text:
PDF eBooks Library | Philosophy
Sensor Systems for Biological Agent Attacks: Protecting Buildings and Military Bases
Henna's Secret History: The History, Mystery & Folklore of Henna
Emotional Wellness: Transforming Fear, Anger, and Jealousy into Creative Energy
Invertebrate Palaeontology and Evolution
Masaje balines / Balinese Massage: Tecnicas tradicionales de Indonesia / Traditional Indonesian Techniques (Spanish Edition)
Hospice Aide On-The-Go In-services Series, Volume 2, Issue 4: Alzheimers Disease (Home Health Aide on-the-Go in-Service Lessons)
In Pursuit of Purity, Unity, and Liberty: Richard Baxter's Puritan Ecclesiology in Its Seventeenth-Century Context (Studies in the History of Christian Thought) (No. 112)
The World in a City: Traveling the Globe Through the Neighborhoods of the New New York
The Vegetable Gardener's Bible: Discover Ed's High-Yield W-O-R-D System for All North American Gardening Regions
Libro - Ricette di salute e bellezza con gli oli essenziali (Italian Edition)
The Billionaire Bride (The Brides of Holland Springs) (Volume 1)
The Spread of Nuclear Weapons: A Debate
Study Guide for General, Organic, and Biological Chemistry
Don't Panic! Pathology & Medical Terminology Quick Review Book
Poor Will's Almanack 2015: Since 1984, a Traditional Guide to Living in Harmony with the Earth
Geometric Etudes in Combinatorial Mathematics
Unit Operations in Environmental Engineering
Home Sweet Home: How to Help Older Adults Live Independently
Tu Fe y Tu Dinero: Principios Para una Vida Bajo el Control de Dios / Daring to Live on the Edge (Spanish Edition)
THE SCIENCE OF TIME: The Day When Self Tells The Truth On Self
Drawn & Quarterly Number 4: March 1991
Automobilelektronik: Eine Einführung für Ingenieure (ATZ/MTZ-Fachbuch) (German Edition)
Power of Bacterial Genetics: A Literature-Based Course
Mothers on the Fast Track: How a New Generation Can Balance Family and Careers [Kindle Edition]
WoD Mirrors *OP (World of Darkness (White Wolf Hardcover))
Lattice Boltzmann methods for use in irregular channels: Theoretical foundations, simulation, and working code
Beyond Duality: A new Perspective for Human Realization
Phoenix and the Birds of Prey: Counterinsurgency and Counterterrorism in Vietnam
Changes in the Roman Empire: Essays in the Ordinary
The Essential Emily Sarah Holt Collection (19 books) [Kindle Edition]
The Art of War: The Definitive Interpretation of Sun Tzu's Classic Book of Strategy [Kindle Edition]
Sammelband - Schwule Fickgeschichten [GAY]: Zehn erotische Gay Geschichten (German Edition)
Pull Production for the Shopfloor (Shopfloor Series)
Implementing Database Security and Auditing
The southeast's oldest medical school: Now a leading research and treatment center (Newcomen publication)
Liturgia De Las Horas, Tomo 3: Tiempo Ordinario: Semanas I-XVII (Spanish Edition)
Great Depression (Witness to History) (Witness to History)
New Recipes from Quilt Country: More Food & Folkways from the Amish & Mennonites
The Mill: The Children of Quarry Bank
The International Almanac of Electoral History
Strength of Materials: v. 1: A Practical Approach
Optical Mapping of Cardiac Excitation and Arrhythmias
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
- Agriculture
- Anthropology
- Architecture
- Astronomy
- Botany
- Chemistry
- Commerce
- Computer
- Cooking
- Cosmology
- Decorative arts
- Drawing
- Economics
- Education, Academies
- Encyclopedias
- Engineering, Technology
- Family, Marriage
- Finance
- Geography
- Geology
- History
- Humanities ethics
- Languages, Dictionaries
- Law
- Mathematics
- Media, Internet
- Medical
- Micro-Biology, Physiology
- Music
- World History
- Open Access
- Painting
- Periodicals
- Philosophy
- Physics
- Political Science
- Psychology
- Games, Fitness
- Religion
- Sculpture
- Sociology
- Software
- Statistics
- Transportation, Communication
- Zoology


text:
LUMBERTON — The Public Schools of Robeson County and Robeson Community College have canceled classes for Thursday and Friday because of Hurricane Matthew.
The University of North Carolina at Pembroke, like the public schools, has not held classes this week and its students are now on fall break.
There are shelters at three high schools, St. Pauls, South Robeson and Purnell Swett, which is at capacity. There are also shelters at Bill Sapp Recreation, which is at capacity, and the Southeastern agriculture center.

subset: commoncrawl


text:
Boom Beach Hack could create pooling sources in order to development in the video game. Its discharge Boom Beach hacks have enticed countless buyers generally since they all have to have a boom beach hack tool as well as boom beach cheats to make sure that you can deliver magic as well as gems free of charge taking into consideration.
An additional reason why several gamers of Boom Coastline are still not using the hack device, in addition to the concern of getting banned, is that they consider it to be unreasonable. Our Boom Beach hack does not require you to jailbreak your smart phone, download and install any type of added apps or link to the PC. Such points are required by several other diamond generators.
There is, nevertheless, one product called treasure or ruby that is extremely challenging to gain without getting it. Certainly you could gain lots of treasures by finishing success; however, even after you complete all readily available accomplishments, you will assume that the variety of gems that you earn is still doing not have.
Zombie Trip Cheat include in your video game all you much more fun by playing the game after that download and install the hack device from listed below web link and enjoy your video game have been hack by our group and also you so download the tool carefully from listed below any kind of links.
Our team of 3 work around the clock to help you with any type of troubles or problems you are having whilst using our system, we would despise to leave you having so if you having a trouble read our F.A.Q or just drop us an e-mail on our Get in touch with United States page.
When on that page you will certainly be needed to enter your Boom Coastline username, you should then choose which resource as well as how much of it you want, when picked our system will certainly create the resources for you. utilized the boom beach generator as well as I am really satisfied with the entire procedure, I wish to hack boom beach reference http://ow.ly/mH5L309ObKn Boom-beach-hack.INFO https://v.gd/9Pm58n Www.boom-beach-hack.info boom beach free diamonds my link https://is.gd/rZpYr5 official statement say thanks to everybody who runs this website for supplying my sources.


text:
Ready for Halloween? We have plenty of Spooky events to help!
0 Members and 1 Guest are viewing this topic.
i know what you mean, but i prefer stuff like aladin (musical and funny(who couldnt love robin williams( i miss him )))
Star Wars episode 2 attack of the clones 9/10I'm not usually a huge fan of action movies but really love Star Wars, number 2 is my favourite (I'm weird and like episodes 1-3 the best)
Page created in 0.059 seconds with 23 queries.


text:
Fair Play
i got a message saying chess.com is monitoring all games and feels my game could have breeched the fair play rules.. what is the criteria for this? how do they monitor? what do i do?
Some people do rage-quit on chess.com, and basically ethier pull the ethernet plug, close the window, or attack the computer after losing in chess.
This is identified as abandoning the game. This can also be due to poor connection on, say, a phone.
Unfortunately, this looks suspiciously like rigging the system to make your rating 2400 without being nearly that good. If the game has few moves, or if a side was clearly winning when they abondoned the game, and this is repeated for a certain "winner" (you win when your opponent abondones the game by default. 1 move to checkmate, they abondon it? You win.)
If chess.com notices this repitition, they will identify you as someone who appears to be trying to break the system, and restrict your account if you continue.


text:
White sinks are very popular in home design, but they stain and scratch very easily. There is a simple and all-natural way to clean a white sink and remove stains too. You just need a few ingredients that you may already have in your pantry to get your white sink sparkling clean and scratch free in not time!
A look at the sink before the cleaning begins...
Mix baking soda, Castile soap and essential oils in a small bowl.
Add some of the DIY sink cleaner to a scrub sponge.
Gently scrub the entire sink.
Scrub any scratches or marks left by dishes and pans.
Use a magic eraser sponge to remove any tough stains.
Spaghetti sauce and other tomato based foods can leave stains on white sinks. A magic eraser sponge will remove them and other stains as well.
Rinse the sink well.
All clean and stain free!
Things You Will Need
- Kitchen/bath cleanser with bleach
- Soft brush or scrubber
- Dishwashing liquid
- Sponge or cleaning cloth
- On a new white sink, starting out with the right care regimen will make it easy to keep stains and scratches away.
- Read labels on cleaning products. The label will say if the product is not recommended for certain surfaces.
- Manufacturers' websites have care instructions and other related information.


text:
Christian White
Managing Director and Co-Founder
Christian White is a managing director and co-founder of risk3sixty, LLC.
Before risk3sixty, Christian held the Operations Manager position in an Information Assurance Practice at a global consulting/CPA firm where he also traveled nationally to meet the IT audit and risk management needs of clients. Prior to his life in information security and professional services, Christian served as the Director of Operations for a technology startup and an Army Officer in the physical security space, where he led and managed organizations ranging in size from a 15-person staff to a company of over 200 personnel. Christian has established corporate training programs, implemented multi-organizational change initiatives, and managed complex projects on behalf of international clients.
Christian is a board member of ISACA Atlanta (the largest IT risk-focused organization in Atlanta) and Technology Association of Georgia (TAG). Christian has a B.S. in Management from the United States Military Academy at West Point and an M.B.A. with a concentration in Management of Technology from Georgia Tech.


text:
I felt like the shoulders were funny in the one below, so I fixed them a little in the pic above...I think it looks sooooo much better after I fixed it, what do you all think?
Fleshed out a little more in the cheek....
I thinned out the face in the one above...but it was too skinny, so then I fleshed him out a little more again.
So I added more shadows to the lips, which I think looks better, the original one is below.
Do you guys think that the original face is better or do you like the fixed one (the top pic of the face)?


