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As digital media has expanded at a dizzying pace and social media outlets have grown, certain pundits have suggested books would diminish in importance. Mobile devices and shorter attention spans would create an environment where books would not matter as much as the onslaught of information and innumerable choices available at our fingertips every moment. Certainly reading habits have morphed as digital options have increased, but despite these changes, books are as important as ever because their very form enables them to impact lives in ways no digital media can. Here are four reasons why I believe that is so.
A book is permanent
With so many media forms today, like Snap Chat or Instagram, the information or images conveyed are instantaneous, but soon forgotten after the next tidbit fills the feed. Not so with a book. The very form of a book means it can be preserved and revisited with ease. In fact, the presence of a book shelf in a home or an office points to the fact that books are meant to be a fixture, not fleeting. The information in a book is enduring and has a different importance than the latest click bait.
A book is transcendent
Because of its form, a book is able to cross time, geography and even language. Certainly in a digital world, blogs and Facebook have the ability to do this to some degree. But you can't lend or give someone a blog in the same way you give someone a book. Books are carried across continents, translated into local languages, given or shipped or lent to people who the author has never met or will never know.
Author Susan Norris, who wrote the book Rescuing Hope, talks about this idea in the video below. She points out that one of the reasons she wrote her book is because if she speaks to a group of people, she impacts those people in the room. But with a book she has the power to impact people who she will never meet. Having a book drastically changed her scope of influence.
A book is a complete thought or story
Digital media is a collection of sound bites and image snippets, but a book gives you a full idea or story. And there is something satisfying about that just like it is often more satisfying to eat a meal than a handful of snacks. Books allow for authors to complete their arguments or story because they are not bound by the limits of most digital media. They can take as many pages as needed to finish the job without concern about how long the scroll will be.
The title "author" still commands respect
A number of years ago a writer said to me, "there is a certain cache that comes with being an author". At the time, I did not fully appreciate what he meant, but now I think his statement was very insightful. While being known as a blogger is certainly something to be proud of, it does not carry the same social weight as the title, "author". I think that is because even if we have never written a book ourselves, we respect anyone who has made the effort to finish a manuscript and put down their ideas or story in this permanent, transcendent form.


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Verizon Wireless Expands 4G LTE Network In Chautauqua-Cattaraugus-Allegany, New York Area
WHO: Verizon Wireless, operator of the nation's largest 4G LTE network and largest, most reliable 3G network
WHAT: Verizon Wireless recently activated new 4G LTE coverage on three sites in the Chautauqua-Cattaraugus-Allegany Counties area, expanding and filling in coverage on the high-speed data network it launched locally in recent months. 4G LTE lets Verizon Wireless customers use their 4G LTE-enabled devices to surf the Web, post status updates and photos, share music, and download files at speeds up to 10 times faster than customers on 3G networks.
WHERE: New 4G LTE sites are located in Pomfret (Chautauqua County), Freedom (Cattaraugus County), and Alfred Station (Allegany County).
For street-level detail of coverage and more, please visit www.verizonwireless.com/4GLTE.
BACKGROUND: The Verizon Wireless 4G LTE network offers more 4G LTE coverage than all other competitors' networks combined. As of November 15, the network is available to more than 250 million people in more than 440 markets throughout the United States. In real-world, fully loaded network environments, users will see average data rates of 5 to 12 megabits per second (Mbps) on the downlink and 2 to 5 Mbps on the uplink.
To learn more about how 4G LTE is changing the ways Verizon Wireless customers communicate, please visit http://www.verizonwireless.com/news/article/2012/11/4G-LTE-network-innovation.html
For a full list of 4G LTE markets please visit www.verizonwireless.com/lte.
About Verizon WirelessVerizon Wireless operates the nation's largest 4G LTE network and largest, most reliable 3G network. The company serves nearly 96 million retail customers, including 90.4 million retail postpaid customers. Headquartered in Basking Ridge, N.J., with more than 75,000 employees nationwide, Verizon Wireless is a joint venture of Verizon Communications (NYSE, NASDAQ: VZ) and Vodafone (LSE, NASDAQ: VOD). For more information, visit www.verizonwireless.com. To preview and request broadcast-quality video footage and high-resolution stills of Verizon Wireless operations, log on to the Verizon Wireless Multimedia Library at www.verizonwireless.com/multimedia.

subset: commoncrawl


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(Gallbladder Removal—Open Surgery)
Cholecystectomy is the surgical removal of the gallbladder. The gallbladder is near the liver. It stores bile that is made by the liver. Bile helps in the digestion of fatty foods. The gallbladder releases bile into a system of ducts that lead to the small intestine.
The open version of this surgery is done when a less invasive version called laparoscopic surgery cannot be done.
Laparoscopic Cholecystectomy vs. Open Cholecystectomy
Copyright © Nucleus Medical Media, Inc.
Reasons for Procedure
Reasons for Procedure
This surgery is used to remove a diseased or damaged gallbladder. The damage is typically caused by infection or inflammation. This is often due to gallstones, which are crystals of bile that can form in the gallbladder. Sometimes, these get stuck in the ducts that bile normally flows through. This blockage in the ducts can damage the gallbladder and the liver.
Possible Complications
Possible Complications
Problems from the procedure are rare, but all procedures have some risk. Your doctor will review potential problems, like:
- Gallstones that have entered the abdominal cavity
- Bleeding
- Infection
- Injury to other nearby structures or organs
- Reactions to general anesthesia
- Blood clots
Some factors that may increase the risk of complications include:
- Increased age
- Pregnancy
- Obesity
- Smoking
- Malnutrition
- Recent or chronic illness
- Diabetes
- Heart or lung problems
- Bleeding disorders
- Alcoholism and illegal drugs
- Use of certain medications
What to Expect
What to Expect
Prior to Procedure
Your doctor will probably do some or all of the following:
- Blood tests to evaluate liver function
- Ultrasound to view gallstones
- Hepatobiliary iminodiacetic acid (HIDA) scan—an x-ray test that uses a chemical injected into the gall bladder to create pictures of your liver, gallbladder, ducts, and small intestines
- MRI or CT scan to better view the gallbladder
- Electrocardiogram (EKG) and chest x-ray to make sure that your heart and lungs are healthy enough before surgery
Leading up to your procedure:
- Talk to your doctor about your current medications. Certain medications may need to be stopped before the procedure, such as:
- Arrange for a ride to and from the procedure. Also arrange for help at home when you return from the hospital.
- The night before, eat a light meal. Do not eat or drink anything after midnight.
- You may be given laxatives and/or an enema to clean out your intestines.
- You may be given antibiotics.
- You may be asked to shower the morning before surgery. You may be given a special soap to use.
General anesthesia will be used. You will be asleep for the procedure.
Description of Procedure
An incision will be made in the upper right area of your abdomen. The gallbladder will be separated from the structures around it, including the liver, bile ducts, and arteries.
After the gallbladder is gone, dye may be squirted into the bile ducts. This will help show if there are gallstones in the ducts. The duct may be opened to remove any stones. While your abdomen is open, the other organs and structures will be examined. This will be done to make sure that you do not have any other problems. The incision will be closed with sutures or staples. It will then be covered with a bandage.
A tiny, flexible tube may be placed into the area where the gallbladder was removed. This tube will exit from your abdomen into a little bulb. This is to drain any fluids that may build during the first few days after surgery. The tube is usually removed within one week of your operation.
Immediately After Procedure
The gallbladder will be examined by a specialist. You will be taken to a room to recover. You will be monitored closely.
How Long Will It Take?
About 30-60 minutes
How Much Will It Hurt?
Anesthesia will prevent pain during surgery. Pain and discomfort after the procedure can be managed with medications.
Average Hospital Stay
2-6 days
Post-procedure Care
At the Hospital
In the recovery room, the staff will monitor you for problems. In addition:
- You may have a nasogastric tube, which is a tube that will go from your nose, down your throat, and into your stomach. The tube will help to drain fluids and stomach acid. You will not be able to eat or drink until this is removed and you are no longer nauseated. You will continue to receive fluids and sugar through an IV.
- When you are able to take things by mouth, you will be started on a liquid diet. Your diet will be progressed through soft foods to a regular diet.
Your bowels will work more slowly than usual. Chewing gum may help speed the process of your bowel function returning to normal.
Preventing Infection
During your stay, the hospital staff will take steps to reduce your chance of infection, such as:
- Washing their hands
- Wearing gloves or masks
- Keeping your incisions covered
There are also steps you can take to reduce your chance of infection, such as:
- Washing your hands often and reminding your healthcare providers to do the same
- Reminding your healthcare providers to wear gloves or masks
- Not allowing others to touch your incision
At Home
Recovery takes about 4-6 weeks. You will have a special diet and physical activity plan to help with your recovery. Follow instructions on wound care to prevent infection. Your doctor may advise pain medications for discomfort. Your liver will take over the functions of the gallbladder. Some people notice that they have a little more trouble digesting fatty foods, particularly for the first month after surgery.
Call Your Doctor
Call Your Doctor
It is important for you to monitor your recovery after you leave the hospital. Alert your doctor to any problems right away. If any of the following occur, call your doctor:
- Signs of infection, including fever and chills
- Redness, swelling, increasing pain, excessive bleeding, or discharge at the incision site
- Cough, shortness of breath, chest pain
- Increased abdominal pain
- Pain that you cannot control with the medications you have been given
- Blood in the stool
- Persistent nausea and/or vomiting
- Bloating and gas that last for more than a month
- Pain and/or swelling in your feet, calves, or legs
- Dark urine, light stools, or yellowing of the skin or eyes
If you think you have an emergency, call for medical help right away.
National Digestive Diseases Information Clearinghouse http://digestive.niddk.nih.gov
Canadian Digestive Health Foundation http://www.cdhf.ca
Cholecystectomy. EBSCO DynaMed website. Available at:
Updated May 17, 2013. Accessed May 28, 2013.
Clayton ES, Connor S, et al. Meta-analysis of endoscopy and surgery versus surgery alone for common bile duct stones with the gallbladder in situ. Br J Surg. 2006;93:1185-1191.
Gallbladder surgery: laparoscopic cholecystectomy. University of California at Davis website. Available at:
Accessed May 28, 2013.
Martin DJ, Wernon DR, et al. Surgical versus endoscopic treatment of bile duct stones. Cochrane Database Syst Rev. Apr 2006;19(2):CD003327.
3/23/2015 DynaMed's Systematic Literature Surveillance
Short V, Herbert G, et al. Chewing gum for postoperative recovery of gastrointestinal function. Cochrane Database Syst Rev. 2015 Feb 20;2.
Last Updated: 3/23/2015


