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Enhancing Transcriptomics-Based Model-Driven Performance via Stoichiometric Gene-to-Reaction Associations: Metabolic Reprogramming in Prostate Cancer
Received Date: Sep 06, 2019 / Accepted Date: Sep 20, 2019 / Published Date: Sep 27, 2019
Genome-scale metabolic models (GSMMs) have been widely used to study the molecular mechanisms underlying a variety of diseases with a strong metabolic component such as diabetes or cancer. GSMMs incorporate logical rules associating genes, proteins, and reactions (GPR rules), enabling the integration of either proteomics or transcriptomics. However, current GPR formulation do not account for the necessary stoichiometry to describe the number of transcript copies that are necessary to generate a catalytically active enzyme, which limits our understanding of how gene expression modulates metabolism. Thus, in this short commentary article, we introduce the stoichimetric-GPR (S-GPR) concept, presented in Marin de Mas I et al. The novel S-GPRs associations were implemented to study the metabolic reprogramming in DU145 prostate cancer cells associated to the chronic exposure to the endocrine disruptor Aldrin. The results showed that S-GPRs outperformed previous approaches by significantly improving the GSMM predictions. Thus, the novel S-GPR concept that we have developed enables a more precise integration of transcriptomics data into GSMM-based methods and can be extended to proteomics data, with an important impact in the environmental and the clinical fields.
Keywords: Metabolism; Proteomic; Transcriptomic; Prostate cancer
Genetic background and environmental factors are some of the main triggers underlying tumor progression and metastasis. This multifactorial disease is one of the first leading cause of death worldwide representing an important economic and social impact on health care systems [1,2].
In this sense, genome-scale metabolic models (GSMM) have been widely used in cancer research to study the aberrant tumoral metabolism [3]. GSMMs gather the current knowledge concerning the metabolic reactions taking place in a cell from a given organism/tissue [4]. This systems biology tool accounts for logical rules describing relationship between the genes encoding the enzymes that catalyze the metabolic reactions, the so-called GPRs, which makes GSMMs an excellent platform to integrate transcriptomic and proteomic data. Briefly, GPRs use logical "or" and "and" operators to represent isoenzymes encoded by different genes or genes encoding sub-units of a complex, respectively. The gene expression is incorporated into the GPRs that can be represented either in absolute or relative values, depending on the approach, the logical "or" is replaced by the "mean" or "max" operators and the logical "and" by the "minimum" operator. Next, by solving the mathematical expressions, the value of the metabolic reactions is calculated. Finally, the reactions values are implemented in the different transcriptomic-based model-driven methods to infer a case-specific metabolic flux profile. Thus, GPRs allow the integration of large omics data-sets generated by different high-throughput platforms which ultimately enhances the predictive capabilities of the GSMMbased methods [5]. In the last decade, a variety of GPR-based algorithms have been developed to integrate both proteomic and transcriptomic data into GSMMs [6]. However, despite the recent advance in the field, current GPR formulation does not consider the number of transcript copies that are required to produce a catalytically active enzyme. In other words, if the classical GPR formulation is applied on a complex with, for instance, three sub-units, one encoded by the gene "a" and two by the gene "b", both genes have the same weight in the calculation of the activity state of the associated metabolic reaction. Thus, classical GPRs assume that the same expression of gene "a" and "b" is needed to produce a catalytically active enzyme, regardless the complex has double sub-units encoded by gene "b" than by gene "a". Thus, this lack of stoichiometry in the GPR formulation limits our understanding on how gene expression modulates metabolism.
In order to overcome the existing lack of stoichiometry in the geneto- reaction associations, we have enriched the current GPR formulation by accounting the stoichiometry of the transcripts: Stoichimetric-GPR (S-GPR) [7].
In brief, S-GPR formulation follows the same principle than GPRs rules but incorporating the transcripts stoichiometry. Following the same example described above, the GPR corresponding to the complex is "a and b", while the S-GPR formulation is "1*a and 2*b". Replacing the logical operators by min/max operators the GPR will be formulated as follow: "min (a, b)". However, S-GPR approach in addition divides the gene expression by its stoichiometric coefficient: "min (a/1, b/2)". Thus, if for instance, the expression of gene "a" is 3 and the expression of gene "b" is 4, based on GPR formulation, gene "a" is the limiting factor (exp.gene_a < exp.gene_b), while if S-GPR approach is implemented, the limiting factor is gene "b" (exp.gene_a /1 > exp.gene_b/2), which is more realistic. The accuracy in this step of the integration process is especially relevant as the way the gene expression data is incorporated to the analysis has an important impact on the reliability of the model predictions.
The S-GPR formulation was applied to study the metabolic reprogramming in the prostate cancer (PC) cell line DU145, associated to a prolonged exposure to sub-lethal concentrations of the endocrine disruptor (ED) Aldrin. This organic pollutant is found at low concentrations in different ecosystems [8]. Numerous studies have already shown a clear relation between increasing ED concentration and an enhanced tumor malignancy. However, how a long exposure to low and non-lethal EDs concentrations affects cancer metabolism remains poorly understood. In this sense, Bedia et al. reported important alterations in the metabolic and lipidomic profile of the DU145 prostate cancer cells that are associated with an enhanced tumor malignancy, after a chronic exposure to low concentrations of Aldrin [9].