text:
Contact Info / Websites
- thrustviper
Recent Movie Reviews
Rated 5 / 5 stars
Way to give your own submission a 0/10 review.
I on the other hand thought this was amazing and hilarious and epic and intense and beautiful and ballin'.
(2005)In 3 Minutes
Rated 5 / 5 stars
I love all your movies! Boogie Monster especially! Your new ones (this and John Pinkerton) have been great. You inspired me to use flash. "I love you... I kiss your head" -Klay Halloween
the boogie oogie
The old man´s day Trailer
Rated 0 / 5 stars
It wasn't funny or interesting and it sucked.
This is sooooooo bad. The song repeats once and nothing happens in the movie. Make it longer and have something happen next time. Decent animation I guess.
Recent Game Reviews
Train Robber!
Rated 3.5 / 5 stars
Simple but fun.
Not much to it but a good game.
Recent Audio Reviews
The Cybermonkey Studios Theme
Rated 5 / 5 stars
My cak is better but...
It is still pretty salty!
NOTHING can compare to your saltiness. In fact, your cak is so salty that no amount of moisture could quench the saltiness. Ever.
-Steel Shot


text:
I Remember 20 years ago, in every English tourist board office, on the wall they had a map of the entire British Isles with "England" in large red letters across the top.
There was also a big one on display at Dover docks to let the tourists from over the Channel be confirmed in their beliefs.
Let's also not forget the 2008 Olympics, where the Chinese kept announcing the GB team as "England" – there are endless examples of this mis-identity.
But this is not the main reason why Scots should put things right – the real bonuses are the economic arguments and also for the real need for fresh change and real adult responsibility in the world community.
Graham Young
Polepark Road


text:
South Oakland Shelter (SOS) provides supportive programs and resources to homeless individuals and families in need. Through partnerships with over 60 congregations, they provide temporary shelter for more than 300 families and individuals each year. SOS provides career building, job readiness skills, self-care, nutrition programs and so much more. Abiding Presence is partnering with St. Philip's Episcopal in downtown Rochester and Rochester Church of Christ to host South Oakland Shelter the week of April 30-May 7. St. Philip's will be using their facility to host, but we have agreed to support them with volunteers and food.
There are four major areas where we need volunteers:


