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well see our clever little trickster soon , jasper promised , i always find something new on my travels .

kendra looked across the yard .

`` coop , thank you . ''

`` romantic ? ''

adrian quickly rolled his head back and looked away .

however , the piece de resistance came after waiting another forty-five minutes when she was informed that all of her luggage had been lost .

she 'd meant to snap at him-anything was better than this torturous anticipation-but the words were breathless , all her need shining through .

i do n't want to think about him .

it has nothing to do with you . ''

jeff , look out !

`` but as you said , mari , we 're doomed anyway . ''

hayden studies starkey for a moment , and starkey just smiles back .

her nipples hardened and she clenched her legs together , trying to relieve the pressure there .

some very large undergarments flopped out that may have been fabricated by a hot air balloon company .

`` there 's a lot of rain , which means a lot of vegetation , so there 's plenty of feed .

she reacted more out of the fear of her response than to his soft challenge .

`` you did tell them to go f**k themselves , right ? ''

why '' `` shit '' with that , wells quickly got to his feet .

there have also been some minor quakes in the mammoth mountain area , but again , the strength hasnt spiked to anything unusual .

max threw his arm over her shoulder and she snuggled closer , not ripping her eyes off the stage even once .

he lifted the tray and revealed her breakfast selection .

i think in the books to come we are going to find out a lot more surprises about averys current friends .

however , after mortimer had promised to call sam the moment it arrived , dani had allowed decker to chivvy her into the shower and then hustle her into sam 's car to come to the mall .

`` which it seems it has .

she has long flowing hair , almost white its so blond , and she walks with long strides , somehow both elegant and purposeful .

`` george ? ''

no way , she 'd never been stung before ; that could n't happen from just one sting , right ?

the cards worked well for currency because they were durable , compact , and while there was always the possibility of discovering more , there was a limited number available at any one time .

help !