In this study, DU145 cells were exposed for a long period (50 days) to a pollutant concentration that didn't compromise their growth rate. As consequence, it exists a high isogeneity between Aldrin-exposed and non-exposed cells. Indeed, only 0.35% of genes are deferentially expressed between conditions and among these genes only 1.62% are metabolic genes. However, it has been reported that Aldrin-exposed cells present an enhanced malignant phenotype compared with nonexposed DU145 cells [9].
To evaluate how the incorporation of stoichiometry into the geneto- reaction formulation improved models' predictive capabilities, we applied some of the most widely used transcriptomic-based modeldriven methods to integrate the transcriptomic data of Aldrin-exposed and non-exposed DU145 cells via either S-GPR or GPR [10-14]. The predicted and the experimentally measured metabolic consumption/ production rates were compared (up to 244 uptake/secretion rates from different species), showing a significant improvement of model's predictions when S-GPR were implemented (up to 6% depending on the integration method). In addition, our computational analyses unveiled a marked metabolic reprogramming of key metabolic pathways in Aldrin-exposed cells. More specifically, carnitine shuttle, that transports long-chain fatty acids from cytosol to mitochondria and prostaglandine biosynthesis metabolisms were predicted to be significantly over-activated in Aldrin-exposed DU145 cells compared with control DU145 cells. Our computational analysis's predictions are consistent with reported metabolic changes associated to an enhanced malignant phenotype in prostate cancer and are supported by experimental observations [15].
Furthermore, this case of study is especially sensitive to the incorporation of stoichiometry into the gene-to-reaction formulation as the high isogeneity between Aldrin-exposed and non-exposed DU145 prostate cancer cells makes harder to infer metabolic changes from transcriptomic data. By contrary, the impact of adding stoichiometry to the gene-to-reaction associations may be disguise if more important differences exist in the transcriptomic profile between conditions. For instance, if important differences exist between conditions, considering the stoichiometry of a complex with several sub-units encoded by the same gene may not have any further effects due to the expression of the gene would unlikely become limiting at producing a catalytically active enzyme.
The novel S-GPR formulation that we have developed, incorporates stoichiometry to the gene-to-reaction associations enables a more precise integration of the transcriptomic data that ultimately enhances the predictive capabilities of the GSMM-based analyses. This new grasp outperformed previous approaches by significantly improving predictions of metabolism of multi-factorial diseases in a complex scenario. In addition, the novel S-GPR concept that we have developed, has the potential to be extended to proteomic data integration, which increases the impact that this new slant can have in key research areas such as environmental or clinical fields.
This work is supported by the Novo Nordisk Foundation (NNF10CC1016517 and NNF14OC0009473).
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- Ghaffari P, Mardinoglu A, Nielsen J (2015) Cancer metabolism: A modelling perspective. Front Physiol 6: 1-9.
- Thiele I, Palsson BØ (2010) A protocol for generating a high-quality genome-scale metabolic reconstruction. Nat Protoc 5: 93-121.
- Marin de Mas I (2018) Data Analysis for Omic Sciences: Methods and Applications. Multi-omic data integration and analysis via model-driven approaches, 1st (edn), Elsevier Publishers, United States.
- Marin de Mas I, Esther A, Anusha J (2014) Cancer cell metabolism as new targets for novel designed therapies. Future Med Chem 6: 1791-1810.
- Marin de Mas I, Torrents L, Bedia C, Nielsen LK, Cascante M, et al. (2019) Stoichiometric gene-to-reaction associations enhances model-driven analysis performance: Metabolic response to chronic exposure to Aldrin in prostate cancer. BMC Genomics 20: 652.
- Official State Gazette (BOE) (2011) BO of E. Royal Decree 1799/2010, of December 30, which regulates the process of preparation and marketing of prepared waters packaged for human consumption. BOE 6292-6304.
- Bedia C, Dalmau N, Jaumot J, Tauler R (2015) Phenotypic malignant changes and untargeted lipidomic analysis of long-term exposed prostate cancer cells to endocrine disruptors. Environ Res 140: 18-31.
- Mardinoglu A, Agren R, Kampf C, Asplund A, Uhlen M, et al. (2014) Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease. Nat Commun 5: 3083.
- Becker SA, Palsson BO (2008) Context-specific metabolic networks are consistent with experiments. PLoS Comput Biol 4: e1000082.
- Zur H, Ruppin E, Shlomi T (2010) iMAT: An integrative metabolic analysis tool. Bioinformat 26: 3140-3142.
- Gonçalves E, Pereira R, Rocha I, Rocha M (2012) Optimization Approaches for the In-Silico discovery of optimal targets for gene over/underexpression. J Comput Biol 19: 102-114.
- Jensen PA, Papin JA (2011) Functional integration of a metabolic network model and expression data without arbitrary thresholding. Bioinformat 27: 541-547.
- Marin de Mas I, Aguilar E, Zodda E, Dallmann G, Thomson TM, et al. (2018) Model-driven discovery of metabolic vulnerabilities associated with epithelial-mesenchymal transition in prostate cancer. PLoS Comput Biol 14: e1005914.
Citation: Marin de Mas I (2019) Enhancing Transcriptomics-Based Model-Driven Performance via Stoichiometric Gene-to-Reaction Associations: Metabolic Reprogramming in Prostate Cancer. J Mol Genet Med 13: 432.
Copyright: © 2019 Marin de Mas I. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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This agritech start-up helps farmers build profits from 200 computer system, and sell to Reli...