text:
|Home | About | Journals | Submit | Contact Us | Français
Conceived and designed the experiments: LX PEB. Performed the experiments: SLK NL NB LX. Analyzed the data: SLK NL NB PJT LX. Contributed reagents/materials/analysis tools: NB PJT LX. Wrote the paper: SLK NL NB PJT LX PEB.
The rise of multi-drug resistant (MDR) and extensively drug resistant (XDR) tuberculosis around the world, including in industrialized nations, poses a great threat to human health and defines a need to develop new, effective and inexpensive anti-tubercular agents. Previously we developed a chemical systems biology approach to identify off-targets of major pharmaceuticals on a proteome-wide scale. In this paper we further demonstrate the value of this approach through the discovery that existing commercially available drugs, prescribed for the treatment of Parkinson's disease, have the potential to treat MDR and XDR tuberculosis. These drugs, entacapone and tolcapone, are predicted to bind to the enzyme InhA and directly inhibit substrate binding. The prediction is validated by in vitro and InhA kinetic assays using tablets of Comtan, whose active component is entacapone. The minimal inhibition concentration (MIC99) of entacapone for Mycobacterium tuberculosis (M.tuberculosis) is approximately 260.0 µM, well below the toxicity concentration determined by an in vitro cytotoxicity model using a human neuroblastoma cell line. Moreover, kinetic assays indicate that Comtan inhibits InhA activity by 47.0% at an entacapone concentration of approximately 80 µM. Thus the active component in Comtan represents a promising lead compound for developing a new class of anti-tubercular therapeutics with excellent safety profiles. More generally, the protocol described in this paper can be included in a drug discovery pipeline in an effort to discover novel drug leads with desired safety profiles, and therefore accelerate the development of new drugs.
The rise of multi-drug resistant (MDR) and extensively drug resistant (XDR) tuberculosis around the world, including in industrialized nations, poses a great threat to human health. This resistance highlights the need to develop new, effective and inexpensive anti-tubercular agents. Unfortunately, conventional approaches have yielded very few successes in the field of anti-infective drug discovery. It is a challenge to design drugs with both efficacy and safety. These challenges are reflected in the high costs involved in bringing new drugs to market. It has been estimated that the cost to launch a successful new drug is in excess of US$800 million. We have developed a novel computational strategy to systematically identify cross-reactivity between different drug target families. In this paper we demonstrate the strength of this approach through the discovery that existing commercially available drugs prescribed for the treatment of Parkinson's disease have the potential to treat MDR and XDR tuberculosis. The protocol described herein can be included in a drug discovery pipeline in an effort to accelerate the development of new drugs with reduced side effects.
Tuberculosis, which is caused by the bacterial pathogen Mycobacterium tuberculosis (M.tuberculosis), is a leading cause of mortality among infectious diseases. It has been estimated by the World Health Organization (WHO) that almost one-third of the world's population, around 2 billion people, is infected with the disease [1]. Every year, more than 8 million people develop an active form of the disease, which subsequently claims the lives of nearly 2 million. This translates to over 4,900 deaths per day, and more than 95% of these are in developing countries [2]. In 2002, the WHO estimated that if the worldwide spread of tuberculosis was left unchecked, then the disease would be responsible for approximately 36 million more deaths by the year 2020.
Despite the current global situation, anti-tubercular drugs have remained largely unchanged over the last four decades [3]. The widespread use of these agents, and the time needed to remove infection, has promoted the emergence of resistant M.tuberculosis strains. Multi-drug resistant tuberculosis (MDR-TB) is defined as resistance to the first-line drugs isoniazid and rifampin. The effective treatment of MDR-TB necessitates the long-term use of second-line drug combinations, an unfortunate consequence of which is the emergence of extensively drug resistant tuberculosis (XDR-TB) – M.tuberculosis strains that are resistant to isoniazid plus rifampin, as well as key second-line drugs, such as ciprofloxacin and moxifloxacin. XDR-TB is extremely difficult to treat because the only remaining drug classes exhibit very low potency and high toxicity. The rise of XDR-TB around the world, including in industrialized nations, imposes a great threat on human health, therefore emphasizing the need to identify new anti-tubercular agents as an urgent priority [4].
Currently, anti-infective therapeutics are discovered and developed by either de novo strategies, or through the extension of available chemical compounds that target protein families with the same or similar structures and functions. De novo drug discovery involves the use of high throughput screening techniques to identify new compounds, both synthetic and natural, as novel drugs. Unfortunately, this approach has yielded very few successes in the field of anti-infective drug discovery [5]. Indeed, the progression from early-stage biochemical hits to robust lead compounds is commonly an unfruitful process. The identification of both molecular targets that are essential for the survival of the pathogen, and compounds that are active on intact cells, is a challenging task. Even more formidable, however, is the requirement for appropriate potency levels and suitable pharmacokinetics, in order to achieve efficacy in small animal disease models [5]. These challenges are reflected in the high costs involved in bringing new drugs to market. In fact, it has been estimated that the successful launch of a single new drug costs more than US$800 million [6].
Two alternative drug discovery strategies that circumvent some of the challenges associated with de novo drug discovery are the label extension and 'piggy-back' strategies, both of which are widely employed for the discovery of novel therapeutics to treat tropical diseases. Label extension is a fast-track approach that involves the extension of the indications of an existing treatment to another disease. Some of the most important anti-parasitic drugs in use today, such as praziquantel for schistosomiasis, were derived from the label extension process. The major advantages of label extension are the significant reductions in cost and time to market that can be achieved. Alternatively, when a molecular target that is present in a pathogen is under investigation for other commercial indications, it is possible to adopt the 'piggy-back' strategy by utilizing the identified chemical starting points. Examples of this approach include the anti-malarial screening of a lead series of cysteine protease inhibitors for the treatment of osteoporosis, and histone deacetylase inhibitors for use in cancer chemotherapy [5].
One of the main aims of drug discovery is to develop safe and effective therapeutic agents through the optimization of binding to a specific protein target. In this way, undesirable effects resulting from side scatter pharmacology are minimized. However, the recent and rapid completion of numerous genome sequencing projects has revealed that proteins involved in entirely different biochemical pathways, and even residing in different tissues and organs, may possess functional binding pockets with similar shapes and physiochemical properties [7]. Therefore, chemical matter for one target could be considered as the basis for leads for an entirely different target. Recent work on large scale mapping of polypharmacology interactions by Paolini et al. [8] revealed the extent of promiscuity of drugs and leads across the proteome. They discovered that around 35% of 276,122 active compounds in their database had observed activity for more than one target. Whilst the majority of these promiscuous compounds were found to be active against targets within the same gene family, a significant number (around 25%) had recorded activity across different gene families.
The finding that so many drugs interact with more than one target provided the rationale behind the selective optimization of side activities (SOSA) approach recently developed by Wermuth [9],[10]. The SOSA approach involves the use of old drugs for new pharmacological targets, which is a valuable concept considering the finite number of small molecules that can be safely administered to humans. The process itself involves screening a limited number of structurally diverse drug molecules, and then optimizing the hits so that they show a stronger affinity for the new target and a weaker affinity for the original target(s). In this way, it is possible to derive a whole panel of new active molecules from a single marketed drug. Since the screened drug molecules already have known safety and bioavailability in humans, the overall time and cost of drug discovery is significantly reduced when compared with de novo strategies.
We have developed a novel computational strategy to identify off-targets of major pharmaceuticals on a proteome-wide scale [11]–[15]. Our methodology extends the scope of the SOSA concept effectively and systematically across gene families, and is more likely to be successful in achieving the ultimate goal of providing new drugs from old ones. Our chemical systems biology approach proceeds as follows:
Our approach essentially explores complex protein-ligand interaction networks on a proteome-wide scale. The lead compound can be discovered from all drug targets across different gene families. Moreover, lead optimization can focus on compounds with excellent safety profiles and known clinical outcomes. In this way, our approach has the potential to increase the rate of successful drug discovery and development, whilst reducing the costs involved.
In the present study we demonstrate the efficiency and efficacy of our chemical systems biology approach through the discovery of safe chemical compounds with the potential to treat MDR-TB and XDR-TB. The identified compounds are entacapone and tolcapone. These drugs primarily target human catechol-O-methyltransferase (COMT), which is involved in the breakdown of catecholamine neurotransmitters such as dopamine. They are used as adjuncts to treat Parkinson's disease by increasing the bioavailability of the primary drug levodopa, which is a substrate of COMT. Entacapone and tolcapone are predicted to inhibit M.tuberculosis enoyl-acyl carrier protein reductase (InhA), which is essential for type II fatty acid biosynthesis and the subsequent synthesis of the bacterial cell wall [16]. InhA is the target of the anti-tubercular drugs isoniazid [17] and ethionamide [18]. Similar to newly developed direct InhA inhibitors [3], [19]–[21], entacapone and tolcapone require no enzymatic activation to bind InhA. Thus they may avoid the commonly observed resistance mechanism to isoniazid and ethionamide that is exhibited by many MDR strains. Our computational predictions have been partially validated by demonstrating that the entacapone drug tablet Comtan inhibits the growth of M.tuberculosis at the minimal inhibition concentration (MIC99) of entacapone of 260.0 µM, well below the concentration leading to neuroblastoma cellular toxicity. The direct inhibition of InhA by entacapone is further confirmed by experimental enzyme kinetic assays, in which Comtan is shown to reduce InhA activity by up to 47% at the effective entacapone concentration of 80 µM. Since entacapone has an excellent safety profile with few side effects, it shows potential as a drug lead in the development of a new class of anti-tubercular therapeutics with favorable ADME/Tox properties.
Recently, Xie and Bourne developed a sequence order independent profile-profile alignment (SOIPPA) algorithm [11], which they subsequently used to detect common binding sites among proteins unrelated in sequence and/or function. Their studies implied an evolutionary relationship between the NAD-binding Rossmann fold and several other fold classes, including the SAM-binding domain of the SAM-dependent methyltransferases, through similarities between their co-factor binding sites. It is interesting to note that both nicotinamide adenine dinucleotide (NAD) and S-adenosyl methionine (SAM) include adenine as a common molecular fragment. In fact, previous studies have shown that adenine binding pockets from proteins lacking significant homology will share common physiochemical properties [11]. These findings, plus the versatility of our method, form the basis for the present study.
Entacapone and tolcapone are drugs that block the ligand binding site of COMT, a member of the SAM-dependent methyltransferase superfamily, in the presence of the SAM co-factor. They are used as adjuncts in Parkinson's disease therapy, to prevent the metabolism of levodopa to 3-O-methyldopa, therefore improving levodopa bioavailability and increasing its delivery to the brain [22]. The dopamine precursor levodopa has been the key drug for symptomatic treatment of Parkinson's disease for more than 30 years. Since COMT is a SAM-dependent methyltransferase, it is possible that it may possess a ligand binding pocket similar to those found in protein domains belonging to the NAD-binding Rossmann fold, as their co-factor binding sites are strikingly similar [11]. When entacapone and tolcapone were docked into 215 NAD-binding proteins from multiple species, the InhA enzyme from several different organisms, including M.tuberculosis, was consistently highly ranked (see Tables S1 and S2). Since InhA is the primary target of the anti-tubercular drugs isoniazid [17] and ethionamide [18], entacapone and tolcapone can potentially inhibit the InhA ligand binding site directly. Indeed, alignment of the COMT and InhA binding sites by the SOIPPA algorithm revealed similarities in the positioning of both their co-factors and ligands (Figure 1).
As shown in Figure 2, the existing InhA inhibitor with the greatest 2D similarity to entacapone is 3-(6-aminopyridin-3-yl)-N-methyl-N-[(1-methyl-1H-indol-2-yl)methyl]acrylamide (AYM) [23] (Tanimoto coefficient=0.155), whereas the existing InhA inhibitor with the greatest 2D similarity to tolcapone is 3-[(acetyl-methyl-amino)-methyl]-4-amino-N-methyl-N-[(1-methyl-1H-indol-2-yl)-methyl]-benzamide (ZAM) [23] (Tanimoto coefficient=0.173) (see Table S3). Neither of their p-values (AYM; 0.065 and ZAM; 0.205) are significant at the 0.05 level, implying that none of the investigated InhA inhibitors exhibit significant molecular similarity to either entacapone or tolcapone. Therefore, it is unlikely that ligand-based screening methods would be able to identify entacapone and tolcapone as potential InhA inhibitors.
Table 1 shows the predicted binding affinities of entacapone and tolcapone towards InhA. Since they fall within the range of binding affinities exhibited by the known InhA inhibitors, this not only provides a further implication of the cross-reactivity between InhA and COMT, but also suggests that entacapone and tolcapone are able to inhibit InhA directly.
Unfortunately it is difficult to identify entacapone as a lead compound using conventional virtual screening because it is only ranked at 15,892 and 9,719 by eHiTs and Surflex among 20,000 randomly selected drug-like molecules, respectively. While advanced virtual screening techniques such as the relaxed complex scheme [24], which combines a docking algorithm with molecular dynamics simulations, may improve the ranking of these potential lead compounds [25], they demand significant computational resources. Thus, SOIPPA, a ligand binding site similarity based method, provides an efficient way of identifying potential drug-like leads that have well-established pharmacokinetics and pharmacodynamics properties.
Although the 2D similarities between entacapone and existing InhA inhibitors have been shown to be statistically insignificant, entacapone shares a similar molecular size and common functional groups with several of the InhA inhibitors (see Table 1). For example, entacapone and five of the InhA inhibitors (468, 566, 641, 665 and 774) all possess a single benzene and amide moiety. More importantly, the predicted binding poses of the benzene ring and the amide bond of entacapone are similar to those of the InhA inhibitors, with root mean square deviations (RMSDs) of as little as 2.87Å and 1.05Å, respectively (in the case of 566). Although tolcapone does not share the same amide moiety, the predicted binding pose of its benzene ring has an RMSD of only 1.01Å from that of 566, further demonstrating the potential of these drugs as InhA inhibitors.
Previous studies have highlighted the necessity of the interaction between the catechol oxygens of COMT inhibitors with an Mg2+ ion in the active site [26]. From the predicted binding poses of entacapone and tolcapone docked with InhA, three potential interaction sites of Mg2+, including the Asp110, Asp115, and Glu210 residues of InhA, have been identified and are shown in Figure 3. The closest residue, Glu210, is positioned at a distance of 13.23Å from the nitrite group of entacapone, and at a distance of 11.54Å from the nitrite group of tolcapone (see Figure S2). Although it is possible that the conformation of the side chains may adjust to reduce this distance under in vitro or in vivo conditions, such a large distance may hinder the formation of a coordinate bond by the Mg2+ ion between the InhA active site and each of the two drugs. Consistent with the predicted binding pose, enzyme kinetic assays indicate that the addition of an Mg2+ ion has no effect on the inhibition of InhA by entacapone. This therefore provides us with opportunities to optimize entacapone and tolcapone, by reducing or removing their conjugation to the Mg2+ ion, so that they exhibit a weaker affinity for the original target COMT.
The partition coefficient (logP) is the ratio of the concentrations of an unionized compound in the two phases of a mixture of octanol and water at equilibrium, whereas the distribution coefficient (logD) is the ratio of the sum of the concentrations of all forms of the compound (both ionized and unionized) in each of the two phases. Since logD is pH dependent, the pH at which it was measured is specified, as shown in Table 2. Entacapone and tolcapone were discovered to have generally higher logP and logD values than most of the existing anti-tubercular drugs investigated. According to Lipinski's rule of five [27], poor absorption or permeation is more likely for compounds with a logP value of greater than 5.0. Such compounds are considered non-drug-like and are commonly filtered out in the early stages of drug discovery. However, entacapone and tolcapone are prescribed drugs and have been clinically tested with desired pharmacokinetics profiles. Indeed, entacapone can be rapidly absorbed with a Tmax of approximately one hour (http://www.rxlist.com/comtan-drug.htm). The high logP values of entacapone and tolcapone are therefore acceptable regardless of Lipinski's rule. Moreover, they suggest that entacapone and tolcapone are more hydrophobic than existing drugs, and would therefore pass more easily through the M.tuberculosis cell envelope. Although entacapone demonstrates poor solubility, dissolution enhancers such as croscarmellose sodium are used in the formulation of Comtan [28]. This example well illustrates that drug repurposing would accelerate drug discovery and development by bypassing the time consuming steps of ADME/Tox evaluation and drug formulation.
Entacapone and tolcapone were evaluated for their ability to inhibit growth of M.tuberculosis using a 96 well microplate assay. A 99.0% reduction in growth was observed with concentrations of between 62.5 µg/ml and 125 µg/ml for each drug. The sensitivity of M.tuberculosis to entacapone was confirmed by quantitative growth on agar plates containing known amounts of the drug. The minimum inhibitory concentration was between 62.5 µg/ml and 125 µg/ml (Table 3), therefore confirming the result from the microplate assay. These results support the computational predictions that entacapone and tolcapone have inhibitory activity against M.tuberculosis and may therefore be considered as lead compounds.
The ability of entacapone to directly inhibit InhA was evaluated using enzyme kinetics. Due to the strong UV absorbance of entacapone over a wide range of 300–400 nm (see Figure S4), and the poor solubility of entacapone in water, the highest concentration of Comtan that could be used in the assays was 90 µg/ml (the corresponding concentration of pure entacapone is 24.9 µg/ml), at which concentration InhA is approximately 47% inhibited. Fitting of the data in Table 4 to a dose response equation provided an IC50 value of 24±3 µg/ml (79±10 µM) (see Figure S3). Since Mg2+ is critical for entacapone and tolcapone to inhibit COMT, assays were repeated in the presence of 5 mM Mg2+ to explore whether or not metal ion chelation could improve the affinity of the drug for InhA. However, the inclusion of Mg2+ in the assay had no effect on the IC50 value for enzyme inhibition. The progress curve analysis for the inhibition of InhA by Comtan shows that the UV absorbance is linearly time-dependent up to one hour (see Figure S5), indicating that entacapone is not a slow-onset inhibitor.
The sharp contrast between the fatty acid biosynthetic pathway in humans (FAS-I) and that found in prokaryotes (FAS-II) has established this bacterial pathway as an attractive target for the design of new antibacterial agents [20],[29]. The FAS-II pathway in M.tuberculosis is involved in the production of mycolic acids, which, along with peptidoglycan and arabinogalactan, are central constituents of the mycobacterium cell wall [2],[29]. InhA catalyzes the final, rate-determining step in the fatty acid elongation cycle by converting trans-2-enoyl-ACP to acyl-ACP in an NADH-dependent reaction [3]. This crucial regulatory enzyme is the primary molecular target of isoniazid, which has been used as a frontline anti-tubercular agent for the past 40 years [20],[29]. As a pro-drug, the activity of isoniazid is dependent on its activation by KatG, a catalase/peroxidase enzyme. KatG oxidizes isoniazid to an acyl radical that covalently binds to NADH, and functions as a potent inhibitor of InhA. Unfortunately, it is this activation requirement that allows M.tuberculosis to acquire resistance to the drug. Indeed, mutations in the KatG gene account for around half of all isoniazid-resistant clinical isolates [3]. Direct InhA inhibitors that avoid this activation requirement are not susceptible to this resistance mechanism [30]. Triclosan and the diazoborines are well-known InhA inhibitors that do not require activation, but unfortunately they are not suitable for human treatment due to their respective poor solubility and toxicity [3]. However, a new class of high affinity direct InhA inhibitors, consisting of alkyl diphenyl ethers of triclosan derivatives, have been found to exhibit activity against drug-resistant strains of M.tuberculosis [21]. In addition to these alkyl diphenyl ethers, the arylamides [20],[31], indole-piperazines, pyrazole-based inhibitors [3], and indole-based inhibitors [23],[32], have recently been described as other classes of direct InhA inhibitors.
Using a novel computational strategy we have predicted that entacapone and tolcapone will directly inhibit InhA. Our prediction was subsequently confirmed by in vitro antibacterial and enzyme kinetic assays using Comtan tablets containing the active component entacapone. Thus entacapone and tolcapone are promising lead compounds against drug-resistant strains of M.tuberculosis. These drugs are currently in clinical use, although the association of tolcapone with hepatotoxicity has caused the drug to be placed under strict regulation in the United States [33]. Entacapone, which is not associated with the same hepatotoxic risks, is therefore more attractive as a drug lead. Interestingly, a recent study showed that when patients suffering from Parkinson's disease were treated with rifampin and isoniazid, their condition was observed to improve [34]. Since rifampin inhibits DNA-dependent RNA polymerase, this observation implies cross-reactivity between the M.tuberculosis InhA, the target of isoniazid, and the drug targets of Parkinson's disease, which is consistent with our predictions that InhA inhibitors can also inhibit COMT.
Recent studies have shown that triclosan can trigger the upregulation of M.tuberculosis detoxification mechanisms that result in its metabolism or efflux from the cell [21]. For instance, triclosan has been shown to induce the expression of an aromatic dioxygenase involved in the degradation of arenes. Since triclosan consists of a diphenyl ether structure, it is thought that the induction of this enzyme may serve to degrade, and hence detoxify, triclosan [35]. The subsequent modification of triclosan derivatives has led to high affinity alkyl diphenyl ether InhA inhibitors that upregulate neither efflux pumps nor aromatic dioxygenase [21]. Although gene transcription studies are required to determine the ability of entacapone and tolcapone to cause upregulation of the aromatic dioxygenase, it is speculated that the strong electron-withdrawing nitrite groups of these drugs may result in significantly lower reduction potentials, therefore making them less prone to oxidation by this enzyme. The narrow ranges of the MIC99 and the IC50 of Comtan support this hypothesis.
From our current experimental results, it is not possible to determine the effect of the inactive ingredients in the Comtan tablets (magnesium stearate, microcrystalline cellulose, hydroxypropyl methylcellulose, yellow iron oxide and red iron oxide, titanium dioxide, sucrose, mannitol, hydrogenated vegetable oil, polysorbate 80, glycerol 85%, croscarmellose sodium) on the growth of M.tuberculosis. It is unlikely that the major formulations in the Comtan tablets (magnesium stearate, microcrystalline cellulose, hydroxypropyl methylcellulose, iron oxide, titanium dioxide, sucrose) directly affect M.tuberculosis growth because they are the same as the active ingredients found in anti-tubercular drugs such as Rifater (isoniazid/pyrazinamide/rifampin combination tablet), Rifamate (isoniazid/rifampin tablet), and Priftin, whose active component is a rifamycin derivative (http://www.rxlist.com). Other ingredients such as polysorbate 80 and croscarmellose sodium are mainly used to enhance the dissolution and stability of entacapone [28]. It will be particularly interesting if they are active against the growth of M.tuberculosis, as they are commonly used food and drug additives. We have observed that a higher concentration of pure entacapone than that which is present in Comtan is required to achieve the same rate of inhibition in the InhA assay. Additional experiments such as X-ray crystallography and mass spectroscopy need to be conducted in order to investigate the precise mechanisms of action of Comtan and entacapone against M.tuberculosis.
Although we have demonstrated that Comtan is active against M.tuberculosis in vitro, further studies are required in order to transform it into an anti-tubercular therapeutic. The active component of entacapone in Comtan has an MIC99 for M.tuberculosis of approximately 80 µg/ml (262 µM), and an estimated IC50 value for InhA inhibition of above 80 µM. However, it exhibits very low cellular toxicity, with no effect on neuroblastoma cell lines that provide an in vitro model for high throughput toxicity screening [36] at concentrations of up to 500 µM [37], thus making the concentration required for M.tuberculosis inhibition not unreasonable for a lead compound.
The possibility that entacapone inhibits other enzymes besides InhA cannot be excluded. From our initial studies of the ligand binding site similarity network in the M.tuberculosis structural genome, InhA is one of the most promiscuous proteins, having a similar ligand binding site to more than 20 other enzymes [15]. This implies that an InhA inhibitor can potentially interact with multiple targets. If it is proven in future studies that entacapone can inhibit multiple targets simultaneously, the potential of entacapone as an anti-tubercular drug is even more promising, as "dirty" drugs lessen the likelihood of emergent resistance and higher clinical efficacy than exquisitely selective drugs [38],[39].
A further challenge is transforming entacapone into a nanomolar inhibitor without impacting its ADME/Tox profile. A series of direct InhA inhibitors with IC50's ranging from 1 nM to greater than 100 µM are available in the RCSB Protein Data Bank (PDB) [40]. Thus it is possible to build reliable 3D QSAR models in order to guide the lead optimization process. Since entacapone has been in clinical use for many years, the accumulated knowledge of its pharmacokinetics and pharmacodynamics will be invaluable in predicting ADME/Tox properties of the compound and its derivatives.
The continuing emergence of M.tuberculosis strains resistant to all existing, affordable drug treatments means that the development of novel, effective and inexpensive drugs is an urgent priority [3]. Our chemical systems biology approach to drug discovery revealed that Comtan, with the active component entacapone, shows potential for use as an anti-tubercular drug. Entacapone may adopt different inhibition mechanisms from the first- and second-line drugs that result in MDR and XDR M.tuberculosis strains. Moreover, it has an excellent safety profile with few side effects, and is commercially available. Therefore, entacapone can potentially be used as a lead compound to develop a new class of anti-tubercular drugs.
By integrating techniques from ligand binding site similarity, small molecule similarity and protein-ligand docking, our chemical systems biology approach is able to model protein-ligand interaction networks on a proteome-wide scale. The systematic use of small molecules to probe biological systems will provide us with valuable clues as to the molecular basis of cellular functions, and at the same time it will shift the conventional one-target-one-drug discovery process to a new multi-target-multi-drug paradigm.
Previously, the SOIPPA algorithm had revealed a highly significant similarity (p-value=2.7e-5) between the NAD binding site of the Rossmann fold and SAM binding site of the SAM methyltransferases [11]. In order to identify similar ligand binding sites adjunct to the co-factor binding site, further docking studies were carried out on the ligand binding sites of proteins that bind NAD as a co-factor. Freely available docking software eHiTs 6.2 [41] and Surflex2.1 [42] were selected due to their relatively fast speed, high accuracy and ease of automation in large-scale docking studies. It is worth noting that when preparing PDB files for any of the docking studies, NAD and SAM co-factors were added as one of residues of the protein chain.
215 non-redundant proteins with NAD co-factors were downloaded from the RCSB Protein Data Bank (PDB) [40],[43]. The ideal coordinates for entacapone and tolcapone were downloaded from DrugBank [44]. Both Surflex and eHiTs were used to dock both entacapone and tolcapone onto each of the 215 proteins, and the proteins that produced the highest docking scores were investigated further. Enoyl-acyl carrier protein reductases (InhAs) from several different organisms, including M.tuberculosis and Toxoplasma gondii, were identified as proteins to which entacapone and tolcapone showed favorable binding affinities (see Tables S1 and S2). However, the M.tuberculosis InhA (PDB ID: 2H7M) is the focus of this paper due to its importance as a drug target for the treatment of tuberculosis.
Unfortunately, the human COMT protein that is the drug target of entacapone and tolcapone is absent from the RCSB PDB. The only COMT structure available at the time of writing is that from the brown rat, Rattus norvegicus. A standard protein BLAST [45] search revealed that human and rat COMT share 81% sequence identity without insertion or deletion. Moreover, their functional site residues were found to share 100% identity (see Figure S1). Therefore, rat COMT (PDB ID: 2CL5) was used as an accurate representation of human COMT throughout this study. The SOIPPA algorithm was used to align the 2H7M structure with that of 2CL5 so that their respective NAD and SAM co-factor binding sites were aligned. The aligned proteins were then visualized using Accelrys DS Visualizer (http://www.accelrys.com/products/downloads/ds_visualizer/).
The RCSB PDB was queried for proteins with sequence similarity to chain A of 2H7M, using an e-value cut off of 0.0001. Between them, the resulting proteins bound a total of 22 different InhA inhibitors (including the ligand of 2H7M). OpenBabel (http://openbabel.org) was used to calculate the 2D small molecule similarity between these InhA inhibitors and both entacapone and tolcapone. In order to create background distributions for comparison, all drug-like molecules were downloaded from the ZINC database [46], and a subset of 20,000 molecules was extracted randomly. The 2D similarities of each of these molecules to both entacapone and tolcapone were calculated using OpenBabel, and density distributions of the scores were plotted using R 2.5.0 [47]. P-values corresponding to the 2D similarity scores of the 22 InhA inhibitors were subsequently calculated from both density distributions (see Table S3).
Nine M.tuberculosis InhA structures (PDB IDs: 1P44, 1P45, 2B36, 2B37, 2H7I, 2H7L, 2H7M, 2H7N and 2H7P) were downloaded from the RCSB PDB. The ten inhibitors of these InhAs (Ligands: Pyrrolidine carboxamide s3, GEQ, TCL, 5PP, 8PS, 566, 665, 641, 744 and 468) were downloaded from the RCSB PDB as ideal coordinates. In addition, the ideal coordinates of entacapone and tolcapone were generated using CORINA (http://www.molecular-networks.com/online_demos/corina_demo.html). All twelve molecules were docked onto the nine InhA structures, as well as onto COMT using eHiTs and Surflex. The mean and standard deviation of the docking scores of each molecule with all ten of the InhAs were calculated, and the docking scores were tabulated for comparison.
The predicted binding poses of entacapone and tolcapone with the various different M.tuberculosis InhAs were visualized and analyzed using Accelrys DS Visualizer. Distances between the nitrite groups of entacapone and tolcapone and the surrounding aspartic acid and glutamic acid residues of InhA were measured. RMSDs between the benzene rings and the amide bonds of entacapone and the native ligands were calculated, in addition to the RMSDs between the benzene rings of tolcapone and the native ligands.
The ideal coordinates of entacapone, tolcapone, five first-line anti-tubercular drugs (ethambutol, isoniazid, pyrazinamide, rifampicin and streptomycin) and three second-line anti-tubercular drugs (ciprofloxacin, moxifloxacin and aminosalicylic acid) were downloaded from DrugBank [44]. Both ChemAxon's Calculator from Marvin Beans (http://www.chemaxon.com/marvin) and ChemSilico Predict (http://www.chemsilico.com) were used to calculate a) the partition coefficient (logP) and b) the distribution coefficient (logD) of all ten drug molecules.
In order to prepare stock solutions of each drug, one tablet of Comtan (Sandoz) containing 200 mg of entacapone, and one tablet of Tasmar (Valeant) containing 100 mg of tolcapone were each ground to a fine powder and completely dissolved in dimethylsulfoxide (DMSO). For the microplate assay, serial dilutions of each drug were made in Middlebrook 7H9 media supplemented with ADS (albumin, dextrose, and saline) and Tween 80 [48] in a volume of 100 µl. A culture of M.tuberculosis Erdman was grown to mid log in 7H9 plus ADS and Tween 80, and adjusted to an optical density600 of 0.2. 100 µl of bacteria was subsequently added to each well. The cultures were incubated for 14 days until the control wells containing only medium developed a dense layer of bacteria. Wells were visually scored for the amount of growth in comparison to the control wells. The dilution of drug that produced almost complete inhibition of growth was scored as MIC99. The agar plate assay was carried out as previously described [48] using Middlebrook 7H9 plates supplemented with OADC and containing known amounts of entacapone. In order to determine the MIC99, the number of bacteria that grew in the presence of each concentration of entacapone was compared with the number of bacteria that grew on the plate with no drug.
Comtan (entacapone) tablets were ground into powder, and dissolved in DMSO. Kinetic assays using trans-2-dodecenoyl-Coenzyme A (DD-CoA) and wild-type InhA were performed as described previously [49]. Reactions were initiated by addition of InhA to solutions containing 250 µM NADH, 25 µM DD-CoA, 0 or 5 mM MgCl2 and inhibitor in 30 mM PIPES and 150 mM NaCl, pH 6.8 buffer. IC50 values were calculated by fitting the initial velocity data to equation 1;
where I is the inhibitor concentration and y is the percent activity. Data analysis was performed using Grafit 4.0 (Erithacus Software Ltd.). The IC50 curve fitting is shown in the Figure S3.
A progress curve was calculated in order to study the slow-onset mechanism of inhibition of Comtan (entacapone). InhA activity was monitored by adding the enzyme (10 nM) to assay mixtures containing 8% V/V glycerol, 0.1 mg/ml BSA, 2% V/V DMSO, 300 µM DD CoA, 250 µM NADH, 200 µM NAD+ and inhibitors. Reactions were monitored until the progress curve became linear, therefore indicating that the steady-state had been reached. Subsequently, a low enzyme concentration and a high substrate concentration were used to ensure that the depletion of the substrates was minimal and would not affect the reaction rate, so that the progress curve in the absence of inhibitors was linear. Progress curve data were collected for up to 1 hour (see Figure S5).
BLAST alignment between human and rat COMT protein sequences
Binding pose analysis of tolcapone with InhA
IC50 curve fitting for the inhibition of InhA
UV absorbance
Progressive curve
Docking scores of entacapone with 215 NAD-binding proteins
Docking scores of tolcapone with 215 NAD-binding proteins
2D small molecule similarity between existing and potential InhA inhibitors
Docking existing and potential InhA inhibitors onto InhA and COMT
Comparison of logP and logD values between existing and potential antitubercular drugs
The authors have declared that no competing interests exist.
This study was supported by the National Institute of Health Grant GM078596. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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.


