, websites, recipes or anything else you're interested in. We will be having regular playdates, coffee meet ups, a walking group and girls nights out.
I look forward to meeting all of you lovely ladies very soon!


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Title: 6th Annual Organic Gardening Series
Everything you need to know to get your garden started or expanded this year!
Dates: 6 Tuesdays: March 14, 21, & 28; April 4, 18, & 25 in 2017.
The classes are paired with each other. Best results when you take the whole series but you may purchase separately as pairs. Classes 1&2 are paired together, 3&4 are paired together, and 5&6 are paired together.
- Classes 1, 3, & 5: Lenoir-Rhyne University, Asheville, 36 Montford Ave, Asheville, NC 28801. Spacious parking and easy-off-the-highway location.
- Classes 2, 4, & 6: Dr. John Wilson Community Garden, 99 White Pine Dr. in Black Mountain. These classes will be more hands-on education and tours of the community garden which features a variety of garden methods: French Intensive, square foot, hugelkultur, no-till and more. These garden-based classes offer an opportunity to review topics from the previous classroom sessions, see these techniques in practice, as well as build your confidence through experiential learning.
Registration: Register here.
This exciting six-part series covers all aspects of Growing: planning, planting, production, and pests.
Get Growing CLASS 1 in the Classroom: Tuesday, March 14, 2017 from 7:00 PM – 9:00 PM
Why you should consider growing organically; important site, size, and design considerations for your garden; growing the soil & nutrient basics; garden seasons; and useful tools will be discussed. Q & A session.
Get Growing CLASS 2 in the Garden: Tuesday, March 21, 2017 from 6 to 7:30 PM (sunsets at 7:45)
On-site review and real-life examples from Class 1. Held at the Black Mountain Community Garden.
Get Growing CLASS 3 in the Classroom : Tuesday, March 28, 2017 from 7:00 PM – 9:00 PM
Techniques for starting seeds and transplants; dealing with common problems; how much to plant; composting & vermicomposting; converting your lawn to garden; an edible yard; and maximizing your garden space. Q & A session.
Get Growing CLASS 4 in the Garden: Tuesday, April 4, 2017 from 6 to 7:30 PM (sunsets at 7:55)
On-site review and real-life examples from Class 3. Held at the Black Mountain Community Garden.
Get Growing CLASS 5 in the Classroom: Tuesday, April 18, 2017 from 7:00 PM – 9:00 PM
The virtues of mulch; water and fertilization considerations; compost tea; cover cropping and n-p-k; organic disease and insect control; and tips for Fall gardening. Q & A session.
Get Growing CLASS 6 in the Garden: Tuesday, April 25, 2017 from 6:00 PM – 7:30 (sunsets at 8:15)
On-site review and real-life examples from Class 5. Held at the Black Mountain Community Garden.
Photo Album from 2016 Garden Tour at the Black Mountain Community Garden
Diana Schmitt McCall
Garden Manager at Dr. John Wilson Community Garden
Eat Smart Black Mountain, a program of Black Mountain Parks and Recreation
Diana McCall manages the Dr. John Wilson Community Garden which is home to nearly 70 gardening families, over 100 fruit and nut trees, mushroom logs, a native species trail and a biodynamic donation garden which produces 4000 pounds of produce annually for distribution in Black Mountain. Her work also includes school garden programs, expanding community gardens in the town, and partnering with numerous agencies and institutions to educate her community on how to grow, access and prepare healthy food for themselves and their families.
Sponsored by:


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June 2014, TruckingInfo.com - WebXclusive
By Tom Sanderson, CEO, Transplace
In late April, Tom Sanderson, CEO of the third-party logistics company Transplace, participated in a roundtable on Capitol Hill about highway funding. As we inch closer to the deadline and the Highway Trust Fund is heading into the red, he offers his impressions of that event.
Tags: Legislation, Highway Funding, U.S. Senate, Highway Trust Fund, Transplace
May 2013, TruckingInfo.com - WebXclusive
By J.K. Jones, Contributor
Shippers must work smarter and cooperate closely with their carrier partners to offset expected losses in truck capacity caused by government regulation, according to presentations at the 11th Annual Transplace Shipper Symposium held earlier this month in Dallas.