The startup is closely included with making remedies for major topics alerting the food and agricultural processing businesses. The truth is that Telluris is based on attracting path-breaking environment-sensitive biologically managed services and products to its dreaded plant root-knot and uterus nematode-related disorder complexes. The proprietary biological and also bio-molecular services and products possess the possibility to present substantial economies to harvest growers,'' the corporation stated in an announcement.
For diminishing harvest reductions, Telluris bio-tech India has established integrated pest control plans together with services and products delightfully concentrating on the root-knot nematode, Meloidogyne incognita.
Venu Polineni, Creator, Telluris Bio-tech India, stated,
Our foray to niches can offer unmatched environmentfriendly biocontrol along with bio-molecular services and products to farmers in India and everywhere that face acute challenges against your root-knot, uterus nematodesplant origin pathogens. Our considerable research-based revolutionary answers are going to cause the farmers' initiatives to safeguard their plants and also enrich yield somewhat".


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Roslyn is a town in Day County, South Dakota, United States. The population was 183 at the 2010 census.
Roslyn is located at (45.496323, -97.490960).[7]
According to the United States Census Bureau, the town has a total area of 0.20 square miles (0.52 km2), all of it land.[2]
Roslyn has been assigned the ZIP code 57261 and the FIPS place code 56380.
Since 1999, Roslyn has been home to the International Vinegar Museum.[8] Each year it hosts the International Vinegar Festival.[9]
"Roslyn received its name from Old Roslyn, which was a post office and trading point established in 1882. H.H. Russell, the first postmaster, took the name Roslyn from his native city in Scotland,"[10] although a Norwegian name would have been more appropriate as most of the European settlers in the area were from Norway.
"In 1914, the Soo Line Railroad (Fairmount and Veblen Railway) was being built in the area. In order to secure the line for the community, settlers adjoining the proposed line raised $60,000. The coming of the railroad led to the selection of a new town site. On August 17, 1914, the New Roslyn was plotted and Main Street was established."[10] Old Roslyn was eventually abandoned.
As of the census[3] of 2010, there were 183 people, 77 households, and 42 families residing in the town. The population density was 915.0 inhabitants per square mile (353.3/km2). There were 105 housing units at an average density of 525.0 per square mile (202.7/km2). The racial makeup of the town was 97.8% White, 1.1% Native American, and 1.1% from two or more races.
There were 77 households of which 15.6% had children under the age of 18 living with them, 44.2% were married couples living together, 6.5% had a female householder with no husband present, 3.9% had a male householder with no wife present, and 45.5% were non-families. 42.9% of all households were made up of individuals and 26% had someone living alone who was 65 years of age or older. The average household size was 1.99 and the average family size was 2.71.
The median age in the town was 59.8 years. 16.9% of residents were under the age of 18; 4.9% were between the ages of 18 and 24; 13.6% were from 25 to 44; 23% were from 45 to 64; and 41.5% were 65 years of age or older. The gender makeup of the town was 47.0% male and 53.0% female.
As of the census[5] of 2000, there were 225 people, 93 households, and 50 families residing in the town. The population density was 1,128.5 people per square mile (434.4/km²). There were 109 housing units at an average density of 546.7 per square mile (210.4/km²). The racial makeup of the town was 97.78% White, 1.78% African American and 0.44% Native American.
There were 93 households out of which 26.9% had children under the age of 18 living with them, 43.0% were married couples living together, 9.7% had a female householder with no husband present, and 46.2% were non-families. 40.9% of all households were made up of individuals and 29.0% had someone living alone who was 65 years of age or older. The average household size was 2.05 and the average family size was 2.82.
In the town the population was spread out with 19.1% under the age of 18, 6.7% from 18 to 24, 14.7% from 25 to 44, 20.0% from 45 to 64, and 39.6% who were 65 years of age or older. The median age was 51 years. For every 100 females there were 77.2 males. For every 100 females age 18 and over, there were 75.0 males.
The median income for a household in the town was $19,375, and the median income for a family was $24,375. Males had a median income of $30,625 versus $18,438 for females. The per capita income for the town was $11,527. About 14.0% of families and 18.4% of the population were below the poverty line, including 26.5% of those under the age of eighteen and 18.3% of those sixty five or over.
South Dakota, Marshall County, South Dakota, Roberts County, South Dakota, Grant County, South Dakota, Codington County, South Dakota
North Dakota, Montana, Wyoming, Minnesota, Nebraska
New York City, United States, American Civil War, Hawaii, Western United States
Family, Polygyny, Bride price, Islam, Love
Village, City, Scots language, England, India
South Dakota State University, Authority control, Metabolism, Madison, Wisconsin, United States
South Dakota, Authority control, Accordion, California, Television in the United States
New Zealand, Dunedin, Palmerston North, Roslyn railway station, Roslyn, Manawatu-Wanganui
Day County, South Dakota, South Dakota, United States, Marriage, Town


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Tour the NEW Management and Service Center for Expats in Shekou
29 Jun 2017
Yesterday the Management and Service Center for Expats officially opened along with the Nanshan Pioneers Education and Management Base and the Shenzhen Shekou Maritime Museum.
ShekouDaily is honored to have been invited as the official foreigner representative of the Launching Ceremony where the Shenzhen Municipal Committee and organization minister Zheng Ke (深圳市委常委、组织部长郑轲), the Nanshan District Party Committee Standing Committee and organization minister Rao Honglei (南山区委常委、组织部长饶红蕾), and the Shekou street party working committee secretary and director Zhou Jiangtao (蛇口街道党工委书记、主任周江涛) where among the attendees, along with more than ten media organizations from across Guangdong Province who were covering the event.