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- Research
- Open Access
Computational prediction of human metabolic pathways from the complete human genome
© Romero et al.; licensee BioMed Central Ltd. 2004
- Received: 25 June 2004
- Accepted: 2 December 2004
- Published: 22 December 2004
We present a computational pathway analysis of the human genome that assigns enzymes encoded therein to predicted metabolic pathways. Pathway assignments place genes in their larger biological context, and are a necessary first step toward quantitative modeling of metabolism.
Our analysis assigns 2,709 human enzymes to 896 bioreactions; 622 of the enzymes are assigned roles in 135 predicted metabolic pathways. The predicted pathways closely match the known nutritional requirements of humans. This analysis identifies probable omissions in the human genome annotation in the form of 203 pathway holes (missing enzymes within the predicted pathways). We have identified putative genes to fill 25 of these holes. The predicted human metabolic map is described by a Pathway/Genome Database called HumanCyc, which is available at http://HumanCyc.org/. We describe the generation of HumanCyc, and present an analysis of the human metabolic map. For example, we compare the predicted human metabolic pathway complement to the pathways of Escherichia coli and Arabidopsis thaliana and identify 35 pathways that are shared among all three organisms.
Our analysis elucidates a significant portion of the human metabolic map, and also indicates probable unidentified genes in the genome. HumanCyc provides a genome-based view of human nutrition that associates the essential dietary requirements of humans with a set of metabolic pathways whose existence is supported by the human genome. The database places many human genes in a pathway context, thereby facilitating analysis of gene expression, proteomics, and metabolomics datasets through a publicly available online tool called the Omics Viewer.
- Metabolic Network
- Additional Data File
- Pathway Prediction
- Pathway Family
- Human Metabolic Network
The human genome is a blueprint, but for what machinery? One approach to understanding the complex processes encoded by the human genome is to assign its enzyme products to biochemical pathways that define regulated sequences of biochemical transformations. Pathway and interaction assignments place genes in their larger biological context, and enable causal inferences about the likely effects of mutations, drug interventions and changes in gene regulation. They are a first step toward quantitative modeling of metabolism. Assignment of genes to pathways also permits a validation of the human genome annotation because patterns of pathway assignments spotlight likely false-positive and false-negative genome annotations. For example, false-negative assignments appear as pathway holes: missing enzymes within a pathway that are likely to be hiding in the genome.
SRI's Bioinformatics Research Group has developed a pathway-bioinformatics technology called a pathway/genome database (PGDB), which describes the genome, the proteome, the reactome and the metabolome of an organism. A PGDB describes the replicons of an organism (chromosome(s) or plasmid(s)), its genes, the product of each gene, the biochemical reaction(s), if any, catalyzed by each gene product, the substrates of each reaction, and the organization of those reactions into pathways. Pathway Tools is a reusable software environment for constructing and managing PGDBs [1]. It supports many operations on PGDBs including PGDB creation, querying and visualization, analysis, interactive editing, web publishing, and prediction of the metabolic-pathway complement of an organism.
The power of Pathway Tools is derived from both its database schema, and its software components. Both were originally developed for the EcoCyc project [2, 3]. A PGDB can be thought of as a symbolic computational theory of a species' metabolic functions and genetic interactions [4], encoding knowledge in a manner suitable for computational analysis. Indeed, once an organism's genome and biochemical network are encoded within the schema of a PGDB, new possibilities for symbolic computational analysis arise, because many important semantic relationships are described in a computable fashion.
PathoLogic is one of the Pathway Tools software components. Its primary function is to generate a new PGDB from an organism's annotated genome. PathoLogic predicts the metabolic pathways of the organism, providing new global insights about its biochemistry, and generates reports that summarize the evidence for the presence of each predicted metabolic pathway. We used PathoLogic to generate HumanCyc, a PGDB for Homo sapiens, from the annotated human genome. The genome data used as input to PathoLogic combined data from the Ensembl database [5], the LocusLink database [6] and GenBank [7].
Our analysis assigns 2,709 human enzymes to 135 predicted metabolic pathways. It provides a genome-based view of human nutrition that associates the essential dietary requirements of humans that were previously derived mainly from animal and tissue extract studies to a set of metabolic pathways whose existence is derived from the human genome. The analysis also identifies probable omissions in the human-genome annotation in the form of pathway holes (missing enzymes within the predicted pathways); we have identified putative genes to fill some of those pathway holes. This paper describes the generation of HumanCyc, and presents an analysis of the human metabolic map. The computationally predicted pathways are consistent with known human dietary requirements. We compare the predicted human metabolic pathway complement to the pathways of Escherichia coli and Arabidopsis thaliana and identify 35 pathways that are shared among all three organisms, and therefore define an upper bound on a potential set of universally occurring metabolic pathways.
Prediction of human metabolic pathways
We applied PathoLogic to the input files containing the H. sapiens annotated genome, as described in Materials and methods, generating HumanCyc.
The number of human proteins that were assigned enzyme activities (which caused them to become connected to reaction objects within HumanCyc), according to the mechanism of reaction matching
Type of match
Number of proteins
PathoLogic matched by EC number
PathoLogic matched by name
Unmatched by PathoLogic
Probable enzymes
Manually matched
HumanCyc statistics
PGDB objects
Protein genes
Enzyme genes
RNA genes
Protein complexes
Enzymatic Reactions
With enzyme in HumanCyc
Database links
The entire set of pathways in HumanCyc, grouped by classes using the MetaCyc pathway classification hierarchy
Betaine biosynthesis
Betaine biosynthesis II
Spermine biosynthesis
Polyamine biosynthesis II
Ornithine spermine biosynthesis
Polyamine biosynthesis
UDP-N-acetylgalactosamine biosynthesis
UDP-N-acetylglucosamine biosynthesis
De novo biosynthesis of purine nucleotides
Purine and pyrimidine metabolism
Purine biosynthesis 2
De novo biosynthesis of pyrimidine ribonucleotides
Salvage pathways of pyrimidine ribonucleotides
De novo biosynthesis of pyrimidine deoxyribonucleotides
Salvage pathways of pyrimidine deoxyribonucleotides
Fatty acids and lipids
Fatty acid elongation - saturated
Fatty acid biosynthesis - initial steps
Phospholipid biosynthesis
Phospholipid biosynthesis II
Mevalonate pathway
Triacylglycerol biosynthesis
Cofactors, prosthetic groups, electron carriers
Heme biosynthesis II
NAD biosynthesis II
NAD biosynthesis III
NAD phosphorylation and dephosphorylation
Pyridine nucleotide biosynthesis
Pyridine nucleotide cycling
Glutathione-glutaredoxin redox reactions
Glutathione biosynthesis
Thioredoxin pathway
Pantothenate and coenzyme A biosynthesis
Pyridoxal 5'-phosphate salvage pathway
FormylTHF biosynthesis
Polyisoprenoid biosynthesis
Methyl-donor molecule biosynthesis
Cell structures
Colanic acid building blocks biosynthesis
GDP-mannose metabolism
Mannosyl-chito-dolichol biosynthesis
UDP-N-acetylglucosamine biosynthesis
GDP-D-rhamnose biosynthesis
Mannosyl-chito-dolichol biosynthesis
Trehalose degradation - low osmolarity
tRNA charging pathway
Amino acid biosynthesis
Alanine biosynthesis II
Arginine biosynthesis 4
Citrulline biosynthesis
Asparagine biosynthesis I
Aspartate biosynthesis II
Cysteine biosynthesis II
Glutamate biosynthesis II
Glutamine biosynthesis II
Glycine cleavage
Glycine biosynthesis I
Methionine salvage pathway
Proline biosynthesis I
Serine biosynthesis
Tyrosine biosynthesis II
Sugars and polysaccharides
Lactose degradation 4
Lactose degradation 2
Sucrose degradation III
Galactose metabolism
Glucose 1-phosphate metabolism
Glycogen degradation
Mannose degradation
Non-phosphorylated glucose degradation
UDP-glucose conversion
Ribose degradation
Trehalose degradation - low osmolarity
Sugar derivatives
Lactate oxidation
Mannitol degradation
Sorbitol degradation
Glucosamine catabolism
Other degradation
Removal of superoxide radicals
Methylglyoxal degradation
Nucleosides and nucleotides
(Deoxy)ribose phosphate metabolism
Periplasmic NAD degradation
Fatty acids
Fatty acid oxidation pathway
Triacylglycerol degradation
Lipases pathway
Carboxylates, other
Propionate metabolism - methylmalonyl pathway
2-Oxobutyrate degradation
Acetate degradation
Pyruvate metabolism
N-acetylneuraminate degradation
C1 compounds
Carbon monoxide dehydrogenase pathway
Serine-isocitrate lyase pathway
Amino acids, amines
Alanine degradation 3
Arginine degradation III
Arginase degradation pathway
Arginine proline degradation
Asparagine degradation 1
Aspartate degradation 1
Malate/aspartate shuttle pathway
L-cysteine degradation IV
L-cysteine degradation VI
Cysteine degradation I
Glutamate degradation I
Glutamate degradation IV
Glutamate degradation VII
Glutamine degradation 1
Glutamine degradation II
Glycine degradation II
Glycine degradation I
Histidine degradation III
Histidine degradation I
Homocysteine degradation I
Isoleucine degradation I
Isoleucine degradation III
Leucine degradation II
Leucine degradation I
Lysine degradation I
Methionine degradation 1
4-Hydroxyproline degradation
S-adenosylhomocysteine degradation
Phenylalanine degradation I
Proline degradation III
Proline degradation II
L-serine degradation
Threonine degradation 2
Tryptophan degradation I
Tryptophan degradation III
Tryptophan kynurenine degradation
Tyrosine degradation
Valine degradation I
Aerobic glycerol degradation II
Glycerol metabolism
Glycerol degradation I
Ethanol degradation
Amines and polyamines, other
Citrulline degradation
N-acetylglucosamine, N-acetylmannosamine and N-acetylneuraminic acid dissimilation
Glucosamine catabolism
Energy metabolism
Glycolysis 3
Glycolysis 2
Glyceraldehyde 3-phosphate degradation
Non-oxidative branch of the pentose phosphate pathway
Oxidative branch of the pentose phosphate pathway
Aerobic respiration - electron donors reaction list
Pyruvate dehydrogenase
TCA cycle - aerobic respiration
Entner-Doudoroff pathway
HumanCyc 7.5 contains 1,093 biochemical reactions, 896 of which have been assigned to one or more of the 2,709 enzymes in HumanCyc. There are more enzymes than reactions because of the existence of isozymes in the human genome. This leaves 203 reactions that have no assigned enzyme. These reactions correspond to the above-mentioned pathway holes for the HumanCyc pathways. Of the 896 reactions that have assigned enzymes, 428 have multiple isozymes assigned.
Filling holes in HumanCyc pathways
The PathoLogic-based analysis of the annotated human genome inferred 135 metabolic pathways. A total of 203 pathway holes (missing enzymes) were present across 99 of these pathways; that is, 38 pathways were complete. Using our hole-filling algorithm [9], no candidate enzymes were found for 115 of the 203 pathway holes. For the remaining 88 pathway holes, candidates were obtained and evaluated. In 25 of these 88 cases putative enzymes were identified with sufficiently strong support that the enzyme and pathway annotations within HumanCyc have been updated to reflect these findings. See the HumanCyc release note history [10] for a list of these 25 hole fillers added to HumanCyc version 7.6.
The original annotations of the human proteins that were identified as candidate hole fillers fell into several classes: A description of each class is presented below, with examples included for some.
Open reading frames (ORFs) with no assigned function (6 candidates)
Putative enzymes were identified, for example, for the N-acetylneuraminate lyase (LocusLink ID 80896), aldose 1-epimerase (LocusLink ID 130589) and imidazolonepropionase (LocusLink ID 144193) reactions. In each of these cases, the function of the protein was previously unknown.
Proteins assigned a nonspecific function (7 candidates)
The pathway hole filler assigned an enzyme previously annotated with a general function. For example, 'amine oxidase (flavin-containing) B' (LocusLink ID 4129), was assigned to a more specific reaction, putrescine oxidase. A 'fatty acid synthase' (LocusLink ID 54995) was identified to fill the 3-oxoacyl-ACP synthase reaction.
Proteins assigned a single function but which our analysis indicates are multifunctional (9 candidates)
In these cases the program is postulating an additional function for a gene that already has an assigned function. The pathway hole filler identified the enoyl-CoA hydratase enzyme (LocusLink ID 1892) as a potential hole filler for the 3-hydroxybutyryl-CoA dehydratase reaction in the lysine degradation and tryptophan degradation pathways. The dihydrofolate synthase hole in formylTHF biosynthesis was filled by the enzyme (LocusLink ID 2356) catalyzing the folylpolyglutamate synthase reaction.
Proteins that may have been assigned an incorrect specific function
Although our analyses of other pathway/genome databases have revealed examples we consider to have been assigned an incorrect function in the original annotation, our analysis of the 25 HumanCyc pathway holes that we filled revealed no candidates in this category.
A comparison of candidates for three missing enzymes
P (has-function)
Number of hits
Best E-value
Average rank
Percentage of query aligned
Reaction hole: imidazolonepropionase
ENSG00000139344-MONOMER Functional annotation: UNKNOWN
ENSG00000119125-MONOMER Functional annotation: Guanine deaminase
Reaction hole: N-acetylglucosamine-6-phosphate deacetylase
ENSG00000162066-MONOMER Functional annotation:CGI-14 protein
ENSG00000119125-MONOMER Functional annotation: Guanine deaminase
Reaction hole: aldose 1-epimerase
ENSG00000143891-MONOMER Functional annotation:AMBIGUOUS
ENSG00000117308-MONOMER Functional annotation:UDP-glucose 4-epimerase
In the first example, 28 imidazolonepropionase sequences from other organisms were retrieved from Swiss-Prot and the Protein Information Resource (PIR). Using BLAST, each sequence was used to query the human genome for candidate enzymes. Protein A was found in all of the 28 lists of BLAST hits. From the numbers in the table, it is fairly obvious that protein A is more likely to catalyze the imidazolonepropionase reaction than is protein B. In the second example, given the best E-value (1e-110) it is again not surprising that the computed probability that protein C has N-acetylglucosamine-6-phosphate deacetylase activity approaches 1.0. In the last example, both proteins have excellent BLAST E-values; in fact, the E-value for protein F indicates a better match with the query sequences than the E-value for protein E. In this case, protein E is found in 19 lists of BLAST hits versus four for protein F, and on average aligns with a much larger fraction of each query sequence. When examined in more detail, we discover that the four query sequences that identified candidate F in their BLAST output are multifunctional proteins with both aldose-1-epimerase activity and UDP-glucose 4-epimerase activity. Protein F aligns with the amino-terminal region of each of the four query sequences, and has no detected similarity in the carboxy-terminal regions. The UDP-glucose 4-epimerase activity lies in the amino-terminal region of each multifunctional query protein.
Nutritional analysis of the human metabolic network
Nutritional requirements and their genetic and biochemical basis are thought to have evolved principally in prokaryotes, over billions of years [11]. Specific nutritional challenges have driven the evolution of metabolic pathways and the functional capabilities mediated by them. Indeed, eukaryotic life acquired the basic building blocks of metabolism, that is, sets of genes encoding enzymes that mediate specific metabolic pathways, from prokaryotic ancestors. One may define a metabolic pathway as a conserved set of genes that endow an organism with specific nutritional/metabolic capabilities, for example, the ability to grow in the absence of phenylalanine because of the ability to synthesize phenylalanine.
Current knowledge of human nutrition based on metabolic pathways is derived from various sources. One is clinical observation of inherited human metabolic diseases and nutrient deficiency states. For some pathways, like oxidative phosphorylation and the TCA cycle, direct studies of human tissues, such as human muscle biopsies, have been made. Nuclear magnetic resonance (NMR) has been used directly on humans to study aspects of carbohydrate and energy metabolism. Stable isotopes have been used to trace human metabolism, from which inferences about nutrition have been made. Dietary studies have been made in experimental mammals such as rats and mice and metabolic pathways experimentally elucidated in model organisms.