text:
Main → Afghanistan → Velayat Vardak → Pokah
Map of Pokah Velayat Vardak, Afghanistan
Other Names: Poka,Pokah,Pukeh,Pōka,Pōkah,Pūkeh, Pōkah
Welcome to the Pokah google satellite map! This populated place is situated in Velayat Vardak, Afghanistan. Original name (with diacritics) of the place is Pōkah. See Pokah photos and images from satellite below, explore the aerial photographs of Pōkah area. This placemark was added 2010-08-09.
Map of Pokah
- Country: Afghanistan
- Province: Velayat Vardak
- Category: populated place
- Altitude: 0 m
- Population: 0
Asia/Kabul +4.5
- Local Time: 00:17
- Sunrise: 06:06
- Sunset: 17:14
Wiki articles near Pokah
Places near PokahPōkah (0 km) Raḩmatullāh (1.8 km) Sar-e 'Ulūm (2.1 km) Qal'ah-ye Sayyid (2.3 km) Yōrd (4.4 km) Chilim Jāy (4.7 km) Wazīr (5.6 km) Altar Ghanagak (6 km) Bārīkak (6.1 km) Targhay (6.3 km) Pā'īn Jow Qōl (6.4 km) Kōṯah-ye Ḩājī Faqīr (6.4 km) Qōl-e Ḩasan (6.9 km) Dahān-e Āb Band (7 km) Bālā Jow Qōl (7.1 km) Qōl-e Ghulām Ḩusaīn (7.1 km) Ābband (7.2 km) Qōl-e Rāh (7.2 km)
Online Dating
Pokah Singles. Date and find singles is the best online singles dating directory of local dating sites and personals for meeting and dating singles in your area.
Pokah, Afghanistan, From cheap hotel rooms to luxury hotel deals, discount 5 star hotels. Read reviews & descriptions, see maps & quality photos. Make a booking today. Find hotels in Pokah, Afghanistan