Tags: drivers, Transplace, Shippers
We offer e-newsletters that deliver targeted news and information for the entire fleet industry.
The expert, Scott Sutarik from Geotab, will answer your questions
The expert, Steve Carlson from Xantrex, will answer your questions
On the Spot: First Impressions of Volvo's SuperTruck
Ultimate Test Drive: New Cascadia Sleeper Lounge [Video]
Ultimate Test Drive: Freightliner's New Cascadia Pt. 2 [Video]
Ultimate Test Drive: Freightliner's New Cascadia Pt. 1 [Video]
Program Promises 'Instant ROI' For Tire Inflation System
Truck-Lite's Road Ready Trailer Telematics
Rotary Lift Expands Mach Flex Mobile Column Lineup
Sumitomo Offers New Steer, Drive Tires


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More Videos...
Engine Running NO OIL - NO SUMP - Seized Soild on Camera
Messing with a Mitsubishi Lancer There are loads of videos where people run an engine at full rev with no oil in it, and the engine seizes. Running it a medium rev, I wanted to see how long it would run with no lubrication, and I was surprised. However if the car was driving and the engine was under load, it would be dead in minutes!
Super car driver idiots [NO pics, only videos]
I got bored with all the "super car crashes"-videos here on YouTube that only contained PICTURES, CRAPPY MUSIC or/and clips of pure racing cars on official racing events. This compilation DOES NOT include pure racing cars on official racing events - only real life FAILures on the STREETS, made by people with more money than driving skills... (Though, even the best car drivers can crash too of course.) Notice 1: The "Dodge Ram" may not be a super car, but still it's a SRT10 with the 8.3L Viper V10 which produces 510hp. Pretty super for a pick up, don't you think? It has more power than several of the cars in this video. The intention with this video was to show that skills doesn't come with money. Notice 2: Tire is the preferred spelling in the U.S. and Canada. Tyre is preferred in most varieties of English outside North America. And I'm from Sweden. So please think outside your box (country), you who claims "tyre" is incorrect spelling.
Top 30 Dyno Tuning Disasters - HD
Top 30 all time Dyno and tuning failures
BEST of DYNO Crash and FAIL ( Pure Sound ) EPIC
Channel: https://www.youtube.com/user/henrico21?feature=watch Subscribe: http://www.youtube.com/subscription_center?add_user=henrico21 Facebook: https://www.facebook.com/pages/247-Videos/1408371946058246?ref=hl Twitter: https://twitter.com/HPieters1985


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Originally written on The Sports Bank | Last updated 9/22/14
In a sport full of "bad boys" three-time Sprint Cup champion Tony Stewart has crafted and cultivated an enduring image as the "baddest boy" in NASCAR. Stewart's cocksure personality and unique driving style characterized by equal parts audacity and bravado, is a perfect fit for the audacious and wild motor sport that he has dominated for the past 15 years. Jack Payton is a car nut and motorsports fanatic in the purest form. He loves to write about everything gear related, and rebuilt his first engine at 15. He works as a freelance writer for the online tire retailer Tires Easy. In his spare time he enjoys cruising, following NASCAR, and collecting vinyl. Whether he is sparring with fellow drivers, NASCAR officials, or equipment manufacturers, Tony Stewart has a way of always making things interesting. The sharp-tongued Tony Stewart is unafraid to say exactly what it is on his mind, which sometimes gets him into trouble, but certainly succeeds in ensuring that he will always have a ...
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Voting starts in March for the Drupal Association Board election.
In multilingual sites, it is often necessary to translate vocabulary names in sitemap. Translations for vocabulary names can be entered in backend, but sitemap does not use them.
It's very easy to make sitemap honor translations, so I propose this little change that implements the functionality:
site_map.module, line 461:
$title = $name ? check_plain($name) : ''; --> $title = $name ? check_plain(t($name)) : '';
I believe there are not side effects.
Comment #1frjo CreditAttribution: frjo commented
Committed to 5-dev and 6-dev, thanks for the reminder fpedraza :-).