Here we compare previously accepted human nutritional requirements with pathways derived from the human genome to evaluate their agreement. For example, biosynthetic pathways for essential human nutrients, that is, substances that must be provided in the diet such as the essential amino acids and vitamins, would not be expected to occur in the human genome.
Integration of human genome data with clinical, biochemical, physiological and other data obtained both directly from humans and indirectly from model organisms should, over time, lead to a deeper understanding of human metabolism and its nutritional implications in health and disease. When the genome sequences of individuals are available, it may be possible to address questions about the variation in optimal nutrition from person to person. Explicit identification of specific areas of inconsistency will serve to focus ongoing experimental efforts to elucidate the molecular basis of human nutrition and metabolism.
Comparison of known essential human nutrients with corresponding biosynthetic pathways in MetaCyc and in HumanCyc
Essential nutrient in humans
Biosynthetic pathway in MetaCyc?
Biosynthetic pathway inferred in humans?
Amino acids
Ascorbic acid (Vitamin C)
Biotin (Vitamin H)
Folic acid (Vitamin M)
Niacin (Vitamin B3)
Pantothenic acid
Pyridoxine (Vitamin B6)
Riboflavin (Vitamin B2)
Thiamine (Vitamin B1)
Cobalamin (Vitamin B12)
Retinol (Vitamin A)
Vitamin D
Tocopherol (Vitamin E)
Vitamin K
Comparative analysis of the metabolic networks of human, E. coli and Arabidopsis
Pathways (including superpathways) that are common to human, bacteria and plant PGDBs
Betaine biosynthesis
Polyamine biosynthesis
Fatty acids and lipids
Phospholipid biosynthesis
Fatty acid biosynthesis - initial steps
Fatty acid elongation - saturated
Cofactors, prosthetic groups, electron carriers
Pyridine nucleotide biosynthesis
Thioredoxin pathway
Glutathione biosynthesis
Pantothenate and coenzyme A biosynthesis
Pyridoxal 5'-phosphate salvage pathway
Polyisoprenoid biosynthesis
FormylTHF biosynthesis
Cell structures
Colanic acid building blocks biosynthesis
GDP-mannose metabolism
Trehalose degradation - low osmolarity
tRNA charging pathway
Amino acid biosynthesis
Proline biosynthesis I
Glycine biosynthesis I
Serine biosynthesis
Sugars and polysaccharides
Glucose 1-phosphate metabolism
Galactose metabolism
Trehalose degradation - low osmolarity
Glycogen degradation
Ribose degradation
Other degradation
Removal of superoxide radicals
Nucleosides and nucleotides
(Deoxy)ribose phosphate metabolism
Fatty acids
Fatty acid oxidation pathway
Carboxylates, other
Acetate degradation
Amino acids, amines
L-serine degradation
Glycerol metabolism
Energy metabolism
Pyruvate dehydrogenase
TCA cycle - aerobic respiration
Oxidative branch of the pentose phosphate pathway
Nonoxidative branch of the pentose phosphate pathway
We propose that the cofactor biosynthesis pathways shared among all three organisms have been conserved because first, they produce complex molecules that are not available from the environments of these organisms; second, these molecules are used as cofactors in so many reactions within the metabolic networks that the requirement for them is absolute; and third, no other pathway to accomplish the synthesis of that molecule has evolved. A study by Ouzounis and Karp surveyed global properties of the E. coli metabolic network, including the most frequently used substrates and cofactors [14]. Together, the two pyridine nucleotides NAD and NADP are the third most common substrate in the E. coli metabolic network (after water and ATP): removing the ability to synthesize NAD would disable so many reactions as to be insurmountable. Pyridoxal-5'-phosphate is the second most common cofactor (after Mg2+). Coenzyme A and acetyl-CoA together constitute the seventh most common substrate in E. coli, formylTHF constitutes the 23rd most common substrate, and thioredoxin and glutathione constitute the 40th and 41st most common substrates.
Pathway variants
The level of metabolic pathway variation in the biosphere remains to be determined. Metabolic pathways have been experimentally elucidated in a small number of model prokaryotic and eukaryotic organisms. Despite the relatively small number of carefully studied organisms, significant pathway variation has been observed both between distinct organisms and within a given organism. For example, at least four variants of the 'glycolytic pathway' have been described [15]. Sets of variant pathways for glycolysis [16], leucine degradation [17], and NAD biosynthesis [18] can be viewed through the MetaCyc website. In MetaCyc, variant pathways are named with roman numerals; for example, 'NAD biosynthesis I' and 'NAD biosynthesis II'.
Metabolic pathways appear to have diverged in a manner analogous to the divergence of biological sequences. The demonstrated existence of pathway variants and ongoing uncertainty as to the full extent of such variation has significant implications for ongoing efforts to predict biochemical pathways from incomplete genomic data. First, it means that the precision with which we can infer pathways in one organism from another solely on the basis of genomic data remains to be determined, because when genomic evidence is found in organism Ok for the presence of a pathway, Pj, that was experimentally elucidated in an organism Oj, this alone does not constitute conclusive evidence for the presence of Pj in Ok, since a variant of Pj (Pk) may be present in Ok (note that any such Pk variant may not even have been experimentally characterized). Second, for those pathways with known closely related variants (for example, two pathways differing by only a single step with one step differing from the other only at the level of co-reactants/products, such as one using NADP/NADPH the other using NAD/NADH as cosubstrates/products) it is often impossible to choose among these variants on the sole basis of genomic data because of the limited resolution of sequence analysis.
We have developed a general approach to representing the presence of pathway variants. MetaCyc pathways (approximately 500) have been grouped using a function-based classification system. Each grouping defines a 'pathway family', each member of which (a pathway variant) endows an organism with one or more specific functional capabilities, for example, the ability to grow in the absence of phenylalanine. Within a given pathway family, variants may be clustered into one or more subfamilies. Subfamilies are groups of pathways that show significant overlap/similarity in terms of individual reaction steps (reactants and products of each reaction); enzymatic activities that catalyze these steps; and genes encoding the enzymes that mediate these activities
The similarity between variants within a given subfamily suggests they evolved from a common ancestor pathway. For example, at least four variants of the glycolytic pathway have been described; all enable the conversion of glucose to pyruvate and show significant overlap/similarity in their component reactions. Other pathway variants have been observed that show little similarity to each other (for example, some of the amino-acid degradation pathways) and these are therefore believed to have evolved from distinct ancestor pathways. The existence of pathway subfamilies indicates that multiple pathways have coevolved to meet common nutritional/metabolic challenges.
For the purposes of this paper, genomic evidence for the presence of a specific biochemical pathway, P1, in humans is taken as evidence that P1 and/or other members of the pathway family to which P1 belongs are likely to be present in humans (including those not yet included in MetaCyc and/or experimentally elucidated). Indeed, PathoLogic sometimes inferred the presence of multiple variant pathways in humans. This occurred because when evidence was found in the genome for the presence of one member of a pathway family/subfamily, this evidence often also supported the presence of other members of this family/subfamily. In these cases, all inferred variants were included in HumanCyc. Of course, the specific members of a given pathway family actually present in humans may include one or more of those inferred from MetaCyc or other members of this pathway family not yet described in MetaCyc and/or not yet experimentally elucidated from any organism. It is attractive to think that multiple variant pathways might refer to metabolically differentiated tissues in the body, or to different regulatory states available to the same tissue. An example of the latter would be the liver; at different times of day it either synthesizes glycogen, taking glucose from the blood, or it degrades glycogen to maintain the blood glucose level.
HumanCyc as a tool
The HumanCyc PGDB is freely available for use by the scientific community from the SRI website [19]. Basic queries to HumanCyc can be issued through the BioCyc Query Page [20]. This page supports a number of query types. For text searches through the DB, for example, enter 'tryptophan' next to the 'Query All (by name)' box, and then click 'submit' to retrieve a list of all enzymes, pathways, compounds, and reactions whose name includes that word. Click on 'Choose from a list of pathways' to generate a list of all pathways within HumanCyc. Click 'submit' near 'Browse Ontology' to browse one of several possible classification hierarchies, such as the ontology that classifies metabolic pathways according to their physiological role.
When viewing a HumanCyc pathway display, be aware that the software omits enzyme names for pathway holes. That is, when no human protein has been identified that catalyzes a reaction within a pathway, no enzyme name is drawn next to that reaction.
The cellular overview [21], a full human metabolic pathway map, provides a tool for analysis of high-throughput datasets. The Omics Viewer [22] allows the user to visualize gene-expression data, protein-expression data, metabolomics measurements, or reaction flux data in a pathway context by painting reaction steps in the metabolic overview with colors that represent the expression levels of the genes coding for enzymes that catalyze those steps.
The PathoLogic summary page for H. sapiens includes a report that lists the evidence for each predicted pathway in HumanCyc, with pathways sorted according to the MetaCyc pathway ontology [23].
HumanCyc is currently available for local installation at your institution [24] as a set of flat files, and as part of an executable program running on Windows/Intel, Linux/Intel and Solaris/Sun. The latter configuration can function as both a desktop application, and as a local mirror of the HumanCyc website on the user's intranet.
Related work
Related databases of human metabolic pathways include the GenMAPP [25] collection of 14 drawings of human metabolic pathways that are available through the web; the KEGG [26] metabolic pathway website, which allows coloring of a set of reference pathway maps to indicate which enzymatic steps have corresponding human enzymes; and the Reactome (Cold Spring Harbor Laboratory, European Bioinformatics Institute (EBI) and the Gene Ontology (GO) Consortium) project, which has curated human metabolic pathways in a web-accessible database [27].
PathoLogic was the first program for automated inference of genome-scale pathway reconstructions from genome data [28]. Additional methods for prediction of metabolic pathways include methods that infer 'extreme pathways' and 'elementary modes' from flux-balance models of reaction networks [29], which have been applied to the human mitochondrion [30]. Rather than recognizing known, historically defined pathways in a large reaction network, as does PathoLogic, these methods infer pathways from the stoichiometric matrix representing a biochemical network by convex analysis. The biological utility and meaning of these pathways, and their correspondence to known metabolic pathways that have been established through experimental studies, remains to be demonstrated. One benefit of pathway analysis by projecting previously known pathways onto a genome using PathoLogic is the fact that projection of known pathways tells us what reactions to expect to occur in another organism, leading to the identification of pathway holes, and the directed search for their fillers. In fact, the occurrence of hundreds of pathway holes in every genome we have analyzed raises the question of how the extreme pathways method can work given that the reaction networks it relies on must omit hundreds of reactions (the pathway holes) as a result of the incompleteness of genome annotations.
The following additional pathway prediction methods are related to this work, but have not been applied on a genome scale and have received little validation. Zien and colleagues use gene-expression data to score pathways that are enumerated combinatorially from a reaction database. Van Helden and colleagues use clustering of gene-expression data to generate seed reactions that are used to combinatorially enumerate pathways [31, 32]. McShan et al. infer novel biotransformation rules for xenobiotics from the molecular graphs of compounds [33]. A recent review discusses the potential for reconstruction of metabolic networks using metabolomics technology [34].
Limitations of HumanCyc and future work
The user of HumanCyc should be aware of several potential limitations that influence the interpretation of the DB contents. First, HumanCyc is incomplete in the sense that some known (and unknown) human metabolic pathways are not present in it. It will require a significant database curation effort to enter all known pathways. Second, HumanCyc probably contains false-positive pathway predictions. Our approach is to err on the side of being more inclusive in our pathway predictions so that all potential pathways are brought to the attention of the scientific community for evaluation. For example, HumanCyc sometimes contains multiple pathway variants that we currently lack the evidence to choose between, and in other cases the actual human pathway may be a variant of the pathway present in HumanCyc. Third, HumanCyc does not encode information about the location (compartment(s), cell type(s) or tissue(s)) in which a pathway occurs. Each pathway is defined using all identified human enzymes, meaning that location-specific versions of a pathway are not specifically identified. Furthermore, the presence of a pathway could be incorrectly inferred because the enzymes that make up a pathway are found in different locations and are never expressed in a common location, meaning that the pathway can never occur in its entirety. Fourth, HumanCyc does not contain nucleotide or amino-acid sequences. Our future work will address the first three of these limitations, and will include a significant effort to manually refine and update HumanCyc with pathway and enzyme information from the biomedical literature. To date, three pathways have been added to HumanCyc through manual curation. Experimentally elucidated pathways in HumanCyc will be annotated as such with evidence codes; pathways predicted by PathoLogic are annotated as computationally inferred.
HumanCyc can be used to develop an agenda for experimental refinement of the human metabolic map. Predicted pathways should be experimentally verified, with particular attention to choosing among multiple pathway variants. Candidate 'fillers' for the 178 unresolved pathway holes identified herein should be identified.
PGDBs endow genomic information with an extended dimension that allows researchers to analyze an organism's genome with respect to the causal relationships inherent to a metabolic network. In this sense, HumanCyc provides the opportunity to look at human metabolic processes within the context of the annotated human genome, and vice versa. The computationally predicted metabolic network provided a rational framework for understanding the genetic basis of some well-characterized human dietary requirements, that is, 11 nonessential amino acids and 22 essential nutrients (9 essential amino-acids and 13 essential vitamins).
PathoLogic's pathway prediction process provides a reasonably accurate picture of the metabolic network, and Pathway Tools provides the user with extensive capabilities for refining the DB to reflect improvements in our understanding of the human metabolic network. The query and visualization capabilities of the Pathway Tools software (such as the visualization of gene-expression data superimposed on the metabolic map) will facilitate novel approaches for analyzing the complexity of functional relationships within the human genome.
Materials and methods
Data gathering and preparation
The PathoLogic program generates a new PGDB starting from the annotated genome of an organism, meaning a complete genome sequence (closed or gapped) for which gene prediction and sequence analyses have already identified the locations of likely coding regions, and have predicted the functions of these genes. We used Ensembl Build 31 as our main data source for the annotated human genome, and complemented that information with data from LocusLink, the National Center of Biotechnology Information (NCBI) database of genetic loci. We used GenBank as our source for the mitochondrion genome, as this information was not included in Ensembl. LocusLink mitochondrial loci were used to complement this information when applicable.
