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Sample records for energetics ketone bodies

  1. Improved cerebral energetics and ketone body metabolism in db/db mice.

    PubMed

    Andersen, Jens V; Christensen, Sofie K; Nissen, Jakob D; Waagepetersen, Helle S

    2017-03-01

    It is becoming evident that type 2 diabetes mellitus is affecting brain energy metabolism. The importance of alternative substrates for the brain in type 2 diabetes mellitus is poorly understood. The aim of this study was to investigate whether ketone bodies are relevant candidates to compensate for cerebral glucose hypometabolism and unravel the functionality of cerebral mitochondria in type 2 diabetes mellitus. Acutely isolated cerebral cortical and hippocampal slices of db/db mice were incubated in media containing [U-(13)C]glucose, [1,2-(13)C]acetate or [U-(13)C]β-hydroxybutyrate and tissue extracts were analysed by mass spectrometry. Oxygen consumption and ATP synthesis of brain mitochondria of db/db mice were assessed by Seahorse XFe96 and luciferin-luciferase assay, respectively. Glucose hypometabolism was observed for both cerebral cortical and hippocampal slices of db/db mice. Significant increased metabolism of [1,2-(13)C]acetate and [U-(13)C]β-hydroxybutyrate was observed for hippocampal slices of db/db mice. Furthermore, brain mitochondria of db/db mice exhibited elevated oxygen consumption and ATP synthesis rate. This study provides evidence of several changes in brain energy metabolism in type 2 diabetes mellitus. The increased hippocampal ketone body utilization and improved mitochondrial function in db/db mice, may act as adaptive mechanisms in order to maintain cerebral energetics during hampered glucose metabolism.

  2. The inverse problem of brain energetics: ketone bodies as alternative substrates

    NASA Astrophysics Data System (ADS)

    Calvetti, D.; Occhipinti, R.; Somersalo, E.

    2008-07-01

    Little is known about brain energy metabolism under ketosis, although there is evidence that ketone bodies have a neuroprotective role in several neurological disorders. We investigate the inverse problem of estimating reaction fluxes and transport rates in the different cellular compartments of the brain, when the data amounts to a few measured arterial venous concentration differences. By using a recently developed methodology to perform Bayesian Flux Balance Analysis and a new five compartment model of the astrocyte-glutamatergic neuron cellular complex, we are able to identify the preferred biochemical pathways during shortage of glucose and in the presence of ketone bodies in the arterial blood. The analysis is performed in a minimally biased way, therefore revealing the potential of this methodology for hypothesis testing.

  3. Ketone bodies as signaling metabolites

    PubMed Central

    Newman, John C.; Verdin, Eric

    2014-01-01

    Traditionally, the ketone body β-hydroxybutyrate (βOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, βOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which βOHB functions to link the environment, in this case the diet, and gene expression via chromatin modifications. Here, we review the regulation and functions of ketone bodies, the relationship between ketone bodies and calorie restriction, and the implications of HDAC inhibition by the ketone body βOHB in the modulation of metabolism, and diseases of aging. PMID:24140022

  4. Ketone body metabolism and cardiovascular disease

    PubMed Central

    Cotter, David G.; Schugar, Rebecca C.

    2013-01-01

    Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states. PMID:23396451

  5. Ketone body metabolism and its defects.

    PubMed

    Fukao, Toshiyuki; Mitchell, Grant; Sass, Jörn Oliver; Hori, Tomohiro; Orii, Kenji; Aoyama, Yuka

    2014-07-01

    Acetoacetate (AcAc) and 3-hydroxybutyrate (3HB), the two main ketone bodies of humans, are important vectors of energy transport from the liver to extrahepatic tissues, especially during fasting, when glucose supply is low. Blood total ketone body (TKB) levels should be evaluated in the context of clinical history, such as fasting time and ketogenic stresses. Blood TKB should also be evaluated in parallel with blood glucose and free fatty acids (FFA). The FFA/TKB ratio is especially useful for evaluation of ketone body metabolism. Defects in ketogenesis include mitochondrial HMG-CoA synthase (mHS) deficiency and HMG-CoA lyase (HL) deficiency. mHS deficiency should be considered in non-ketotic hypoglycemia if a fatty acid beta-oxidation defect is suspected, but cannot be confirmed. Patients with HL deficiency can develop hypoglycemic crises and neurological symptoms even in adolescents and adults. Succinyl-CoA-3-oxoacid CoA transferase (SCOT) deficiency and beta-ketothiolase (T2) deficiency are two defects in ketolysis. Permanent ketosis is pathognomonic for SCOT deficiency. However, patients with "mild" SCOT mutations may have nonketotic periods. T2-deficient patients with "mild" mutations may have normal blood acylcarnitine profiles even in ketoacidotic crises. T2 deficient patients cannot be detected in a reliable manner by newborn screening using acylcarnitines. We review recent data on clinical presentation, metabolite profiles and the course of these diseases in adults, including in pregnancy.

  6. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  7. Renal conservation of ketone bodies during starvation.

    PubMed

    Sapir, D G; Owen, O E

    1975-01-01

    Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.

  8. New approach to determination of total ketone bodies in serum.

    PubMed

    Siegel, L; Robin, N I; McDonald, L J

    1977-01-01

    We describe a one-step assay for total ketone bodies in serum. D-BETA-Hydroxybutyrate is enzymatically oxidized by NAD+ to acetoacetate. This thermodynamically unfavorable reaction is driven to completion by coupling it with the enzymatic reduction of pyruvate by NADH. The acetoacetate so formed, as well as the pre-existing acetoacetate, is quantitatively decarboxylated to acetone in a gas chromatograph and measured directly. Thus by a single measurement for acetone, all three ketone bodies are simultaneously determined. In light of the ubiquity of situations associated with augmented ketone body production, the clinical implications of this approach are extensive.

  9. Successful adaptation to ketosis by mice with tissue-specific deficiency of ketone body oxidation.

    PubMed

    Cotter, David G; Schugar, Rebecca C; Wentz, Anna E; d'Avignon, D André; Crawford, Peter A

    2013-02-15

    During states of low carbohydrate intake, mammalian ketone body metabolism transfers energy substrates originally derived from fatty acyl chains within the liver to extrahepatic organs. We previously demonstrated that the mitochondrial enzyme coenzyme A (CoA) transferase [succinyl-CoA:3-oxoacid CoA transferase (SCOT), encoded by nuclear Oxct1] is required for oxidation of ketone bodies and that germline SCOT-knockout (KO) mice die within 48 h of birth because of hyperketonemic hypoglycemia. Here, we use novel transgenic and tissue-specific SCOT-KO mice to demonstrate that ketone bodies do not serve an obligate energetic role within highly ketolytic tissues during the ketogenic neonatal period or during starvation in the adult. Although transgene-mediated restoration of myocardial CoA transferase in germline SCOT-KO mice is insufficient to prevent lethal hyperketonemic hypoglycemia in the neonatal period, mice lacking CoA transferase selectively within neurons, cardiomyocytes, or skeletal myocytes are all viable as neonates. Like germline SCOT-KO neonatal mice, neonatal mice with neuronal CoA transferase deficiency exhibit increased cerebral glycolysis and glucose oxidation, and, while these neonatal mice exhibit modest hyperketonemia, they do not develop hypoglycemia. As adults, tissue-specific SCOT-KO mice tolerate starvation, exhibiting only modestly increased hyperketonemia. Finally, metabolic analysis of adult germline Oxct1(+/-) mice demonstrates that global diminution of ketone body oxidation yields hyperketonemia, but hypoglycemia emerges only during a protracted state of low carbohydrate intake. Together, these data suggest that, at the tissue level, ketone bodies are not a required energy substrate in the newborn period or during starvation, but rather that integrated ketone body metabolism mediates adaptation to ketogenic nutrient states.

  10. Ketone Body Metabolic Enzyme OXCT1 Regulates Prostate Cancer Chemoresistance

    DTIC Science & Technology

    2015-12-01

    and cellular energy homeostasis . Analysis of patient data indicated that higher OXCT1 levels are associated with docetaxel chemotherapy resistance...knock down induced metabolic inefficiency upon docetaxel treatment Since OXCT1 is a metabolic enzyme involved in energy homeostasis , next, to...ketone body metabolism and cellular energy homeostasis . Analysis of our previous data from patient needle biopsy samples indicated that higher

  11. Ketone body metabolism and sleep homeostasis in mice.

    PubMed

    Chikahisa, Sachiko; Shimizu, Noriyuki; Shiuchi, Tetsuya; Séi, Hiroyoshi

    2014-04-01

    A link has been established between energy metabolism and sleep homeostasis. The ketone bodies acetoacetate and β-hydroxybutyrate, generated from the breakdown of fatty acids, are major metabolic fuels for the brain under conditions of low glucose availability. Ketogenesis is modulated by the activity of peroxisome proliferator-activated receptor alpha (PPARα), and treatment with a PPAR activator has been shown to induce a marked increase in plasma acetoacetate and decreased β-hydroxybutyrate in mice, accompanied by increased slow-wave activity during non-rapid eye movement (NREM) sleep. The present study investigated the role of ketone bodies in sleep regulation. Six-hour sleep deprivation increased plasma ketone bodies and their ratio (acetoacetate/β-hydroxybutyrate) in 10-week-old male mice. Moreover, sleep deprivation increased mRNA expression of ketogenic genes such as PPARα and 3-hydroxy-3-methylglutarate-CoA synthase 2 in the brain and decreased ketolytic enzymes such as succinyl-CoA: 3-oxoacid CoA transferase. In addition, central injection of acetoacetate, but not β-hydroxybutyrate, markedly increased slow-wave activity during NREM sleep and suppressed glutamate release. Central metabolism of ketone bodies, especially acetoacetate, appears to play a role in the regulation of sleep homeostasis.

  12. Enzymatic method for determining ketone body ratio in arterial blood.

    PubMed

    Uno, S; Takehiro, O; Tabata, R; Ozawa, K

    1995-12-01

    We have developed a new, sensitive, and rapid method for measuring the ketone body concentration in arterial blood and determining the arterial blood ketone body ratio. The procedure involves the sequential use of the enzymes 3-hydroxybutyrate dehydrogenase (3-HBDH; EC 1.1.1.30) and NADH oxidase, followed by a color-generating reaction with the hydrogen peroxide produced by the oxidase reaction. The amount of oxidized chromogen produced is proportional to the 3-hydroxybutyrate (3-HBA) concentration. The acetoacetate (AcAc) concentration is obtained after complete conversion of the AcAc to 3-HBA, in the presence of 3-HBDH. The total 3-HBA concentration is measured and then subtracted from the total ketone body concentration to give the AcAc concentration. This procedure may be applied to plasma samples and the absorbance change measured with an automated chemistry analyzer. Ketone body concentration may be determined over the range 0 to 400 mumol/L. The analysis takes approximately 12 min and requires only 30 microL of plasma.

  13. Cardiomyocyte-specific deficiency of ketone body metabolism promotes accelerated pathological remodeling

    PubMed Central

    Schugar, Rebecca C.; Moll, Ashley R.; André d’Avignon, D.; Weinheimer, Carla J.; Kovacs, Attila; Crawford, Peter A.

    2014-01-01

    Objective Exploitation of protective metabolic pathways within injured myocardium still remains an unclarified therapeutic target in heart disease. Moreover, while the roles of altered fatty acid and glucose metabolism in the failing heart have been explored, the influence of highly dynamic and nutritionally modifiable ketone body metabolism in the regulation of myocardial substrate utilization, mitochondrial bioenergetics, reactive oxygen species (ROS) generation, and hemodynamic response to injury remains undefined. Methods Here we use mice that lack the enzyme required for terminal oxidation of ketone bodies, succinyl-CoA:3-oxoacid CoA transferase (SCOT) to determine the role of ketone body oxidation in the myocardial injury response. Tracer delivery in ex vivo perfused hearts coupled to NMR spectroscopy, in vivo high-resolution echocardiographic quantification of cardiac hemodynamics in nutritionally and surgically modified mice, and cellular and molecular measurements of energetic and oxidative stress responses are performed. Results While germline SCOT-knockout (KO) mice die in the early postnatal period, adult mice with cardiomyocyte-specific loss of SCOT (SCOT-Heart-KO) remarkably exhibit no overt metabolic abnormalities, and no differences in left ventricular mass or impairments of systolic function during periods of ketosis, including fasting and adherence to a ketogenic diet. Myocardial fatty acid oxidation is increased when ketones are delivered but cannot be oxidized. To determine the role of ketone body oxidation in the remodeling ventricle, we induced pressure overload injury by performing transverse aortic constriction (TAC) surgery in SCOT-Heart-KO and αMHC-Cre control mice. While TAC increased left ventricular mass equally in both groups, at four weeks post-TAC, myocardial ROS abundance was increased in myocardium of SCOT-Heart-KO mice, and mitochondria and myofilaments were ultrastructurally disordered. Eight weeks post-TAC, left ventricular

  14. Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia

    PubMed Central

    2014-01-01

    Background Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy. Results We observed reduced glycolytic flux in tumor cells upon treatment with ketone bodies. Ketone bodies also diminished glutamine uptake, overall ATP content, and survival in multiple pancreatic cancer cell lines, while inducing apoptosis. A decrease in levels of c-Myc, a metabolic master regulator, and its recruitment on glycolytic gene promoters, was in part responsible for the metabolic phenotype in tumor cells. Ketone body-induced intracellular metabolomic reprogramming in pancreatic cancer cells also leads to a significantly diminished cachexia in cell line models. Our mouse orthotopic xenograft models further confirmed the effect of a ketogenic diet in diminishing tumor growth and cachexia. Conclusions Thus, our studies demonstrate that the cachectic phenotype is in part due to metabolic alterations in tumor cells, which can be reverted by a ketogenic diet, causing reduced tumor growth and inhibition of muscle and body weight loss. PMID:25228990

  15. A focused review of the role of ketone bodies in health and disease.

    PubMed

    Akram, Muhammad

    2013-11-01

    Ketone bodies are produced in the liver and are utilized in other tissues in the body as an energy source when hypoglycemia occurs in the body. There are three ketone bodies: acetoacetate, beta hydroxy butyrate, and acetone. Ketone bodies are usually present in the blood, and their level increases during fasting and starvation. They are also found in the blood of neonates and pregnant women. In diabetic ketoacidosis, high levels of ketone bodies are produced in response to low insulin levels and high levels of counter-regulatory hormones.

  16. Advanced selective non-invasive ketone body detection sensors based on new ionophores

    NASA Astrophysics Data System (ADS)

    Sathyapalan, A.; Sarswat, P. K.; Zhu, Y.; Free, M. L.

    2014-12-01

    New molecules and methods were examined that can be used to detect trace level ketone bodies. Diseases such as type 1 diabetes, childhood hypo-glycaemia-growth hormone deficiency, toxic inhalation, and body metabolism changes are linked with ketone bodies concentration. Here we introduce, selective ketone body detection sensors based on small, environmentally friendly organic molecules with Lewis acid additives. Density functional theory (DFT) simulation of the sensor molecules (Bromo-acetonaphthone tungstate (BANT) and acetonaphthophenyl ether propiono hydroxyl tungstate (APPHT)), indicated a fully relaxed geometry without symmetry attributes and specific coordination which enhances ketone bodies sensitivity. A portable sensing unit was made in which detection media containing ketone bodies at low concentration and new molecules show color change in visible light as well as unique irradiance during UV illumination. RGB analysis, electrochemical tests, SEM characterization, FTIR, absorbance and emission spectroscopy were also performed in order to validate the ketone sensitivity of these new molecules.

  17. Ketones urine test

    MedlinePlus

    Ketone bodies - urine; Urine ketones; Ketoacidosis - urine ketones test; Diabetic ketoacidosis - urine ketones test ... Urine ketones are usually measured as a "spot test." This is available in a test kit that ...

  18. Fenofibrate Induces Ketone Body Production in Melanoma and Glioblastoma Cells

    PubMed Central

    Grabacka, Maja M.; Wilk, Anna; Antonczyk, Anna; Banks, Paula; Walczyk-Tytko, Emilia; Dean, Matthew; Pierzchalska, Malgorzata; Reiss, Krzysztof

    2016-01-01

    Ketone bodies [beta-hydroxybutyrate (bHB) and acetoacetate] are mainly produced in the liver during prolonged fasting or starvation. bHB is a very efficient energy substrate for sustaining ATP production in peripheral tissues; importantly, its consumption is preferred over glucose. However, the majority of malignant cells, particularly cancer cells of neuroectodermal origin such as glioblastoma, are not able to use ketone bodies as a source of energy. Here, we report a novel observation that fenofibrate, a synthetic peroxisome proliferator-activated receptor alpha (PPARa) agonist, induces bHB production in melanoma and glioblastoma cells, as well as in neurospheres composed of non-transformed cells. Unexpectedly, this effect is not dependent on PPARa activity or its expression level. The fenofibrate-induced ketogenesis is accompanied by growth arrest and downregulation of transketolase, but the NADP/NADPH and GSH/GSSG ratios remain unaffected. Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma. PMID:26869992

  19. Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype?

    PubMed

    Pinckaers, Philippe J M; Churchward-Venne, Tyler A; Bailey, David; van Loon, Luc J C

    2017-03-01

    Elite athletes and coaches are in a constant search for training methods and nutritional strategies to support training and recovery efforts that may ultimately maximize athletes' performance. Recently, there has been a re-emerging interest in the role of ketone bodies in exercise metabolism, with considerable media speculation about ketone body supplements being routinely used by professional cyclists. Ketone bodies can serve as an important energy substrate under certain conditions, such as starvation, and can modulate carbohydrate and lipid metabolism. Dietary strategies to increase endogenous ketone body availability (i.e., a ketogenic diet) require a diet high in lipids and low in carbohydrates for ~4 days to induce nutritional ketosis. However, a high fat, low carbohydrate ketogenic diet may impair exercise performance via reducing the capacity to utilize carbohydrate, which forms a key fuel source for skeletal muscle during intense endurance-type exercise. Recently, ketone body supplements (ketone salts and esters) have emerged and may be used to rapidly increase ketone body availability, without the need to first adapt to a ketogenic diet. However, the extent to which ketone bodies regulate skeletal muscle bioenergetics and substrate metabolism during prolonged endurance-type exercise of varying intensity and duration remains unknown. Therefore, at present there are no data available to suggest that ingestion of ketone bodies during exercise improves athletes' performance under conditions where evidence-based nutritional strategies are applied appropriately.

  20. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester

    PubMed Central

    Hashim, Sami A.; VanItallie, Theodore B.

    2014-01-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer’s disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson’s disease. PMID:24598140

  1. Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.