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VinylTimes – Classic Vinyl Records
Welcome to the NEW VinylTimes.com – Classic Vinyl Records, Cool Vinyl Stuff,
|2015 – The 50th Anniversary
of the famous 1965 album cover
Click image for more cool info on Dolores.
A little something about our "Very Special Lady"
Dolores Erickson visited NC almost 10-years ago to attend a "Vinyl-Only" record show sponsored by VinylTimes.com. She traveled from her home near Seattle, WA to autograph many of her famous album covers, meet local classic vinyl records collectors, and pose for a few "Grip & Grin" photos. She was quite impressed with the the reception she received and, following the show, Dolores asked VinylTimes.com to be the exclusive promotional and marketing entity for her line of products. Her autographed album covers and other "Whipped Cream" items are now available for purchase. VinylTimes.com is proud to host the on-line home of one of the music industry's most famous icons, Dolores Erickson – "The Whipped Cream Lady".
|Click on the image to the right and get more information on Dolores' upcoming appearance at the Vinylfest Weekend Of Music in Louisville, KY Aug 14-16th. You'll be able to meet Dolores in-person at the VinylTimes.com display and vinyl sales tables.
**** COOL LINK to an ABC News Nightline report on the resurgence of Vinyl Records!!! ****
|Some other really cool links and info on classic vinyl records:
|Vinyl Record Shows
|Vinyl Record Stores
|Links to Other Vinyl Sites


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Chicken Breast Cacciatore
|Canned whole tomatoes
|16 Ounce, cut up (1 Can)
|Green pepper
|1⁄2 Medium, cut into thin strips
|1 Medium, sliced and separated into rings
|Dry white wine
|1⁄4 Cup (4 tbs)
|Oregano leaves
|1⁄4 Teaspoon
|Parsley flakes
|1⁄2 Teaspoon
|1⁄4 Teaspoon
|Whole chicken breasts
|2 , halved, skin removed (Bone In)
|7 Ounce, cooked (1 Package)
|Shredded romano cheese
|2 Tablespoon
In 2-qt casserole combine tomatoes, green pepper, onion, wine and seasonings; cover.
Microwave at High 5 to 7 minutes, or until vegetables are tender, stirring once.
Arrange chicken in 12 x 8-in baking dish with meatiest portions to outside of dish.
Pour sauce and vegetables over chicken.
Cover with wax paper.
Microwave at High 14 to 18 minutes, or until chicken is tender and no longer pink; rearrange and spoon sauce over chicken twice during cooking time.
Serve chicken over vermicelli that has been tossed with Romano cheese.
Recipe Summary
Rate It
Nutrition Rank
Nutrition Facts
Serving size: Complete recipe
Calories 1528 Calories from Fat 159
% Daily Value*
Total Fat 18 g27%
Saturated Fat 6.6 g32.9%
Trans Fat 0.1 g
Cholesterol 230.7 mg76.9%
Sodium 1692 mg70.5%
Total Carbohydrates 203 g67.8%
Dietary Fiber 21.2 g84.7%
Sugars 18.5 g
Protein 124 g248.9%
Vitamin A 78.5% Vitamin C 207.6%
Calcium 60.9% Iron 85.6%
*Based on a 2000 Calorie diet


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Tea for RubySimon & Schuster/Paula Wiseman Books 2010; US$ 7.99
Ruby gets a princess-worthy primer on manners in this charming picture book from #1 New York Times bestselling illustrator Robin Preiss Glasser and author Sarah Ferguson, The Duchess of York. Ruby does her best to have good manners?yet no matter her efforts, she just can?t seem to succeed. But when Ruby receives a mysterious surprise invitation... more...
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Lynne Cheney and Robin Preiss Glasser collaborated on America: A Patriotic Primer, which captured the imagination of American children and became a national best-seller. Now they turn their hands to A is for Abigail: An Almanac of Amazing American Women and bring the great women of American history to life. Filled to the brim with words and pictures... more...
AmericaSimon & Schuster/Paula Wiseman Books 2016; US$ 6.50
America: A Patriotic Primer is a succinct history of the United States, an ABC of the principles on which this country was founded, and a book for children and families to pore over, discuss, and cherish. A is for America, the land that we love. B is for the Birthday of this country of ours.... To choose the twenty-six people and ideas... more...