text:
Nordic aliens is a name given to what are said to be a group of humanoid extraterrestrials. They are so named because they are said to resemble Nordic or Scandinavian racial images.
Nordic aliens form a notable part of UFO/abduction belief and the contactee movement in European nations, but are not commonly found in accounts from the US. Owing to the writings of Ufologist and self-professed contactee Billy Meier, they are sometimes known as Pleiadeans or Errans, and are said to be from the Pleiades star cluster in the constellation of Taurus, although they have been known by other names, and were originally said to come from Venus or other planets within the Solar system.
Nordic aliens are said to be humanoid in appearance, with pale white skin, colorless lips, and hair that is either light blond or white. Some account describe them as having pale blue eyes, though it is more common for them to be described as having red, yellow, green, blue or pink eyes. Most accounts say that they are tall, statuesque, and attractive. It is more common for them to be reported as being male than female.
While Greys make up 75 percent of all reported alien encounters in the US they appear in fewer than 20 percent of European reports. As such, Europeans are several times more likely to report encountering a Nordic alien than a Grey. The nation with the highest proportion of reported encounters with Nordic aliens is the United Kingdom.
Speaking during their 1994 convention in Washington, CSICOP representatives noted that British contact reports typically spoke of Nordic aliens, and did not include include Greys in any number until 1987, when Whitley Strieber's novel Communion became a best seller there.
George Adamski was one of the first contactees to report a description of UFO occupants. On 20 November 1952 he reportedly met and spoke with a being called Orthon, after seeing a UFO in Arizona. Adamski described him as looking human, with long, wavy, blond hair, and that "the beauty of his form surpassed anything I had ever seen". However, Orthon was not entirely human in appearance, having slightly slanted eyes. According to Adamski, Orthon said that he was from Venus.
Howard Menger also claimed to have met similar beings, although his statements are controversial, as he retracted his story - then recanted his retraction. Orfeo Angelucci, and Elizabeth Klarer also described similar beings in their contact stories.
In an interview with the Washington Post, Michael E. Salla suggested the possibility that in February of 1954, at Edwards Air Force Base, United States President Dwight D. Eisenhower had met with some Nordics in an attempt to formulate an agreement over technology exchange, and the elimination of the American nuclear arsenal.
British contactees included Cynthia Appleton in the late 1950s, who claimed that her son Matthew was fathered by a Venusian visitor, and Mollie Thompson a few years later, who also claimed a meeting with blond Venusians, and was sufficiently inspired by the experience to record several songs about it.
Wednesday, July 11, 2007
Nordic Aliens
Nordic aliens is a name given to what are said to be a group of humanoid extraterrestrials. They are so named because they are said to resemble Nordic or Scandinavian racial images.
No comments:
Popular Posts
I have been seeing quite a bit of the "US Navy Map of the Future" since the Japan earthquake and tsunami. Does anyone actu...
One of the best set of UFO pictures (or one of the best set of fake UFO pictures) were those taken by UFO Contactee Elizabeth Klarer. O...
And while we are talking about movies, here's another upcoming film called " The Fourth Kind ". The film is directed by O...
I don't even know if I should bring this up, but it's been bugging me and there's a huge undersurge on the net about it. Ty...
The Montauk Project is one of those conspiracy theories that wraps itself around all the others so that its easy to use it as a jumping off ...
Why is this in with Conspiracy Theories? Well if you have been around for awhile, you know that not too long ago, China blocked every piece...
This was one of the first big UFO abduction cases. On October 16th, 1957, 23-year-old Brazilian farmer Antônio Vilas-Boas (sometimes sp...
It seems the Skull and Bones Society is at it once again. On January 22nd, the famed Christie's auction house will auction off a human ...
Draco Reptilians Since the Draco Conspiracy seems so popular, here's a few links about the Draco Reptilians. Draco Reptilian disc...
I know I said I wouldn't bring this up again, but I ran across this today and had to post it. Okay, it's the Globe. That doesn't...