    PubMed

    Hashim, Sami A; VanItallie, Theodore B

    2014-09-01

    Ketone bodies (KBs), acetoacetate and β-hydroxybutyrate (βHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of βHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease.

  2. Regulation of Ketone Body Metabolism and the Role of PPARα

    PubMed Central

    Grabacka, Maja; Pierzchalska, Malgorzata; Dean, Matthew; Reiss, Krzysztof

    2016-01-01

    Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions. PMID:27983603

  3. Regulation of Ketone Body Metabolism and the Role of PPARα.

    PubMed

    Grabacka, Maja; Pierzchalska, Malgorzata; Dean, Matthew; Reiss, Krzysztof

    2016-12-13

    Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.

  4. Biomarkers, ketone bodies, and the prevention of Alzheimer's disease.

    PubMed

    VanItallie, Theodore B

    2015-03-01

    Sporadic Alzheimer's disease (spAD) has three successive phases: preclinical, mild cognitive impairment, and dementia. Individuals in the preclinical phase are cognitively normal. Diagnosis of preclinical spAD requires evidence of pathologic brain changes provided by established biomarkers. Histopathologic features of spAD include (i) extra-cellular cerebral amyloid plaques and intracellular neurofibrillary tangles that embody hyperphosphorylated tau; and (ii) neuronal and synaptic loss. Amyloid-PET brain scans conducted during spAD's preclinical phase have disclosed abnormal accumulations of amyloid-beta (Aβ) in cognitively normal, high-risk individuals. However, this measure correlates poorly with changes in cognitive status. In contrast, MRI measures of brain atrophy consistently parallel cognitive deterioration. By the time dementia appears, amyloid deposition has already slowed or ceased. When a new treatment offers promise of arresting or delaying progression of preclinical spAD, its effectiveness must be inferred from intervention-correlated changes in biomarkers. Herein, differing tenets of the amyloid cascade hypothesis (ACH) and the mitochondrial cascade hypothesis (MCH) are compared. Adoption of the ACH suggests therapeutic research continue to focus on aspects of the amyloid pathways. Adoption of the MCH suggests research emphasis be placed on restoration and stabilization of mitochondrial function. Ketone ester (KE)-induced elevation of plasma ketone body (KB) levels improves mitochondrial metabolism and prevents or delays progression of AD-like pathologic changes in several AD animal models. Thus, as a first step, it is imperative to determine whether KE-caused hyperketonemia can bring about favorable changes in biomarkers of AD pathology in individuals who are in an early stage of AD's preclinical phase.

  5. Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics.

    PubMed

    Puchalska, Patrycja; Crawford, Peter A

    2017-02-07

    Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations.

  6. Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation

    PubMed Central

    Carneiro, Lionel; Geller, Sarah; Hébert, Audrey; Repond, Cendrine; Fioramonti, Xavier; Leloup, Corinne; Pellerin, Luc

    2016-01-01

    Ketone bodies have been shown to transiently stimulate food intake and modify energy homeostasis regulatory systems following cerebral infusion for a moderate period of time (<6 hours). As ketone bodies are usually enhanced during episodes of fasting, this effect might correspond to a physiological regulation. In contrast, ketone bodies levels remain elevated for prolonged periods during obesity, and thus could play an important role in the development of this pathology. In order to understand this transition, ketone bodies were infused through a catheter inserted in the carotid to directly stimulate the brain for a period of 24 hours. Food ingested and blood circulating parameters involved in metabolic control as well as glucose homeostasis were determined. Results show that ketone bodies infusion for 24 hours increased food intake associated with a stimulation of hypothalamic orexigenic neuropeptides. Moreover, insulinemia was increased and caused a decrease in glucose production despite an increased resistance to insulin. The present study confirms that ketone bodies reaching the brain stimulates food intake. Moreover, we provide evidence that a prolonged hyperketonemia leads to a dysregulation of energy homeostasis control mechanisms. Finally, this study shows that brain exposure to ketone bodies alters insulin signaling and consequently glucose homeostasis. PMID:27708432

  7. Skeletal muscle PGC-1α modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice

    PubMed Central

    Svensson, Kristoffer; Albert, Verena; Cardel, Bettina; Salatino, Silvia; Handschin, Christoph

    2016-01-01

    Ketone bodies are crucial energy substrates during states of low carbohydrate availability. However, an aberrant regulation of ketone body homeostasis can lead to complications such as diabetic ketoacidosis. Exercise and diabetes affect systemic ketone body homeostasis, but the regulation of ketone body metabolism is still enigmatic. Using mice with either a knockout or overexpression of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle, we show that PGC-1α regulates ketolytic gene transcription in muscle. Furthermore, ketone body homeostasis of these mice was investigated during fasting, exercise, ketogenic diet feeding and after streptozotocin injection. In response to these ketogenic stimuli, we show that modulation of PGC-1α levels in muscle affects systemic ketone body homeostasis. Moreover, our data demonstrate that skeletal muscle PGC-1α is necessary for the enhanced ketolytic capacity in response to exercise training and overexpression of PGC-1α in muscle enhances systemic ketolytic capacity and is sufficient to ameliorate diabetic hyperketonemia in mice. Using cultured myotubes, we also show that the transcription factor estrogen related receptor α (ERRα) is a partner of PGC-1α in the regulation of ketolytic gene transcription. Collectively, these results demonstrate a central role of skeletal muscle PGC-1α in the transcriptional regulation of systemic ketolytic capacity. PMID:26849960

  8. Altered ketone body metabolism during gram-negative sepsis in the rat.

    PubMed

    Lanza-Jacoby, S; Rosato, E; Braccia, G; Tabares, A

    1990-11-01

    To investigate why blood ketone bodies are depressed during sepsis, the production and utilization of ketone bodies was studied in fasted control, fasted, Escherichia coli-treated, fed control, and fed E coli-treated rats. Gram-negative sepsis was induced by intravenous (IV) injection of 8 x 10(7) live colonies of E coli per 100 g body weight. Food was removed from the fasted rats after E coli injection. Fed rats were infused intragastrically with a nutritionally adequate diet for 5 days before inducing sepsis. Twenty-four hours after E coli injection, blood ketone bodies were reduced in fasted septic rats and fed septic rats compared with their respective control rats. Ketogenesis and oxidation of labeled palmitate was not altered in hepatocytes from fasted E coli-treated rats. Yet, ketogenesis declined significantly in hepatocytes from fed E coli-treated rats. Oxidation of labeled palmitate was also significantly reduced in hepatocytes from fed E coli-treated rats. Utilization of ketone bodies as measured by the incorporation of [3-14C]beta-hydroxybutyrate into CO2, increased over threefold in the diaphragm, 12% in the heart, and 19% in the kidneys from the fasted E coli-treated rats. In the fed state, incorporation of [3-14C]beta-hydroxybutyrate into CO2 was elevated fivefold in the heart, fourfold in the diaphragm, and over threefold in the kidneys from the septic rats. These results suggest that in the fasted state, plasma ketone bodies remain low during gram-negative sepsis because peripheral tissues use more ketone bodies and because liver ketogenesis is not increased to compensate for the increased utilization. In the fed state, the reduction in blood ketone bodies appears to be attributed to both impaired ketogenic capacity and increased peripheral utilization.

  9. THE NEUROPROTECTIVE PROPERTIES OF CALORIE RESTRICTION, THE KETOGENIC DIET, AND KETONE BODIES

    PubMed Central

    Maalouf, Marwan A.; Rho, Jong M.; Mattson, Mark P.

    2008-01-01

    The therapeutic potential of calorie restriction and the ketogenic diet have been repeatedly demonstrated in clinical settings and in various animal models of neurological disease. The underlying mechanisms involve an improvement in mitochondrial function, a decrease in the expression of apoptotic factors and an increase in the activity of neurotrophic factors. Clinical applications of ketogenic diets have been significantly hampered however by poor tolerability and potentially serious side-effects. Recent research aimed at identifying a mediator that can reproduce the neuroprotective effects of calorie restriction with less demanding changes to dietary intake suggests that ketone bodies might represent an appropriate candidate. Ketone bodies protect neurons against multiple types of neuronal injury and the underlying mechanisms are similar to those of calorie restriction and of the ketogenic diet. The present review describes the neuroprotective effects of calorie restriction, the ketogenic diet and ketone bodies and compare the molecular mechanisms of action of these interventions. PMID:18845187

  10. Ketones blood test

    MedlinePlus

    ... Ketones - serum; Nitroprusside test; Ketone bodies - serum; Ketones - blood ... A blood sample is needed. ... When the needle is inserted to draw blood, some people feel slight ... there may be some throbbing or a slight bruise. This soon ...

  11. Regulation of hypothalamic neuronal sensing and food intake by ketone bodies and fatty acids.

    PubMed

    Le Foll, Christelle; Dunn-Meynell, Ambrose A; Miziorko, Henri M; Levin, Barry E

    2014-04-01

    Metabolic sensing neurons in the ventromedial hypothalamus (VMH) alter their activity when ambient levels of metabolic substrates, such as glucose and fatty acids (FA), change. To assess the relationship between a high-fat diet (HFD; 60%) intake on feeding and serum and VMH FA levels, rats were trained to eat a low-fat diet (LFD; 13.5%) or an HFD in 3 h/day and were monitored with VMH FA microdialysis. Despite having higher serum levels, HFD rats had lower VMH FA levels but ate less from 3 to 6 h of refeeding than did LFD rats. However, VMH β-hydroxybutyrate (β-OHB) and VMH-to-serum β-OHB ratio levels were higher in HFD rats during the first 1 h of refeeding, suggesting that VMH astrocyte ketone production mediated their reduced intake. In fact, using calcium imaging in dissociated VMH neurons showed that ketone bodies overrode normal FA sensing, primarily by exciting neurons that were activated or inhibited by oleic acid. Importantly, bilateral inhibition of VMH ketone production with a 3-hydroxy-3-methylglutaryl-CoA synthase inhibitor reversed the 3- to 6-h HFD-induced inhibition of intake but had no effect in LFD-fed rats. These data suggest that a restricted HFD intake regimen inhibits caloric intake as a consequence of FA-induced VMH ketone body production by astrocytes.

  12. Mechanisms involved in ketone body release by rat liver cells: influence of pH and bicarbonate

    SciTech Connect

    Fafournoux, P.; Demigne, C.; Remesy, C.

    1987-02-01

    The aim of the present work is to study the intra- and extracellular concentration gradient of ketone bodies across the hepatic cell membrane, ketone bodies released by liver cells, and the effects of changes in acid-base status on these processes. Ketone bodies appeared to be released by liver cells against a concentration gradient both in vivo and in vitro. In vitro, a decrease in external pH and bicarbonate gradient measured with ( UC)- and (TH)-labelled compounds, and efflux rates. Analysis of the distribution ratio of ketone bodies as a function of pH across the cell membrane indicates that additional factors must be invoked to account for the observed distribution ratios. These data along with measurement of ketone body efflux are consistent with the existence of a system promoting the efflux of ketone bodies from liver cells, which is trans-stimulated by external bicarbonate. In vivo, ketogenesis was also inhibited by acidosis, and slightly enhanced by bicarbonate infusion, although this was not solely due to effects on transfer across the cell membrane. The study indicates that the hepatic release of ketone bodies might be auto-limited by ketoacidosis.

  13. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer.

    PubMed

    Seyfried, T N; Sanderson, T M; El-Abbadi, M M; McGowan, R; Mukherjee, P

    2003-10-06

    Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and elevate ketone bodies in the CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice were fed either a standard diet unrestricted (SD-UR), a ketogenic diet unrestricted (KD-UR), the SD restricted to 40% (SD-R), or the KD restricted to 40% of the control standard diet (KD-R). Body weights, tumour weights, plasma glucose, beta-hydroxybutyrate (beta-OHB), and insulin-like growth factor 1 (IGF-1) were measured 13 days after tumour implantation. CT-2A growth was rapid in both the SD-UR and KD-UR groups, but was significantly reduced in both the SD-R and KD-R groups by about 80%. The results indicate that plasma glucose predicts CT-2A growth and that growth is dependent more on the amount than on the origin of dietary calories. Also, restriction of either diet significantly reduced the plasma levels of IGF-1, a biomarker for angiogenesis and tumour progression. Owing to a dependence on plasma glucose, IGF-1 was also predictive of CT-2A growth. Ketone bodies are proposed to reduce stromal inflammatory activities, while providing normal brain cells with a nonglycolytic high-energy substrate. Our results in a mouse astrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevate ketone bodies.

  14. A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting.

    PubMed

    Hugo, Sarah E; Cruz-Garcia, Lourdes; Karanth, Santhosh; Anderson, Ryan M; Stainier, Didier Y R; Schlegel, Amnon

    2012-02-01

    To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by adequate nutrition. Adult rmn mutants show increased liver neutral lipids and induction of hepatic lipid biosynthetic genes when fasted. Positional cloning of the rmn locus reveals a loss-of-function mutation in slc16a6a (solute carrier family 16a, member 6a), a gene that we show encodes a transporter of the major ketone body β-hydroxybutyrate. Restoring wild-type zebrafish slc16a6a expression or introducing human SLC16A6 in rmn mutant livers rescues the mutant phenotype. Radiotracer analysis confirms that loss of Slc16a6a function causes diversion of liver-trapped ketogenic precursors into triacylglycerol. Underscoring the importance of Slc16a6a to normal fasting physiology, previously fed rmn mutants are more sensitive to death by starvation than are wild-type larvae. Our unbiased, forward genetic approach has found a heretofore unrecognized critical step in fasting energy metabolism: hepatic ketone body transport. Since β-hydroxybutyrate is both a major fuel and a signaling molecule in fasting, the discovery of this transporter provides a new direction for modulating circulating levels of ketone bodies in metabolic diseases.

  15. Rapid Blood Ketone Body Estimation in the Diagnosis of Diabetic Ketoacidosis

    PubMed Central

    Alberti, K. G. M. M.; Hockaday, T. D. R.

    1972-01-01

    Different methods of assessing ketone body concentrations in blood and plasma of ketoacidotic patients have been compared. We confirmed that Ketostix reacts strongly with acetoacetate, giving a useful range of 0 to 10 mM for plasma acetoacetate, that acetone reacts weakly, and that 3-hydroxybutyrate does not react at all. Plasma Ketostix readings correlated only moderately well with enzymatically determined whole-blood acetoacetate. All samples giving a + + + reaction contained more than 1·6 mM acetoacetate while only 4 out of 21 samples showing 0 contained more than 0·4 mM. Comparison of Ketostix readings with total blood ketone body content showed poor correlation. One reason for this was the large variation in the ratio of 3-hydroxybutyrate to acetoacetate in ketoacidosis; another was that often Ketostix had been stored in such a way that they had become damp, which impairs their reliability. If the Ketostix reading and estimation of the blood pH show a discrepancy we suggest that an enzymatic assay should be used to determine the ketone bodies and lactate. PMID:4624389

  16. A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting

    PubMed Central

    Hugo, Sarah E.; Cruz-Garcia, Lourdes; Karanth, Santhosh; Anderson, Ryan M.; Stainier, Didier Y.R.; Schlegel, Amnon

    2012-01-01

    To find new genes that influence liver lipid mass, we performed a genetic screen for zebrafish mutants with hepatic steatosis, a pathological accumulation of fat. The red moon (rmn) mutant develops hepatic steatosis as maternally deposited yolk is depleted. Conversely, hepatic steatosis is suppressed in rmn mutants by adequate nutrition. Adult rmn mutants show increased liver neutral lipids and induction of hepatic lipid biosynthetic genes when fasted. Positional cloning of the rmn locus reveals a loss-of-function mutation in slc16a6a (solute carrier family 16a, member 6a), a gene that we show encodes a transporter of the major ketone body β-hydroxybutyrate. Restoring wild-type zebrafish slc16a6a expression or introducing human SLC16A6 in rmn mutant livers rescues the mutant phenotype. Radiotracer analysis confirms that loss of Slc16a6a function causes diversion of liver-trapped ketogenic precursors into triacylglycerol. Underscoring the importance of Slc16a6a to normal fasting physiology, previously fed rmn mutants are more sensitive to death by starvation than are wild-type larvae. Our unbiased, forward genetic approach has found a heretofore unrecognized critical step in fasting energy metabolism: hepatic ketone body transport. Since β-hydroxybutyrate is both a major fuel and a signaling molecule in fasting, the discovery of this transporter provides a new direction for modulating circulating levels of ketone bodies in metabolic diseases. PMID:22302940

  17. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth

    PubMed Central

    De Feyter, Henk M.; Behar, Kevin L.; Rao, Jyotsna U.; Madden-Hennessey, Kirby; Ip, Kevan L.; Hyder, Fahmeed; Drewes, Lester R.; Geschwind, Jean-François; de Graaf, Robin A.; Rothman, Douglas L.

    2016-01-01

    Background The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models. Methods Ketone body oxidation was studied using 13C MR spectroscopy in combination with infusion of a 13C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue. Results The level of 13C–beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas. Conclusions These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism. PMID:27142056

  18. Ketone bodies and islet function: sup 45 Ca handling, insulin synthesis, and release

    SciTech Connect

    Malaisse, W.J.; Lebrun, P.; Yaylali, B.; Camara, J.; Valverde, I.; Sener, A. )

    1990-07-01

    D-(-)-beta-Hydroxybutyrate and acetoacetate cause a rapid, sustained, and rapidly reversible stimulation of insulin release from rat pancreatic islets incubated in the presence, but not absence, of D-glucose. This coincides with stimulation of both proinsulin biosynthesis and {sup 45}Ca net uptake. The ketone bodies also decrease {sup 45}Ca outflow from prelabeled islets perifused in the absence of Ca{sup 2+} and, in contrast, enhance effluent radioactivity in the presence of Ca{sup 2+}. In the presence of D-glucose, the secretory response to D-(-)-beta-hydroxybutyrate is concentration related in the 2.5-20 mM range, abolished in the absence of Ca{sup 2+} or presence of KCN, and enhanced by theophylline and forskolin. It corresponds grossly to a shift to the left of the sigmoidal curve relating insulin output to the ambient concentration of D-glucose. The secretory, biosynthetic, and cationic response to acetoacetate is less marked than that evoked by an equimolar concentration of D-(-)-beta-hydroxybutyrate. These features are compatible with the view that the insulinotropic action of ketone bodies would be causally linked to their metabolism in islet cells.

  19. Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain

    PubMed Central

    Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

    2015-01-01

    Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging. PMID:25896951

  20. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth.