The information from these different sources required special preprocessing to make it available to PathoLogic. That preprocessing addressed three needs: first, to convert the disparate data formats used by these sources into a format parsable by PathoLogic; second, to extract information useful to PathoLogic; and third, to remove redundancy among the sources.
In the case of Ensembl, the standard Ensembl flat files included just a subset of the information needed for the PGDB generation process. We therefore used the EnsMart facility provided by Ensembl [5] to generate files with the required data. EnsMart allows the user to select subsets of the genome (from small regions to entire chromosomes) and output desired data about each gene in different tabular formats. Additional data file 1 lists the genetic element files generated using EnsMart. One file was generated for each human chromosome and contig, with the file names corresponding to the chromosome and contig names in Ensembl. When the corresponding chromosome for a given contig was known, the contig's file name would be constructed by prepending the chromosome's name to the contig's name, otherwise 'Un', for unknown, was prepended to the contig's name.
Information extracted from different data sources
Data source (version)
Information extracted (for each gene or locus)
Number of genes
Ensembl (Build 31)
Gene name, chromosome or contig, start and end positions, strand (transcription direction), exons, gene-product (including function name(s) or description(s), synonyms and EC number(s)), cross references (IDs) to other databases (SwissProt, HUGO, PDB, GO, RefSeq, OMIM, Entrez, SPTREMBL, EMBL, LocusLink).
LocusLink (03/29/2003)
Gene name, chromosome, gene product (function name or description), function synonyms, EC number(s), gene and protein comments, cross references (IDs) to other databases (Entrez, UCSC Genome, RefSeq, GO, OMIM, UniGene, PubMed)
GenBank NC_001807 (mitochondrion)
Gene name, start and end positions, transcription direction, gene product (function name or description)
When generating the input files for PathoLogic, information from Ensembl and LocusLink was combined only when the Ensembl record for a gene included a cross reference to a LocusLink ID. In such a case, data from the LocusLink entry was merged with that of the Ensembl gene, meaning that when both databases provide an attribute such as a gene name, the Ensembl data is preferred. This approach created gene objects for HumanCyc that include information from both the Ensembl and the LocusLink entries. Those HumanCyc gene objects use the Ensembl ID as their unique identifier, and have database links to the corresponding LocusLink entries. For the mitochondrial data, the number of LocusLink mitochondrial loci was small enough so that they were easily checked for matches with corresponding genes in the GenBank files.
LocusLink loci that had no direct counterpart in either the Ensembl data or the GenBank mitochondrial data (for example, LocusLink loci that were not directly referenced in any Ensembl gene record) were assigned their own record in the PathoLogic input files. The LocusLink ID was used as the unique identifier for these gene objects. Only loci corresponding to 'real' genes (not models, phenotypes or pseudogenes) were included in HumanCyc. We must point out that records corresponding only to LocusLink loci lack gene position information, so they cannot be precisely placed on a chromosome map. We were aware that adding these LocusLink-only-based records to HumanCyc would produce some redundancy in the database, but this was accepted for the sake of completeness. Manual analysis of similar Ensembl and LocusLink-based gene objects after building HumanCyc led to the fusion of gene objects corresponding to the same gene. The number of LocusLink gene objects that were not merged to corresponding gene objects from Ensembl or GenBank is shown in the 'nonredundant' column of Table 7.
It is readily apparent from Table 7 that HumanCyc, thanks to the combination of the Ensembl and LocusLink data sources, has excellent cross-reference coverage to many other biological databases (including Ensembl and LocusLink themselves). In addition to the databases mentioned in Table 7, we added links to the GeneCards genomic database for those genes with known HUGO IDs.
Seventy-six PathoLogic input files were generated from the preceding data sources: 24 for the human chromosomes, one for the mitochondrion, 50 for the different contigs not yet integrated to the chromosomal sequences, and one called 'unknown' for all the loci that had no chromosome information. A replicon object was created in HumanCyc for each of these files.
Prediction of human metabolic pathways using PathoLogic
This section summarizes the PathoLogic algorithm (for a more detailed description of the method see [36, 37]). For an evaluation of the accuracy of PathoLogic see [36].
After initializing the schema of the new PGDB, a database object is created for each replicon and contig, and for each gene and its corresponding gene product. PathoLogic then tries to determine the metabolic reaction catalyzed (if any) by each gene product in the organism by using its EC number, if provided in the annotation, and by matching the name of each gene product against the extensive dictionary of enzyme names within the MetaCyc DB [15]. Finally, the list of reactions now known to be catalyzed by the organism is matched against all the pathways in MetaCyc. For pathways with significant numbers of matches (see [36] for a detailed description of this algorithm), PathoLogic imports the pathway and its associated reactions and substrates from MetaCyc into the new PGDB. This method of pathway prediction is analogous to predicting the function of a protein based on sequence similarity to a protein of known function, in that both methods recognize the presence of something known (a known pathway versus a known protein function) based on a similarity between patterns (a pattern of enzymes present versus a sequence pattern). The two methods share similar limitations: just as sequence similarity cannot predict protein functions that are not in the sequence database, PathoLogic cannot predict pathways that are not in MetaCyc.
As mentioned above, PathoLogic will assign reactions for those enzymes that have an exact EC number match or name match against MetaCyc. A gene product name may not exactly match that of any enzyme in MetaCyc. Some enzyme names will produce ambiguous matches or no match at all. PathoLogic assembles a list of 'probable enzymes' that includes both ambiguous matches and nonmatched proteins whose names suggest enzymatic activity. This list is examined manually through a PathoLogic module that helps the user evaluate possible matching candidates within MetaCyc and assign probable enzymes to the correct reaction, if possible.
An alternative to our strategy of using the existing EC number and function assignments from LocusLink and Ensembl would be for us to discard those assignments and to reanalyze the genome using sequence analysis methods to produce new assignments. We rejected this approach for two reasons: first, it would discard some experimentally derived function assignments in place of less reliable computational assignments; and second, we consider the Ensembl function predictions to be of high quality, and we are aware of no evidence that our group, or any other group, has a sequence analysis methodology that will produce function assignments that are substantially more accurate than those of Ensembl.
Finally, PathoLogic generates reports summarizing the amount of evidence supporting each pathway in the new PGDB, and listing the pathway holes, that is, the enzymes missing from each predicted pathway. This information helps the user identify pathways that should be deleted from the PGDB, such as variant pathways and false-positive predictions made by PathoLogic. For example, MetaCyc includes eight variants of the TCA cycle. Several of these might appear in a newly predicted PGDB. False-positive pathways, some of which are predicted because they share reactions with other pathways in MetaCyc, should be removed from the PGDB. Once variant or false-positive pathways are eliminated by the user, PGDB generation has been completed.
Filling holes in HumanCyc pathways
To determine the function of a protein sequence, researchers typically use a single sequence to search for potential homologs in a large public database. To identify sequences to fill pathway holes, we have, in effect, reversed this search process. We search the genome for a sequence that will provide the enzymatic function needed to fill each pathway hole. Our method uses multiple isozyme sequences (retrieved via MetaCyc from Swiss-Prot and PIR) to search a genome for similar sequences (hole-filler candidates). We then evaluate each candidate to determine the probability that the sequence has the desired function based on homology and pathway-based data. A hole-filler tool that implements this pathway-driven gene-finding methodology has been developed [9].
Analysis of HumanCyc metabolic network
Once HumanCyc was built and manually refined, as explained above, we examined the metabolic network within HumanCyc in order to make a preliminary assessment of the quality of PathoLogic's predictions and to check for pathways not previously thought to occur in humans. We also compared the metabolic network of HumanCyc to that of two of our curated PGDBs, corresponding to a bacterium and a plant. These PGDBs are EcoCyc (E. coli) and AraCyc (A. thaliana).
Additional data files
The following additional data are available with the online version of this article. Additional data file 1 contains a table listing the data file names generated from EnsMart for each human chromosome or contig and provided as input to PathoLogic, thus indicating which contigs are associated with which chromosomes.
This work was supported by funds from a major pharmaceutical company, and by grants R01-HG02729-01 from the NIH National Human Genome Research Institute, R01-GM65466-01 from the NIH National Institute for General Medical Sciences, and DE-FG03-01ER63219 from the US Department of Energy. The contents of this article are solely the responsibility of the authors and do not necessarily represent the views of these sponsors.
Authors' Affiliations
- Karp PD, Paley S, Romero P: The Pathway Tools software. Bioinformatics. 2002, 18: S225-S232.View ArticleGoogle Scholar
- EcoCyc: encyclopedia of Escherichia coli K12 genes and metabolism. [http://EcoCyc.org]
- Karp PD, Riley M, Saier M, Paulsen IT, Collado-Vides J, Paley SM, Pellegrini-Toole A, Bonavides C, Gama-Castro S: The EcoCyc Database. Nucleic Acids Res. 2002, 30: 56-58. 10.1093/nar/30.1.56.View ArticleGoogle Scholar
- Karp PD: Pathway databases: a case study in computational symbolic theories. Science. 2001, 293: 2040-2044. 10.1126/science.1064621.View ArticleGoogle Scholar
- Clamp M, Andrews D, Barker D, Bevan P, Cameron G, Chen Y, Clark L, Cox T, Cuff J, Curwen V, et al: Ensembl 2002: accommodating comparative genomics. Nucleic Acids Res. 2003, 31: 38-42. 10.1093/nar/gkg083.View ArticleGoogle Scholar
- Pruitt KD, Maglott DR: RefSeq and LocusLink: NCBI gene-centered resources. Nucleic Acids Res. 2001, 29: 137-140. 10.1093/nar/29.1.137.View ArticleGoogle Scholar
- Benson DA, Karsch-Mizrachi I, Lipman DJ, Ostell J, Wheeler DL: GenBank. Nucleic Acids Res. 2003, 31: 23-27. 10.1093/nar/gkg057.View ArticleGoogle Scholar
- HumanCyc pathways. [http://biocyc.org/HUMAN/class-subs-instances?object=Pathways]
- Green ML, Karp PD: A Bayesian method for identifying missing enzymes in predicted metabolic pathway databases. BMC Bioinformatics. 2004, 5: 76-10.1186/1471-2105-5-76.View ArticleGoogle Scholar
- HumanCyc release note history. [http://biocyc.org/humancyc/release-notes.shtml]
- Peregrin-Alvarez JM, Tsoka S, Ouzounis CA: The phylogenetic extent of metabolic enzymes and pathways. Genome Res. 2003, 13: 422-427. 10.1101/gr.246903.View ArticleGoogle Scholar
- McGraw-Hill Dictionary of Bioscience. Edited by: Parker SP. 1997, New York: McGraw-HillGoogle Scholar
- Mueller LA, Zhang P, Rhee SY: AraCyc: a biochemical pathway database for Arabidopsis. Plant Physiol. 2003, 132: 453-460. 10.1104/pp.102.017236.View ArticleGoogle Scholar
- Ouzounis CA, Karp PD: Global properties of the metabolic map of Escherichia coli. Genome Res. 2000, 10: 568-576. 10.1101/gr.10.4.568.View ArticleGoogle Scholar
- Karp PD, Riley M, Paley SM, Pellegrini-Toole A: The MetaCyc Database. Nucleic Acids Res. 2002, 30: 59-61. 10.1093/nar/30.1.59.View ArticleGoogle Scholar
- MetaCyc glycolysis. [http://biocyc.org/META/new-image?object=GLYCOLYSIS-VARIANTS]
- MetaCyc leucine. [http://biocyc.org/META/new-image?object=LEUCINE-DEG]
- MetaCyc NAD. [http://biocyc.org/META/new-image?object=NAD-SYN]
- HumanCyc: Encyclopedia of Homo sapiens genes and metabolism. [http://HumanCyc.org]
- BioCyc query page. [http://biocyc.org/HUMAN/server.html]
- H. sapiens metabolic overview map. [http://biocyc.org/HUMAN/new-image?type=OVERVIEW]
- The Pathway Tools Omics Viewer. [http://biocyc.org/expression.html]
- PathoLogic summary pages for H. sapiens. [http://biocyc.org/HUMAN/pathologic-index.html]
- BioCyc introduction to downloads. [http://biocyc.org/download.shtml]
- Dahlquist KD, Salomonis N, Vranizan K, Lawlor SC, Conklin BR: GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat Genet. 2002, 31: 19-20. 10.1038/ng0502-19.View ArticleGoogle Scholar
- Kanehisa M, Goto S, Kawashima S, Nakaya A: The KEGG databases at GenomeNet. Nucleic Acids Res. 2002, 30: 42-46. 10.1093/nar/30.1.42.View ArticleGoogle Scholar
- Reactome. [http://www.reactome.org]
- Karp PD, Ouzounis C, Paley SM: HinCyc: a knowledge base of the complete genome and metabolic pathways of Haemophilus influenzae. Proc Int Conf Intell Syst Mol Biol. 1996, 4: 116-124.Google Scholar
- Papin JA, Stelling J, Price ND, Klamt S, Schuster S, Palsson BO: Comparison of network-based pathway analysis methods. Trends Biotechnol. 2004, 22: 400-405. 10.1016/j.tibtech.2004.06.010.View ArticleGoogle Scholar
- Vo TD, Greenberg HJ, Palsson BO: Reconstruction and functional characterization of the human mitochondrial metabolic network based on proteomic and biochemical data. J Biol Chem. 2004, 279: 39532-39540. 10.1074/jbc.M403782200.View ArticleGoogle Scholar
- van Helden J, Wernisch L, Gilbert D, Wodak SJ: Graph-based analysis of metabolic networks. Ernst Schering Res Found Workshop. 2002, 38: 245-274.Google Scholar
- Zien A, Kuffner R, Zimmer R, Lengauer T: Analysis of gene expression data with pathway scores. Proc Int Conf Intell Systems Mol Biol: 2000. 2000, San Diego, CA: Morgan Kauffman Publishers, 407-417.Google Scholar
- McShan DC, Updadhayaya M, Shah I: Symbolic inference of xenobiotic metabolism. Pac Symp Biocomput. 2004, 545-556.Google Scholar
- Kell DB: Metabolomics and systems biology: making sense of the soup. Curr Opin Microbiol. 2004, 7: 296-307. 10.1016/j.mib.2004.04.012.View ArticleGoogle Scholar
- Boeckmann B, Bairoch A, Apweiler R, Blatter MC, Estreicher A, Gasteiger E, Martin MJ, Michoud K, O'Donovan C, Phan I, et al: The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res. 2003, 31: 365-370. 10.1093/nar/gkg095.View ArticleGoogle Scholar
- Paley SM, Karp PD: Evaluation of computational metabolic-pathway predictions for Helicobacter pylori. Bioinformatics. 2002, 18: 715-724. 10.1093/bioinformatics/18.5.715.View ArticleGoogle Scholar
- Romero P, Karp P: PseudoCyc, a pathway-genome database for Pseudomonas aeruginosa. J Mol Microbiol Biotechnol. 2003, 5: 230-239. 10.1159/000071075.View ArticleGoogle Scholar
- H. sapiens Pathway: oxidative ethanol degradation . [http://biocyc.org/HUMAN/NEW-IMAGE?type=PATHWAY&object=PWY66-21]
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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Perl Module Monday: Chart::Clicker
I've been interested in the Chart::Clicker package for a while, and today it came up in a series of Twitter messages in my #perl search. So that seemed like a sign that it would be a good pick for this week's feature.
Chart::Clicker is a mature, very feature-rich charting package that comes with a cookbook and many examples (the code for the examples is available on GitHub). There's also a tutorial POD in the distribution. It does pie charts, line graphs, bar graphs, area graphs, stacked bar or area or line graphs, points, bubbles, or candlestick-style charts. In short, it makes pretty pictures in Perl:
The above is just one of the images shown as examples of what Chart::Clicker can do.
The module bases its rendering on Graphics::Primitive, specifically Graphics::Primitive::Driver::Cairo. This means it can render the chart in any format Cairo supports; PNG, PDF, even SVG among others. The internal object-model is based on Moose, which leads to keeping potentially-duplicate code to a minimum. Using the package is about as complex as you need your graph to be: a simple graph with a single set of data can be created in just 5 lines of code or so, while some of the examples are much more complicated scripts.
I'm surprised to see (according to CPANTS) that this module is not a component in any other packages' lists of dependencies. It would seem to me to be a logical bit of functionality to integrate into a Catalyst view, or any stats package. I won't be surprised if this changes in the near future, as (hopefully) more people start using the package.Tags: CPAN, module-monday, Perl