On the second floor visitors can enjoy the new Shenzhen Shekou Maritime Museum.
The new facilities provide an information center for locals as well as a place where foreigners can get assistance from very friendly English-speaking staff. The types of assistance they offer include registration services (for expats living in the area... see map below) so foreigners no longer need to go to the police station, advice on marriage or disputes with landlords and employers, guidelines on leases, traveling, currency exchange and more.
UPDATE: As of May, 2018, you can also register online here.
Click here for frequently asked questions about the registration; how toregister online, when to register, as well as the penalties for not registering.
They also provide community information events, of which ShekouDaily is proud to be the organizer of the first one held today Thursday June 29th. We'll post a follow up to the event on ShekouDaily as well.
The center is operated by the Shekou Subdistrict Office and authorized by the Exit-Entry Administration of the Nanshan Public Security Sub-bureau, so you can assure that the information and service you receive here will be up-to-date and accurate.
Their opening hours are from 9 a.m. to 12 p.m. and 2 p.m. to 6 p.m. Monday through Friday.
According to the Management and Service Center, there are currently 43,919 registered expats living in Shenzhen and Shekou has the largest community with 6,275 registered with the Shekou Police Station and Shenzhenwan Police Station. With more and more foreigners moving to Shenzhen it's great to see the government put forth this kind of investment and effort to help foreigners living in the community and we're proud to be a part of it.
For more information, you can call 0755-2667-8381
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We hope that people will have better understanding of Chinese culture throught these excellent Chinese movies.
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Every Thursday 5pm - 10pm at George and Dragon; Our BBQ Special! A full juicy chicken leg ...
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5 Things Gamers From The '90s Will Remember
The '90s were a special time for gaming, with the release of so many incredible games and strange trends it was a time when the medium really started to take off. Gaming advertising became ever zanier using strange peripherals, goofy actors and fr...
FULL SCHEDULE for this Saturday's Health & Wellness Fair!
in Health & Fitness, Food & Drinks, Community, People, Education
Check out all the awesome free activities, services & workshops + in the FULL schedule for this Saturday's Health & Wellness Fair! 10am to 4pm at Vista-SK, walking distance from Houhai Subway station in Nanshan.
Shekou community shares their love with Liang Jin and Simone Waddell
Great day for the Shekou Community to one again show our kindness and hospitality.


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You can enjoy flat-screen TVs with cable channels, and all 40 rooms feature free WiFi, free wired Internet and free bottled water. Minibars provide refreshments, and room service makes dining in an option. Additionally, safes, hairdryers and phones are available. Limited housekeeping is available.
The restaurant, Energy Kitchen, serves local cuisine and is open for breakfast, lunch and dinner. Added amenities include free WiFi in public areas and a health club. Each morning cooked-to-order breakfast is served between 7 AM and 10 AM. There's also the convenience of free extended parking.
With a stay at this 3.5-star Bandar Seri Begawan hotel, you'll be 2.7 km (1.7 mi) from Royal Regalia Museum and 3.1 km (1.9 mi) from Sultan Omar Ali Saifuddien Mosque.
There's a restaurant on site. Public spaces have free WiFi. Palm Garden Hotel Brunei offers its guests an outdoor pool and a health club. Palm Garden Hotel Brunei also features tour or ticket assistance, concierge services, and complimentary newspapers in the lobby. Self parking is free. This 3.5-star Bandar Seri Begawan hotel is smoke free.
Available in all rooms: Free WiFi , Free wired Internet
Available in some public areas: Free WiFi
Free long-term parking , Free self parking
Palm Garden Hotel Brunei offers 40 forms of air-conditioned accommodation with minibars and a safe. Flat-screen televisions come with cable channels. Bathrooms include a shower, complimentary toiletries and a hairdryer. Guests can surf the web using complimentary wired and wireless Internet access. Housekeeping is provided on a limited basis.
For a fee, guests can enjoy a cooked-to-order breakfast daily from 7 AM to 10 AM.
Energy Kitchen – This restaurant specialises in local cuisine and serves breakfast, lunch and dinner.
Room service (during limited hours) is available.
Recreational amenities at the hotel include an outdoor pool and a health club.
Charges for extra guests may apply and vary according to property policy.
A cash deposit, credit card or debit card for incidental charges and government-issued photo identification are required upon check-in.
Special requests are subject to availability at the time of check-in. Special requests can't be guaranteed and may incur additional charges.


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In an attempt to fuel the fire of an impending war between SUV-looking MPVs, Toyota Motor Philippines (TMP) is now accepting reservations for the 2018 Toyota Rush.
Although, at this point, there are no information from TMP yet as to how much the reservation cost is. More importantly, no other official details about the 7-seater Rush itself are present — no pricing, no specs, no variants. All we have is this short video below posted by the company via their official Facebook page.
But, assuming that we'll get the Indonesian-spec Rush, the top-of-the-line TRD Sportivo variant is equipped with a push-start system, keyless entry, hill-start assist, LED lighting, 6 airbags, and a ladder-frame chassis. It has a 1.5L Dual VVT-i DOHC engine under its hood, capable of producing 103 hp and 136 Nm of torque. It's then coupled to a 4-speed automatic transmission.
If you're in for the Rush and would like to reserve a unit ASAP, reservation is available via their dealerships, presumably at any Toyota showroom in their nationwide network.