    PubMed

    De Feyter, Henk M; Behar, Kevin L; Rao, Jyotsna U; Madden-Hennessey, Kirby; Ip, Kevan L; Hyder, Fahmeed; Drewes, Lester R; Geschwind, Jean-François; de Graaf, Robin A; Rothman, Douglas L

    2016-08-01

    The dependence of tumor cells, particularly those originating in the brain, on glucose is the target of the ketogenic diet, which creates a plasma nutrient profile similar to fasting: increased levels of ketone bodies and reduced plasma glucose concentrations. The use of ketogenic diets has been of particular interest for therapy in brain tumors, which reportedly lack the ability to oxidize ketone bodies and therefore would be starved during ketosis. Because studies assessing the tumors' ability to oxidize ketone bodies are lacking, we investigated in vivo the extent of ketone body oxidation in 2 rodent glioma models. Ketone body oxidation was studied using (13)C MR spectroscopy in combination with infusion of a (13)C-labeled ketone body (beta-hydroxybutyrate) in RG2 and 9L glioma models. The level of ketone body oxidation was compared with nontumorous cortical brain tissue. The level of (13)C-beta-hydroxybutyrate oxidation in 2 rat glioma models was similar to that of contralateral brain. In addition, when glioma-bearing animals were fed a ketogenic diet, the ketone body monocarboxylate transporter was upregulated, facilitating uptake and oxidation of ketone bodies in the gliomas. These results demonstrate that rat gliomas can oxidize ketone bodies and indicate upregulation of ketone body transport when fed a ketogenic diet. Our findings contradict the hypothesis that brain tumors are metabolically inflexible and show the need for additional research on the use of ketogenic diets as therapy targeting brain tumor metabolism. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Ketone body β-hydroxybutyrate blocks the NLRP3 inflammasome-mediated inflammatory disease

    PubMed Central

    Youm, Yun-Hee; Nguyen, Kim Y.; Grant, Ryan W.; Goldberg, Emily L.; Bodogai, Monica; Kim, Dongin; D'Agostino, Dominic; Planavsky, Noah; Lupfer, Christopher; Kanneganti, Thirumala D.; Kang, Seokwon; Horvath, Tamas L.; Fahmy, Tarek M.; Crawford, Peter A.; Biragyn, Arya; Alnemri, Emad; Dixit, Vishwa Deep

    2015-01-01

    Ketone bodies , β-hydroxybutyrate (BHB) and acetoacetate support mammalian survival during states of energy deficit by serving as alternative source of ATP1. BHB levels are elevated during starvation, high-intensity exercise or by the low carbohydrate ketogenic diet2. Prolonged caloric restriction or fasting reduces inflammation as immune system adapts to low glucose supply and energy metabolism switches towards mitochondrial fatty acid oxidation, ketogenesis and ketolysis2-6. However, role of ketones bodies in regulation of innate immune response is unknown. We report that BHB, but neither acetoacetate nor structurally-related short chain fatty acids, butyrate and acetate, suppresses activation of the NLRP3 inflammasome in response to several structurally unrelated NLRP3 activators, without impacting NLRC4, AIM2 or non-canonical caspase-11 inflammasome activation. Mechanistically, BHB inhibits NLRP3 inflammasome by preventing K+ efflux and reducing ASC oligomerization and speck formation. The inhibitory effects of BHB on NLRP3 were not dependent on chirality or classical starvation regulated mechanisms like AMPK, reactive oxygen species (ROS), autophagy or glycolytic inhibition. BHB blocked NLRP3 inflammasome without undergoing oxidation in TCA cycle, independently of uncoupling protein-2 (UCP2), Sirt2, receptor Gpr109a and inhibition of NLRP3 did not correlate with magnitude of histone acetylation in macrophages. BHB reduced the NLRP3 inflammasome mediated IL-1β and IL-18 production in human monocytes. In vivo, BHB attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases like Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory syndrome (FCAS) and urate crystal induce body cavity inflammation. Taken together, these findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be mechanistically linked to BHB-mediated inhibition of the NLRP3 inflammasome, and point to the potential

  2. Regulation of myocardial ketone body metabolism by the gut microbiota during nutrient deprivation.

    PubMed

    Crawford, Peter A; Crowley, Jan R; Sambandam, Nandakumar; Muegge, Brian D; Costello, Elizabeth K; Hamady, Micah; Knight, Rob; Gordon, Jeffrey I

    2009-07-07

    Studies in mice indicate that the gut microbiota promotes energy harvest and storage from components of the diet when these components are plentiful. Here we examine how the microbiota shapes host metabolic and physiologic adaptations to periods of nutrient deprivation. Germ-free (GF) mice and mice who had received a gut microbiota transplant from conventionally raised donors were compared in the fed and fasted states by using functional genomic, biochemical, and physiologic assays. A 24-h fast produces a marked change in gut microbial ecology. Short-chain fatty acids generated from microbial fermentation of available glycans are maintained at higher levels compared with GF controls. During fasting, a microbiota-dependent, Ppar alpha-regulated increase in hepatic ketogenesis occurs, and myocardial metabolism is directed to ketone body utilization. Analyses of heart rate, hydraulic work, and output, mitochondrial morphology, number, and respiration, plus ketone body, fatty acid, and glucose oxidation in isolated perfused working hearts from GF and colonized animals (combined with in vivo assessments of myocardial physiology) revealed that the fasted GF heart is able to sustain its performance by increasing glucose utilization, but heart weight, measured echocardiographically or as wet mass and normalized to tibial length or lean body weight, is significantly reduced in both fasted and fed mice. This myocardial-mass phenotype is completely reversed in GF mice by consumption of a ketogenic diet. Together, these results illustrate benefits provided by the gut microbiota during periods of nutrient deprivation, and emphasize the importance of further exploring the relationship between gut microbes and cardiovascular health.

  3. Effects of fatty acids and ketone bodies on basal insulin secretion in type 2 diabetes.

    PubMed

    Boden, G; Chen, X

    1999-03-01

    The objective of this study was to assess the role of free fatty acids (FFAs) as insulin secretagogues in patients with type 2 diabetes. To this end, basal insulin secretion rates (ISR) in response to acute increases in plasma FFAs were evaluated in patients with type 2 diabetes and in age- and weight-matched nondiabetic control subjects during 1) intravenous infusion of lipid plus heparin (L/H), which stimulated intravascular lipolysis, and 2) the FFA rebound, which followed lowering of plasma FFAs with nicotinic acid (NA) and was a consequence of increased lipolysis from the subject's own adipose tissue. At comparable euglycemia, diabetic patients had similar ISR but higher plasma beta-hydroxybutyrate (beta-OHB) levels during L/H infusion and higher plasma FFA and beta-OHB levels during the FFA rebound than nondiabetic control subjects. Correlating ISR with plasma FFA plus beta-OHB levels showed that in response to the same changes in FFA plus beta-OHB levels, diabetic patients secreted approximately 30% less insulin than nondiabetic control subjects. In addition, twice as much insulin was secreted during L/H infusion as during the FFA rebound in response to the same FFA/beta-OHB stimulation by both diabetic patients and control subjects. Glycerol, which was present in the infused lipid (272 mmol/l) did not affect ISR. We concluded that 1) assessment of FFA effects on ISR requires consideration of effects on ISR by ketone bodies; 2) ISR responses to FFA/beta-OHB were defective in patients with type 2 diabetes (partial beta-cell lipid blindness), but this defect was compensated by elevated plasma levels of FFAs and ketone bodies; and 3) approximately two times more insulin was released per unit change in plasma FFA plus beta-OHB during L/H infusion than during the FFA rebound after NA. The reason for this remains to be explored.

  4. Effects of ketone bodies in Alzheimer's disease in relation to neural hypometabolism, β-amyloid toxicity, and astrocyte function.

    PubMed

    Hertz, Leif; Chen, Ye; Waagepetersen, Helle S

    2015-07-01

    Diet supplementation with ketone bodies (acetoacetate and β-hydroxybuturate) or medium-length fatty acids generating ketone bodies has consistently been found to cause modest improvement of mental function in Alzheimer's patients. It was suggested that the therapeutic effect might be more pronounced if treatment was begun at a pre-clinical stage of the disease instead of well after its manifestation. The pre-clinical stage is characterized by decade-long glucose hypometabolism in brain, but ketone body metabolism is intact even initially after disease manifestation. One reason for the impaired glucose metabolism may be early destruction of the noradrenergic brain stem nucleus, locus coeruleus, which stimulates glucose metabolism, at least in astrocytes. These glial cells are essential in Alzheimer pathogenesis. The β-amyloid peptide Aβ interferes with their cholinergic innervation, which impairs synaptic function because of diminished astrocytic glutamate release. Aβ also reduces glucose metabolism and causes hyperexcitability. Ketone bodies are similarly used against seizures, but the effectively used concentrations are so high that they must interfere with glucose metabolism and de novo synthesis of neurotransmitter glutamate, reducing neuronal glutamatergic signaling. The lower ketone body concentrations used in Alzheimer's disease may owe their effect to support of energy metabolism, but might also inhibit release of gliotransmitter glutamate. Alzheimer's disease is a panglial-neuronal disorder with long-standing brain hypometabolism, aberrations in both neuronal and astrocytic glucose metabolism, inflammation, hyperexcitability, and dementia. Relatively low doses of β-hydroxybutyrate can have an ameliorating effect on cognitive function. This could be because of metabolic supplementation or inhibition of Aβ-induced release of glutamate as gliotransmitter, which is likely to reduce hyperexcitability and inflammation. The therapeutic

  5. Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency-related leukodystrophy.

    PubMed

    Gautschi, Matthias; Weisstanner, Christian; Slotboom, Johannes; Nava, Esmeralda; Zürcher, Theres; Nuoffer, Jean-Marc

    2015-01-01

    Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once. We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈ 3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging. During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay. NaHB is a highly effective and safe treatment that needs further controlled studies.

  6. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy

    PubMed Central

    2011-01-01

    Background Even in the presence of oxygen, malignant cells often highly depend on glycolysis for energy generation, a phenomenon known as the Warburg effect. One strategy targeting this metabolic phenotype is glucose restriction by administration of a high-fat, low-carbohydrate (ketogenic) diet. Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells. Methods To investigate whether a ketogenic diet might selectively impair energy metabolism in tumor cells, we characterized in vitro effects of the principle ketone body 3-hydroxybutyrate in rat hippocampal neurons and five glioma cell lines. In vivo, a non-calorie-restricted ketogenic diet was examined in an orthotopic xenograft glioma mouse model. Results The ketone body metabolizing enzymes 3-hydroxybutyrate dehydrogenase 1 and 2 (BDH1 and 2), 3-oxoacid-CoA transferase 1 (OXCT1) and acetyl-CoA acetyltransferase 1 (ACAT1) were expressed at the mRNA and protein level in all glioma cell lines. However, no activation of the hypoxia-inducible factor-1α (HIF-1α) pathway was observed in glioma cells, consistent with the absence of substantial 3-hydroxybutyrate metabolism and subsequent accumulation of succinate. Further, 3-hydroxybutyrate rescued hippocampal neurons from glucose withdrawal-induced cell death but did not protect glioma cell lines. In hypoxia, mRNA expression of OXCT1, ACAT1, BDH1 and 2 was downregulated. In vivo, the ketogenic diet led to a robust increase of blood 3-hydroxybutyrate, but did not alter blood glucose levels or improve survival. Conclusion In summary, glioma cells are incapable of compensating for glucose restriction by metabolizing ketone bodies in vitro, suggesting a potential disadvantage of tumor cells compared to normal cells under a carbohydrate-restricted ketogenic diet. Further investigations are necessary to identify co-treatment modalities, e.g. glycolysis inhibitors or antiangiogenic agents that efficiently

  7. Interference of 3-hydroxyisobutyrate with measurements of ketone body concentration and isotopic enrichment by gas chromatography-mass spectrometry.

    PubMed

    Des Rosiers, C; Montgomery, J A; Desrochers, S; Garneau, M; David, F; Mamer, O A; Brunengraber, H

    1988-08-15

    Concentrations and 13C2 molar percentage enrichments of blood R-3-hydroxybutyrate and acetoacetate are measured by selected ion monitoring gas chromatography-mass spectrometry. Samples are treated with NaB2H4 to reduce unlabeled and labeled acetoacetate to corresponding deuterium-labeled RS-3-hydroxybutyrate species. Only the gas chromatographic peak for the tert-butyldimethylsilyl derivative of 3-hydroxybutyrate needs to be monitored. The various compounds are quantitated using an internal standard of RS-3-hydroxy-[2,2,3,4,4,4-2H6]-butyrate. Concentrations of ketone bodies are obtained by monitoring the m/z 159 to 163 fragments of tert-butyldimethylsilyl derivatives of labeled and unlabeled 3-hydroxybutyrate species. High correlations were obtained between ketone body concentrations assayed (i) enzymatically with R-3-hydroxybutyrate dehydrogenase and (ii) by gas chromatography-mass spectrometry. The limit of detection is about 10 nmol of substrate in blood samples. The current practice of monitoring the m/z 275 to 281 fragments overestimates the concentration of endogenous R-3-hydroxybutyrate, due to co-elution of 3-hydroxyisobutyrate, a valine metabolite. The method presented is used to measure ketone body turnover in vivo in 24-h-fasted dogs.

  8. Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate.

    PubMed

    Tyzio, Roman; Allene, Camille; Nardou, Romain; Picardo, Michel A; Yamamoto, Sumii; Sivakumaran, Sudhir; Caiati, Maddalena D; Rheims, Sylvain; Minlebaev, Marat; Milh, Mathieu; Ferré, Pascal; Khazipov, Rustem; Romette, Jean-Louis; Lorquin, Jean; Cossart, Rosa; Khalilov, Ilgam; Nehlig, Astrid; Cherubini, Enrico; Ben-Ari, Yehezkel

    2011-01-05

    GABA depolarizes immature neurons because of a high [Cl(-)](i) and orchestrates giant depolarizing potential (GDP) generation. Zilberter and coworkers (Rheims et al., 2009; Holmgren et al., 2010) showed recently that the ketone body metabolite DL-3-hydroxybutyrate (DL-BHB) (4 mM), lactate (4 mM), or pyruvate (5 mM) shifted GABA actions to hyperpolarizing, suggesting that the depolarizing effects of GABA are attributable to inadequate energy supply when glucose is the sole energy source. We now report that, in rat pups (postnatal days 4-7), plasma D-BHB, lactate, and pyruvate levels are 0.9, 1.5, and 0.12 mM, respectively. Then, we show that DL-BHB (4 mM) and pyruvate (200 μM) do not affect (i) the driving force for GABA(A) receptor-mediated currents (DF(GABA)) in cell-attached single-channel recordings, (2) the resting membrane potential and reversal potential of synaptic GABA(A) receptor-mediated responses in perforated patch recordings, (3) the action potentials triggered by focal GABA applications, or (4) the GDPs determined with electrophysiological recordings and dynamic two-photon calcium imaging. Only very high nonphysiological concentrations of pyruvate (5 mM) reduced DF(GABA) and blocked GDPs. Therefore, DL-BHB does not alter GABA signals even at the high concentrations used by Zilberter and colleagues, whereas pyruvate requires exceedingly high nonphysiological concentrations to exert an effect. There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain.

  9. Ketone Bodies Mediate Anti-Seizure Effects Through Mitochondrial Permeability Transition

    PubMed Central

    Kim, Do Young; Simeone, Kristina A.; Simeone, Timothy A.; Pandya, Jignesh D.; Wilke, Julianne C.; Ahn, Younghee; Geddes, James W.; Sullivan, Patrick G.; Rho, Jong M.

    2015-01-01

    Objective Ketone bodies (KB) are products of fatty acid oxidation and serve as essential fuels during fasting or treatment with the high-fat anti-seizure ketogenic diet (KD). Despite growing evidence that KB exert broad neuroprotective effects, their role in seizure control has not been firmly demonstrated. The major goal of this study was to demonstrate the direct anti-seizure effects of KB and to identify an underlying target mechanism. Methods We studied the effects of both the KD and KB in spontaneously epileptic Kcna1-null mice using a combination of behavioral, planar multi-electrode, and standard cellular electophysiological techniques. Thresholds for mitochondrial permeability transition (mPT) were determined in acutely isolated brain mitochondria. Results KB alone were sufficient to: (1) exert anti-seizure effects in Kcna1-null mice; (2) restore intrinsic impairment of hippocampal long-term potentiation (LTP) and spatial learning-memory defects in Kcna1-null mutants; and (3) raise the threshold for calcium-induced mPT in acutely prepared mitochondria from hippocampi of Kcna1-null animals. Targeted deletion of the cyclophilin D (CypD) subunit of the mPT complex abrogated the effects of KB on mPT, and in vivo pharmacological inhibition and activation of mPT were found to mirror and reverse, respectively, the anti-seizure effects of the KD in Kcna1-null mice. Interpretation The present data reveal the first direct link between mPT and seizure control, and provide a potential mechanistic explanation for the KD. Given that mPT is increasingly being implicated in diverse neurological disorders, our results suggest that metabolism-based treatments and/or metabolic substrates might represent a worthy paradigm for therapeutic development. PMID:25899847

  10. Induction of the apolipoprotein AI gene by fasting: a relationship with ketosis but not with ketone bodies.

    PubMed

    Haas, M J; Reinacher, D; Pun, K; Wong, N C; Mooradian, A D

    2000-12-01

    Apolipoprotein AI (apoAI) expression is inversely related to the incidence of atherosclerosis. ApoAI expression is also influenced by the nutritional state and diabetes. We used both cell culture and animal models to examine the effect of fasting and ketoacidosis on apoAI gene expression. Two days of food deprivation in rats increased hepatic and intestinal apoAI mRNA by 2.6- and 2.3-fold, respectively (P < .05). The absolute concentration of plasma apoAI did not change. However, the plasma apoAI concentration relative to the plasma concentration of serum proteins was increased 23% (P < .05). In fasting rats, there was a significant positive correlation between the serum beta-hydroxybutyrate concentration and hepatic or intestinal apoAI mRNA level. Despite this correlation, changes in apoAI mRNA are probably not mediated by ketone bodies, since neither hepatic nor intestinal apoAI mRNA levels were altered in rats maintained on a ketogenic diet for 10 days or treated with isobutyramide, an orally active ketone analog. In addition, the activity of the rat apoAI promoter was not altered in Hep G2 cells treated with isobutyramide or fatty acids or exposed to hypoglycemic conditions, while dexamethasone increased promoter activity 1.9-fold (P < .05). These data indicate that metabolic changes other than ketone bodies, such as an increase in plasma glucocorticoids, may account for starvation-induced expression of apoAI.

  11. [Development and analytical validation according COFRAC recommendations of pyruvate and ketone body assay on open automated analyser].