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Suzanne Lescure
My story begins in September 2003. I had a freckled spot on the inner corner of my eye. I had always thought it was just a freckle. One day I noticed a growth on the surface of my eye, it was flesh colored. My opthalmologist was not worried. He thought it was a pterygium, which is a benign growth, and he said those are usually 99.1% benign. I was scheduled for surgery right away.
Well, guess what? The doctor called me two days after the operation and said that the initial pathology report showed that it was malignant melanoma. He then referred me to an Ocular Oncologist in San Francisco. Thus began my journey of surgeries (over 12 at least), proton beam radiation and chemotherapy eye drops, Mitomycin and 5-FU. This was my course for the next three years.
In November 2006, I noticed a swollen lymph gland under my jawline. I was hoping that I was just coming down with a bug. I was put on antibiotics and after two weeks it was still there, same size. I had a fine needle biopsy and it was positive for melanoma. Great, now it has spread. I was scheduled for a radical neck dissection. The surgeon removed several nodes and almost half were positive. What I didn't know at the time was that on my chest xray I had for the pre-op, there was a spot on my lung. My surgeon informed me of the news when I went to my post operative appointment.
Now that I was thrust to stage IV status, my case was put before a tumor board. The lead doctor came in to the exam room and said with stage IV melanoma I had six to nine months to live if I did not choose a radical treatment. It was Biochemotherapy. That was the ONLY treatment offered to me. I was scared to my very core. I saw my life flash before my eyes, I still had a 14 and 19 year old to raise.
By now I had an oncologist that set me up for Biochemo. I started the treatment one week before Christmas of 2006. Due to the toxicity of the treatment, it is only done in a hospital inpatient setting.
Every month for 18 months I packed my bag and headed off to California Pacific Medical Center in San Francisco.. The first six cycles consisted of Biochemotherapy with Interleukin 2. The remaining twelve cycles were IL-2 only. I felt all the side effects my doctor said I would get, no matter if it was the first six months or the last twelve, it didn't matter, it was just extremely brutal.
During the time of my treatment, my mother was dying from cancer just as I was fighting cancer. Unfortunately she passed away three months before I completed my treatment.
I have been cancer free since November 2006 (my oncologist explained to me that you count the time when you first start treatment rather than the the finishing date. Something I hadn't known!). I still continued to get the pigmented spots on the surface of my eye once I finished up with treatment. Then began the same cycle of eye surgery after eye surgery about every four months.
My oncologist suggested that I have my eye removed because now, not only was I getting the pigments ON my eye, but I was getting some on my eyelid and underneath my eye.
In the beginning of October 2011, I flew to Philadelphia and saw my doctors from the Wills Eye Hospital. I had gone to seek a second opinion and really liked their team. My primary Ocular Oncologist agreed with my oncologist from home that that would be a wise thing to do.
On October 14th, I underwent an exenteration, where they not only take out the eye but remove the surrounding lid and tissues as well. To me it would be far scarier not knowing at what point melanoma goes systemic. I did not want to take that chance to have that happen like it did in 2006.
I had surgery at Jefferson University Hospital in Philadelphia and had a whole team of head and neck doctors along with my ocular doctor performing the surgery. My surgery was ten hours long. They grafted a piece of tissue from my thigh and used that to cover the eye cavity. My thigh was in more pain than my eye area!
In a few months time, when I am healing, I will meet with an Anaplastologist who will construct a prosthetic eye "mask" made up with an artificial eye with the surrounding skin. It looks totally life like. I can attach this to my face with adhesive.
I have always been an optimistic person and now I feel like I have a whole new lease on life. I am hopeful that I will be here for a long time and that I will live to see a cure for melanoma!
Suzanne Lescure, California, 11/28/11
Re: Suzanne Lescure(2/22/2012 - 4:36pm)
I am a 2nd year medical student avidly interested in Dermatology. Your story was poignant and encouraging. I am incredibly touched by your experiences and feel extremely motivated to pursue my dream.
I wish you the best in your fight against Melanoma.
Annalise A., MS II
Re: Suzanne Lescure(7/23/2012 - 9:11pm)
Suzanne, I would love to talk to you. I also had a spot on the inside corner of my right eye removed. It is conjunctival melanoma. It was small at .27mm thick. I am interested in hearing more of your story I haven't found anyone whose story is so close to mine. I had positive margins after the initial "freckle-ectomy" so had to go back for a second surgery. Ins approved a ct scan after 5 request nd all was good. I try to read everything I can find on this disease to be as informed as possible without becoming completely obsessed. It is a fine line for sure. But any headache sets my mind into overdrive of "what if ".... My email is email@example.com I hope you are well and I look forward to hearing from you. Zsa Zsa
Never flirt with a freckle ; )