Nutriepigenomics is the study of food nutrients and their effects on human health through epigenetic modifications. There is now considerable evidence that nutritional imbalances during gestation and lactation are linked to non-communicable diseases, such as obesity, cardiovascular disease, diabetes, hypertension, and cancer. If metabolic disturbances occur during critical time windows of development, the resulting epigenetic alterations can lead to permanent changes in tissue and organ structure or function and predispose individuals to disease. Overview Epigenetics relates to heritable changes in gene function that occur independently of alterations in primary DNA sequence. Two major epigenetic mechanisms implicated in nutriepigenomics are DNA methylation and histone modification. DNA methylation in gene promoter regions usually results in gene silencing and influences gene expression. While this form of gene silencing is extremely important in development and cellular differentiation, aberrant DNA methylation can be detrimental and has been linked to various disease processes, such as cancer. The methyl groups used in DNA methylation are often derived from dietary sources, such as folate and choline, and explains why diet can have a significant impact on methylation patterns and gene expression. Gene silencing can also be reinforced through the recruitment of histone deacetylases to decrease transcriptional activation. Conversely, histone acetylation induces transcriptional activation to increase gene expression. Dietary components can influence these epigenetic events, thereby altering gene expression and disturbing functions such as appetite control, metabolic balance and fuel utilization. Various genetic sequences can be targeted for epigenetic modification. A transcriptome-wide analysis in mice found that a protein-restricted (PR) diet during gestation resulted in differential gene expression in approximately 1% of the fetal genes analyzed (235/22,690). Specifically, increased expression was seen in genes involved in the p53 pathway, apoptosis, negative regulators of cell metabolism, and genes related to epigenetic control. Additional studies have investigated the effect of a PR-diet in rats and found changes in promoter methylation of both the glucocorticoid receptor and peroxisome proliferator-activated receptor (PPAR). Altered expression of these receptors can result in elevated blood glucose levels and affect lipid and carbohydrate metabolism. Feeding a PR-diet to pregnant and/or lactating mice also increased expression of glucokinase, acetyl-CoA carboxylase, PPARα, and acyl-CoA oxidase. Changes in expression were reportedly due to epigenetic regulation of either the gene promoter itself, or promoters of transcription factors that regulate gene expression. Additional genes that have been shown, either by in vitro or in vivo studies, to be regulated by epigenetic mechanisms include leptin, SOCS3, glucose transporter (GLUT)-4, POMC, 11-β-hydroxysteroid dehydrogenase type 2 and corticotrophin releasing hormone. Epigenetic modification of these genes may lead to “metabolic programming” of the fetus and result in long-term changes in metabolism and energy homeostasis. Nutriepigenomics and development The period of development in which the nutritional imbalance occurs is very important in determining which disease-related genes will be affected. Different organs have critical developmental stages, and the time point at which they are compromised will predispose individuals to specific diseases. Epigenetic modifications that occur during development may not be expressed until later in life depending on the function of the gene. While the majority of studies implicate prenatal and perinatal periods as critical time windows, some research has shown that nutritional intake during adulthood can also affect the epigenome. Prenatal Developmental plasticity is the process in which fetuses adapt to their environment. Environmental cues, including dietary components, present in the in utero environment can induce significant changes in the expression of the genome through epigenetic modifications. Fetal developmental plastic responses can cause changes in lean body mass, endocrinology, blood flow and vascular loading, and lead to increased risk of various diseases in adulthood. Low birth weight Fetal exposure to calcium, folate, magnesium, high or low protein, and zinc have all been associated with birth weight. Numerous studies have investigated the link between birth weight and risk of disease and have found that low birth weight is significantly associated with coronary heart disease, stroke and type-2 diabetes. Most importantly, these associations occurred after adjusting for lifestyle factors, implying a genetic basis for onset of disease. Impaired insulin secretion is associated with low birth weight and can lead to insulin resistance as babies accumulate body fat. Studies using intrauterine