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|Property type
Perfect location to explore southern Vermont with convenient access to skiing, hiking, biking, paddling. Five minutes to Mt. Snow, our home comfortably accommodates a large group or a couple of families with plenty of space for everyone to spread out on three levels. Enclosed indoor hot tub, pool table, foosball, darts, Wifi DSL internet connection, lots of games, puzzles, videos & books will provide fun after enjoying fun-filled days. Three separate rooms to hang out (living room, den, game room). Early/Late Check-in!
Welcoming front porch & large deck off the rear of the house. Large, one-car garage offers space for parking & storing gear. Sit around the stone fire pit roasting marshmallows & listen to the babbling steam in the private back yard. Private location on a small, quiet cul-de-sac in an area of nice homes. Easy-access on a town-maintained road with plenty of off-street parking.
Balsam Cottage - see our Shutterfly Page with Area Info
Mt Snow & Local Events: Check out Mt. Snow's calendar for current events & activities:
'On Mount Snow's four mountain faces you'll find tons of trails everyone in the entire family can enjoy.. With over 580 acres of skiable terrain it will be easy to find your smiley face on one of ours. Groomers, moguls, trees, or jumps it's all here at Mount Snow – The Gateway to Vermont.
Carinthia is the East Coast's #1 Terrain Park as voted on by Transworld Magazine, SKI Magazine, and Skiing Magazine readers. Carinthia boasts 12 full park areas loaded with rails, jumps and pipes, nearly five miles of trails, tree-skiing zone, all-natural terrain area, mini-pipe and Mount Snow's monster superpipe'.
Our family likes to ski and snowboard, hike, go boating, kayaking, fishing. Southern Vermont and the Deerfield Valley offers all that and more.
Greg & Marie Quill purchased this house in 2008
Mt. Snow offers fantastic skiing and snowboarding. We also wanted to be close by to take care of our home.
We love how close our home is to the mountain and how much room there is for everyone to spread out or gather around to play games or enjoy a nice dinner. Our home has nice, comfortable furnishings and decor, but everyone can feel relaxed and right at home.
We enjoyed staying in your beautiful home! The setting is gorgeous. We had lots of snow which made for a perfect ski vacation. We will leave with some wonderful memories. What a great way to bring in the New Year.
This home had more conveniences than any other home we have stayed in. Plenty of room for everyone. Lots of games and fun things in the basement. Love the huge master bedroom and the back deck with grill. Greg and Marie were awesome to deal with. We had an unfortunate incident with the stove and within a few hours a brand new stove was delivered. Thanks so much for renting your home home to us. CF Live Oak, FL
Eight of us (4 adults, 4 children) had the pleasure of staying at the cottage for the long Columbus Day weekend. Everything was as advertised, a lot of space and sleeping areas, great activities, hot tub and fully loaded kitchen. This is a can't miss place to go if you love Vermont. Convenient to everything you will need to make your trip the best it can be. Owners were very responsive and easy to get a hold of. We also got our deposit back in a timely manner. My family and I would recommend this house to anyone.
-Randy L.
This is our second straight year staying at Balsam Cottage and hopefully we will be back. Great location close to conveniences and with a lot of privacy, amazing weather and everything you could need to be comfortable. We hoped to see a moose like we did last year, but no such luck, only saw a porcupine!
Had a great week at Balsam Cottage! The owners were really accommodating and helpful (but not over bearingly helpful). This is a great place to have a quiet summer getaway, close enough to "big" towns of Bennington and Brattleboro, small towns of Jacksonville and Wilmington. Lots of great hikes nearby including Lye Brook Falls. we even pushed north a few hours to summit Camel's Hump at sunset. It was great to have this place waiting at the end of an adventure, a nice deck to sit in the sun and a nice grill to use. An unplanned bonus was that an adolescent moose decided to stroll by on our first day, the first one I've ever seen! Great time, great house. Thanks a bunch!
A group of 9 of us stayed at Balsam Cottage over the long MLK weekend. We found the instructions provided by the owner resourceful and helpful throughout our stay. The property was well cleaned and furnished upon our arrival. We took full advantage of the fire place and board games- great amenities to the property. I would definitely recommend this to anyone looking to ski at Mount Snow as it's also a quick 5 minute drive to the mountain.