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Earth Day is a worldwide yearly event held on April 22nd each year. Connect with your friends around the world and help spread the awareness.View More
Easter in 2019 takes place on Sunday, April 21. For kids, Easter is usually a fun time to enjoy activities such as painting and decorating hard-boiled eggs.View More


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DENVER Democrats passed their five remaining gun bills through the Senate on Monday, a major milestone on the bills torturous journey through the Legislature.
Mondays votes came after a daylong debate Friday that lasted until nearly midnight and that saw Democrats withdraw two of their most controversial bills.
The bills that died Friday would have banned concealed weapons on college campuses and imposed legal liability on the owners and sellers of many types of guns.
The surviving bills would require background checks on private-party gun sales, charge gun buyers for their background checks, mandate in-person training for concealed weapons permits, force some domestic violence suspects to give up their guns and ban ammunition magazines larger than 15 rounds.
Sen. Morgan Carroll, D-Aurora, argued for her background-check bill, saying it will prevent criminals from getting guns.
There is no way other than a background check to make sure those folks dont access firearms, Carroll said. If we fail to close this loophole, we are saying that the difference between law-abiding citizens and criminals isnt worth making.
Republicans saved their strongest opposition for the bill banning larger ammunition magazines.
Sen. Greg Brophy, R-Wray, said he would break the law if it passes.
Im going to tell you right now: I will not obey this law, Brophy said.
Sen. Ellen Roberts, R-Durango, said Republicans are not right-wing wackos for opposing the magazine limit because some gun owners fear civil unrest.
I look at Syria today, I look at Egypt today again, I dont think its lunatic fringe to have concerns about that, Roberts said.
Also, people in rural areas are often far away from police protection, she said.
Throughout the debate, Republicans have charged Democrats with kowtowing to the White House and New York City Mayor Michael Bloomberg, a gun-control advocate.
Please do not be confused that the goals and objectives of Barack Hussein Obama, of Joe Biden, of Michael Bloomberg, are the same goals and objectives of the majority of your constituents, said Sen. Steve King, R-Grand Junction.
King made reference to a call that Biden made to Rep. Mike McLachlan, D-Durango, to lobby for several of the bills. Opponents are trying to recall McLachlan for his votes on gun control.
I look forward to the vice president of the United States coming to Colorado and going to Durango to help the representative on his recall election. He owes him that, King said.
The debate has put legislators through a trying month, sometimes with violent overtones.
Sen. Jessie Ulibarri, D-Commerce City, said he and other legislators have gotten death threats. One man told him he carried an AR-15 to keep Mexicans out of Colorado.
In one breath, someone says, Im a law-abiding gun owner, and in the next says, I really cant wait until your child is raped, Ulibarri said. It is very, very difficult for me to stand here and say this debate has been civil, or that there are folks who arent wishing me and my family harm using the tools and implements that were discussing today.
Roberts became one of the first two Republicans to support any of the Democrats gun bills when she voted to require in-person training to get a concealed-weapons permit.
Most of the bills will have to go to the House for further votes before they pass the full Legislature.