    PubMed

    Boulet, Lysiane; Van Noolen, Laetitia; Bosson, Caroline; Faure, Patrice; Corne, Christelle

    2014-01-01

    Measurements of pyruvate and ketones bodies (acetoacetate and 3-hydroxybutyrate) are essential to the investigation of intermediary metabolism. Indeed, their blood levels reflect energy balance influenced by nutritional status. This balance can be disturbed in certain diseases such as diabetes and some inherited metabolic disorders. We have developed methods for assays on open automated biochemistry analyser, Konelab 20 XT (ThermoFischer, Whaltham USA), using kits marketed by Sobioda (Montbonnot, France) for pyruvate and Wako Chemicals GmbH (Neuss, Germany) for ketones, on deproteinised blood sample. We have validated the performance of these three quantitative methods using NF EN ISO 15189 (range B) standard criteria. We obtain satisfactory results concerning fidelity (precision measured as within and between batch CVs are respectively less than 7% and less than 6%), measuring ranges (from 7.7 to 228 μmol/L for pyruvate and from 22.6 to 650 μM for total ketone bodies), accuracy (10.4 μmol/L in physiological range for pyruvate and 7.1 μmol/L for 3-hydroxybutyrate) and comparing methods (versus manual assay with spectrophotometry on Uvikon XL). Establishment of reference ranges (35 to 74 μmol/L for pyruvate, less than 100 μM for 3-hydroxybutyrate and less than 44 μmol/L for acetoacetate) and reagents stability study (up to 12 weeks if frozen) have enabled us to finalize method validation and to add these assays to our routine laboratory repertoire.

  12. Transition states and energetics of nucleophilic additions of thiols to substituted α,β-unsaturated ketones: substituent effects involve enone stabilization, product branching, and solvation.

    PubMed

    Krenske, Elizabeth H; Petter, Russell C; Zhu, Zhendong; Houk, K N

    2011-06-17

    CBS-QB3 enthalpies of reaction have been computed for the conjugate additions of MeSH to six α,β-unsaturated ketones. Compared with addition to methyl vinyl ketone, the reaction becomes 1-3 kcal mol(-1) less exothermic when an α-Me, β-Me, or β-Ph substituent is present on the C=C bond. The lower exothermicity for the substituted enones occurs because the substituted reactant is stabilized more by hyperconjugation or conjugation than the product is stabilized by branching. Substituent effects on the activation energies for the rate-determining step of the thiol addition (reaction of the enone with MeS(-)) were also computed. Loss of reactant stabilization, and not steric hindrance, is the main factor responsible for controlling the relative activation energies in the gas phase. The substituent effects are further magnified in solution; in water (simulated by CPCM calculations), the addition of MeS(-) to an enone is disfavored by 2-6 kcal mol(-1) when one or two methyl groups are present on the C=C bond (ΔΔG(‡)). The use of CBS-QB3 gas-phase energies in conjunction with CPCM solvation corrections provides kinetic data in good agreement with experimental substituent effects. When the energetics of the thiol additions were calculated with several popular density functional theory and ab initio methods (B3LYP, MPW1PW91, B1B95, PBE0, B2PLYP, and MP2), some substantial inaccuracies were noted. However, M06-2X (with a large basis set), B2PLYP-D, and SCS-MP2 gave results within 1 kcal mol(-1) of the CBS-QB3 benchmark values.

  13. Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes.

    PubMed

    Pelletier, Amélie; Coderre, Lise

    2007-05-01

    In aerobic conditions, the heart preferentially oxidizes fatty acids. However, during metabolic stress, glucose becomes the major energy source, and enhanced glucose uptake has a protective effect on heart function and cardiomyocyte survival. Thus abnormal regulation of glucose uptake may contribute to the development of cardiac disease in diabetics. Ketone bodies are often elevated in poorly controlled diabetics and are associated with increased cellular oxidative stress. Thus we sought to determine the effect of the ketone body beta-hydroxybutyrate (OHB) on cardiac glucose uptake during metabolic stress. We used 2,4-dinitrophenol (DNP), an uncoupler of the mitochondrial oxidative chain, to mimic hypoxia in cardiomyocytes. Our data demonstrated that chronic exposure to OHB provoked a concentration-dependent decrease of DNP action, resulting in 56% inhibition of DNP-mediated glucose uptake at 5 mM OHB. This was paralleled by a diminution of DNP-mediated AMP-activated protein kinase (AMPK) and p38 MAPK phosphorylation. Chronic exposure to OHB also increased reactive oxygen species (ROS) production by 1.9-fold compared with control cells. To further understand the role of ROS in OHB action, cardiomyocytes were incubated with H(2)O(2). Our results demonstrated that this treatment diminished DNP-induced glucose uptake without altering activation of the AMPK/p38 MAPK signaling pathway. Incubation with the antioxidant N-acetylcysteine partially restored DNP-mediated glucose but not AMPK/p38 MAPK activation. In conclusion, these results suggest that ketone bodies, through inhibition of the AMPK/p38 MAPK signaling pathway and ROS overproduction, regulate DNP action and thus cardiac glucose uptake. Altered glucose uptake in hyperketonemic states during metabolic stress may contribute to diabetic cardiomyopathy.

  14. Study of ketone body kinetics in children by a combined perfusion of /sup 13/C and /sup 2/H3 tracers

    SciTech Connect

    Bougneres, P.F.; Ferre, P.

    1987-11-01

    Ketone body kinetics were quantified in six children (3-5 yr old), who were fasted for 13-22 h, by a combined perfusion of (3-/sup 13/C)acetoacetate ((/sup 13/C)AcAc) and D-(-)-beta-(4,4,4-/sup 2/H3)hydroxybutyrate (beta-(/sup 2/H3)OHB) and gas chromatography-mass spectrometry analysis. Results were analyzed according to the single-pool (combined enrichments) or the two-accessible pools models. After 20-22 h of fasting, ketone body turnover rate was 30-50 mumol.kg-1.min-1, a rate achieved after several days of fasting in adults. At low ketosis, acetoacetate was the ketone body preferentially synthesized de novo and utilized irreversibly. When ketosis increased, acetoacetate irreversible disposal was not enhanced, since it was largely converted into beta-OHB, whereas beta-OHB irreversible disposal was very much increased. The single-pool and two-pool models gave similar ketone body turnover rates when (/sup 13/C)AcAc was the tracer, whereas the use of beta-(/sup 2/H3)OHB gave some more divergent results, especially at low ketosis. These studies demonstrate that ketogenesis is very active in short-term fasted children and that the use of a combined infusion of (/sup 13/C)AcAc and beta-(/sup 2/H3)OHB is a convenient way to give insight into individual ketone body kinetics.

  15. Raspberry Ketone

    MedlinePlus

    ... and breast-feeding: There is not enough reliable information about the safety of taking raspberry ketone if you are pregnant or breast feeding. Stay on the safe side and avoid use. Diabetes: Raspberry ketone might lower blood sugar levels. In theory, raspberry ketone might make blood sugar drop too ...

  16. Effects of hypo- and hyper-thyroidism on liver composition, blood glucose, ketone bodies and insulin in the male rat

    PubMed Central

    Aranda, Ana; Montoya, Eladio; Herrera, Emilio

    1972-01-01

    1. Thyroidectomized rats injected daily with 0, 0.1, 2 or 25μg of l-thyroxine/100g body wt. were compared with intact controls. In plasma, the protein-bound iodine was decreased in the rats given the 0 or 0.1μg doses and increased in those given the 25μg dose. 2. Blood glucose decreased in those given 2μg and was augmented in those given 25μg, and ketone bodies were the same in all the groups. 3. Plasma insulin was lowest in the rats given the 0 or 0.1μg doses and was highest in those given the 2 or 25μg doses of thyroxine. 4. After 48h starvation, the decrease in blood glucose and increase in ketone bodies observed in all the groups was greatest in the group not supplemented with thyroxine. 5. Plasma insulin concentrations remained at the value for fed animals in the rats given the 25μg dose of thyroxine but decreased in the other groups. 6. In fed animals, concentrations of hepatic DNA P, citrate, total fatty acids and acetyl-CoA were similar in all the groups, and glycogen was low only in the rats given the 25μg dose of thyroxine. 7. After 48h starvation, liver DNA P, total fatty acids and acetyl-CoA increased in all the groups, except in the rats given the 25μg dose, where both total fatty acids and acetyl-CoA remained at the value for fed animals. Liver citrate did not change in the groups given the 0 or 25μg doses of thyroxine, but decreased in the other groups. 8. The results are discussed in relation to the regulation of intermediary metabolism in hypo- and hyper-thyroidism. PMID:4634830

  17. Analysis of ketone bodies in exhaled breath and blood of ten healthy Japanese at OGTT using a portable gas chromatograph.

    PubMed

    Tanda, Naoko; Hinokio, Yoshinori; Washio, Jumpei; Takahashi, Nobuhiro; Koseki, Takeyoshi

    2014-11-24

    Ketone bodies including acetone are disease biomarkers for diabetes that sometimes causes severe ketoacidosis. The present study was undertaken to clarify the significance of exhaled acetone and plasma ketone bodies at bedside in a clinical setting. The oral glucose tolerance test (OGTT) was performed in 10 healthy Japanese volunteers (five females and five males). Exhaled breath acetone and volatile sulfide compounds (VSCs) in mouth air were measured simultaneously with blood sampling during the OGTT using a portable gas chromatograph equipped with an In2O3 thick-film type gas sensor and a VSC monitor. Acetone, β-hydroxybutyrate (β-OHB) and acetoacetate (AcAc) in blood plasma as well as glucose and insulin were examined. Oral conditions were examined based on the Community Periodontal Index (CPI) by one dentist. In addition, the same type of analysis was applied to two uncontrolled type 2 diabetes mellitus patients hospitalized at Tohoku University Hospital. Exhaled acetone was measured at the same time as blood withdrawal in the morning before breakfast and at night before bed at the beginning, the middle, and the end of hospitalization. All volunteers showed normal OGTT patterns with no ketonuria and periodontitis; however, there were significant correlations between breath acetone and plasma β-ΟΗΒ and between breath acetone and plasma AcAc under fasting conditions. Breath acetone of the type 2 diabetes mellitus patients showed positive correlations with plasma glucose when the level of plasma glucose tended to decrease during hospitalization. In spite of a very limited number of cases, our results support the idea that exhaled breath acetone may be related to plasma β-OHB and AcAc, which reflect glucose metabolism in the body.

  18. Early Energetic Particle Irradiation of the HED Parent Body Regolith

    NASA Technical Reports Server (NTRS)

    Bogard, D. D.; Garrison, D. H.; Rao, M. N.

    1996-01-01

    Previous studies have shown that many individual grains within the dark phase of the Kapoeta howardite were irradiated with energetic particles while residing on the surface of the early HED regolith. Particle tracks in these grains vary in density by more than an order of magnitude and undoubtedly were formed by energetic heavy (Fe) ions associated with early solar flares. Early Irradiation of HED Regolith: Concentrations of excess Ne alone are not sufficient to decide between competing galactic and solar irradiation models. However, from recent studies of depth samples of oriented lunar rocks, we have shown that the cosmogenic 21-Ne/22-Ne ratio produced in feldspar differs substantially between Galactic Cosmic Radiation (GCR) and solar protons, and that this difference is exactly that predicted from cross-section data. Using Ne literature data and new isotopic data we obtained on acid-etched, separated feldspar from both the light and dark phases of Kapoeta, we derive 21-Ne/22-Ne = 0.80 for the recent GCR irradiation and 21-Ne/22-Ne = 0.68 for the early regolith irradiation. This derived ratio indicates that the early Ne production in the regolith occurred by both galactic and solar protons. If we adopt a likely one-component regolith model in which all grains were exposed to galactic protons but individual grains had variable exposure to solar protons, we estimate that this early GCR irradiation lasted for about 3-6 m.y. More complex two-component regolith models involving separate solar and galactic irradiation would permit this GCR age to be longer. Higher-energy solar protons would permit the GCR to be longer. Higher-energy solar protons would permit the GCR age to be shorter. Further, cosmogenic 126(Xe) in Kapoeta dark is no more than a factor of about 2 higher than that observed in Kapoeta light. Because 126(Xe) can only be formed by galactic protons and not solar protons, these data support a short GCR irradiation for the HED regolith. This would also be

  19. Lipid, ketone body and oxidative metabolism in the African lungfish, Protopterus dolloi following 60 days of fasting and aestivation.

    PubMed

    Frick, Natasha Therese; Bystriansky, Jason Scott; Ip, Yuen Kwong; Chew, Shit Fun; Ballantyne, James Stuart

    2008-09-01

    The potential importance of lipids and ketone bodies as fuels in the African lungfish, Protopterus dolloi, and the role of oxidative metabolism, were examined under control, fasted and aestivated conditions. In aestivating but not fasting lungfish, the activities of citrate synthase (CS) and cytochrome c oxidase (CCO) (enzymes of oxidative metabolism) showed tissue-specific changes. Significant reductions in CS activity occurred in the kidney, heart, gill and muscle, and in CCO in the liver and kidney tissues. Aestivation, but not fasting, also had a tissue-specific effect on mitochondrial state 3 respiration rates (using succinate as a substrate), with a >50% reduction in the liver, yet no change within muscle mitochondria. There is no indication that enzymes involved in lipid catabolism are up-regulated during periods of fasting or aestivation; however, both 3-hydroxyacyl CoA dehydrogenase (HOAD) and carnitine palmitoyl CoA transferase (CPT) activities were sustained in the liver despite the approximately 42% reduction in CCO activity, potentially indicating lipid metabolism is of importance during aestivation. Lungfish are able to utilize both the d- and l-stereoisomers of the ketone body beta-hydroxybutyrate (beta-HB); however, beta-HB does not appear to be an important fuel source during aestivation or fasting as no changes were observed in beta-HB tissue levels. This study demonstrates that an important aspect of metabolic depression during aestivation in lungfish is the tissue-specific down regulation of enzymes of aerobic metabolism while maintaining the activities of enzymes in pathways that supply substrates for aerobic metabolism.

  20. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

    PubMed

    Thevenet, Jonathan; De Marchi, Umberto; Domingo, Jaime Santo; Christinat, Nicolas; Bultot, Laurent; Lefebvre, Gregory; Sakamoto, Kei; Descombes, Patrick; Masoodi, Mojgan; Wiederkehr, Andreas

    2016-05-01

    Medium-chain triglycerides have been used as part of a ketogenic diet effective in reducing epileptic episodes. The health benefits of the derived medium-chain fatty acids (MCFAs) are thought to result from the stimulation of liver ketogenesis providing fuel for the brain. We tested whether MCFAs have direct effects on energy metabolism in induced pluripotent stem cell-derived human astrocytes and neurons. Using single-cell imaging, we observed an acute pronounced reduction of the mitochondrial electrical potential and a concomitant drop of the NAD(P)H signal in astrocytes, but not in neurons. Despite the observed effects on mitochondrial function, MCFAs did not lower intracellular ATP levels or activate the energy sensor AMP-activated protein kinase. ATP concentrations in astrocytes were unaltered, even when blocking the respiratory chain, suggesting compensation through accelerated glycolysis. The MCFA decanoic acid (300 μM) promoted glycolysis and augmented lactate formation by 49.6%. The shorter fatty acid octanoic acid (300 μM) did not affect glycolysis but increased the rates of astrocyte ketogenesis 2.17-fold compared with that of control cells. MCFAs may have brain health benefits through the modulation of astrocyte metabolism leading to activation of shuttle systems that provide fuel to neighboring neurons in the form of lactate and ketone bodies.-Thevenet, J., De Marchi, U., Santo Domingo, J., Christinat, N., Bultot, L., Lefebvre, G., Sakamoto, K., Descombes, P., Masoodi, M., Wiederkehr, A. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

  1. Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with Advanced Glycation End Products in Normal and Diabetic Rats

    PubMed Central

    de Assis, Adriano M.; da Silva, Jussemara S.; Rech, Anderson; Longoni, Aline; Nonose, Yasmine; Repond, Cendrine; de Bittencourt Pasquali, Matheus A.; Moreira, José C. F.; Souza, Diogo O.; Pellerin, Luc

    2016-01-01

    Diabetes mellitus (DM) causes important modifications in the availability and use of different energy substrates in various organs and tissues. Similarly, dietary manipulations such as high fat diets also affect systemic energy metabolism. However, how the brain adapts to these situations remains unclear. To investigate these issues, control and alloxan-induced type I diabetic rats were fed either a standard or a high fat diet enriched with advanced glycation end products (AGEs) (HAGE diet). The HAGE diet increased their levels of blood ketone bodies, and this effect was exacerbated by DM induction. To determine the effects of diet and/or DM induction on key cerebral bioenergetic parameters, both ketone bodies (β-hydroxybutyric acid) and lactate oxidation were measured. In parallel, the expression of Monocarboxylate Transporter 1 (MCT1) and 2 (MCT2) isoforms in hippocampal and cortical slices from rats submitted to these diets was assessed. Ketone body oxidation increased while lactate oxidation decreased in hippocampal and cortical slices in both control and diabetic rats fed a HAGE diet. In parallel, the expression of both MCT1 and MCT2 increased only in the cerebral cortex in diabetic rats fed a HAGE diet. These results suggest a shift in the preferential cerebral energy substrate utilization in favor of ketone bodies in animals fed a HAGE diet, an effect that, in DM animals, is accompanied by the enhanced expression of the related transporters. PMID:27877108

  2. Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with Advanced Glycation End Products in Normal and Diabetic Rats.

    PubMed

    de Assis, Adriano M; da Silva, Jussemara S; Rech, Anderson; Longoni, Aline; Nonose, Yasmine; Repond, Cendrine; de Bittencourt Pasquali, Matheus A; Moreira, José C F; Souza, Diogo O; Pellerin, Luc

    2016-01-01

    Diabetes mellitus (DM) causes important modifications in the availability and use of different energy substrates in various organs and tissues. Similarly, dietary manipulations such as high fat diets also affect systemic energy metabolism. However, how the brain adapts to these situations remains unclear. To investigate these issues, control and alloxan-induced type I diabetic rats were fed either a standard or a high fat diet enriched with advanced glycation end products (AGEs) (HAGE diet). The HAGE diet increased their levels of blood ketone bodies, and this effect was exacerbated by DM induction. To determine the effects of diet and/or DM induction on key cerebral bioenergetic parameters, both ketone bodies (β-hydroxybutyric acid) and lactate oxidation were measured. In parallel, the expression of Monocarboxylate Transporter 1 (MCT1) and 2 (MCT2) isoforms in hippocampal and cortical slices from rats submitted to these diets was assessed. Ketone body oxidation increased while lactate oxidation decreased in hippocampal and cortical slices in both control and diabetic rats fed a HAGE diet. In parallel, the expression of both MCT1 and MCT2 increased only in the cerebral cortex in diabetic rats fed a HAGE diet. These results suggest a shift in the preferential cerebral energy substrate utilization in favor of ketone bodies in animals fed a HAGE diet, an effect that, in DM animals, is accompanied by the enhanced expression of the related transporters.