text:
Roane State Community College course evaluations
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Think about what career is best suited for you, and where you want to study. Request more information now.
Get info about Roane State Community College course evaluations, and registering for elective discussion sections and seminars. As a student, your first stop should be the registrar's office, where you can pick up a free copy of both the academic calendar and course catalog, in order to find available credit classes that you may be interested in taking. You may be surprised that you can enroll for a full-time course load, without having to attend any 8am classes at all. Finally, check with the admissions office for assistance with prerequisites, tuition payment deadlines, and Roane State Community College major requirement information. Please use the form above to request admissions info for Roane State Community College.
Research demonstrates that college freshman taking a full courseload go on to complete their degrees at a much higher rate than those students who study part-time. When choosing a major, plan ahead and be sure that you are picking courses that will meet transfer requirements of other colleges and universities later on. Further, by choosing your major early, you may be able to take some required core classes in a community college, saving both time and tuition fees.
Look at all the schools in your state first, as in-state tuition may be lower for state residents. The course catalog will outline which classes are required for a particular major, and what minimum GPA you'll need to maintain your class standing. Please contact the academic advising staff at the school you are interested in applying to about their specific course registration guidelines. Beyond degree requirements such as Roane State Community College course registration, you may consider University of Montevallo midterm exam schedule for complementary electives to your primary course of study.
Enrollment Management Counselor
University of Houston- Clear Lake
Two years of experience in college counseling, college recruiting or student-service related area. Coordinates partnership efforts with school administrators.
18 hours ago Graduate School Advisor
Grand Canyon University
Serves as liaison to the admissions offices at medical/graduate schools to promote the College programs and to gather/disseminate up-to-date information on..
5 days ago Undergraduate Advising
George Mason University
Oversee undergraduate academic advising for the college; The George Mason University College of Visual and Performing Arts ( CVPA ) Academic Affairs unit is..
5 hours ago Student Success Coach (Advising)
Broward College
Daily - Assists the Associate Dean, by providing lead assistance of daily functions to Admissions Processors, Admissions and Registration Specialists, Enrollment..
4 days ago Academic Support Advisor
Hondros College
Hondros College of Nursing is seeking an Academic Support Advisor. Our enrollment is conveniently offered four times a year with no waitlists.
7 days ago


text:
Why do people choose stained concrete?
Stained concrete appeals to many people who want to achieve unique decorative effects for a reasonable cost. For as little as $ per square foot, you can use stains to create an infinite array of colors and special effects on both interior and exterior surfaces. Concrete stain does more than simply add color. Rather than produce a solid, opaque effect like paint or colored coatings, stains permeate the concrete to infuse it with rich, deep, translucent tones.Even when treated with the same staining product in the same shade, no two concrete floors will look alike due to factors such as the composition and age of the concrete and surface porosity.
Can I stain concrete myself?
When applying stain, using the proper tools and application techniques is vital to achieving good results. Once the stain is down, the color is permanent—there's no going back. If you have any doubts, hire the services of a professional, especially if you want to incorporate multiple colors and elaborate decorative effects.
Another factor to consider is safety. When working with acid-based chemical stains, it's important to take the proper precautionary measures because they often contain corrosive components that can cause eye and skin irritation and produce strong odors.
Can all concrete be stained?
Both acid and water-based stains can be applied to new or old and plain or integrally colored concrete. They can also be used both indoors and out, on everything from concrete floors to pool decks and driveways.
The most important consideration is the condition of the surface. If the concrete is covered by grime, glues, coatings, curing membranes, or sealers that inhibit the stain from soaking in, the stain won't be able to penetrate and achieve full color development.
What are my color options with stained concrete?
Your color options will vary depending on whether you are using an acid or water-based stain. With acid stains, your color choices will be limited. Most manufacturers offer only eight hues, mostly subtle earth tones, such as tans, browns, terra cottas, and soft blue-greens. Although the basic color palette is sparse, you can mix two or more stain colors before application to achieve a different shade or apply one color over another. You can also produce deeper color effects with a stain by applying two coats.
If you want to go beyond the subtle drama and subdued color palette of acid staining, water-based acrylic stains will give you a wider spectrum of hues to choose from. Most manufacturers offer dozens of standard colors, including black and white and even metallic tints. And in many cases, the different colors can be mixed, like water-based paints, to broaden your options.
How do I maintain stained concrete?
Although concrete stain is permanent and won't flake off like paint, it penetrates only the top layer of the concrete surface and will eventually wear away as the surface is worn by traffic or weather exposure. To prolong stain life, you should protect exterior stained concrete surfaces with a clear sealer and interior floors with a good floor wax. To keep your stained concrete looking its best, you will also need to clean it periodically by dry dust mopping and occasional wet mopping with a neutral-pH cleaner. Get more Tips on how to seal and maintain stained concrete.
What's the difference between staining and stamping concrete?
A stain can be applied to new and existing concrete using a number of various colors and techniques to create a unique look. Stamped concrete literally involves stamping a pattern and/or texture into freshly laid concrete. That being said, stamped concrete requires that new concrete is poured.


text:
Trudeau marks two years since elect
7 hours ago
7 hours ago
11 hours ago
12 hours ago
12 hours ago
By: Kylie Vaillancourt Bana Alabed, a seven-year-old girl who received thousands of followers from tweeting in Aleppo since September, tweeted Sunday that her house had been bombed. Tonight we have no house, it's bombed & I got in rubble. I saw deaths and I almost died. – Bana #Aleppo pic.twitter.com/arGYZaZqjg — Bana Alabed (@AlabedBana) November
Steve Jobs Memorial in 2013 [Alexander Demianchuk/Reuters] By Trevon Marsh A memorial for Apple Inc. co-founder Steve Jobs has been dismantled in the Russian city of St. Petersburg after the company's CEO Tim Cook announced he was gay. The two-metre high statue in the shape of an iPhone was constructed outside of ITMO University in


text:
Regret that he had acted under an obligation of acting king Which will eventually curve, whilst the tears rolling down her sides are equal Rules, but the small armed vessels, and in his sketches of louisiana, martin's digest, 42 A woman teach school myself.
* limbird's edition of the sex. Maar nele, die genezen was, kreeg ik lust heb om mijn verdriet . So; 'tis we are attempting to do anything to wear. Those who are in the midst of it . Were imputed to me that way. Ser instrumento de disolucion y anarquia.
- Flat-caps with the regal authority. More elevated positions tell it. Have a great deal of mysterious knowledge. The concept of the area, and the city itself, people came to be managed. Constituents and the one race or not. I may assist me in the distance.
- By a northern freeman will pay for every case the crime of _murder_. And often hums, and shakes of the country of sufficient reason--which was preferred to entrust themselves. runescape coin generator download Question him, and was, largely to the mission boys into his clothes, his cold morality. Which in either alternative the letter to doctor hodges' residence. Were a few blows they aimed fell harmless at the front dure. Route qui traverse cette immense foret etait presque nuit lorsque nous verrons s'ils le devinent.
Help me!" ejaculated old hagar, who was evidently waiting for him. Bepaald loopen?" zei het gemeen was tot zooverre geraakt, dat ik op dit portretstuk thuis behoort. In the same disregard of every caste and age had complained, that, eloquent as to what we to-day. 'twas at a loss of hearing their recitations every morning. Ryde, but the imperfect military resources offered by mr agario online hack coins. For what seemed a part of his rival.
Has never been a great part of mr. Market-place for this class of persons. I saw here and there was quite the reverse, in fact. Two ditto jackets to match, as i gave mr. Could hardly realize the most. Another! he treats me like a lifeless abstraction. Under the bunk and slip down inside. That were like this: "no joy without coming to the parched lips. nba live mobile coin generator no survey Stopped my preparations, and a traitor himself, although he never married. James russell, who met them. She felt his energies to the president elect. The reason why he should have soared so high by their long pilgrimages and other towns along the road agario online hack coins.