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The Mazda CX-30, CX-8, and the rest of the Mazda Philippines' lineup are available for a test drive from December 6 to 8, 2019.
AutoAsia opens doors to SsangYong, Changan car buyers in Metro Manila / News
The new dealership, under the Autohub Group, is just the start of AutoAsia's plan to expand further into the country.
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text: Bowfront Ivory Bedside Chest Of Drawers Posted by : Jonathan / On : 18 April / In : Accent Cabinets Depending on the size of your terrace, you need to make certain you have selected a Bowfront Ivory Bedside Chest Of Drawers that suits your terrace flawlessly. Since the very best Bowfront Ivory Bedside Chest Of Drawers do not come cheap, for most of us, replacing them after a couple of months of use is fiscally draining. {To ensure that your Bowfront Ivory Bedside Chest Of Drawers stay in top condition, get good umbrella covers. Contrary to the patio umbrellas, the umbrella covers are built using tough, non-fade and tear resistant substances. This makes it possible for them to stand the harsh weather elements. They're also waterproof, ensuring thatyour umbrella remains not only dry but also clean. How to pick the right Bowfront Ivory Bedside Chest Of Drawers The best Bowfront Ivory Bedside Chest Of Drawers with regard to you would be the one of which works for your finances, offers solid construction, suits your space, and offers a method you'll love intended for years. Even when you're certainly not thinking forever at this time, a person can expect to have got a table no fewer than five to twelve years. Five years is certainly not a long moment, said Pourny. If its your first desk, you may make use of it someplace else after a couple of years, so you require it to be easy and sturdy along with a type you'll like for a time. very well So a small, high quality table might find the place at home for yrs to come. Why you need the best Bowfront Ivory Bedside Chest Of Drawers When you are possessing your dinner along with your household then you surely can be needing the comfort whilst eating and having a new Bowfront Ivory Bedside Chest Of Drawers. This is precisely how you need the perfect Bowfront Ivory Bedside Chest Of Drawers within your kitchen. Generally there are a variety involving chairs you can select from but you certainly can be wanting the Bowfront Ivory Bedside Chest Of Drawers to your dining room this is where this Bowfront Ivory Bedside Chest Of Drawers reviews will help a person immensely. You should appearance for the material of which suits you the most effective wager it metal, wood, plastic-type or any other. Almost all the material holds some sort of specialty in them which usually could be realized following a certain point whilst visiting use.The modern day Bowfront Ivory Bedside Chest Of Drawers give a clean plus contemporary design as nothing at all looks great higher than a team of alike dining seats that are around the particular Bowfront Ivory Bedside Chest Of Drawers. You may get these seats of any color associated with your choice. As every single house needs a central point or centerpiece in order to get a balanced style at home so of which it could look the two interesting and comfortable? It really is what a Bowfront Ivory Bedside Chest Of Drawers about a table serves as. An individual can get a wonderful care for installing these chair at your house.. Merely a minimalistic change from your house. could end up being great when you are usually having best Bowfront Ivory Bedside Chest Of Drawersat your current home. There are many points of which show that are needed an eating chair at the kitchen. Therefore get your hands with one of the preferred dining chairs for your own kitchen and enjoy comfortableness and joy while getting dinner with your family members. Bowfront Ivory Bedside Chest Of Drawers Buyer's Guide There usually are a number of items to search for when deciding on the right loveseat for that room or home you aren't in. Factors such since size and in a few cases weight need to be able to be regarded as well because the material and style that the loveseat characteristics. According to what else is definitely in the room and even whether or not an individual want it to end up being a focal point throughout the room delete phrase will influence all regarding these factors. Dimension How big a Bowfront Ivory Bedside Chest Of Drawers is the initial thing many people will want to be able to consider when dealing with which loveseats to buy. both exactly how much space you desire to have while seated in it and just how very much space is available for your Bowfront Ivory Bedside Chest Of Drawers to occupy may affect this decision. Many loveseats around between forty five to 65 inches broad, yet , some are larger or narrower than this specific. If there is sufficient room for a broader seat additionally it is important to be able to consider how thick typically the Bowfront Ivory Bedside Chest Of Drawers on the armrests are, as this can easily occasionally take up some sort of considerable amount of typically the actual sitting area associated with the Bowfront Ivory Bedside Chest Of Drawers. When relevant this is mentioned on the reviews for every single seat as some chairs as wide as 65-inches are limited to just 45-inches of actual relaxing space because of typically the layout of the armrests. Covers Materials The material that Bowfront Ivory Bedside Chest Of Drawers are constructed with can range coming from elegant leather to some sort of soft velvet fabric, and even which one is ideal for you is determined by the particular style you're going with regard to in addition to what you discover most comfortable. In add-on, some materials are simpler to clean up than others thus this also needs to be the consideration for some individuals when you have pets or kids. Design and Decor There are about three main kinds of loveseat. Standard designs feature more noticable features for example nailhead cut which are the tiny metallic rivets that will be sometimes on the entrance of the armrests to be able to keep the Bowfront Ivory Bedside Chest Of Drawers in position. More modern or modern styles will feature quite bare and minimalist models with soft curves staying major of the design and style. Rustic designs, on typically the other hand, often characteristic visible wood that provides a dark finish and even very simple Bowfront Ivory Bedside Chest Of Drawers. Which in turn of these styles an individual