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Dear all…
Diantara 12 jenis teks yang dipelajari di tingkat menengah atas, Teks Narrative adalah jenis teks yang paling sering dipelajari. Setiap semester kalian pasti mendapatkan pelajaran tentang teks yang satu ini.
Teks Narrative kita kenal juga sebagai teks naratif dalam bahasa Indonesia. Hanya saja dalam bahasa Inggris, teks Narrative memiliki lingkup yang lebih sempit. Seperti kita tahu yang namanya teks naratif yang ada dalam pelajaran bahasa Indonesia itu adalah teks tentang cerita, baik itu cerita tentang pengalaman seseorang, cerita lucu, dongeng, mitos, legenda, fable, dll. Namun dalam pelajaran bahasa Inggris contoh teks tersebut dibagi dalam Teks Narrative, Spoof, dan Recount. Misalnya saja kalau teks tentang pengalaman seseorang dalam pelajaran bahasa Inggris disebut Recount, teks cerita yang lucu disebut Spoof. Nah.. kalau Narrative adalah teks yang berupa dongeng, mitos, legenda, fable, dll.
Namanya juga narrative atau cerita, teks Narrative adalah teks yang menceritakan sebuah kisah yang sudah terjadi di masa lampau. Makanya kata kerja yang digunakan menggunakan bentuk Past Form. Misalnya:
Long time ago, there lived a woman near the river.
Finally, one of the frogs took heed to what the other frogs were saying and gave up.
Text *1 (Fabel)
A group of frogs were travelling through the woods, and two of them fell into a deep pit. When the other frogs saw how deep the pit was, they told the two frogs that they were as good as dead. The two frogs ignored the comments and tried to jump up out of the pit with all their might. The other frogs kept telling them to stop, that they were as good as dead.
Finally, one of the frogs took heed to what the other frogs were saying and gave up. He fell down and died.
The other frog continued to jump as hard as he could. Once again, the crowd of frogs yelled at him to stop the pain and just die. He jumped even harder and finally made it out.
When he got out, the other frogs said, "Did you not hear us?" The frog explained to them that he was deaf. He thought they were encouraging him the entire time.
Note: Fabel menceritakan kisah yang diperankan oleh hewan di mana kita bisa mendapatkan pesan moral dalam cerita tersebut yaitu 'There is power of life and death in the tongue'.
Text *2 (Myth)
Once upon a time in the heavens the Batara Guru commanded all the gods and goddesses to contribute their power in order to build a new palace. Anybody who disobeyed this commandment would lose his or her head.
Upon hearing the Batara Guru''s commandment, one of the gods, Anta, was very anxious. He didn't have arms or legs and he wasn't sure how he could possibly do the job. Anta was shaped as a snake and he couldn't work. He sought advice from one of his friends but unfortunately his friend was also confused by Anta's bad luck. Anta became very upset and cried.
As he was crying three teardrops fell to the ground. Amazingly, after touching the ground those teardrops became three eggs. His friend advised him to offer those eggs to the Batara Guru hoping that he would give a fair judgement.
With the three eggs in his mouth Anta went to the Batara Guru's palace. On the way there he was approached by a black bird who asked him a question. He couldn't answer because of the eggs in his mouth but the bird thought that Anta was being arrogant. It became furious and began to attack Anta and as a result one egg was shattered. Anta quickly tried to hide in the bushes but the bird was waiting for him.
The second attack left Anta with only one egg to offer to the Batara Guru.
Finally he arrived at the palace and offered his teardrop (in the shape of an egg) to the Batara Guru. The offer was accepted and the Batara Guru asked him to nest the egg until it hatched. Miraculously the egg hatched into a very beautiful girl. He gave the baby girl to the Batara Guru and his wife.
Nyi Pohi Sanghian Sri was her name and she grew up into a beautiful princess becoming more and more beautiful as the days passed by. As her beauty grew every man who saw her became attracted to her. Even her stepfather the Batara Guru started to feel an attraction toward her.
Seeing the Batara Guru's new attitude toward Nyi Pohaci, all the gods became so worried about the situation that they conspired to separate Nyi Pohaci and the Batara Guru.
To keep the peace in the heavens and to maintain Nyi Pohaci's good name, all the gods planned for her death. She was poisoned and her body buried on earth in a hidden place. But the graveyard was to hold a strange sign, for at the time of her burial, up grew a very useful plant that would forever benefit all human beings.
From her eyes grew the plant that is called padi (rice paddy).
Note: Mitos adalah teks yang menceritakan tentang terjadinya alam semesta, dunia, kisah para dewa, dll. Mitos di Indonesia biasanya menceritakan tentang terjadinya alam semesta, terjadinya susunan para dewa, terjadinya manusia pertama, dunia dewata, dan terjadinya makanan pokok. Mengenai mitos terjadinya padi, dikenal adanya Dewi Sri yang dianggap sebagai dewi padi orang Jawa.
Text *3 (Legend)
A long long time ago in west Sumatra, Indonesia there was a fisherman and his wife who lived in a village by the sea. They had only one son. His name was Malin Kundang. They lived a simple life because as a fisherman the husband did not earn much money. Life got harder for Malin and his mother when his father did not return from the sea. Perhaps a storm had swollen his boat or maybe a big fish attacked him. Day by day passed and they kept waiting for him. But Malin's father never returned. So little Malin had to help her mother sold cookies in a local market.
One day there was a big ship came to the beach of their village. It was a merchant ship. Everybody came to see it including Malin. He was very impressed by what he saw. Hoping to change his life he applied for a job and he was lucky. He was recruited by the ship owner. Then Malin left his mother and his village.
Many years gone by without any news from Malin. Malin's mother missed him so much. Everyday she looked at the sea, hoping to see Malin came home. She always prayed to God that Malin become a successful merchant. Then God heard her pray.
On a beautiful day there was a big ship came to the beach. Many people came there to see it. Malin's mother was expectant. She was sure that it was Malin's ship. So she hurriedly came to the beach. When she was there she asked someone that she wanted to see the owner of the ship. Then a lovely lady met her. She wore a luxurious dress and jewellry. She was Malin's wife.
'Is Malin Kundang here?'
"Do you know Malin?"
'Yes, of course I know him, he's my son!'
'But Malin told me he had no mother. She passed away a long time ago'.
Malin's mother was very surprised to hear her answer. Then Malin came. Her wife asked him.
'This poor woman said that you are his son'
Malin Kundang who had became a rich merchant and had a wife from a rich family was ashame with his mother who looked poor. He denied his humble background. So when her mother hugged him he repelled her.
'Malin, my son, I miss you so much'.
'Who are you? I am not your son'.
Malin's mother was was crying. She was really irritated. Her heart was deeply hurt. Then she prayed to God. And she cursed Malin.
Suddenly there was a storm. The sea was raging. Big wave came and Malin's ship was rushed ashore and destroyed. And Malin suddenly changed into a stone statue. Today people can see Malin's statue in Teluk Bayur beach in west Sumatra. When there is a storm or rain people often hear someone's crying. They believe it is Malin's cry.
Note: Legenda adalah cerita yang dipercaya oleh sebagian masyarakat benar-benar terjadi.
legenda adalah dongeng tentang hal-hal yang berdasarkan sejarah yang mengandung sesuatu hal yang ajaib atau kejadian yang menandakan kesaktian.
The social function of Narrative is to amuse or entertain the readers with actual or imaginary experience in different ways. Narrative always deals with some problems which lead to the climax and then turn into a solution to the problem.
There are three kinds of Generic Structure:
1. Orientation (who was involved, when and where was it happened)
2. Complication (a problem arises and followed by other problems)
3. Resolution (provide solution to the problem)
Language features:
1. Use of noun phrases (a beautiful princess, a huge temple)
2. Use of adverbial phrases of time and place (In the garden, two days ago)
3. Use of simple past tense (He walked away from the village)
4. Use of action verbs (walked, slept)
5. Use of adjectives phrases (long black hair)