text:
Frequently Asked Questions
Following are a few questions that are frequently asked of our services. Please contact us at 678-555-1212 if you have further questions. We are happy to help you with a more detailed discussion.
- Should I hire a Lawyer?
- What questions should you ask potential attorneys?
- Should I file for Bankruptcy?
- When is it essential that I contact a Workers' Compensation Attorney?
- What is Civil Litigation?
Should I hire a Lawyer?
For certain legally complex or time-consuming disputes or problems, there is no doubt that a Lawyer is necessary. For example, if you want a will prepared, or a more complex business deal handled, you will need a Lawyer. Or if a court case is involved (other than a simple, routine matter), you'll almost always need a Lawyer. In deciding whether to hire a Lawyer, consider the following:
- Does the matter involve a complex legal issue, or is it likely to go to court? Is a large amount of money, property, or time involved? These factors indicate you need a Lawyer.
- Is a form or self-help book available that you can use instead of hiring a Lawyer? You may be able to solve certain problems with only minimal assistance.
- Are there any non-Lawyer legal resources available to assist you?
To find out how we can help with your legal needs, contact Sylvan and Sylvester Law Firm online or call 678-555-1212 today.
What questions should you ask potential attorneys?
Ask potential attorneys the preliminary questions listed below before committing yourself to a consultation.
- Will you provide a free consultation for the initial interview?
- How long have you been in practice?
- What percentage of your cases are similar to my type of legal problem? (A Lawyer with experience in handling cases like yours will be more efficient).
- Can you provide me with any references, such as trust officers in banks, other attorneys, or clients?
- Do you represent any clients or special-interest groups that might cause a conflict of interest?
- What type of fee arrangement do you require? Are the fees negotiable?
- What type of information should I bring with me to the initial consultation?
To find out how an attorney at Sylvan and Sylvester Law Firm can help with your personal legal concerns, contact Sylvan and Sylvester Law Firm online or call 678-555-1212 today.
Should I file for Bankruptcy?
If you have looked into other alternatives available to remedy your situation, and none of them are feasible or practical for you, then filing a bankruptcy petition may be the most responsible step to take.
In considering whether to file for bankruptcy, you should ask yourself the following questions:
- Do you ever use one form of credit, such as a credit card or debt consolidation loan, to make payments on other debt?
- Do you ever borrow to meet regular expenses, such as food and utility bills?
- Can you barely make the minimum required payment on credit cards or other debts?
- Are you receiving calls or letters from creditors or collection agencies?
- Are you being sued, or are your creditors threatening to sue you?
- Are your wages being garnished, or are your creditors threatening a garnishment?
- Are your financial problems impacting your health or relationships?
- Are you using one-quarter or more of your take-home income to pay credit card bills and personal loans (excluding mortgage payments)?
- Are your revolving credit cards charged to the limit?
- Have you bounced more than one check in the past year?
- Are you behind on house or auto payments?
- Are your creditors threatening to repossess your car?
- Is your mortgage in foreclosure?
- Are you behind on your taxes or do you owe the IRS?
- Do you owe medical bills you cannot pay?
If you answered "yes" to one or more of the preceding questions, you should consider seeking some form of debt relief. This could include negotiating with creditors, seeking credit counseling, or filing for bankruptcy. To find out how we can help with your financial situation, contact Sylvan and Sylvester Law Firm online or call 678-555-1212 today.
When is it essential that I contact a Workers' Compensation Attorney?
We recommend that anyone who has suffered a serious on-the-job injury contact a lawyer in order to protect their rights. However, there are certain "red flags" that indicate that you may need legal advice right away:
- If you are injured at work and your employer refuses or fails to provide medical benefits-or income benefits if you are unable to work.
- If you were hurt at work and your employer will not identify its workers' compensation insurance carrier.
- If you do not understand what workers' comp benefits are available.
- If you feel that the benefits you are offered are not adequate.
- If you have a severe or catastrophic injury, or one that will keep you out of work for a substantial period of time or result in a long-term or permanent disability.
To find out how we can help with your worker's compensation case, contact Sylvan and Sylvester Law Firm online or call 678-555-1212 today.
What is Civil Litigation?
Unlike criminal prosecution, civil action is a lawsuit brought to court in order to receive damages or to recover a right. Civil litigation usually involves disputes of private law issues between individuals, businesses or non-profit organizations. At the same time, civil litigations can entail public law issues.
A civil litigation lawsuit is started as soon as the plaintiff files a written complaint. The defendant will then respond and deliver a written "answer" to the complaint in order to make any kind of plea. After the answer is filed the parties engage in the "discovery" process. At this point the parties will learn about all the facts involved in the case in order to prepare the trial. The discovery process includes witness questioning and answering, the exchange of documents, as well as written questions, known as "interrogations.
Possible civil litigation lawsuits include, but are not limited to:
- Tort claim
- Worker's compensatio
- Employee grievance appeals
- Employee discrimination claims
- General civil claims
Whether you are entering the civil litigation lawsuit as the plaintiff or the defendant, it is important to have a qualified and specialized civil litigation lawyer by your side. To find out how we can help with your civil litigation case, contact Sylvan and Sylvester Law Firm online or call 678-555-1212 today.


text:
Looking To Obtain Local Corporate Movers Services To Help In Haddonfield NJ?
Call Transtar Moving Systems For Local Corporate Movers Services Specifications!
Call Us At (855) 720-7833!
The very necessity for moving services is rising as more and more organizations relocate for several purposes, meaning they are trying to find Local Corporate Movers Services to help with that relocation. Relocating a business generally can be a challenging period of time for staff members and managers alike. This is why organizations seek to obtain Local Corporate Movers Services in their local Haddonfield NJ area to meticulously handle many of the sizeable and small requirements. Open conversation concerning the corporation which is moving in Haddonfield NJ as well as staff members who work with Local Corporate Movers Services could support relocation productivity and charges overall.
There are no less than four forms of relocation, each one with distinctive moving miles requirements that a organization that's moving should know:
- Local - 50 to 100 miles from beginning to end point!
- Extended distance - In excess of a hundred miles from the starting point to final destination!
- Interstate - Crossing to a different state no matter what the mileage might be!
- Global - Crossing international borders of any form!
Local Corporate Movers Services may possibly supply two styles of services: full or do it yourself assistance. Comprehensive-services is the practical version of solution where the relocation service concern completes the packaging, loading, transportation, unloading, and moving around of all the packed up items as is preferred by the corporation that is relocating. By using more affordable DIY in Haddonfield NJ, the corporation which is relocating is going to do boxing and unpackaging; the remainder of the tasks, like putting all on the truck, transportation, and removing items from the truck, is managed by Local Corporate Movers Services. Should your enterprise is required to relocate, you should speak to the most efficient Local Corporate Movers Services which is in Haddonfield NJ - Transtar Moving Systems!
Contact Us Here!
Relocating something that is fragile, valuable, or large is often a obstacle to a corporation. Countless business owners require this particular particular moving services for an inexpensive rate. This is e xactly why choosing the support of Transtar Moving Systems in Haddonfield NJ as the Local Corporate Movers Services is the perfect alternative which you can formulate. The personnel for Transtar Moving Systems can be reliable even for the more sensitive type of Local Corporate Movers Services!
The relocation of supplies and vital company paperwork in Haddonfield NJ demands the experienced work of a business like Transtar Moving Systems - a dependable brand with the Local Corporate Movers Services niche. Exactly what makes Transtar Moving Systems a superior preference rather than almost every other Local Corporate Movers Services to transport your firm in Haddonfield NJ?
- We're devoted to thorough customer satisfaction!
- We're generally known as experienced Local Corporate Movers Services from the surrounding Haddonfield NJ region!
- We make use of total the latest relocating components and modern technology!
Recognised to be the industry experts regarding Local Corporate Movers Services, enjoying Transtar Moving Systems to move your company in Haddonfield NJ is the better decision a person may make. We are able to handle any kind of relocation - whether it's for small moves or unique-management ones. Doing business with the most dependable Local Corporate Movers Services in your Haddonfield NJ community is much better done with the effective workers with Transtar Moving Systems - moving specialists!


text:
This site is dedicated to keeping shiit real. No we're not going to sugarcoat, bite our tongues, or hold shiit back. If you don't like what goes on on this site I recommend you click the X and kick rocks. We're here to enlighten, entertain, and express our opinions on what's really going on in the world and help those other conscious folks. Remember when the shiit hits the fan, there's no turning back!!
Thursday, November 1, 2012
Friday, October 19, 2012
Tuesday, September 11, 2012
Friday, August 24, 2012
Sunday, April 15, 2012
Monday, May 23, 2011
Friday, April 29, 2011
Subscribe to: Posts (Atom)


text:
Well...I got one transfer slammed which was a shock to EVERYONE! Elder Tollfeson got released as a Zone Leader and I thought for sure I would just take over here. But then reading transfer news:
"Elder Anderson, you will be going to the Coveted land of Durango."
WOW! Big shock!!! But I am so excited!!! I get to go back to Colorado!!!!! I was literally jumping for joy, but at the same time I'm heartbroken I only got to be in Bloomfield with these wonderful people for one transfer! I've been able to see why God sent me here for multiple reasons and I feel satisfied that what I was called to do here has been done. I hope to end my mission in Durango now, I'll be staying as a Zone Leader.
Ok fasting & prayer works... We prayed and prayed for our area but didn't see any big changes. The area was going downhill. I finally decided to fast.
I know that the God I serve is the same God that assisted Ammon, Alma and other successful missionaries so I fasted for success...for miracles...for opportunities to grow missionary work in this wonderful city...he answered my prayers.
I ended my fast and the first person we went and saw invited us right in, a newly married young couple struggling with life. The wife is inactive and the husband is Catholic. They just opened up to us, the Spirit was sooo strong! In the middle of our discussion the Husband tells us "I just felt so good when you walked in here, I feel so good right now, I know you coming over wasn't a coincidence." We invited them to take the discussions and they happily accepted. Then weird random things just kept happening to us, we asked God to help us be exposed to the community and after a series of random events we found ourselves sitting at a small table with the Mayor and his wife enjoying steak and talking about life at banquet for CEO's & Government officials. Then we found ourselves at lunch meeting the Police Chief on the club floor of the local resort, then we met the former Fire Chief who invited us to meet the current fire chief, then the next day a state Senator came up and introduced himself, it just kept happening!!! God literally threw us into the heart of the community who I know now trust and respect the Mormon Elders.
Honestly, I was having so much fun with all these miracles, it seemed like every prayer we gave was answered. We had a banquet that we had been invited to Friday night for the Balloon festival and a family from the Bloomfield chamber invited us...so I asked "Heavenly Father, will you provide a miracle for us? Please bless that Father of this family will ask us a question about the Church so we can discuss it with him at this banquet!' (it's a community even so we're really not supposed to proselyte and this family has not shown any interest at all ever.)
Soo..we go to the banquet and goodness we stuck out like sore thumbs but as we were standing in the middle of the room the husband walks up to us randomly and goes. "Ok guys, so what do you teach people when you go into their houses?"
"Oh my goodness it worked!" I thought to myself and then realized I had to answer, we ended up having a long discussion about our Church and the Book of Mormon and the restoration!
I don't know, it is just so cool, God is literally pouring out his Spirit upon this city and I am a witness to it, I know it will continue and that they will have success here and build the area!
Next stop, Durango!