  3. Ketones and Human Performance.

    PubMed

    Scott, Jonathan M; Deuster, Patricia A

    Everyone is seeking nutritional strategies that might benefit performance. One approach receiving much attention is ketones, or ketosis. Ketones are very simple compounds made of hydrogen, carbon, and oxygen, and ketosis is a metabolic state whereby the body uses predominantly ketones. Ketosis can be achieved by fasting for longer than 72 hours or by following a very lowcarbohydrate, high-fat diet (ketogenic diet) for several days to weeks. Alternatively, ketone supplements purportedly induce ketosis rapidly and do not require strict adherence to any specific type of diet; however, much of the touted benefits are anecdotal. A potential role for ketosis as a performance enhancer was first introduced in 1983 with the idea that chronic ketosis without caloric restriction could preserve submaximal exercise capability by sparing glycogen or conserving the limited carbohydrate stores. Few human studies on the effects of a ketogenic diet on performance have yielded positive results, and most studies have yielded equivocal or null results, and a few negative results. Many questions about ketones relevant to Special Operations Forces (SOF) remain unanswered. At present, a ketogenic diet and/or a ketone supplement do not appear confer performance benefits for SOF. Instead, Operators should engage with their unit dietitian to develop individualized nutritional strategies based on unique mission requirements. The authors review the concept of a ketogenic diet, describe some potential benefits and risks of ketosis, review the performance literature and how to measure ketone status, and then summarize the landscape in 2017. 2017.

  4. BDNF Mediates Adaptive Brain and Body Responses to Energetic Challenges

    PubMed Central

    Marosi, Krisztina; Mattson, Mark P.

    2014-01-01

    Emerging findings suggest that brain-derived neurotrophic factor (BDNF) serves widespread roles in regulating energy homeostasis by controlling patterns of feeding and physical activity, and by modulating glucose metabolism in peripheral tissues. BDNF mediates beneficial effects of energetic challenges such as vigorous exercise and fasting on cognition, mood, cardiovascular function and peripheral metabolism. By stimulating glucose transport and mitochondrial biogenesis BDNF bolsters cellular bioenergetics and protects neurons against injury and disease. By acting in the brain and periphery, BDNF increases insulin sensitivity and parasympathetic tone. Genetic factors, a ‘couch potato’ lifestyle and chronic stress impair BDNF signaling, which may contribute to the pathogenesis of metabolic syndrome. Novel BDNF-focused interventions are being developed for obesity, diabetes and neurological disorders. PMID:24361004

  5. Monolayer patterning using ketone dipoles.

    PubMed

    Kim, Min Kyoung; Xue, Yi; Pašková, Tereza; Zimmt, Matthew B

    2013-08-14

    The self-assembly of multi-component monolayers with designed patterns requires molecular recognition among components. Dipolar interactions have been found to influence morphologies of self-assembled monolayers and can affect molecular recognition functions. Ketone groups have large dipole moments (2.6 D) and are easily incorporated into molecules. The potential of ketone groups for dipolar patterning has been evaluated through synthesis of two 1,5-disubstituted anthracenes bearing mono-ketone side chains, STM characterization of monolayers self-assembled from their single and two component solutions and molecular mechanics simulations to determine their self-assembly energetics. The results reveal that (i) anthracenes bearing self-repulsive mono-ketone side chains assemble in an atypical monolayer morphology that establishes dipolar attraction, instead of repulsion, between ketones in adjacent side chains; (ii) pairs of anthracene molecules whose self-repulsive ketone side chains are dipolar complementary spontaneously assemble compositionally patterned monolayers, in which the two components segregate into neighboring, single component columns, driven by side chain dipolar interactions; (iii) compositionally patterned monolayers also assemble from dipolar complementary anthracene pairs that employ different dipolar groups (ketones or CF2 groups) in their side chains; (iv) the ketone group, with its larger dipole moment and size, provides comparable driving force for patterned monolayer formation to that of the smaller dipole, and smaller size, CF2 group.

  6. Inhibition of testosterone biosynthesis by ethanol. Relation to hepatic and testicular acetaldehyde, ketone bodies and cytosolic redox state in rats.

    PubMed Central

    Eriksson, C J; Widenius, T V; Ylikahri, R H; Härkönen, M; Leinonen, P

    1983-01-01

    In experiments in which liver and testis freeze-stops were performed on pentobarbital-anaesthetized rats, ethanol (1.5 g/kg body wt.) reduced plasma testosterone concentration from 13.1 to 3.2 nmol/litre. 4-Methylpyrazole abolished the ethanol-induced hepatic and testicular increase in the lactate/pyruvate ratio, and the testicular acetaldehyde level, but did not diminish the reduction in plasma testosterone concentration. In testes, but not in liver, ethanol decreased the 3-hydroxybutyrate/acetoacetate ratio, and 4-methylpyrazole did not prevent this effect. In experiments in which freeze-stop was performed after cervical dislocation, ethanol decreased the testis testosterone concentration from 590 to 220 pmol per g wet wt. The effects of ethanol and 4-methylpyrazole on testis acetaldehyde, lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios were the same as found during anaesthesia. The NAD+-dependent ethanol oxidation capacity in testis ranged from 0.1 to 0.2 mumol/min per g wet wt. and seemed to be inhibited by 4-methylpyrazole both in vivo and in vitro. In additional experiments, ethanol doses between 0.3 and 0.9 g/kg body wt. did not alter the plasma testosterone concentration in rats treated, or not treated, with cyanamide, which induced elevated acetaldehyde levels in blood and testes. The results suggest that ethanol-induced inhibition of testosterone biosynthesis was not caused by extratesticular redox increases, or by extra- or intra-testicular acetaldehyde per se. The inhibition is accompanied by changes in testicular ketone-body metabolism. PMID:6847648

  7. Effect of the Ketone Body Beta-Hydroxybutyrate on the Innate Defense Capability of Primary Bovine Mammary Epithelial Cells

    PubMed Central

    Flinspach, Claudia; Pfaffl, Michael W.; Kliem, Heike

    2016-01-01

    Negative energy balance and ketosis are thought to cause impaired immune function and to increase the risk of clinical mastitis in dairy cows. The present in vitro study aimed to investigate the effect of elevated levels of the predominant ketone body β-hydroxybutyrate on the innate defense capability of primary bovine mammary epithelial cells (pbMEC) challenged with the mastitis pathogen Escherichia coli (E. coli). Therefore, pbMEC of healthy dairy cows in mid- lactation were isolated from milk and challenged in culture with 3 mM BHBA and E. coli. pbMEC stimulated with E. coli for 6 h or 30 h showed an up-regulation of several innate immune genes, whereas co-stimulation of pbMEC with 3 mM BHBA and E. coli resulted in the down-regulation of CCL2, SAA3, LF and C3 gene expression compared to the challenge with solely the bacterial stimulus. These results indicated that increased BHBA concentrations may be partially responsible for the higher mastitis susceptibility of dairy cows in early lactation. Elevated levels of BHBA in blood and milk during negative energy balance and ketosis are likely to impair innate immune function in the bovine mammary gland by attenuating the expression of a broad range of innate immune genes. PMID:27310007

  8. The role of OXCT1 in the pathogenesis of cancer as a rate-limiting enzyme of ketone body metabolism.

    PubMed

    Zhang, Song; Xie, Caifeng

    2017-08-15

    Cancer cells are well documented to reprogram their metabolism in order to support the maintenance and reproduction. 3-oxoacid CoA-transferase 1 (OXCT1) is a key enzyme in ketone body metabolism that catalyzes the first and rate-determining step of ketolysis. The product of OXCT1 converts to acetyl-CoA and finally fed into the tricarboxylic acid cycle for oxidation and ATP production. However, little is known of its regulation right now. Recently, some studies suggested that OXCT1 participates in tumorigenesis and signaling in cancer cells. Furthermore, our recent work showed that a marked elevation of OXCT1 expression in different categories of cancer cells. Here we review the metabolic functions of OXCT1 and its surprising roles in supporting the biological hallmarks of malignancy. We also review recent efforts in exploring the mechanism responsible for the tumor promoting effect of OXCT1 and suggest a novel therapeutic target for cancer therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Combination of aerobic exercise and an arginine, alanine, and phenylalanine mixture increases fat mobilization and ketone body synthesis.

    PubMed

    Ueda, Keisuke; Sanbongi, Chiaki; Takai, Shoko; Ikegami, Shuji; Fujita, Satoshi

    2017-07-01

    During exercise, blood levels of several hormones increase acutely. We hypothesized that consumption of a specific combination of amino acids (arginine, alanine, and phenylalanine; A-mix) may be involved in secretion of glucagon, and when combined with exercise may promote fat catabolism. Ten healthy male volunteers were randomized in a crossover study to ingest either A-mix (3 g/dose) or placebo (3 g of dextrin/dose). Thirty minutes after ingesting, each condition subsequently performed workload trials on a cycle ergometer at 50% of maximal oxygen consumption for 1 h. After oral intake of A-mix, the concentrations of plasma ketone bodies and adrenalin during and post-exercise were significantly increased. The area under the curve for glycerol and glucagon was significantly increased in the post-exercise by A-mix administration. These results suggest that pre-exercise ingestion of A-mix causes a shift of energy source from carbohydrate to fat combustion by increasing secretion of adrenalin and glucagon.

  10. Inhibition of lactate removal by ketone bodies in rat liver. Evidence for a quantitatively important role of the plasma membrane lactate transporter in lactate metabolism.

    PubMed Central

    Metcalfe, H K; Monson, J P; Welch, S G; Cohen, R D

    1986-01-01

    We studied the effect of DL-3-hydroxybutyrate and acetoacetate on lactate transport into isolated hepatocytes and on lactate removal in the isolated perfused rat liver. Ketone bodies inhibited lactate transport into isolated hepatocytes (maximum, 35% at concentrations of 10-20 mM). Lactate removal and glucose production by perfused livers were examined before and after the introduction of a constant infusion of hydroxybutyrate, acetoacetate, or appropriate control into the portal venous limb. Lactate removal was significantly inhibited within 10 s of the appearance of increasing concentrations of ketone bodies in the effluent. Corresponding decreases in glucose production were observed. The dependence of inhibition on D-3-hydroxybutyrate concentration was documented in isolated perfused livers (maximum inhibition of lactate removal, 58% at 14 mM). This phenomenon could be a factor in the development of lactic acidosis accompanying ketoacidosis, and indicates that plasma membrane lactate transport may determine the rate of hepatic lactate removal. PMID:3745435

  11. Impact of preoperative fasting times on blood glucose concentration, ketone bodies and acid-base balance in children younger than 36 months: A prospective observational study.

    PubMed

    Dennhardt, Nils; Beck, Christiane; Huber, Dirk; Nickel, Katja; Sander, Björn; Witt, Lars-Henrik; Boethig, Dietmar; Sümpelmann, Robert

    2015-12-01

    In contrast to preoperative fasting guidelines in paediatric anaesthesia, actual fasting times are often too long. The objective of this study was to evaluate the effect of preoperative fasting on glucose concentration, ketone bodies and acid-base balance in children. A prospective, noninterventional, clinical observational study. A single-centre trial, study period from June 2014 to November 2014. One hundred children aged 0 to 36 months scheduled for elective paediatric surgery. Patient demographics, fasting times, haemodynamic data, glucose and ketone body concentrations, and acid-base parameters after induction of anaesthesia were documented using a standardised case report form. Mean fasting period was 7.8 ± 4.5 (3.5 to 20) h, and deviation from guideline (ΔGL) was 3.3 ± 3.2 (-2 to 14) h. Linear regression showed a significant correlation between fasting times and ketone bodies, anion gap, base excess, osmolality as well as bicarbonate (for each, P < 0.05), but not glucose or lactate. In children with ΔGL more than 2 h (54%), ketone bodies, osmolality and anion gap were significantly higher and base excess significantly lower than children with ΔGL less than 2 h (for each, P < 0.05). After prolonged preoperative fasting, children younger than 36 months can present with ketoacidosis and (low) normal blood glucose concentrations. Actual fasting times should be optimised according to existing guidelines. In small infants, deviations from fasting guidelines should be as short as possible and not longer than 2 h.

  12. Tor-Sch9 deficiency activates catabolism of the ketone body-like acetic acid to promote trehalose accumulation and longevity

    PubMed Central

    Hu, Jia; Wei, Min; Mirzaei, Hamed; Madia, Federica; Amparo, Mario; Chagoury, Shawna; Kennedy, Brian; Longo, Valter D

    2014-01-01

    In mammals, extended periods of fasting leads to the accumulation of blood ketone bodies including acetoacetate. Here we show that similar to the conversion of leucine to acetoacetate in fasting mammals, starvation conditions induced ketone body-like acetic acid generation from leucine in S. cerevisiae. Whereas wild-type and ras2Δ cells accumulated acetic acid, long-lived tor1Δ and sch9Δ mutants rapidly depleted it through a mitochondrial acetate CoA transferase-dependent mechanism, which was essential for lifespan extension. The sch9Δ-dependent utilization of acetic acid also required coenzyme Q biosynthetic genes and promoted the accumulation of intracellular trehalose. These results indicate that Tor-Sch9 deficiency extends longevity by switching cells to an alternative metabolic mode, in which acetic acid can be utilized for the storage of stress resistance carbon sources. These effects are reminiscent of those described for ketone bodies in fasting mammals and raise the possibility that the lifespan extension caused by Tor-S6K inhibition may also involve analogous metabolic changes in higher eukaryotes. PMID:24649827

  13. Tor-Sch9 deficiency activates catabolism of the ketone body-like acetic acid to promote trehalose accumulation and longevity.

    PubMed

    Hu, Jia; Wei, Min; Mirzaei, Hamed; Madia, Federica; Mirisola, Mario; Amparo, Camille; Chagoury, Shawna; Kennedy, Brian; Longo, Valter D

    2014-06-01

    In mammals, extended periods of fasting leads to the accumulation of blood ketone bodies including acetoacetate. Here we show that similar to the conversion of leucine to acetoacetate in fasting mammals, starvation conditions induced ketone body-like acetic acid generation from leucine in S. cerevisiae. Whereas wild-type and ras2Δ cells accumulated acetic acid, long-lived tor1Δ and sch9Δ mutants rapidly depleted it through a mitochondrial acetate CoA transferase-dependent mechanism, which was essential for lifespan extension. The sch9Δ-dependent utilization of acetic acid also required coenzyme Q biosynthetic genes and promoted the accumulation of intracellular trehalose. These results indicate that Tor-Sch9 deficiency extends longevity by switching cells to an alternative metabolic mode, in which acetic acid can be utilized for the storage of stress resistance carbon sources. These effects are reminiscent of those described for ketone bodies in fasting mammals and raise the possibility that the lifespan extension caused by Tor-S6K inhibition may also involve analogous metabolic changes in higher eukaryotes.

  14. Impact of feeding and post prandial time on plasma ketone bodies in sows during transition and lactation.

    PubMed

    Theil, P K; Olesen, A K; Flummer, C; Sørensen, G; Kristensen, N B

    2013-02-01

    Two experiments were conducted with the aim of studying how dietary fat source, reproductive stage (Exp. 1), and diurnal variation (Exp. 2) affect plasma ketone bodies in sows. In Exp. 1, 40 second-parity sows were fed 1 of 5 lactation diets from 7 d prepartum until 28 d postpartum, with low or high levels (3% or 8%) of dietary fats with different proportions of medium- and long-chain fatty acids. Blood was obtained by jugular venipuncture on d 3 and 7 prepartum, and d 1, 10, 17, and 28 postpartum, and concentrations of plasma beta-hydroxy butyric acid (BHBA), acetoacetate + acetone (AcAc+Ac), glucose, NEFA, lactate, acetate, and butyrate were determined. For 4 out of 5 treatments, plasma BHBA decreased slightly, whereas plasma AcAc+Ac remained stable. However, plasma BHBA (P < 0.01) and AcAc+Ac (P < 0.001) doubled after d 10 of lactation in sows fed 4% octanoic acid and 4% fish oil diet (4+4% FO; P < 0.001), compared with earlier in lactation (P < 0.001). Plasma AcAc+Ac was positively related to BHBA (P < 0.01), glucose (P < 0.05), and butyrate (P < 0.001), and negatively related to the acetate:butyrate ratio (P < 0.001). In addition, plasma BHBA was positively related to lactate (P < 0.01), acetate, and butyrate (P < 0.05). In Exp. 2, diurnal variations of plasma metabolites were studied in 5 sows sampled every second hour from a jugular catheter throughout a 24-h period on d 5 and 17 of lactation and analyzed as in Exp. 1. In addition, milk and urine samples were collected and analyzed for BHBA and AcAc+Ac. No diurnal variations in plasma BHBA or AcAc+Ac were observed and plasma AcAc+Ac was unchanged from d 5 to 17 of lactation (3.7 μM), whereas BHBA declined from 58 μM on d 5 of lactation to 52 μM on d 17 of lactation (P < 0.05). Minor amounts of AcAc+Ac were found in urine (8.6 μM) and this was not affected by days in milk, whereas the content of AcAc+Ac in milk and BHBA in milk and urine were less than the detection limit in 4 of 5 sows. In conclusion

  15. Effect of phenylalanine metabolites on the activities of enzymes of ketone-body utilization in brain of suckling rats.

    PubMed Central

    Benavides, J; Gimenez, C; Valdivieso, F; Mayor, F

    1976-01-01

    1. The effects of phenylalanine and its metabolites (phenylacetate, phenethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) 3-oxo acid CoA-transferase (EC 2.8.3.5) and acetoacetyl-CoA thiolase (EC 2.3.1.9) in brain of suckling rats were investigated. 2. The 3-hydroxybutyrate dehydrogenase from the brain of suckling rats had a Km for 3-hydroxybutyrate of 1.2 mM. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the enzyme activity with Ki values of 0.5, 1.3 and 4.7 mM respectively. 3. The suckling-rat brain 3-oxo acid CoA-transferase activity had a Km for acetoacetate of 0.665 mM and for succinyl (3-carboxypropionyl)-CoA of 0.038 mM. The enzyme was inhibited with respect to acetoacetate by phenylpyruvate (Ki equals 1.3 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). The reaction in the direction of acetoacetate was also inhibited by phenylpyruvate (Ki equals 1.6 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). 4. Phenylpyruvate inhibited with respect to acetoacetyl-CoA both the mitochondrial (Ki equals 3.2 mM) and cytoplasmic (Ki equals 5.2 mM) acetoacetyl-CoA thiolase activities. 5. The results suggest that inhibition of 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities may impair ketone-body utilization and hence lipid synthesis in the developing brain. This suggestion is discussed with reference to the pathogenesis of mental retardation in phenylketonuria. PMID:12750

  16. The addition of ketone bodies alleviates mitochondrial dysfunction by restoring complex I assembly in a MELAS cellular model.