In regards to "the step", which seemed to be the only cause for concern on some previous reviews. We didn't find this to be a huge issue. We did have a few take a little stumble but there is a clear sign hanging above the stairs cautioning everyone to watch their step. It's also outlined in the arrival instructions the owners provide prior to checking in. Keep an eye out for it and you should be fine!
This is our second year in a row staying at the Cottage. We really enjoy everything about it. There was 10 of us and we had plenty of room. The house, kitchen, and appliances are always clean and easy to use. The house is less than 5 minutes from mount snow. We really love the big living room that had enough space for all of us to hang out by the fire and play games.
Our home is located in the Mt. Snow Valley, a quintessential Vermont destination just 25 minutes from Brattleboro. Only 5 minutes to the slopes, restaurants, and nightlife at Mt Snow. Stratton, Bromley & Magic Mountain are just a short drive away. The nearby villages of Wilmington's, Newfane, Grafton offer quaint shops & restaurants. Close to the VAST snowmobile trails & cross-country skiing, sleigh rides. During the summer, enjoy boating and fishing on Harriman Reservoir. Somerset Reservoir offers peaceful kayaking & canoeing. Deerfield River for white-water rafting or tubing. Golfing at any of the areas mountain resorts. Our home puts you in the heart of it all.
Other Activities: Boating on Harriman Reservoir, Kayak & canoeing on Somerset, Tubing/rafting on the Deerfield River
|Rate Period
|Weekend Night
President Weekend
Feb 17 2017 - Feb 19 2017
3 night minimum stay
Flat fee
My Standard Rate
1 night minimum stay
|Refundable damage deposit
|$100 + Tax
|Tax Rate
Mid-week Winter Special: $1,250++ 3 nights! (non-holiday)
Holiday & Special Events Rate = $800/per night with 3-night minimum
Discounts for weekly and monthly rentals.


text: Bossip: You Can't Be Serious: Iowa Woman Fired By Thirsty Azz Boss For Being "Too Attractive" Info Post durga dherange 7:30 AM No Comment Bossip Henny Without Any Coke! You Can't Be Serious: Iowa Woman Fired By Thirsty Azz Boss For Being "Too Attractive" Dec 23rd 2012, 15:29 Should bosses be allowed to fire employees for being hot? Woman Fired For Being Too Attractive Via RadarOnline reports: Melissa Nelson was fired from her job as a dental assistant after her boss, Fort Dodge dentist James Knight, claimed she was an 'irresistible attraction' and the all-male Iowa Supreme Court upheld the termination. "I don't think this is fair. I don't think this is right," Nelson, a happily married mother, told CNN. Nelson worked for Knight for 10 years when, according to her defense in the case, the dentist began texting her that her clothes were too tight. He also allegedly complained to her about his "infrequent" sex with his wife and commented that seeing Nelson in the office was "like having a Lamborghini in the garage and never driving it," the AP reports. Knight's wife, who also worked at her husband's office, demanded Nelson be fired and the dentist did just that. His attorney argued that the court got it right; that a boss has the right to honor the wishes of a family member without committing discrimination. "These judges sent a message to Iowa women that they don't think men can be held responsible for their sexual desires and that Iowa women are the ones who have to monitor and control their bosses' sexual desires," Nelson attorney Paige Fielder said of the decision. "If they get out of hand, then the women can be legally fired for it." WTF!?!?!? So she was fired based on her looks? And this is ok in Iowa? Can't her husband sue the employer for financial loss due to his inability to contain his sexual desires in the workplace? It seems just as ridiculous as their reasoning in her firing. Sorry ladies, if you're too good looking, you might as well turn your two-week notice in now. Media files: melissa-nelson-cnn-pixelated deolacola melissa-nelson-cnn-pixelated You are receiving this email because you subscribed to this feed at blogtrottr.com. If you no longer wish to receive these emails, you can unsubscribe from this feed, or manage all your subscriptions Posted by durga dherange at 7:30 AM Email ThisBlogThis!Share to TwitterShare to Facebook Share: Facebook Twitter Google+ StumbleUpon Digg Delicious LinkedIn Reddit Technorati