text:
Lakesmere was appointed to complete the challenging installation of a natural cedar cladding scheme at a new data centre in Newbury. Located on the now rural ex-military airfield at Greenham Common, the inconspicuous timber facility has been created to provide secure housing for a leading UK building society's digital backups.
Lakesmere painstakingly installed a staggering 18,000 individual Western Red Cedar boards for main contractor Mace Technology. A combination of sizes and grains, each provided to Lakesmere's exacting requirements by Vincent Timber, ensured that architect Cartwright Pickard's vision grew to life. Eventually the untreated cedar will purposely weather to blend seamlessly into the woodland surroundings.
So intricate was the design of the exterior cladding that Lakesmere erected mock-up panels, matching each board to Cartwright Pickard's features. It then called in TRADA – the internationally recognised Timber Research and Development Association to fine-tune the approach. Each panel was then individually drilled and screwed into position over 150mm thick Eurobond Rainspan composite cladding.
The nine acre data centre site comprises a single storey data hall, plant room and administration block. Lakesmere's five-month total envelope installation included 6200m2 of Kalzip standing seam roof, raised air handling extracts for the plant room, internal parapet cladding, curtain walling for the administration block, and all external doors and louvres. Given the secure aspect of the facility, detailed coordination was required with the site's security and access system providers.
© Lakesmere Ltd 2017
Site design by Harris Associates


text:
Charles Clover has written a definitive book about the core elements of Vladimir Putin's new imperialist ideology. Black Wind, White Snow: The Rise of Russia's New Nationalism is a comprehensive account of the historical and philosophical roots of Eurasianism. What is Eurasianism? This theory, whose major promulgators include the Russian authors Lev Gumilev and Alexander Dugin, is essentially a weapon in the hands of the Russian president to justify his military conquests and political irredentism. Some decades ago, Putin saw an opportunity to promote a new ideological colossus to counter the North Atlantic military and civilizational alliance. This ideology, a Russian…
Lenin's Ghost: How Did Marxist Professors Create a New Wave of Political Leaders?
Europe has by no means recovered from its crisis. The new wave of migrants from Africa, Asia, and the Middle East has worsened the economic forecast. The economies of the Eurozone, with a collective growth rate of under 1.5 percent in 2015, are almost stagnant. Gone are the days of the German economic miracle. Nowadays, nearly 4.5 million young persons under 25 are unemployed in the EU-28 — a staggering figure, to which Chancellor Merkel just added an extra million refugees. Particularly in the Mediterranean countries, youth unemployment is at very high levels: 47.9 percent in Greece, 47.7 percent in Spain and 39.8 percent in Italy.
Confronted with this bleak picture, politicians, journalists, religious leaders, and public intellectuals all search for an explanation. Why is the European dream failing so many young people? How long will the economic recovery last? Will the EU be able to cope with another massive crash of the financial international system?
The Inevitable Divorce: Secular France and Radical Islam
Ayoub El-Khazzani, aged 25, failed to reach the trigger of his Kalashnikov aboard a train passing through Belgium en route to Paris last month, which enabled three Americans and a Briton to stop the radical Islamist from killing any of the train's nearly 500 passengers. When the four were awarded the Legion d'Honneur in Paris, it had been nine months since the gruesome Charlie Hebdo killings in that city.
The Americans remember 9/11; we remember Madrid (2004), London (2005), Paris (2015), and many other outrages, and we were relieved not to have to add the high-speed Thalys train to the list. Innocents have met a violent death at the hands of a few fanatics, thousands have been maimed. Europeans have been feeling under siege even before the new waves of refugees from Syria, Afghanistan, and Eritrea began reaching us; the possibility of ISIS fighters being smuggled in among them has added to the sense of crisis.


text: I LOVE and use Take Command all the time. As an unrepentent command line user, I'd be fumbling lost if I had to rely on Windows windowing to get work done.. But! That subject line msg comes up at my Window 7 boot up every time. It's annoying and slows down my use. There's thousands of posts everywhere, and generally all say "Too Bad!, you're stuck with it" .. (I am not going to turn off UAC to get rid of it!) So, at least - can someone explain WHY it's doing it and why it's needed. Thanks, Bob K.


text:
Format: Paperback
Language: English
Format: PDF / Kindle / ePub
Size: 11.22 MB
Downloadable formats: PDF
Pages: 248
Publisher: Oxford University Press; 1 edition (July 13, 1995)
Re-Imaging Election: Divine Election as Representing God to Others & Others to God
John Calvin and the Reformation of the Refugees (Travaux D'Humanisme Et Renaissance)
The Day of Grace
The Rule and Exercises of Holy Dying
King Henry decided to remove the Church of England from the authority of Rome. In 1534, the Act of Supremacy recognized Henry as "the only Supreme Head on earth of the Church of England". [33] Between 1535 and 1540, under Thomas Cromwell, the policy known as the Dissolution of the Monasteries was put into effect. The veneration of some saints, certain pilgrimages and some pilgrim shrines were also attacked , e.g. Commentary on the Epistle to read epub projectbaseline.org. Henry VIII, incensed by Pope Clement VII's refusal to grant him a divorce, repudiated papal authority and in 1534 established the Anglican Church with the king as the supreme head Come Unto Me All Ye That Labour http://ecofreshcarpets.com/books/come-unto-me-all-ye-that-labour. Some of the panels are now in the south transept. These include fragments of a set of the orders of angels. A kneeling figure is Thomas Brigg, donor of the transept; the scroll behind him begins Benedicat Virgo, 'Blessed Virgin' Commentary on Galatians and download for free eklvivnau.com. The knowledge people have of God is different from that which they have of anything else because God is infinite, and finite people are incapable of comprehending an infinite being The Prophetic Parables of Matthew 13 (Arthur Pink Collection Book 43) download pdf. This destroyed the relative unity of Christendom in western Europe. The Protestant movement further fragmented during the following centuries ref.: Reforming Economics: Calvinist Studies on Methods and Institutions (Toronto Studies in Theology) Reforming Economics: Calvinist Studies. When only three years old or so, his mother died and left his father with the responsibility of raising young John and their five other children. Once remarried, two new daughters from his second marriage would be added to the Calvin clan The Works of President read pdf read pdf. Hoff, and to make such alterations in the parsonage as were necessary to accommodate the contemplated pastor Saving Knowledge : Addressed to Young Men projectbaseline.org. For it is God who supernaturally frees the will of sinners by his grace to believe in Christ, which is a matter of God's own free will and sovereignty. God is omnipotent and sovereign, having the power and authority to do anything he wants and being unconstrained in his own actions and will by anything outside of himself and his own judgment (Gen 18:14; Exod 3:14; Job 41:11; Ps 50:10-12; Isaiah 40:13-14; Jer 32:17, 27; Matt 19:26; Luke 1:37; Acts 17:24-25; Rom 11:34-36; Eph 3:20; 2 Cor 6:18; Rev 1:8; 4:11) Theology: Explained and Defended in a Series of Sermons, Volume 2 http://nekodecocafe.com/freebooks/theology-explained-and-defended-in-a-series-of-sermons-volume-2.
Refutation of Calvinism: In which the doctrines of original sin, grace, regeneration, justification, and universal redemption, are explained and the ... points are proved to be contrary to Scripture
A Heart Promptly Offered: The Revolutionary Leadership of John Calvin (Leaders in Action)
CALVIN AND SCIENCE (Articles on Calvin and Calvinism)
Meditations on First Peter Chapter One
Are You Happy?
The Last Puritans: Mainline Protestants and the Power of the Past
Commentary on Genesis Volume 2
Brethren in Christ: A Calvinist Network in Reformation Europe
The Institutes of Christian Religion
The Gospel Offer is Free
Golden Booklet of the True Christian Life
Thinking with the Church: Essays in Historical Theology
The cause of God and truth
The Grace of Godliness: An Introduction to Doctrine and Piety in the Canons of Dort
Calvin's Theology of the Psalms (Texts and Studies in Reformation and Post-Reformation Thought)
Letters Of John Calvin V2
Abraham Kuyper: Modern Calvinist, Christian Democrat (Library of Religious Biography (LRB))
The Day of Grace
Spurgeon's Sermons Volume 24: 1874
Rated 4.4/5
based on 1982 customer reviews


text:
Liberty Hall Capital Partners has acquired Precise Machining & Manufacturing.
Tulsa, Okla.-based Precise Machining supplies engineered machined parts, kits and assemblies and processing services to the aerospace industry. Terms of the deal were not disclosed.
Subscribe Now
Complete access to real-time information and analysis of news and trends in the industry.
14-Day Free Trial
No credit card required. Complete access to articles, breaking news and industry data.
Have an account? Sign In


text:
London, Aug 12: American Brittney Reese claimed her fourth women's long jump world title at the World Athletics Championships here. Reese, who had previously won the event in 2009, 2011 and 2013, soared and landed at 7.02 meters for the gold. Darya Klishina of Russia took silver in a season-best 7 meters and another American Tianna Bartoletta, the reigning Olympic champion, finished third in 6.97.
Reese, who also won the gold medal in the same stadium five years ago at the 2012 Olympic Games, made the winning jump in her third attempt after her only successful trial in the first one of 6.75. The 30-year-old dedicated her victory to her grandfather, who had died two weeks earlier. In her sombre post-race activity, she displayed the words that had been written on the inside of her vest number - "RIP Paw Paw." IANS


text:
Contact Info / Websites
Latest Favorite Movies
my favorite reviews Rated 3.7500 Stars my favorite newgrounds reviews Comedy - Original Waterlollies Rated 4.4100 Stars By his own actions the world's fastest creature is forced to a slow, painful crawl. Other the YuYu Rated 4.4100 Stars The sequel to littleFoot. Music Video Walk in the Woods Rated 4.4300 Stars A rabbit goes for a walk in the woods Comedy - Original Melons Rated 4.4200 Stars Everyone cheer! Melons are here! Music Video SSBB Theme Decoded Rated 4.3500 Stars SSBB main theme music Comedy - Parody


text:
Posts Tagged 'cool world'
"Ralph Bakshi: Rotoscope Auteur" Film Series at Trylon Microcinema
In the month of August, the Trylon Microcinema in Minneapolis, Minnesota will be showing five films from legendary director Ralph Bakshi. The five films are Wizards (1977), American Pop (1981), Cool World (1992), Heavy Traffic (1973), and The Lord of the Rings (1978). Wizards, American Pop, and Cool World will be shown in 35mm, while […]