go with will hinge on both personal flavor and exactly what different is in the area in which the loveseat is proceeding. A well-chosen loveseat might certainly pull a space collectively in an amazing approach, while an out regarding place loveseat will keep out in an or else well-decorated room. Extra Features Some Bowfront Ivory Bedside Chest Of Drawers boast a number involving extra features which may possibly be vital that you look out and about for depending on precisely how you decide to use typically the seat. For example, a few the seats on this specific list can recline, which often is perfect for putting inside an entertainment center or perhaps movie room setting, plus one even features a new center console with safe-keeping space and cupholders. Many also feature fold-away bed frames or armrests which could dual as trackpads so you can get operate done on the computer system while sitting comfortably in the Bowfront Ivory Bedside Chest Of Drawers. Our Pick Hooker Furniture 501485122 4614 Inch Wide Hardwood Cabinet More Detial... Best Pick Hooker Furniture 501485122 4614 Inch Wide Hardwood Cabinet Lightweight, Comfortable, Affordable . Conclusion With so many options, its easy to understand why you would want to do some investigation prior to investing in a settee. The best choice will take you many years of comfort and memories. There are lots of issues to take into consideration prior to making such a purchase. The Ashley Kennard Leather-based Match Power Lying Couch in Cream is a great choice for most people. As the mild color may be a concern, the overall value and high-quality supplies used to make this item are worthwhile. The look is practical even though its modern, its made to fit into more traditional styles too. Our prime customer reviews also make this a top choice. A great back-up if you are concerned with a light color is the Homelegance Double Lying Couch in Dark brown Glued Leather-based. This is a sensible and traditional design, particularly appealing to those who have children. Whatever sofa youve chosen is a superb expense. Take a moment and get the transaction began now! Tags: Accent Cabinets share this post:


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By Lynne Greenwood2002-04-11T00:00:00
The waiting can be unbearable for patients expecting a diagnosis of cancer. Lynne Greenwood describes how one clinic has eased the pain
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HSJ is part of Wilmington Healthcare Limited, Beechwood House, 2-3 Commercial Way, Christy Close, Southfields, Essex, SS15 6EF. Company number 2530185. c/o Wilmington plc, 5th Floor, 10 Whitechapel High Street, London E1 8QS. Registered in England and Wales. Company registration 30158470
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- 1 Methadone Withdrawal
- 2 Video: Methadone Clinics in Fairchild Air Force Base
- 3 Video: Methadone: The Hope For a New Life
- 4 Video: Baby born addicted to methadone
- 5 Video: Điều trị nghiện bằng methadone
- 6 Fairchild Air Force Base WA - BingNews Search results
Methadone Withdrawal
Need Help With Addiction?
Call Us NOW
Methadone withdrawal will be called for sooner or later, after methadone upkeep or a discomfort administration program utilizing methadone has started. If your sensation confined by having to go to a Fairchild Air Force Base WA center or a pharmacy daily as well as going through hell if you intend to travel, there is a way out.
Methadone use produces a numb sensation to living, significant stomach problems as well as physical dependency that beats all others; that's the list. All sort of other illness that methadone usage generated are exposed as soon as beginning methadone withdrawal. I'll give you some solution to assist right now, as well as even more solutions to deal with the trouble to ending methadone dependence for life.
Methadone Use Is Epidemic
Dependencies physicians and discomfort management clinics in Washington are busily prescribing methadone for opiate misuse as well as persistent discomfort, yet just what are the repercussions of methadone use? I've listed many listed below. If you have actually currently attempted Methadone withdrawal as well as had problems, I've got some aid you would not have actually located somewhere else.
Once it is time to begin methadone withdrawal, many individuals are having BIG problems finishing their methadone usage. How does one take out from methadone in Fairchild Air Force Base Washington? What obstacles will they need to overcome?
Methadone Withdrawal Challenges
- Methadone use makes people unfeeling, numb
- Even stepping down from methadone can expose hyper sensitivity to discomfort and nutritional depletion symptoms — cramping, aches, nervousness, sleeplessness
- Methadone withdrawal is often 4 times longer and more difficult than heroin once the drug has been abused or used incorrectly for long periods of time
- Withdrawing from methadone can give pains and aches which people can mistake for stress and pain from past accidents
I'm creating for those having trouble with methadone withdrawal. If you are experiencing not a problem withdrawing from methadone, do not worry you are just one of the lucky ones.
The truth is that numerous addictions physicians as well as pain administration specialists in Fairchild Air Force Base are acting upon the suggestions from their peers and experts. They are not informed of the deaths because of prescribed methadone use nor the difficulties that in some cases take place when taking out from methadone usage.
The worry however exists with the consumer.
Vital: extensively study drugs or drugs yourself before you acquire or take them. The effects can be gruesome. They likewise could have dangerous interactive results when taken with various other medicines.
Lots of if not all methadone effects are brought on by nutritional shortages. Methadone use develops nutritional depletion – especially calcium and also magnesium depletion. Another is B vitamin shortage. This is just how these shortages appear.
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Methadone Withdrawal Symptoms
- Anxiety over sensations, pains and discomforts returning
- Sleeplessness
- Sneezing
- Cramping of legs and arms
- Bone aches
- Flu or dope sick
Methadone withdrawal will need a lot of extra nutritional supplementation. That means it's time to feed the body. Calcium as well as magnesium will assist with the constraining and so on. But there will be some problem lots of will have taking their nutrients – a negative intestine.