growth retarded (IUGR) rats have found that growth inhibition can lead to decreased expression of Pdx1 transcription factor, which is essential for differentiation and function of pancreatic beta cells. Decreased histone acetylation at the proximal promoter of Pdx1 is responsible for reduced Pdx1 expression and subsequently results in a cascade of histone deacetylation and methylation events that can result in type-2 diabetes. Obesity Obesity during pregnancy and high-fat maternal diets both show strong associations with obesity in offspring. As the number of overweight reproductive-age women increases, the number of overweight children and infants also increases. It has been postulated that maternal obesity causes an accumulation of fat in fetal adipose tissue (adiposity) and predisposes babies for obesity in childhood and adulthood. Animal studies have shown that maternal overnutrition may impact brain development and cause disruptions to programming of the hypothalamus. Offspring that were exposed to a high-fat or high-caloric maternal diet had increased levels of insulin, glucose and leptin. It is hypothesized that these elevations are due to disturbances in the complex neuronal network that includes the neuropeptide Y (NPY) and proopiomelanocortin (POMC) pathways. This altered neuronal signaling can consequently impact food-intake behavior and lead to diet-induced obesity in adulthood. While epigenetic modifications are most likely involved in the development of obesity, the specific target genes have yet to be identified. Genes involved in adipogenesis, such as fibroblast growth-factor-2, phosphatase and tensin homologue, cyclin-dependent kinase inhibitor 1A and oestrogen receptor-alpha, possess multiple CpG islands in their promoter sites and may act as epigenetic targets. Furthermore, it has been shown that prenatal exposure to a hypomethylating agent, such as bisphenol A (BPA), is associated with increased body weight and suggests modified DNA methylation as a mechanism for increasing susceptibility to obesity. Folate It has long been realized that maternal folate intake during pregnancy is linked to fetal development and growth, and can reduce the risk of serious birth defects. Folate is a source of S-adenosyl methionine (SAM), which is used to supply DNA methyltransferases with methyl groups. Therefore, changes in folate supply have a substantial effect on DNA methylation patterns. Low levels of folate are associated with an increased risk of preterm delivery, poor growth of the placenta and uterus, and intrauterine growth retardation. Several complex diseases, including cancer, cardiovascular diseases and autism have also been linked to maternal folate status. Based on animal studies it has been hypothesized that reduced folate intake could increase the risk of neural tube defects by reducing the amount of methylayed DNA during cranial neural tube closure. Recently it was discovered that folate protection from congenital heart defects is linked to epigenetics and Wnt signaling. Multiple environmental factors target the Wnt signaling pathway during embryogenesis and can cause misregulation of the pathway. Folic acid metabolism generates SAM, thereby altering the methylation states of histones H3K9, H3K4, and H3K27 and genetically altering Wnt signaling. Recently a double-blind placebo controlled trial of high dose Folinic Acid (Leucovorin Calcium) demonstrated efficacy at improving verbal communication in children with autism. Perinatal Another critical developmental time window is the perinatal period, the time period immediately before and after birth. It has been shown that maternal diet in late pregnancy and an infant's diet in the beginning weeks can all have significant impacts on gene expression. Therefore, perinatal nutrition is both late-stage in utero nutrition and lactation. Bone health Bone mass and the development of osteoporosis have been studied in relation to perinatal nutrition. An important factor to consider when investigating perinatal nutrition is whether the baby was breast-fed or formula-fed. Studies have shown that breast-fed babies have increased bone mass compared to those were not breast-fed, and that this small increase in bone mass during a period of critical development could potentially program the skeleton to continue along a “healthy” growth trajectory. It has also been shown that maternal vitamin D insufficiency during late pregnancy is associated with reduced bone size and mineral mass in late childhood. Peak bone mass has shown to be a good predictor of risk of fracture and osteoporosis, with even a small increase in peak bone mass resulting in a much lower risk of bone fracture. Research shows that genetic markers explain only a small proportion of variation in bone mass and risk of fracture. Therefore, healthy bone programming is most likely influenced by various epigenetic mechanisms, such as imprinting of the growth promoting genes IGF-2, or changes