text:
All happened in this thread:
[Catalyst] building 'local' lib with dependencies for shipping
where Fernan Aguero asked how to pack a catalyst application with all the needed dependencies. The problem is that if you want to do it platform independent you need to do it by setting list of dependencies (and your current versions of modules) and and use a method to automatically install all of them.
One of the solutions was to use Shipwright, created by Best Practical. It didn't work the first run but seemed the right tool so after a few messages more in the list, Fernan contacted with one of the developers and:
I contacted sunnavy (one of the Shripwright developers) and this is what he said: "I found the archive( PerlMagick ) has an interesting files format, which shipwright didn't handle before. I just released 2.4.25 to fix this, which will show up in cpan soon. in case you are hurry, here it is: http://goo.gl/6Jtzz"; Just tested 2.4.25 and shripwright now imported all of the dependencies for my cat app correctly. I'm now building my ship :) and will get into testing the catalyst app running from the vessel soon.
It is nice to see that collaboration works in the Perl world.


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By Andy Pulverenti, Missouri Valley Sports Information Director
Marshall, Mo. (July 17, 2014) - Missouri Valley College Freshman Safety Chandler Houtman (Owasso, Okla.) is coming home with a gold medal after playing in the International Federation of American Football (IFAF) World Championship in Kuwait City, Kuwait this month.
Houtman was one of 45 players that represented the United States at the 2014 IFAF Under-19 World Championship which consisted of an eight-team tournament featuring teams from the U.S.A., Austria, Canada, France, Germany, Japan, Kuwait and Mexico.
Houtman finished with 5.5 tackles, one interception and one pass break-up in the four victories. In pool play the US team defeated Mexico 49-14, Germany 54-0 and Japan 43-0. In the Gold Medal game, the United States knocked off Canada 40-17.
"I can't even describe how it felt to represent the United States," said Houtman. "Representing millions of people playing the sport that I love is something that is one of a kind."
Houtman was selected to the Under-19 USA team in late May and joined the team for the first time for a training camp at Shenandoah University in Winchester, Va., in late June. From there Houtman and the United States team played four games at the IFAF Under-19 World Championship from July 8-16.
"The team came together at the start of camp just over three weeks ago as complete strangers," said Houtman. "Now after everything is done, I feel like I've known each one of them my whole life. Even the coaches were amazed at how close we were as a group."
Houtman also got the chance to interact with the people of Kuwait and learn about the country's culture.
"Everyone in Kuwait has the greatest respect for Americans," said Houtman. "They were all so nice and were always wanting to take pictures with us."
USA Football is based out of Indianapolis, Ind., and is the sport's National governing body, leading the game's development for youth, high school and other amateur football players and is a nonprofit organization.
"Everyone in the Viking football program is really proud of Chandler and his accomplishments with the National team," said Missouri Valley College Head Football Coach Paul Troth. "Chandler represented the country and the Viking program well. Not many people can say that they won a gold medal at a worldwide competition."
The Missouri Valley College football season begins Sept. 13 with the HAAC/KCAC Challenge. The No. 7 Vikings will host No. 8 Tabor College (Kan.) at Gregg-Mitchell Field in Marshall, Mo., with kickoff at 6:00 p.m.


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JDRF is committed to creating a world without type 1 diabetes (T1D). But we wouldn't be able to fund critical research to get there without the generosity of donors like you.
By supporting JDRF One Walk with a tax-deductible gift today, you're helping fund new treatments to make living with T1D safer and healthier, until there is a cure.
Thank you so much for your support.


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Like most kids, Seattle Seahawks tight end Luke Willson couldn't just pick one sport.
"People would ask me what my favorite sport was growing up," Willson, a former Rice tight end, said Friday afternoon. "Whatever season it was, that was my favorite.
"If it was hockey season, it was hockey. If it was baseball season, it was baseball. If it was football season, it was football. I always knew I wanted to play one of them professionally."
'What a journey'
Far from his hometown LaSalle, a bedroom community for Windsor, Ontario, to the tree-lined Rice campus, Willson, a rookie with the Seahawks, will play on one of the world's biggest sports stages in Sunday's Super Bowl XLVIII against the Denver Broncos.
Willson will become the seventh Rice player to play in a Super Bowl, joining Rodrigo Barnes, O.J. Brigance, Earl Cooper, Darryl Grant, Courtney Hall and Larry Izzo.
Willson (6-5, 251) never set his sights on playing in a Super Bowl, but his time was divided growing up.
He played hockey until his sophomore year in high school. He batted cleanup for the Canadian junior baseball team, and he signed a minor league contract to attend extended spring training with the Toronto Blue Jays before his senior year at Rice.
Just 13 months ago, Willson was playing in his final college game – against Air Force in the Bell Helicopter Armed Forces Bowl.
"What a journey," Willson said.
Willson, a fifth-round selection, was the Seahawks' No. 2 tight end this season. He caught 20 passes for 272 yards and one touchdown, a 39-yard pass from Russell Wilson in Week 14 against San Francisco.
From 'bleak' to bright
With the Seahawks, Willson has proved to be a capable downfield receiving threat as well as an adequate blocker.
"I really feel like I fit in and it's a great place for me," Willson said. "I was extremely blessed to be chosen by Seattle."
Yet Willson wasn't sure if he would get the chance. He wasn't on most NFL team's radar after an injury-plagued senior season limited him to career-low nine receptions for 126 yards.
The two previous seasons Willson was among the Owls' most productive receivers with 62 catches for 738 yards while sharing time with Vance McDonald, a second-round pick by the San Francisco 49ers.
At Rice's pro day, Willson ran the 40-yard dash in 4.51 seconds.
"There was a time in my football career that things looked a little bleak," he said. "I didn't put up huge numbers [my senior year]. I didn't really know what the future held. It was tough, but you have to work through it. I'm here now so I'm thankful for that."
Willson met up with McDonald, his former college roommate, in the NFC championship game, a 23-17 Seattle win. After the game the two former Owls exchanged jerseys.
"It was really an emotional moment, playing in a game of that magnitude against one of your best friends," Willson said.
On Friday, Willson's high school, St. Thomas of Villanova, posted a YouTube video showing a packed gymnasium of students wearing Seahawks colors and chanting for Willson.
"I'm really proud of the support I've gotten from back home in Canada," he said. "The whole school was going crazy and wishing me good luck."


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In Tom Clancy's Ghost Recon 3, players will embody Captain Scott Mitchell as he commands the Ghosts and Special Forces allies equipped with the IWS (Integrated Warfighter System) in the quest to save the president of the United States, recover stolen nuclear codes and eliminate a vicious band of renegade soldiers hell-bent on unleashing catastrophe. The game unfolds entirely in Mexico City, where numerous, meticulously researched and detailed environments will deliver complete immersion into the future of urban warfare.
If you are a fan of the Ghost Recon series, check out the latest game in the series, Tom Clancy's Ghost Recon Future Soldier . Available for the PlayStation 3, Xbox 360 and PC.


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Youth learn cope with issues, stay out of trouble
There was a time to face reality, and a time for having fun.
The time for both was Saturday at the 20th Annual Teen Fest, sponsored by the Young Women�s Outreach Center. The event was held for ages 10-18 at Lenoir Community College.
There were workshops in the morning for the girls and for the boys, as well as classes on subjects such as drugs and alcohol prevention, self esteem, date rape, sexually transmitted diseases, teen pregnancy prevention, bullying and environmental control.
Following a lunch, the teens watched live entertainment in the afternoon.
Brionna Harrison, 16, of Snow Hill, took a workshop on self-esteem. She said a lot of young people have issues with how they feel about themselves.
�Basically,� she said about what she gleaned from the class, �it�s like it doesn�t matter what you have on the outside. It�s what�s on the inside.�
Winta McNeil, 18, of Snow Hill, was moved by her instructor�s experience with date rape. She said she was concerned about abuse.
�(The instructor) said walk away when anybody gets angry,� McNeil said.
Joyce Clark, executive director and founder of the YWOC, said 20 years ago, Eastern North Carolina rated No. 1 across the state in teen pregnancies.
Working in mental health, Clark said she saw that families needed a holistic approach to reduce the teen pregnancy numbers.
�This was a calling,� she said, �and a need to help the youth.�
The goal was to educate not only the youth, but their families, she said. In time, the program evolved to include many other issues the community faces.
Like bullying.
Curtis Speller, a gang prevention specialist, didn�t mince words when he told students not to bully the weaker students in school and to realize the affects bullying has on others.
�Don�t bully teachers,� he said. �Don�t bully everybody at school.�
He warned the class that bullying students could cause what Martin Luther King Jr. fought to change to turn around and segregate them into low-performing schools.
�It taught me how not to bully,� said Phillip Boney, 13, of Kinston, �and be fair to people.�
Kinston Public Safety Director Bill Johnson facilitated a workshop for boys only. His emphasis was on getting young teens to think about how education relates to an expected standard of living.
Students had to choose a career and determine their salary, based on their education. Then they had to figure up a household budget and see whether their salary could meet their expectations.
Johnson wanted them to understand how education relates to income, which relates to a person�s standard of living.
�I think some of them got it,� he said about the students. �Others don�t really look down the road 20 years.�
Sgt. Chad Rouse with Kinston�s Narcotics Division said young people know drugs are illegal and bad, but they don�t realize the �revolving door� of arrests often starts with one marijuana seed.
�But what they don�t understand,� he said, �is the concept of what it costs them monetarily and the damage it does to their family. Their going to jail is just a small portion of what actually occurs.�
Rouse filled a chalkboard with fee after fee and explains how those fees compound as a person continues to mount up charges against them. Additionally, their parents could be charged, as well, in some circumstances. And the charges, particularly felonies, don�t go away.
�I would say 90 percent starts with just what we hear, �It�s just marijuana,� � Rouse said. �And then it extends.�
Clark said she sees young adults who can�t get a job because of their past drug or criminal record.
Isiah McCullum, 17, of Greenville, said the drug and alcohol workshop provided plenty of examples of being in the wrong place at the wrong time.
�It�s going to help me choose who I�m going to hang around with,� he said, �� be more watchful.�
Margaret Fisher can be reached at 252-559-1082 or email@example.com. Follow her on Twitter @MargaretFishr.


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Detective Bell, Joan and Sherlock
Sherlock (Jonny Lee Miller, right ) , Detective Bell (Jon Michael Hill, left) and Joan (Lucy Liu) try to prove that one of people whose body was found in the wreckage of small plane crash was actually killed before the plane went down. Photo Credit: GIOVANNI RUFINO/CBS © 2012 CBS. All Rights Reserved.