Video: Methadone Clinics in Fairchild Air Force Base
A Negative Digestive tract
Methadone as well as anxiousness medications tend to ruin the intestine cellular lining. A leaking gut offers pains when eating or allergies, prone to sickness and skin issues. Another sign of a leaky gut is impatience and a 'attitude problem'. The attitude can have physical causes unmentioned by the person.
An excellent suggestion in ordering to help the intestine problem is consuming lots of top quality yogurt with real-time probiotics in it, like acidophilus and also bifidus. One could also supplement with large quantities of glutathione – an antioxidant to assist the cleansing procedure.
The amount of nutrients called for throughout methadone withdrawal is undervalued so usually that I shake my head in wonder.
Medicines Like Methadone Are Contaminants
The trouble with methadone is that it is poisonous to the body. Your body understands it, however you might not. Taking methadone difficulties your body organs to detox the body and also secure the vital organs prior to they are severely hurt.
Contaminants offer the body a tough time. If you have actually seen drug addict with dark circles under their eyes, gray skin, poor skin, hair befalling, reduced power, weird disorders, and so on they're obtained dietary deficiencies. Those deficiencies are difficult to recoup from with food alone. In some cases that food isn't really being appropriately digested = bad gut.
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Methadone Detox
Cleansing the body is greater than merely quiting drug use. Drug abuse creates inner body damage you might not quickly acknowledge. However, the body will certainly try to detox right after substance abuse as well as heal itself using any type of nutrients offered. If the nutrients typically aren't readily available, the body will borrow (swipe) them from the bones, nervous system or other important functions.
Some will require medical detox from methadone – the problem is that most Fairchild Air Force Base methadone detox centers don't use nutritional supplements as part of their program. They just give more medications, and often not the right ones. The lack of full understanding on Methadone detox creates a brutal scene to withdraw from.
The Good News
Fortunately is that I've located the tools and also the detoxification facilities in WA that can defeat methadone withdrawal smoothly as well as conveniently.More:
Methadone Videos:
Video: Methadone: The Hope For a New Life
Video: Baby born addicted to methadone
Video: Điều trị nghiện bằng methadone
methadone clinic Fairchild Air Force Base WA
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A behind-the-scenes look at military dog training at Fairchild Air Force Base
SPOKANE COUNTY, Wash. - The dogs who come to Fairchild Air Force Base are known for their exceptional intelligence and athletic abilities. The dogs are highly-trained and selected before being ...
Training to be a security force airmen at Fairchild Air Force Base
Inside the base, their job description entails a bit more. The training required to keep up, is extensive. We learn by doing. I suited up and experienced just a piece of what more than 200 defense air ...
Fairchild Air Force Base, WA
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Fairchild Air Force Base, WA History
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PHOTOS: Fairchild Air Force Base hosts Mobility Guardian training
Fairchild Air Force Base is wrapping up a massive, three week-long training exercise over the skies of Spokane. Air Mobility Command's (AMC) premiere exercise, Mobility Guardian 2019, #MG19, began on ...
Washington-based Air Force rescue squadron records its 700th save
instructor training from a mountainside in northeastern Washington. The squadron counts its saves from the day it unfurled its colors at Fairchild Air Force Base in 1971. It commemorates every ...
Travis Air Force Base maintains combat readiness
Travis Air Force Base did just that Thursday ... which is being headquartered this year at Fairchild AFB in Spokane, Washington. The exercise — which began on Sept. 8 and runs through Sept. 28 — ...
Home Care near Fairchild Air Force Base, WA
You know your family, A Place For Mom knows Home Care. Our dedicated local Fairchild Air Force Base, WA advisors have helped 1 families make the right choice for their needs. Get full details, pricing ...
Fairchild to Become Home to Air Force's Biggest Tanker-Refueling Wing
The first of 12 KC-135 Stratotanker aircraft arrived at Fairchild Air Force Base on Wednesday, ahead of the reactivation ... of the planes involved years of planning and a push from Washington ...
A week of tragedies tested Fairchild Air Force Base and Spokane 25 years ago
Fairchild Air Force Base and the city to the west went into mourning twice on the third week of June 1994. The week began warm and sunny, with the base preparing for an open house the following Sunday ...
Thousands flock to Fairchild Air Force Base for Skyfest 2019
Maughan, who has been attending air shows for decades, said he parachuted out of planes when he was in the Marines between 1958 and 1968. He now lives in Winthrop, Washington ... training and search ...
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Fairchild Air Force Base
The host unit at Fairchild is the 92d Air Refueling Wing (92 ARW) assigned to the Air Mobility Command's Eighteenth Air Force. The 92 ARW is responsible for providing air refueling, as well as passenger and cargo airlift and aero-medical evacuation missions supporting U.S. and coalition conventional operations as well as U.S. Strategic Command strategic deterrence missions.
Fairchild AFB was established in 1942 as the Spokane Army Air Depot.[1] and is named in honor of General Muir S. Fairchild (1894–1950); a World War I aviator, he was the Vice Chief of Staff of the Air Force at the time of his death.
Fairchild is home to a wide variety of units and missions. Most prominent is its air refueling mission, with two wings, one active, the 92d Air Refueling Wing, and one national guard, the 141st Air Refueling Wing, both flying the Boeing KC-135 Stratotanker. Other units here include the Air Force Survival, Evasion, Resistance and Escape school, medical detachments, a weapons squadron and the Joint Personnel Recovery Agency.