    PubMed

    Frey, Samuel; Geffroy, Guillaume; Desquiret-Dumas, Valerie; Gueguen, Naig; Bris, Celine; Belal, Sophie; Amati-Bonneau, Patrizia; Chevrollier, Arnaud; Barth, Magalie; Henrion, Daniel; Lenaers, Guy; Bonneau, Dominique; Reynier, Pascal; Procaccio, Vincent

    2017-01-01

    Ketogenic Diet used to treat refractory epilepsy for almost a century may represent a treatment option for mitochondrial disorders for which effective treatments are still lacking. Mitochondrial complex I deficiencies are involved in a broad spectrum of inherited diseases including Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes syndrome leading to recurrent cerebral insults resembling strokes and associated with a severe complex I deficiency caused by mitochondrial DNA (mtDNA) mutations. The analysis of MELAS neuronal cybrid cells carrying the almost homoplasmic m.3243A>G mutation revealed a metabolic switch towards glycolysis with the production of lactic acid, severe defects in respiratory chain activity and complex I disassembly with an accumulation of assembly intermediates. Metabolites, NADH/NAD(+) ratio, mitochondrial enzyme activities, oxygen consumption and BN-PAGE analysis were evaluated in mutant compared to control cells. A severe complex I enzymatic deficiency was identified associated with a major complex I disassembly with an accumulation of assembly intermediates of 400kDa. We showed that Ketone Bodies (KB) exposure for 4weeks associated with glucose deprivation significantly restored complex I stability and activity, increased ATP synthesis and reduced the NADH/NAD+ ratio, a key component of mitochondrial metabolism. In addition, without changing the mutant load, mtDNA copy number was significantly increased with KB, indicating that the absolute amount of wild type mtDNA copy number was higher in treated mutant cells. Therefore KB may constitute an alternative and promising therapy for MELAS syndrome, and could be beneficial for other mitochondrial diseases caused by complex I deficiency.

  17. Excitatory action of GABA on immature neurons is not due to absence of ketone bodies metabolites or other energy substrates.

    PubMed

    Ben-Ari, Yehezkel; Tyzio, Roman; Nehlig, Astrid

    2011-09-01

    Brain slices incubated with glucose have provided most of our knowledge on cellular, synaptic, and network driven mechanisms. It has been recently suggested that γ-aminobutyric acid (GABA) excites neonatal neurons in conventional glucose-perfused slices but not when ketone bodies metabolites, pyruvate, and/or lactate are added, suggesting that the excitatory actions of GABA are due to energy deprivation when glucose is the sole energy source. In this article, we review the vast number of studies that show that slices are not energy deprived in glucose-containing medium, and that addition of other energy substrates at physiologic concentrations does not alter the excitatory actions of GABA on neonatal neurons. In contrast, lactate, like other weak acids, can produce an intracellular acidification that will cause a reduction of intracellular chloride and a shift of GABA actions. The effects of high concentrations of lactate, and particularly of pyruvate (4-5 mm), as used are relevant primarily to pathologic conditions; these concentrations not being found in the brain in normal "control" conditions. Slices in glucose-containing medium may not be ideal, but additional energy substrates neither correspond to physiologic conditions nor alter GABA actions. In keeping with extensive observations in a wide range of animal species and brain structures, GABA depolarizes immature neurons and the reduction of the intracellular concentration of chloride ([Cl(-)](i)) is a basic property of brain maturation that has been preserved throughout evolution. In addition, this developmental sequence has important clinical implications, notably concerning the higher incidence of seizures early in life and their long-lasting deleterious sequels. Immature neurons have difficulties exporting chloride that accumulates during seizures, leading to permanent increase of [Cl(-)](i) that converts the inhibitory actions of GABA to excitatory and hampers the efficacy of GABA-acting antiepileptic

  18. Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency.

    PubMed

    Habarou, F; Bahi-Buisson, N; Lebigot, E; Pontoizeau, C; Abi-Warde, M T; Brassier, A; Le Quan Sang, K H; Broissand, C; Vuillaumier-Barrot, S; Roubertie, A; Boutron, A; Ottolenghi, C; de Lonlay, P

    2017-05-17

    Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r (2) = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of CO2 production after (14)C-labeled 3-hydroxybutyrate supplementation was consistent with improved Krebs cycle activity. However, except in one patient, ketonemia tended to be lower with 3-hydroxybutyrate administration compared to ketogenic diet. 3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.

  19. Activities of enzymes of fat and ketone-body metabolism and effects of starvation on blood concentrations of glucose and fat fuels in teleost and elasmobranch fish

    PubMed Central

    Zammit, Victor A.; Newsholme, Eric A.

    1979-01-01

    1. Activities of 3-oxo acid CoA-transferase and carnitine palmitoyltransferase together with tri- and di-acylglycerol lipase were present in red and heart muscles of the teleost fish. However, d-3-hydroxybutyrate dehydrogenase activity was not detectable. These results suggest that the heart and red muscles of the teleosts should be able to utilize the fat fuels triacylglycerol, fatty acids or acetoacetate, but not hydroxybutyrate. The muscles from the elasmobranchs differed in that d-3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities were present, but carnitine palmitoyltransferase activity was not detectable. This suggests that ketone bodies are the most important fat fuels in elasmobranchs. 2. The concentrations of acetoacetate, 3-hydroxybutyrate, glycerol, non-esterified fatty acids and triacylglycerols were measured in blood or plasma of several species of fish (teleosts and elasmobranchs) in the fed state. Teleosts have a 10-fold higher concentration of plasma non-esterified fatty acids, but a lower blood concentration of ketone bodies; both acetoacetate and 3-hydroxybutyrate are present in blood of elasmobranchs, whereas 3-hydroxybutyrate is absent from that of the teleosts. 3. The effects of starvation (up to 150 days) on the concentrations of blood metabolites were studied in a teleost (bass) and an elasmobranch (dogfish). In the bass there was a 60% decrease in blood glucose after 100 and 150 days starvation. In dogfish there was a large increase in the concentration of ketone bodies, whereas in bass the concentration of acetoacetate (the only ketone body present) remained low (<0.04mm) throughout the period of starvation. The concentration of plasma non-esterified fatty acids increased in bass, but decreased in dogfish. These changes are consistent with the predictions based on the enzyme-activity data. 4. Starvation did not change the activities of ketone-body-utilizing enzymes or that of phosphoenolpyruvate carboxykinase in heart

  20. Toward a theory of energetically optimal body size in growing animals.

    PubMed

    Hannon, B M; Murphy, M R

    2016-06-01

    Our objective was to formulate a general and useful model of the energy economy of the growing animal. We developed a theory that the respiratory energy per unit of size reaches a minimum at a particular point, when the marginal respiratory heat production rate is equal to the average rate. This occurs at what we defined as the energetically optimal size for the animal. The relationship between heat production rate and size was found to be well described by a cubic function in which heat production rate accelerates as the animal approaches and then exceeds its optimal size. Reanalysis of energetics data from the literature often detected cubic curvature in the relationship between heat production rate and body size of fish, rats, chickens, goats, sheep, swine, cattle, and horses. This finding was consistent with the theory for 13 of 17 data sets. The bias-corrected Akaike information criterion indicated that the cubic equation modeled the influence of the size of a growing animal on its heat production rate better than a power function for 11 of 17 data sets. Changes in the sizes and specific heat production rates of metabolically active internal organs, and body composition and tissue turnover rates were found to explain notable portions of the expected increase in heat production rate as animals approached and then exceeded their energetically optimum size. Accelerating maintenance costs in this region decrease net energy available for productive functions. Energetically and economically optimum size criteria were also compared.

  1. Hyperinsulinemia shifted energy supply from glucose to ketone bodies in early nonalcoholic steatohepatitis from high-fat high-sucrose diet induced Bama minipigs.

    PubMed

    Yang, Shu-lin; Xia, Ji-han; Zhang, Yuan-yuan; Fan, Jian-gao; Wang, Hua; Yuan, Jing; Zhao, Zhan-zhao; Pan, Qin; Mu, Yu-lian; Xin, Lei-lei; Chen, Yao-xing; Li, Kui

    2015-09-11

    The minipig can serve as a good pharmacological model for human subjects. However, the long-term pathogenesis of high-calorie diet-induced metabolic syndromes, including NASH, has not been well described in minipigs. We examined the development of metabolic syndromes in Bama minipigs that were fed a high-fat, high-sucrose diet (HFHSD) for 23 months, by using histology and serum biochemistry and by profiling the gene expression patterns in the livers of HFHSD pigs compared to controls. The pathology findings revealed microvesicular steatosis, iron overload, arachidonic acid synthesis, lipid peroxidation, reduced antioxidant capacity, increased cellular damage, and inflammation in the liver. RNA-seq analysis revealed that 164 genes were differentially expressed between the livers of the HFHSD and control groups. The pathogenesis of early-stage NASH was characterized by hyperinsulinemia and by de novo synthesis of fatty acids and nascent triglycerides, which were deposited as lipid droplets in hepatocytes. Hyperinsulinemia shifted the energy supply from glucose to ketone bodies, and the high ketone body concentration induced the overexpression of cytochrome P450 2E1 (CYP2E1). The iron overload, CYP2E1 and alcohol dehydrogenase 4 overexpression promoted reactive oxygen species (ROS) production, which resulted in arachidonic and linoleic acid peroxidation and, in turn, led to malondialdehyde production and a cellular response to ROS-mediated DNA damage.

  2. Longer Food Chains in Pelagic Ecosystems: Trophic Energetics of Animal Body Size and Metabolic Efficiency.

    PubMed

    McGarvey, Richard; Dowling, Natalie; Cohen, Joel E

    2016-07-01

    Factors constraining the structure of food webs can be investigated by comparing classes of ecosystems. We find that pelagic ecosystems, those based on one-celled primary producers, have longer food chains than terrestrial ecosystems. Yet pelagic ecosystems have lower primary productivity, contrary to the hypothesis that greater energy flows permit higher trophic levels. We hypothesize that longer food chain length in pelagic ecosystems, compared with terrestrial ecosystems, is associated with smaller pelagic animal body size permitting more rapid trophic energy transfer. Assuming negative allometric dependence of biomass production rate on body mass at each trophic level, the lowest three pelagic animal trophic levels are estimated to add biomass more rapidly than their terrestrial counterparts by factors of 12, 4.8, and 2.6. Pelagic animals consequently transport primary production to a fifth trophic level 50-190 times more rapidly than animals in terrestrial webs. This difference overcomes the approximately fivefold slower pelagic basal productivity, energetically explaining longer pelagic food chains. In addition, ectotherms, dominant at lower pelagic animal trophic levels, have high metabolic efficiency, also favoring higher rates of trophic energy transfer in pelagic ecosystems. These two animal trophic flow mechanisms imply longer pelagic food chains, reestablishing an important role for energetics in food web structure.

  3. First-principles energetics of water clusters and ice: A many-body analysis

    SciTech Connect

    Gillan, M. J.; Alfè, D.; Bartók, A. P.; Csányi, G.

    2013-12-28

    Standard forms of density-functional theory (DFT) have good predictive power for many materials, but are not yet fully satisfactory for cluster, solid, and liquid forms of water. Recent work has stressed the importance of DFT errors in describing dispersion, but we note that errors in other parts of the energy may also contribute. We obtain information about the nature of DFT errors by using a many-body separation of the total energy into its 1-body, 2-body, and beyond-2-body components to analyze the deficiencies of the popular PBE and BLYP approximations for the energetics of water clusters and ice structures. The errors of these approximations are computed by using accurate benchmark energies from the coupled-cluster technique of molecular quantum chemistry and from quantum Monte Carlo calculations. The systems studied are isomers of the water hexamer cluster, the crystal structures Ih, II, XV, and VIII of ice, and two clusters extracted from ice VIII. For the binding energies of these systems, we use the machine-learning technique of Gaussian Approximation Potentials to correct successively for 1-body and 2-body errors of the DFT approximations. We find that even after correction for these errors, substantial beyond-2-body errors remain. The characteristics of the 2-body and beyond-2-body errors of PBE are completely different from those of BLYP, but the errors of both approximations disfavor the close approach of non-hydrogen-bonded monomers. We note the possible relevance of our findings to the understanding of liquid water.

  4. First-principles energetics of water clusters and ice: a many-body analysis.

    PubMed

    Gillan, M J; Alfè, D; Bartók, A P; Csányi, G

    2013-12-28

    Standard forms of density-functional theory (DFT) have good predictive power for many materials, but are not yet fully satisfactory for cluster, solid, and liquid forms of water. Recent work has stressed the importance of DFT errors in describing dispersion, but we note that errors in other parts of the energy may also contribute. We obtain information about the nature of DFT errors by using a many-body separation of the total energy into its 1-body, 2-body, and beyond-2-body components to analyze the deficiencies of the popular PBE and BLYP approximations for the energetics of water clusters and ice structures. The errors of these approximations are computed by using accurate benchmark energies from the coupled-cluster technique of molecular quantum chemistry and from quantum Monte Carlo calculations. The systems studied are isomers of the water hexamer cluster, the crystal structures Ih, II, XV, and VIII of ice, and two clusters extracted from ice VIII. For the binding energies of these systems, we use the machine-learning technique of Gaussian Approximation Potentials to correct successively for 1-body and 2-body errors of the DFT approximations. We find that even after correction for these errors, substantial beyond-2-body errors remain. The characteristics of the 2-body and beyond-2-body errors of PBE are completely different from those of BLYP, but the errors of both approximations disfavor the close approach of non-hydrogen-bonded monomers. We note the possible relevance of our findings to the understanding of liquid water.

  5. First-principles energetics of water clusters and ice: A many-body analysis

    NASA Astrophysics Data System (ADS)

    Gillan, M. J.; Alfè, D.; Bartók, A. P.; Csányi, G.

    2013-12-01

    Standard forms of density-functional theory (DFT) have good predictive power for many materials, but are not yet fully satisfactory for cluster, solid, and liquid forms of water. Recent work has stressed the importance of DFT errors in describing dispersion, but we note that errors in other parts of the energy may also contribute. We obtain information about the nature of DFT errors by using a many-body separation of the total energy into its 1-body, 2-body, and beyond-2-body components to analyze the deficiencies of the popular PBE and BLYP approximations for the energetics of water clusters and ice structures. The errors of these approximations are computed by using accurate benchmark energies from the coupled-cluster technique of molecular quantum chemistry and from quantum Monte Carlo calculations. The systems studied are isomers of the water hexamer cluster, the crystal structures Ih, II, XV, and VIII of ice, and two clusters extracted from ice VIII. For the binding energies of these systems, we use the machine-learning technique of Gaussian Approximation Potentials to correct successively for 1-body and 2-body errors of the DFT approximations. We find that even after correction for these errors, substantial beyond-2-body errors remain. The characteristics of the 2-body and beyond-2-body errors of PBE are completely different from those of BLYP, but the errors of both approximations disfavor the close approach of non-hydrogen-bonded monomers. We note the possible relevance of our findings to the understanding of liquid water.

  6. Activation of liver carnitine palmitoyltransferase-1 and mitochondrial acetoacetyl-CoA thiolase is associated with elevated ketone body levels in the elasmobranch Squalus acanthias.

    PubMed

    Treberg, Jason R; Crockett, Elizabeth L; Driedzic, William R

    2006-01-01

    Elasmobranch fishes are an ancient group of vertebrates that have unusual lipid metabolism whereby storage lipids are mobilized from the liver for peripheral oxidation largely as ketone bodies rather than as nonesterified fatty acids under normal conditions. This reliance on ketones, even when feeding, implies that elasmobranchs are chronically ketogenic. Compared to specimens sampled within 2 d of capture (recently captured), spiny dogfish Squalus acanthias that were held for 16-33 d without apparent feeding displayed a 4.5-fold increase in plasma concentration of d- beta -hydroxybutyrate (from 0.71 to 3.2 mM) and were considered ketotic. Overt activity of carnitine palmitoyltransferase-1 in liver mitochondria from ketotic dogfish was characterized by an increased apparent maximal activity, a trend of increasing affinity (reduced apparent K(m); P=0.09) for l-carnitine, and desensitization to the inhibitor malonyl-CoA relative to recently captured animals. Acetoacetyl-CoA thiolase (ACoAT) activity in isolated liver mitochondria was also markedly increased in the ketotic dogfish compared to recently captured fish, whereas no difference in 3-hydroxy-3-methylglutaryl-CoA synthase activity was found between these groups, suggesting that ACoAT plays a more important role in the activation of ketogenesis in spiny dogfish than in mammals and birds.

  7. Cerebral ketone metabolism during development and injury.

    PubMed

    Prins, Mayumi L

    2012-07-01

    Cerebral metabolism of ketones is a normal part of the process of brain development. While the mature brain relies on glucose as a primary fuel source, metabolism of ketone bodies remains an alternative energy source under conditions of starvation. The neuroprotective properties of brain ketone metabolism make this alternative substrate a viable therapeutic option for various pathologies. Since the ability to revert to utilizing ketones as an alternative substrate is greatest in the younger post-weaned brain, this particular therapeutic approach remains an untapped resource particularly for pediatric pathological conditions. Published by Elsevier B.V.

  8. Cerebral Ketone Metabolism During Development and Injury

    PubMed Central

    Prins, Mayumi L.

    2011-01-01

    Cerebral metabolism of ketones is a normal part of the process of brain development. While the mature brain relies on glucose as a primary fuel source, metabolism of ketone bodies remains an alternative energy source under conditions of starvation. The neuroprotective properties of brain ketone metabolism make this alternative substrate a viable therapeutic option for various pathologies. Since the ability to revert to utilizing ketones as an alternative substrate is greatest in the younger post-weaned brain, this particular therapeutic approach remains an untapped resource particularly for pediatric pathological conditions. PMID:22104087

  9. Temporal changes in plasma levels and metabolism of ketone bodies by liver and brain after ethanol and/or starvation in C57BL/6J mice.