to the hypothalamic-pituitary-adrenal axis (HPA). Neurodevelopment Imbalances in maternal nutrition can also have a significant effect on fetal neurodevelopment. Brain development occurs most rapidly during fetal development and infancy, and research has shown that exposure to certain environmental conditions can have long-lasting effects on cognition. Specifically, n-3 fatty acids, iodine, iron and choline have been shown to influence brain development and impact cognitive ability and behavior. The greatest evidence for a link between nutrition and neurodevelopment comes from studies that show low birth weight associated with low IQ and increased risk of schizophrenia. Several studies suggest that breast-feeding promotes long-term neurodevelopment by providing the nutrients necessary for proper brain development. A study in mice showed that choline-deficient diets during the late gestation period impaired fetal brain development, including decreased cell proliferation and reduced visual-spatial and auditory memory. These cognitive changes appeared to be due to altered histone and DNA methylation patterns in the fetal hippocampus, thus providing a link between maternal nutrition, epigenetics, and early brain development. Type-1 diabetes It has been postulated that breast-feeding may also protect against type-1 diabetes, with research showing that formula-fed infants are at an increased risk of developing islet autoantibodies. Individuals with type-1 diabetes experience a pre-clinical diabetes phase characterized by autoimmunity against pancreatic islets. The introduction of certain foods in the first few months of life, such as berries and cereal, is significantly associated with increased risk of islet autoantibody development compared to babies who are exposed to solid foods later in life. While the pathogenesis behind development of autoantibodies remains largely unknown, it is very probable that an epigenetic link exists between perinatal diet and risk of type-1 diabetes. Adulthood The majority of research in nutriepigenomics has focused on nutritional imbalances during gestation and lactation periods. However, foods that are consumed during adulthood can also impact gene expression and disease pathogenesis. Cancer is the disease most commonly associated with adult nutrition and epigenetic modifications. DNA hypomethelation promotes cancer progression by allowing increased gene transcription, while hypermethylation can silence tumor suppressor genes and further promote uncontrolled cell division and tumor formation. Compounds found in foods, such as genistein and tea polyphenols, are able to regulate DNA methyltransferases and histone acetylation in cultured cancer cells and may provide protection against certain types of cancer. Other dietary compounds, such as diallyl disulfide present in garlic and sulforaphane present in cruciferous vegetables, have been associated with cancer prevention in clinical trials. This may be due to their ability to inhibit histone deacetylase (HDAC) enzymes and prevent silencing of important regulatory genes. Transgenerational effects Many believe epigenetic regulation is cleared during the fertilization process, yet more evidence for transgenerational effects (TGEs) are being revealed. These TGEs take place when the epigenetic regulatory patterns are not sufficiently erased during fertilization, possibly due to nutrition levels in previous generations. Later generations may be affected from caloric and protein restriction, high-fat interventions and endocrine disruption in earlier generations. Differences within the nutritional behavior of the maternal rat are believed to cause malprogramming in the F1 generation and may then be passed to subsequent generations. Maternal rats fed a PR-diet during the entire length of pregnancy led to metabolic-related problems in the F1 and F2 generations, even with normal nutrition during the F1 pregnancy. These effects have also been seen in the F3 generation depending on the length of protein restriction. If protein restriction occurred solely during pregnancy, the F1 and F2 offspring had higher systolic blood pressure and lower nephron numbers, possibly predisposing them to hypertension. Altered glucose utilization was detected in the grand-offspring of maternal rats fed a PR-diet during pregnancy and lactation, potentially resulting in diabetes later on in life Protein-restriction in the F0 generation led to hypomethylation of promoters involved in metabolism in the F1 and F2 generations, even though the F1 pregnant rat was given a normal diet. The exact mechanism of this situation has yet to be elucidated; however, direct transmission is a distinct possibility, meaning the epigenetic marks were preserved during spermatogenesis and oogenesis, when they are normally erased. Models used in nutriepigenomic studies Most research to date use common rodent models to investigate the role of nutrition on phenotype. Popular