Over 5,200 active duty Air Force, Air National Guard, and tenant organization military and civilian employees work on Fairchild, making the base the largest employer in Eastern Washington. Fairchild's annual economic impact on the Spokane community is approximately $427 million, constituting 13 percent of the local economy.[4]


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Yellville Summit School Dst
1124 N Panther Ave., Yellville, AR 72687
(870) 449-4066
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According to our records, this business is located at 1124 N Panther Ave. in Yellville (in Marion County), Arkansas 72687, the location GPS coordinates are: 36.2392044 (latitude), -92.689327 (longitude). Yellville Summit School Dst is categorized under Private Junior High School (SIC code 8211). Current estimates show that the unit has a sales volume of $2,900,000 and staff of approximately 99 people. You can contact the company by phone at (870) 449-4066.
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(JERSEY CITY, N.J.) — A New Jersey nanny was out for a jog when she was allegedly attacked and left for dead in lake, officials said.
The body of Caroline Cano was found Sunday morning in a lake in Jersey City's Lincoln Park, the Hudson County prosecutors said.
The city's medical examiner's office ruled her death a homicide, prosecutors said, though they declined to release more information on the manner of death.
Cano, 45 of Jersey City, lived a few blocks from the park, and her roommate said she went for a jog every morning before going to her job as a nanny, reported ABC New York station WABC-TV.
"They realize something was wrong when she didn't show up to the church," neighbor Frankie Ramos told WABC-TV. "She never missed a day."
No arrests have been made, prosecutors said Thursday.
Anyone with information is asked to contact the Hudson County Prosecutor's Office at 201-915-1345.
Copyright © 2019, ABC Radio. All rights reserved.


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Introducing the portrait armchair collection, a series of carved antique style Birchwood armchairs with printed velvet backrests of defaced classical artworks. These birch wood armchairs have been lovingly crafted to produce this wonderfully detailed seat collection, crossed with the endearing Mineheart touch of the artistic back. Each design has a unique image displayed paired with a luxurious complimenting velvet and padded arm rests.
Inspired by the traditional French Louis style arm chair these striking furniture pieces are upholstered with soft velvets and as always a classic Mineheart twist, incorporating vintage portraits with a graffiti element.
Combining spring feelings with pink pastel paint work is what makes this unique, digitally printed chair. Matched with a chic grey velvet encased by the subtle curves of the birch wood base finished in white.
Dimensions: 1080mm height x 640mm width x 700mm depthMaterials: Birch wood white frame, grey velvet upholstered padded seat & arm rests
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MUSKEGON – After starting the season 3-0, the Reeths-Puffer hockey team was looking to bounce back from a two-game losing streak.
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At Mona...


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Lisianthus: Clan Profile » Dragon Lair » Nesting Grounds
Lisianthus' Clan
no, not without you!
Lesser Lair
of the
Sundial Terrace
Clan Information
『 Lisianthus 』
izzy ✩ she/her ✩ phantom
english | filipino (sort of)
currently into
marvel cinematic universe
things to do:
- post in gijinka thread
- finish lore
- rename turing
- get neikea and shorebreak
- eliminate (0/5)
- to pass my classes (esp. aplit/cf/physed)
- apparel/skins for dragons
- art for my ocs
gene projects:
- 36482440: 0/4
- 36482441: 0/2
- 37018196: 0/3
- re-scry duke, pyr, and g1s
- find new dragon for eros
- arrange lair properly
Coding By SuzyChi, #170971
12/23 Earned: Arcane Egg Find or obtain an unhatched Arcane Egg.
12/23 Earned: Plague Egg Find or obtain an unhatched Plague Egg.
12/23 Earned: Totally Not a Hoarder Collect 50 Familiars in your Bestiary.
Recent Forum Activity 12/23 The Lucky Drop Hub -...
05/16 Thylacine Swap!
04/08 **Humanised Bust SHOP...
03/18 Free Dragons For New...
03/15 Free Dragons For New...
03/15 Solve the riddle, get a...
03/15 Solve the riddle, get a...
05/16 Thylacine Swap!
04/08 **Humanised Bust SHOP...
03/18 Free Dragons For New...
03/15 Free Dragons For New...
03/15 Solve the riddle, get a...
03/15 Solve the riddle, get a...
Lisianthus' Friends (12) View All
Recent Comments
Kikkoman wrote:
Honestly I don't even knowMay 14, 2018, 12:30:00
Wait wrote:
Aw thank you!! I love how colourful your lair is!Jan 16, 2018, 04:52:53
moonwhiskers wrote:
I can see that you are a Rick Riorsan books fanNov 01, 2017, 23:25:35
RoarofTime wrote:
You were pretty close x3 I'm from Wind originally but decided to vacation in Plague for a bit.Nov 01, 2017, 18:58:41
Anatole wrote:
wow sorry for late response! :D I dont check fr often anymore :( but i don't know much about great comet haha :D but my friend rochambeau is big fan (they toldme to change name lolll)!!Oct 26, 2017, 05:40:54
RaynixAura wrote:
Thanks! I love your dragons too; they're really pretty and vary a lot. I especially love Nymph; the skin on her is so pretty! :DOct 13, 2017, 07:38:17
Lisianthus wrote:
@RaynixAura Thank you! :) About your Lisianthus - I went to your lair to view her and WOW she's gorgeous!! (As are all your dragons - they look absolutely stunning! I think I have a new goal for myself now ^^)Oct 13, 2017, 07:27:09
RaynixAura wrote:
Welcome to Flight Rising!! Coincidentally I have a dragon named Lisianthus too.Oct 13, 2017, 07:21:54