    PubMed

    Schreiber, R A; Yeh, Y Y

    1984-03-01

    The effects of ethanol and starvation on ketone body production and utilization were investigated. In the first experiment, adult C57BL/6J mice were divided into four groups: (i) control (fed); (ii) starvation (up to 31 h); (iii) ethanol (acute 5 g/kg i.p.); (iv) ethanol (ETOH) + starvation. Plasma ketone body (KB) concentrations in control mice remained constant at approx. 0.37 mM. The levels of KBs in starved mice began to increase at about 7 h and rose to a peak of 2.5 mM at about 24 h, then fell to 1.8 mM at 31 h. The levels in mice treated with ETOH began to rise soon after injection, reached 1.5 mM at 10 h, and returned to control levels by 15 h. Although there was no difference in elevated levels of KBs between two groups of mice treated with ETOH plus starvation and ETOH alone at 7-10 h, the level continued to rise steadily to 2.0 mM through 31 h in the former group. At 10 h post ETOH, mice either fed ad lib. or fasted had increased hepatic capacity to synthesize acetoacetate (AcAc) from palmitate; this effect was prolonged and enhanced by continued fasting for 24 h. In the brain, the rate of AcAc oxidation was twice that for beta-hydroxybutyrate (beta OHB) and glucose. Neither ETOH nor starvation affected energy production from KB and glucose. AcAc was also utilized for fatty acid synthesis and the rate of synthesis was stimulated by ETOH at 10 h after injection. The rate of lipogenesis from beta OHB accounted for less than 10% of that from AcAc. Together these experiments demonstrate that ETOH increases both hepatic ketone production and plasma KB levels for at least 10 h. ETOH alone led to elevated KB levels long before the rise due to starvation. In brain, at 10 h, an increased capacity to utilize AcAc for lipogenesis was found. The results indicate that ETOH through the production of KBs could provide an important source of energy and lipid precursors for the brain of mice.

  10. Fueling Performance: Ketones Enter the Mix.

    PubMed

    Egan, Brendan; D'Agostino, Dominic P

    2016-09-13

    Ketone body metabolites serve as alternative energy substrates during prolonged fasting, calorie restriction, or reduced carbohydrate (CHO) availability. Using a ketone ester supplement, Cox et al. (2016) demonstrate that acute nutritional ketosis alters substrate utilization patterns during exercise, reduces lactate production, and improves time-trial performance in elite cyclists.

  11. A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism.

    PubMed

    Lehnen, Tatiana Ederich; da Silva, Marcondes Ramos; Camacho, Augusto; Marcadenti, Aline; Lehnen, Alexandre Machado

    2015-01-01

    Conjugated linoleic acid (CLA) is highly found in fats from ruminants and it appears to favorably modify the body composition and cardiometabolic risk factors. The capacity of CLA to reduce the body fat levels as well as its benefic actions on glycemic profile, atherosclerosis and cancer has already been proved in experimental models. Furthermore, CLA supplementation may modulate the immune function, help re-synthetize of glycogen and potentiate the bone mineralization. CLA supplementation also could increase the lipolysis and reduce the accumulation of fatty acids on the adipose tissue; the putative mechanisms involved may be its action in reducing the lipase lipoprotein activity and to increase the carnitine-palmitoil-transferase-1 (CAT-1) activity, its interaction with PPARγ, and to raise the expression of UCP-1. Although studies made in human have shown some benefits of CLA supplementation as the weight loss, the results are still discordant. Moreover, some have shown adverse effects, such as negative effects on glucose metabolism and lipid profile. The purpose of this article is to review the available data regarding the benefits of CLA on the energetic metabolism and body composition, emphasizing action mechanisms.

  12. Impact of Universal Plasma and Energetic Particle Processes on Icy Bodies of the Kuiper Belt and the Oort Cloud

    NASA Technical Reports Server (NTRS)

    Cooper, John F.; Richardson, J. D.; Hill, M. E.; Sturner, S. J.

    2008-01-01

    Modeling of space plasma and energetic particle interactions with icy bodies of the outer solar system is simplified when there is commonality of the underlying source, acceleration, and transport processes in spatially distinct regions from the supersonic heliosphere through the heliosheath into the local interstellar medium (LISM). Current trends in the Voyager heliosheath measurements suggest strong commonality to processes in the LISM. The Fisk-Gloeckler "universal" spectrum at suprathermal energies apparently plays a strong role in coupling the plasma and high energy particle regimes in the spatial and energetic transitions from the outer heliosphere to the LISM. Dominant processes in consecutive energy regimes project to varying effects versus irradiation depth on exposed upper surfaces of airless small icy bodies and to upper atmospheres of larger bodies such as Titan and Pluto. Relative absence of the universal suprathermal spectrum in the mid-heliospheric region of the classical Kuiper Belt may profoundly affect surface color diversity of icy bodies in this region.

  13. Dielectric Breakdown Weathering by Solar Energetic Particles Charging Airless Bodies in the Inner Solar System

    NASA Astrophysics Data System (ADS)

    Jordan, A.; Stubbs, T. J.; Wilson, J. K.; Schwadron, N.; Spence, H. E.; Hayne, P. O.; Izenberg, N.

    2016-12-01

    Solar energetic particles (SEPs) can penetrate regoliths of airless bodies to depths of 1 mm and cause deep dielectric charging. This charging is predicted to dissipate slowly (on the order of days) in regoliths with low electrical conductivities, which could form subsurface electric fields (> 106 V/m) large enough to cause dielectric breakdown (or "sparking"). Colder regoliths are expected to have lower conductivities, so the coldest regions of airless planetary bodies can become the most deep dielectrically charged. Consequently, large SEP events may cause dielectric breakdown in these regions, possibly contributing to space weathering on airless bodies in the inner solar system. Previous work has predicted that, in permanently shadowed regions (PSRs) on the Moon, breakdown weathering may have melted and/or vaporized 10-25 wt% of the meteoritically gardened regolith, a percentage comparable to weathering by meteoroid impacts. But much of the Moon's nightside can also reach cold (<100 K) temperatures, so we now show how breakdown weathering may have affected 4-11 wt% of the gardened regolith over the entire lunar surface. We use data from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter (LRO) to show two examples of SEP events that may have caused breakdown on the Moon. We also scale large SEP events to the orbit of Mars and predict the rate at which they may cause dielectric breakdown on Phobos and Deimos, whose polar regions remain <100 K during their long winters (nearly half an Eart h yea r). On these satellites, the gardening rates are unknown, so we estimate the percentage of regolith affected in these locations as a function of gardening rate. Finally, we briefly show that dielectric breakdown may occur on asteroids that have either high obliquities or PSRs, like Vesta and Ceres, respectively. This work also emphasizes the need for laboratory experiments to inform both remote sensing observations and the

  14. Energetic proton irradiation history of the HED parent body regolith and implications for ancient solar activity

    NASA Astrophysics Data System (ADS)

    Rao, M. N.; Garrison, D. H.; Palma, R. L.; Bogard, D. D.

    1997-07-01

    Previous studies have shown that the Kapoeta howardite, as well as several other meteorites, contain excess concentrations of cosmogenic neon in the darkened, solar-irradiated phase compared to the light, non-irradiated phase. The two explanations offered for the nuclear production of these Ne excesses in the parent body regolith are either from galactic particle (GCR) irradiation or from a greatly enhanced flux of energetic solar protons (SCR), as compared to the recent solar flux. Combining new isotopic data we obtained on acid-etched, separated feldspar from Kapoeta light and dark phases with literature data, we show that the cosmogenic 21Ne /22Ne ratio of light phase feldspar (0.80) is consistent with only GCR irradiation in space for ~3 Myr. However, the 21Ne/22Ne ratio (0.68) derived for irradiation of dark phase feldspar in the Kapoeta regolith indicates that cosmogenic Ne was produced in roughly equal proportions from galactic and solar protons. Considering a simple model of an immature Kapoeta parent body regolith, the duration of this early galactic exposure was only ~3-6 Myr, which would be an upper limit to the solar exposure time of individual grains. Concentrations of cosmogenic 21Ne in pyroxene separates and of cosmogenic 126Xe in both feldspar and pyroxene are consistent with this interpretation. The near-surface irradiation time of individual grains in the Kapoeta regolith probably varied considerably due to regolith mixing to an average GCR irradiation depth of ~10 cm. Because of the very different depth scales for production of solar ~Fe tracks, SCR Ne, and GCR Ne, the actual regolith exposure times for average grains probably differed correspondingly. However, both the SCR 21Ne and solar track ages appear to be longer because of enhanced production by early solar activity. The SCR/GCR production ratio of 21Ne inferred from the Kapoeta data is larger by a at least a factor of 10 and possibly as much as a factor of ~50 compared to recent solar

  15. Clinical review: ketones and brain injury.

    PubMed

    White, Hayden; Venkatesh, Balasubramanian

    2011-04-06

    Although much feared by clinicians, the ability to produce ketones has allowed humans to withstand prolonged periods of starvation. At such times, ketones can supply up to 50% of basal energy requirements. More interesting, however, is the fact that ketones can provide as much as 70% of the brain's energy needs, more efficiently than glucose. Studies suggest that during times of acute brain injury, cerebral uptake of ketones increases significantly. Researchers have thus attempted to attenuate the effects of cerebral injury by administering ketones exogenously. Hypertonic saline is commonly utilized for management of intracranial hypertension following cerebral injury. A solution containing both hypertonic saline and ketones may prove ideal for managing the dual problems of refractory intracranial hypertension and low cerebral energy levels. The purpose of the present review is to explore the physiology of ketone body utilization by the brain in health and in a variety of neurological conditions, and to discuss the potential for ketone supplementation as a therapeutic option in traumatic brain injury.

  16. Clinical review: Ketones and brain injury

    PubMed Central

    2011-01-01

    Although much feared by clinicians, the ability to produce ketones has allowed humans to withstand prolonged periods of starvation. At such times, ketones can supply up to 50% of basal energy requirements. More interesting, however, is the fact that ketones can provide as much as 70% of the brain's energy needs, more efficiently than glucose. Studies suggest that during times of acute brain injury, cerebral uptake of ketones increases significantly. Researchers have thus attempted to attenuate the effects of cerebral injury by administering ketones exogenously. Hypertonic saline is commonly utilized for management of intracranial hypertension following cerebral injury. A solution containing both hypertonic saline and ketones may prove ideal for managing the dual problems of refractory intracranial hypertension and low cerebral energy levels. The purpose of the present review is to explore the physiology of ketone body utilization by the brain in health and in a variety of neurological conditions, and to discuss the potential for ketone supplementation as a therapeutic option in traumatic brain injury. PMID:21489321

  17. Reduction of increased levels of blood glycerol and ketone bodies by propranolol in human hyperthyroidism: role of the fall of the triiodothyronine level.

    PubMed

    Beylot, M; Riou, J P; Borson, F; Cohen, R; Sautot, G; Mornex, R

    1984-12-01

    Hyperthyroid patients in the postabsorptive state have elevated levels of blood glycerol and ketone bodies (KB): this is believed to be due to increased lipolysis and ketogenesis. These increased glycerol and KB levels return toward normal after oral propranolol administration. In order to investigate the mechanism of action of propranolol in hyperthyroid patients, we compared the effects of the oral administration of propranolol with those of timolol, propylthiouracil (PTU), and a placebo. The placebo had no effect. The free thyroxine index, immunoreactive insulin level and glucagon level were not modified by propranolol, timolol, or PTU. Propranolol decreased the pulse rate (P less than 0.01) and the levels of serum triiodothyronine (T3; P less than 0.05), blood glycerol (P less than 0.01), and KB (P less than 0.01). Like propranolol, timolol decreased the pulse rate (P less than 0.01) but had no effect on the T3, glycerol, or KB levels. Propylthiouracil did not modify the pulse rate, but like propranolol, it decreased the T3 (P less than 0.05), glycerol (P less than 0.01) and KB (P less than 0.01) levels. These results suggest that the metabolic actions of propranolol are not caused by its hemodynamic effects nor its beta-blocking properties but are mediated by the decrease of the T3 level.

  18. "Body-In-The-Loop": Optimizing Device Parameters Using Measures of Instantaneous Energetic Cost

    PubMed Central

    Felt, Wyatt; Selinger, Jessica C.; Donelan, J. Maxwell; Remy, C. David

    2015-01-01

    This paper demonstrates methods for the online optimization of assistive robotic devices such as powered prostheses, orthoses and exoskeletons. Our algorithms estimate the value of a physiological objective in real-time (with a body “in-the-loop”) and use this information to identify optimal device parameters. To handle sensor data that are noisy and dynamically delayed, we rely on a combination of dynamic estimation and response surface identification. We evaluated three algorithms (Steady-State Cost Mapping, Instantaneous Cost Mapping, and Instantaneous Cost Gradient Search) with eight healthy human subjects. Steady-State Cost Mapping is an established technique that fits a cubic polynomial to averages of steady-state measures at different parameter settings. The optimal parameter value is determined from the polynomial fit. Using a continuous sweep over a range of parameters and taking into account measurement dynamics, Instantaneous Cost Mapping identifies a cubic polynomial more quickly. Instantaneous Cost Gradient Search uses a similar technique to iteratively approach the optimal parameter value using estimates of the local gradient. To evaluate these methods in a simple and repeatable way, we prescribed step frequency via a metronome and optimized this frequency to minimize metabolic energetic cost. This use of step frequency allows a comparison of our results to established techniques and enables others to replicate our methods. Our results show that all three methods achieve similar accuracy in estimating optimal step frequency. For all methods, the average error between the predicted minima and the subjects’ preferred step frequencies was less than 1% with a standard deviation between 4% and 5%. Using Instantaneous Cost Mapping, we were able to reduce subject walking-time from over an hour to less than 10 minutes. While, for a single parameter, the Instantaneous Cost Gradient Search is not much faster than Steady-State Cost Mapping, the

  19. Multi-body forces and the energetics of transition metals, alloys, and semiconductors

    SciTech Connect

    Carlsson, A.E.

    1992-01-01

    Progress over the past year is divided into 3 areas: potential-energy functions for transition-metal aluminides; electronic structure and energetics of complex structures and quasicrystals; and ceramic materials (PdO, PtO).

  20. Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies

    PubMed Central

    Mantis, John G; Centeno, Nicole A; Todorova, Mariana T; McGowan, Richard; Seyfried, Thomas N

    2004-01-01

    Background The high fat, low carbohydrate ketogenic diet (KD) was developed as an alternative to fasting for seizure management. While the mechanisms by which fasting and the KD inhibit seizures remain speculative, alterations in brain energy metabolism are likely involved. We previously showed that caloric restriction (CR) inhibits seizure susceptibility by reducing blood glucose in the epileptic EL mouse, a natural model for human multifactorial idiopathic epilepsy. In this study, we compared the antiepileptic and anticonvulsant efficacy of the KD with that of CR in adult EL mice with active epilepsy. EL mice that experienced at least 15 recurrent complex partial seizures were fed either a standard diet unrestricted (SD-UR) or restricted (SD-R), and either a KD unrestricted (KD-UR) or restricted (KD-R). All mice were fasted for 14 hrs prior to diet initiation. A new experimental design was used where each mouse in the diet-restricted groups served as its own control to achieve a 20–23% body weight reduction. Seizure susceptibility, body weights, and the levels of plasma glucose and β-hydroxybutyrate were measured once/week over a nine-week treatment period. Results Body weights and blood glucose levels remained high over the testing period in the SD-UR and the KD-UR groups, but were significantly (p < 0.001) reduced in the SD-R and KD-R groups. Plasma β-hydroxybutyrate levels were significantly (p < 0.001) increased in the SD-R and KD-R groups compared to their respective UR groups. Seizure susceptibility remained high in both UR-fed groups throughout the study, but was significantly reduced after three weeks in both R-fed groups. Conclusions The results indicate that seizure susceptibility in EL mice is dependent on plasma glucose levels and that seizure control is more associated with the amount than with the origin of dietary calories. Also, CR underlies the antiepileptic and anticonvulsant action of the KD in EL mice. A transition from glucose to ketone

  1. A high-resolution thermoelectric module-based calorimeter for measuring the energetics of isolated ventricular trabeculae at body temperature.

    PubMed

    Johnston, Callum M; Han, June-Chiew; Ruddy, Bryan P; Nielsen, Poul M F; Taberner, Andrew J

    2015-07-15

    Isolated ventricular trabeculae are the most common experimental preparations used in the study of cardiac energetics. However, the experiments have been conducted at subphysiological temperatures. We have overcome this limitation by designing and constructing a novel calorimeter with sufficiently high thermal resolution for simultaneously measuring the heat output and force production of isolated, contracting, ventricular trabeculae at body temperature. This development was largely motivated by the need to better understand cardiac energetics by performing such measurements at body temperature to relate tissue performance to whole heart behavior in vivo. Our approach uses solid-state thermoelectric modules, tailored for both temperature sensing and temperature control. The thermoelectric modules have high sensitivity and low noise, which, when coupled with a multilevel temperature control system, enable an exceptionally high temperature resolution with a noise-equivalent power an order of magnitude greater than those of other existing muscle calorimeters. Our system allows us to rapidly and easily change the experimental temperature without disturbing the state of the muscle. Our calorimeter is useful in many experiments that explore the energetics of normal physiology as well as pathophysiology of cardiac muscle. Copyright © 2015 the American Physiological Society.

  2. Oxidative Impairment of Hippocampal Long-term Potentiation Involves Activation of Protein Phosphatase 2A and Is Prevented by Ketone Bodies

    PubMed Central

    Maalouf, Marwan; Rho, Jong M.

    2008-01-01

    Previous studies have shown that ketone bodies (KB) exert antioxidant effects in experimental models of neurological disease. In the present study, we explored the effects of the KB acetoacetate (ACA) and β-hydroxybutyrate (BHB) on impairment of hippocampal long-term potentiation (LTP) in rats by hydrogen peroxide (H2O2) using electrophysiological, fluorescence imaging and enzyme assay techniques. We found that: (1) a combination of ACA and BHB (1 mM each) prevented impairment of LTP by H2O2 (200 μM); (2) KB significantly lowered intracellular levels of reactive oxygen species (ROS) — measured with the fluorescent indicator carboxy-H2DCFDA — in CA1 pyramidal neurons exposed to H2O2; (3) the effect of KB on LTP was replicated by the protein phosphatase 2A (PP2A) inhibitor fostriecin; (4) KB prevented impairment of LTP by the PP2A activator C6 ceramide; (5) fostriecin did not prevent the increase in ROS levels in CA1 pyramidal neurons exposed to H2O2, and C6 ceramide did not increase ROS levels; (6) PP2A activity was enhanced by both H2O2and rotenone – a mitochondrial complex I inhibitor that increases endogenous superoxide production; and (7) KB inhibited PP2A activity in protein extracts from brain tissue treated with either H2O2 or ceramide. We propose that oxidative impairment of hippocampal LTP is associated with PP2A activation, and that KB prevent this impairment in part by inducing PP2A inhibition through an antioxidant mechanism. PMID:18646208

  3. Pharmacodynamic and pharmacokinetic interactions between common antiepileptic drugs and acetone, the chief anticonvulsant ketone body elevated in the ketogenic diet in mice.