areas to investigate include IUGR studies, whereby rodents, and sometimes sheep, are subjected to a variety of nutritional conditions. A model for studying IUGR in rodent was developed by Simmons et al. (2010) and is used to investigate type II diabetes. The maternal rats have their uterine arteries ligated, causing altered use of glucose and insulin in the fetus and can therefore serve as a model for diabetes. These growth-retarded rats were found to be highly similar to human fetuses, as they both display symptoms such as lowered glucose and insulin levels. Gestational diabetes may also be studied through chemical induction using streptozotocin treatment of the pregnant rats. Streptozotocin can cause destruction of the beta cells within the pancreas depending on the concentration given. The predominant means of investigating nutriepigenetics involves varying the nutritional conditions to which a subject is exposed to and monitoring the effects thereafter. Restricting caloric and protein intake are the two most common methods. A pregnant rodent may have their caloric intake reduced up to 30-50% of normal intake. Protein restricted rodents are given 8-9% casein, as opposed to control rats that are fed 20% casein. Micronutrients, such as zinc and iron, may also be restricted to investigate the effects on offspring. Additionally, rats fed diets lacking or including methyl donors are often used to study the effects of diet on epigenomics, as variations within the methylation of DNA are common means of silencing or expressing genes. Supplementing maternal mice with folic acid, vitamin B12, choline and betaine leads to increased levels of DNA methylation at CpG sites and causes a coat color change. This is an example of epigenetically modifiable loci called a “metastable epiallele”, of which only a few have been identified. The above is an example of the “agouti” gene locus, whereby the insertion of a transposable element upstream to the Agouti gene is hypermethylated from the supplementation and causes a change in the mice's coat color. Diets containing higher carbohydrate and fat content attempt to mimic typical Western-style diets may also be used in nutriepigenetic studies. Another method used is “catch-up”, where offspring of rats born to mothers subjected to various diets are subsequently cross-fostered to mothers fed normal diets. Future directions The possibilities of utilizing nutriepigenomics for intervention are quite expansive. This can include preventative therapies, such as providing an optimal regime for nutrition during pregnancy and lactation. It is already common place for pregnant mothers to supplement their diets with choline and folate to prevent the development of neurological disabilities in the fetus. A highly specific diet, termed an "EpiG diet," may be employed for an individual believed to be at higher risk of developing a metabolic disorder. These diets may include supplementation with methyl donors, such as folate. There are also many other natural compounds, such as resveratrol, curcumin and green tea that have been termed “epigenetic modifiers”, as they have anti-cancer capabilities in addition to being used as treatments for metabolic diseases. However, the functions of these compounds still require long-term studies to evaluate their effect over time. There also exists potential for therapeutic treatments that may correct metabolic disorders, such as type II diabetes. Components of garlic and cruciferous vegetables are known to possess HDAC inhibitors that modify the acetylation of histone proteins and may contain a protection against cancer. These same compounds have also been implicated in irritable bowel syndrome (IBS) and colon cancer, as they may modify the histones normally implicated in these diseases. Elucidation of disease pathways is another future direction for nutriepigenomic studies. For example, choline-deficient diets and alcohol metabolism during pregnancy may have very similar metabolic pathways. Therefore, animal studies using choline-restricted diets may assist in investigations of fetal alcohol spectrum disorders. When compared to studies of maternal transmission, investigations into the role of paternal diets are lacking. A review demonstrated the nutrition of both parents do in fact play a role in determining the health of their offspring. A germ-line study reported paternal rats fed a high-fat diet led to insulin dysfunction in the F1 offspring. While this likely occurs via epigenetic modifications similar to those postulated in the maternal diets, the exact mechanism remains to be defined. Assessing the role of epigenetic mechanisms may be easier using paternal inheritance, as sperm transmits epigenetic and genetic information, whereas the female cells also transmit mitochondrial DNA. See also Epigenetics Epigenome Epigenomics Genome Molecular epidemiology Molecular pathological epidemiology Nutritional epidemiology Notes Nutrition Epigenetics

that done , he left again .

`` no , no .

`` that took more out of me than i expected and i have n't fed in days . ''

he screamed .

'you just make with the shears and the sheep 'll do the rest .

not that she minded the looming .

i 'd wait outside , i thought , wishing i had something other than textbooks with me .

after examining each painting , i place them back and open the second box , which holds blank canvases , paintbrushes , and wooden pieces that , once placed together , create an easel .

lavina smiled and handed him one of the few dry towels .

`` you are the best , payton . ''

`` calm down , girl , '' she said .

knowing that they 're getting their son back ? ''

he tugged on the door of the cage that was holding one of rodney 's squad .

actually it was red twos idea .

`` laura is going to be fine ! ''

they 'd gone over to the home of corinne rasmussen , a girl clay had been dating at the time .

or both .

they suddenly feel that they have moral authority over people .

hey , you made it , he said with a smile .

`` i 'm fine . ''

the finality of it took my breath away , leaving my grasping my chest as i struggled to draw in an unchallenged breath .

willows mustang was parked in front of my sorority .

The Williams EJ22 was a small turbofan engine that was being developed by Williams International for very light jet (VLJ) aircraft applications. Development Williams International had been building small turbofan engines for cruise missile applications since the 1960s, and had successfully entered the general aviation market in 1992 with the FJ44 engine. That same year, NASA initiated a program, Advanced General Aviation Transport Experiments (AGATE), to partner with manufacturers and help develop technologies that would revitalize the sagging general aviation industry. In 1996, Williams joined AGATE's General Aviation Propulsion (GAP) program to develop a clean-sheet fuel-efficient turbofan engine that would be even smaller than the FJ44 and designated the FJX-2 engine. This provided $100 million in research and development funding for the new engine. Initially, Williams contracted with Burt Rutan's Scaled Composites to design and build the Williams V-Jet II, a Very Light Jet (VLJ) to use as a testbed and technology demonstrator to showcase the new engine. The aircraft, powered by two interim FJX-1 man-rated version of Williams' cruise-missile engine, debuted at the 1997 Oshkosh Airshow. Development of the FJX-2 engine progressed, most of the design work was completed during 1998 with initial prototype parts being delivered in the second quarter of that year. The program ultimately culminated with altitude testing at the NASA Glenn Research Propulsion Systems Laboratory from March - April 2000. In 2000, Williams joined with Eclipse Aviation to develop an FAA-certified version of the FJX-2, designated the EJ22, to be used on the Eclipse 500 VLJ due for first flight in June 2002. The new EJ22 powered the Eclipse 500 prototype on its first flight in the summer of 2002, but never flew with the EJ22 again and Eclipse terminated their contract in late 2002, stating: "The EJ22 is not a viable solution for the Eclipse 500 aircraft, and Williams International has not met its contractual obligations", while Williams acknowledged "a number of challenges" with the EJ22 but viewed its obligations as accomplished, implying that the aircraft was too heavy. Eclipse switched to the more powerful Pratt & Whitney Canada PW600 series. Following termination of the contract, development work and FAA certification was halted shortly thereafter. Eclipse initially required the engine to produce thrust, exceeding the rating of the FJX-2 by 10%. Design The FJX-2 engine was designed with many experimental systems and manufacturing processes to minimize parts count, lower production costs and have a bypass ratio of 4:1. As a result, there were many technical difficulties and failures of the initial prototype hardware. However, subsequent re-designs and the incorporation of more conventional systems resulted in the engine eventually meeting the NASA requirement of thrust. To achieve the required thrust-specific fuel consumption, the EJ22 turbofan was designed as a three spool engine having a fan, two axial compressors and three expansion turbines. As a result, the engine was significantly more complicated than any prior Williams International engine. While very impressive on the test stand, the EJ22 proved quite temperamental during the two years of its development process and it was frequently subject to problems starting, overheating, part failures and various subsystem issues. Specifications References High-bypass turbofan engines 2000s turbofan engines EJ22 Three-spool turbofan engines

and yesterday , as we were avenging our losses , three warriors rode up to llanlleyn with a hostage .

`` did you think to ask for hot coffee and something to eat ? ''

it wasnt you .

the chanel logo was next to the manga frog .

call me when you get home . ''

just sorta putting feelers out there , trying to figure out whether or not one of us was going to turn the other in .

`` bad choice of phrasing , i guess .

it was n't garlic and weed from the smell of it , but anything that hurt kramer was something i wanted to utilize .

when we saw the ancient ones they were still walking around , then the instantly looked to us for salvation from their oppressors .

`` i did n't book anything yet .

a pulse of air like a godly push , forced akielas to fly backwards over the pit .

karen shrugged .

*** i 'm laying on the dirty floor of the room , staring up at the cracked ceiling .

one : because thats how they were raised .

jason sat down at my side , giving me a warm hug .

i cant imagine , clare , answered ravella .

`` are you always this tenacious ? ''

juice ? ''

but that was too impractical and i did n't do impractical .

he waited until the band struck up the chords to his request .

but i am not doing it for themand so my mission is not pointless .

`` yes , it was , '' nate whispered , then cleared his throat .

i 'll gorge myself on his carcass until i ca n't walk and let my children finish the rest , while i sleep it off with half-breed women .

sorry about that .

sir , yes , sir !

however , sometimes i can manage to dig my way out of a hole i 've dug .

`` or they 'll be hunting you . ''

all he knew in his confused and drugged mind was that something had changed .

a dull ache that got more pronounced every time she stood up this evening .

i saw thayer keeping pace at my side , sliding his arm through mine as we navigated a rocky path in the twilight .

did you think i would change ?

clare looked up in surprise and asked how she knew that ; the woman said she could see it in her palm .

`` i do n't know that the subject 's one that you need to hear about , '' he said kindly .

`` get this nephil out of my face .

he crouched down beside her , touched her chin with gentle fingers .

our conversation cut off as miller , mcavoy , and vin walked into our apartment .

i 'll have a few of the indentures give my boys a hand . ''

`` where do you think we are ? ''

compared with the torrential cacophony of the outer world , the inside of the mill was a blissful oasis of calm .

`` emily , i turned my phone off .

he worked at hawking labs until just a little while ago . ''

or we both live .

a sound of pleasure tears from both of us .

`` can you zoom in and get a street address ? ''

i cringed from the memory .

`` most roboticists shrugged and felt that this was natural .

it was just impossible for me to defend myself , but no one else was going to do it . ''