    PubMed

    Zarnowska, Iwona; Luszczki, Jarogniew J; Zarnowski, Tomasz; Buszewicz, Grzegorz; Madro, Roman; Czuczwar, Stanislaw J; Gasior, Maciej

    2009-05-01

    Acetone is the principal ketone body elevated in the ketogenic diet (KD), with demonstrated robust anticonvulsant properties across a variety of seizure tests and models of epilepsy. Because the majority of patients continue to receive antiepileptic drugs (AEDs) during KD treatment, interactions between acetone and AEDs may have important clinical implications. Therefore, we investigated whether acetone could affect the anticonvulsant activity and pharmacokinetic properties of several AEDs against maximal electroshock (MES)-induced seizures in mice. Effects of acetone given in subthreshold doses were tested on the anticonvulsant effects of carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), topiramate (TPM) and valproate (VPA) against MES-induced seizures in mice. In addition, acute adverse effects of acetone-AEDs combinations were assessed in the chimney test (motor performance) and passive avoidance task (long-term memory). Pharmacokinetic interactions between acetone and AEDs were also studied in the mouse brain tissue. Acetone (5 or 7.5 mmol/kg, intraperitoneally [i.p.]) enhanced the anticonvulsant activity of CBZ, LTG, PB, and VPA against MES-induced seizures; effects of OXC, PHT, and TPM were not changed. Acetone (7.5 mmol/kg) did not enhance the acute adverse-effect profiles of the studied AEDs. Acetone (5 or 7.5 mmol/kg, i.p.) did not affect total brain concentrations of the studied AEDs. In contrast, VPA, CBZ, LTG, OXC, and TPM significantly decreased the concentration of free acetone in the brain; PB and PHT had no effect. Acetone enhances the anticonvulsant effects of several AEDs such as VPA, CBZ, LTG, and PB without affecting their pharmacokinetic and side-effect profiles.

  4. Ketone ester effects on metabolism and transcription.

    PubMed

    Veech, Richard L

    2014-10-01

    Ketosis induced by starvation or feeding a ketogenic diet has widespread and often contradictory effects due to the simultaneous elevation of both ketone bodies and free fatty acids. The elevation of ketone bodies increases the energy of ATP hydrolysis by reducing the mitochondrial NAD couple and oxidizing the coenzyme Q couple, thus increasing the redox span between site I and site II. In contrast, metabolism of fatty acids leads to a reduction of both mitochondrial NAD and mitochondrial coenzyme Q causing a decrease in the ΔG of ATP hydrolysis. In contrast, feeding ketone body esters leads to pure ketosis, unaccompanied by elevation of free fatty acids, producing a physiological state not previously seen in nature. The effects of pure ketosis on transcription and upon certain neurodegenerative diseases make approach not only interesting, but of potential therapeutic value.

  5. Ketone ester effects on metabolism and transcription

    PubMed Central

    Veech, Richard L.

    2014-01-01

    Ketosis induced by starvation or feeding a ketogenic diet has widespread and often contradictory effects due to the simultaneous elevation of both ketone bodies and free fatty acids. The elevation of ketone bodies increases the energy of ATP hydrolysis by reducing the mitochondrial NAD couple and oxidizing the coenzyme Q couple, thus increasing the redox span between site I and site II. In contrast, metabolism of fatty acids leads to a reduction of both mitochondrial NAD and mitochondrial coenzyme Q causing a decrease in the ΔG of ATP hydrolysis. In contrast, feeding ketone body esters leads to pure ketosis, unaccompanied by elevation of free fatty acids, producing a physiological state not previously seen in nature. The effects of pure ketosis on transcription and upon certain neurodegenerative diseases make approach not only interesting, but of potential therapeutic value. PMID:24714648

  6. 21 CFR 862.1435 - Ketones (nonquantitative) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) test system is a device intended to identify ketones in urine and other body fluids. Identification of... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ketones (nonquantitative) test system. 862.1435 Section 862.1435 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  7. 21 CFR 862.1435 - Ketones (nonquantitative) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) test system is a device intended to identify ketones in urine and other body fluids. Identification of... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ketones (nonquantitative) test system. 862.1435 Section 862.1435 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  8. 21 CFR 862.1435 - Ketones (nonquantitative) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) test system is a device intended to identify ketones in urine and other body fluids. Identification of... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ketones (nonquantitative) test system. 862.1435 Section 862.1435 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  9. 21 CFR 862.1435 - Ketones (nonquantitative) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) test system is a device intended to identify ketones in urine and other body fluids. Identification of... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ketones (nonquantitative) test system. 862.1435 Section 862.1435 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  10. Volatilization of ketones

    USGS Publications Warehouse

    Rathbun, R.E.; Tai, D.Y.

    1984-01-01

    Volatilization fluxes of seven ketones were measured over a range of temperatures. Gas-film coefficients were calculated from these volatilization fluxes and related to the gas-film coefficient for the evaporation of water. These relations, when combined with an equation for estimating the gas-film coefficient for evaporation of water from a canal, permit estimating gas-film coefficients for the volatilization of ketones from streams and rivers.

  11. Oxidative metabolism: glucose versus ketones.

    PubMed

    Prince, Allison; Zhang, Yifan; Croniger, Colleen; Puchowicz, Michelle

    2013-01-01

    The coupling of upstream oxidative processes (glycolysis, beta-oxidation, CAC turnover) to mitochondrial oxidative phosphorylation (OXPHOS) under the driving conditions of energy demand by the cell results in the liberation of free energy as ATP. Perturbations in glycolytic CAC or OXPHOS can result in pathology or cell death. To better understand whole body energy expenditure during chronic ketosis, we used a diet-induced rat model of ketosis to determine if high-fat-carbohydrate-restricted "ketogenic" diet results in changes in total energy expenditure (TEE). Consistent with previous reports of increased energy expenditure in mice, we hypothesized that rats fed ketogenic diet for 3 weeks would result in increased resting energy expenditure due to alterations in metabolism associated with a "switch" in energy substrate from glucose to ketone bodies. The rationale is ketone bodies are a more efficient fuel than glucose. Indirect calorimetric analysis revealed a moderate increase in VO2 and decreased VCO2 and heat with ketosis. These results suggest ketosis induces a moderate uncoupling state and less oxidative efficiency compared to glucose oxidation.

  12. Scaling of free-ranging primate energetics with body mass predicts low energy expenditure in humans.

    PubMed

    Simmen, Bruno; Darlu, Pierre; Hladik, Claude Marcel; Pasquet, Patrick

    2015-01-01

    Studies of how a mammal's daily energy expenditure scales with its body mass suggest that humans, whether Westerners, agro-pastoralists, or hunter-gatherers, all have much lower energy expenditures for their body mass than other mammals. However, non-human primates also differ from other mammals in several life history traits suggestive of low energy use. Judging by field metabolic rates of free-ranging strepsirhine and haplorhine primates with different lifestyle and body mass, estimated using doubly labeled water, primates have lower energy expenditure than other similar-sized eutherian mammals. Daily energy expenditure in humans fell along the regression line of non-human primates. The results suggest that thrifty energy use could be an ancient strategy of primates. Although physical activity is a major component of energy balance, our results suggest a need to revise the basis for establishing norms of energy expenditure in modern humans.

  13. Energetics and mechanics of running men: the influence of body mass.

    PubMed

    Taboga, Paolo; Lazzer, Stefano; Fessehatsion, Rezene; Agosti, Fiorenza; Sartorio, Alessandro; di Prampero, Pietro E

    2012-12-01

    We investigated the relationship between mechanical and energy cost of transport and body mass in running humans. Ten severely obese (body mass ranging from 108.5 to 172.0 kg) and 15 normal-weighted (52.0-89.0 kg) boys and men, aged 16.0-45.8 years, participated in this study. The rate of O(2) consumption was measured and the subjects were filmed with four cameras for kinematic analysis, while running on a treadmill at 8 km h(-1). Mass specific energy cost (C (r)) and external mechanical work (W (ext)) per unit distance were calculated and expressed in joules per kilogram per meter, efficiency (η) was then calculated as W (ext) × C (r) (-1)  × 100. Both mass-specific C (r) and W (ext) were found to be independent of body mass (M) (C (r) = 0.002 M + 3.729, n = 25, R (2) = 0.05; W (ext) = -0.001 M + 1.963, n = 25, R (2) = 0.01). It necessarily follows that the efficiency is also independent of M (η = -0.062 M + 53.3298, n = 25, R (2) = 0.05). The results strongly suggest that the elastic tissues of obese subjects can adapt (e.g., thickening) to the increased mass of the body thus maintaining their ability to store elastic energy, at least at 8 km h(-1) speed, at the same level as the normal-weighted subjects.

  14. Methyl ethyl ketone (MEK)

    Integrated Risk Information System (IRIS)

    Methyl ethyl ketone ( MEK ) ( CASRN 78 - 93 - 3 ) Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonc

  15. Methyl isobutyl ketone (MIBK)

    Integrated Risk Information System (IRIS)

    EPA / 635 / R - 03 / 002 TOXICOLOGICAL REVIEW OF METHYL ISOBUTYL KETONE ( CAS No . 108 - 10 - 1 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) March 2003 U.S . Environmental Protection Agency Washington DC DISCLAIMER This document has been reviewed in accordan

  16. Dislocation kink-pair energetics and pencil glide in body-centered-cubic crystals.

    PubMed

    Ngan, A H; Wen, M

    2001-08-13

    When body-centered-cubic crystals undergo plastic deformation, the slip planes are often noncrystallographic. By performing atomistic simulation on the activation pathway of dislocation jumps in bcc iron, we show that the main reason for bcc crystals to exhibit this phenomenon is that one type of kink pair has significantly lower energy than all the other types on the same slip plane. Dislocation motion therefore cannot continue on the same slip plane, and the dislocation has to cross slip onto an intersecting slip plane after each atomic jump. Thus in the long run, the average slip plane would be zigzag and noncrystallographic.

  17. Determination of ketone body kinetics using a D-(-)-3-hydroxy(4,4,4-/sub 2/H/sup 3/)butyrate tracer

    SciTech Connect

    Bougneres, P.F.; Balasse, E.O.; Ferre, P.; Bier, D.M.

    1986-02-01

    In studies where D-(-)-3-hydroxy(4,4,4-/sub 2/H/sup 3/)butyrate is employed as isotopic tracer in vivo, we have described a selected ion monitoring, gas-liquid chromatography-mass spectrometry micromethod which measures (/sub 2/H/sup 3/) tracer enrichment in 3-hydroxybutyrate and acetoacetate from 300-microliters blood samples. For plasma samples in the physiologic range, intra- and interassay precisions for each ketone averaged better than +/- 1% and +/- 2%, respectively. The use of the method was validated by comparing kinetic data obtained with the above tracer with simultaneous flux data obtained with conventional D-(-)-3-hydroxy(3-/sup 14/C)butyrate tracer in five fasted rats.

  18. Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke.

    PubMed

    Yin, Junxiang; Han, Pengcheng; Tang, Zhiwei; Liu, Qingwei; Shi, Jiong

    2015-11-01

    Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD(+)/NADH ratio. In this study, we investigated whether mitochondrial NAD(+)-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD(+)-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway.

  19. Sirtuin 3 mediates neuroprotection of ketones against ischemic stroke

    PubMed Central

    Yin, Junxiang; Han, Pengcheng; Tang, Zhiwei; Liu, Qingwei; Shi, Jiong

    2015-01-01

    Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD+/NADH ratio. In this study, we investigated whether mitochondrial NAD+-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD+-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway. PMID:26058697

  20. Ketones suppress brain glucose consumption.

    PubMed

    LaManna, Joseph C; Salem, Nicolas; Puchowicz, Michelle; Erokwu, Bernadette; Koppaka, Smruta; Flask, Chris; Lee, Zhenghong

    2009-01-01

    The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as beta-hydroxybutyrate (beta HB) and acetoacetate (AcAc), as occurs with fasting, prolonged starvation or chronic feeding of a high fat/low carbohydrate diet (ketogenic diet). In this study, the local cerebral metabolic rate of glucose consumption (CMRglu; microM/min/100g) was calculated in the cortex and cerebellum of control and ketotic rats using Patlak analysis. Rats were imaged on a rodent PET scanner and MRI was performed on a 7-Tesla Bruker scanner for registration with the PET images. Plasma glucose and beta HB concentrations were measured and 90-minute dynamic PET scans were started simultaneously with bolus injection of 2-Deoxy-2[18F]Fluoro-D-Glucose (FDG). The blood radioactivity concentration was automatically sampled from the tail vein for 3 min following injection and manual periodic blood samples were taken. The calculated local CMRGlu decreased with increasing plasma BHB concentration in the cerebellum (CMRGlu = -4.07*[BHB] + 61.4, r2 = 0.3) and in the frontal cortex (CMRGlu = -3.93*[BHB] + 42.7, r2 = 0.5). These data indicate that, under conditions of ketosis, glucose consumption is decreased in the cortex and cerebellum by about 10% per each mM of plasma ketone bodies.

  1. Optimized preoperative fasting times decrease ketone body concentration and stabilize mean arterial blood pressure during induction of anesthesia in children younger than 36 months: a prospective observational cohort study.

    PubMed

    Dennhardt, Nils; Beck, Christiane; Huber, Dirk; Sander, Bjoern; Boehne, Martin; Boethig, Dietmar; Leffler, Andreas; Sümpelmann, Robert

    2016-08-01

    In pediatric anesthesia, preoperative fasting guidelines are still often exceeded. The objective of this noninterventional clinical observational cohort study was to evaluate the effect of an optimized preoperative fasting management (OPT) on glucose concentration, ketone bodies, acid-base balance, and change in mean arterial blood pressure (MAP) during induction of anesthesia in children. Children aged 0-36 months scheduled for elective surgery with OPT (n = 50) were compared with peers studied before optimizing preoperative fasting time (OLD) (n = 50) who were matched for weight, age, and height. In children with OPT (n = 50), mean fasting time (6.0 ± 1.9 h vs 8.5 ± 3.5 h, P < 0.001), deviation from guideline (ΔGL) (1.2 ± 1.4 h vs 3.7 ± 3.1 h, P < 0.001, ΔGL>2 h 8% vs 70%), ketone bodies (0.2 ± 0.2 mmol·l(-1) vs 0.6 ± 0.6 mmol·l(-1) , P < 0.001), and incidence of hypotension (MAP <40 mmHg, 0 vs 5, P = 0.022) were statistically significantly lower and MAP after induction was statistically significantly higher (55.2 ± 9.5 mmHg vs 50.3 ± 9.8 mmHg, P = 0.015) as compared to children in the OLD (n = 50) group. Glucose, lactate, bicarbonate, base excess, and anion gap did not significantly differ. Optimized fasting times improve the metabolic and hemodynamic condition during induction of anesthesia in children younger than 36 months of age. © 2016 John Wiley & Sons Ltd.

  2. Renormalization of myoglobin–ligand binding energetics by quantum many-body effects

    PubMed Central

    Weber, Cédric; Cole, Daniel J.; O’Regan, David D.; Payne, Mike C.

    2014-01-01

    We carry out a first-principles atomistic study of the electronic mechanisms of ligand binding and discrimination in the myoglobin protein. Electronic correlation effects are taken into account using one of the most advanced methods currently available, namely a linear-scaling density functional theory (DFT) approach wherein the treatment of localized iron 3d electrons is further refined using dynamical mean-field theory. This combination of methods explicitly accounts for dynamical and multireference quantum physics, such as valence and spin fluctuations, of the 3d electrons, while treating a significant proportion of the protein (more than 1,000 atoms) with DFT. The computed electronic structure of the myoglobin complexes and the nature of the Fe–O2 bonding are validated against experimental spectroscopic observables. We elucidate and solve a long-standing problem related to the quantum-mechanical description of the respiration process, namely that DFT calculations predict a strong imbalance between O2 and CO binding, favoring the latter to an unphysically large extent. We show that the explicit inclusion of the many-body effects induced by the Hund’s coupling mechanism results in the correct prediction of similar binding energies for oxy- and carbonmonoxymyoglobin. PMID:24717844

  3. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition.

    PubMed

    Hall, Kevin D; Guo, Juen

    2017-05-01

    Weight changes are accompanied by imbalances between calorie intake and expenditure. This fact is often misinterpreted to suggest that obesity is caused by gluttony and sloth and can be treated by simply advising people to eat less and move more. Rather various components of energy balance are dynamically interrelated and weight loss is resisted by counterbalancing physiological processes. While low-carbohydrate diets have been suggested to partially subvert these processes by increasing energy expenditure and promoting fat loss, our meta-analysis of 32 controlled feeding studies with isocaloric substitution of carbohydrate for fat found that both energy expenditure (26 kcal/d; P <.0001) and fat loss (16 g/d; P <.0001) were greater with lower fat diets. We review the components of energy balance and the mechanisms acting to resist weight loss in the context of static, settling point, and set-point models of body weight regulation, with the set-point model being most commensurate with current data. Published by Elsevier Inc.

  4. Thermal conductivity and energetic recoils in UO2 using a many-body potential model

    NASA Astrophysics Data System (ADS)

    Qin, M. J.; Cooper, M. W. D.; Kuo, E. Y.; Rushton, M. J. D.; Grimes, R. W.; Lumpkin, G. R.; Middleburgh, S. C.

    2014-12-01

    Classical molecular dynamics simulations have been performed on uranium dioxide (UO2) employing a recently developed many-body potential model. Thermal conductivities are computed for a defect free UO2 lattice and a radiation-damaged, defect containing lattice at 300 K, 1000 K and 1500 K. Defects significantly degrade the thermal conductivity of UO2 as does the presence of amorphous UO2, which has a largely temperature independent thermal conductivity of ˜1.4 Wm-1 K-1. The model yields a pre-melting superionic transition temperature at 2600 K, very close to the experimental value and the mechanical melting temperature of 3600 K, slightly lower than those generated with other empirical potentials. The average threshold displacement energy was calculated to be 37 eV. Although the spatial extent of a 1 keV U cascade is very similar to those generated with other empirical potentials and the number of Frenkel pairs generated is close to that from the Basak potential, the vacancy and interstitial cluster distribution is different.

  5. Space Weathering of airless bodies in the Solar System - Combining hypervelocity dust impacts with energetic irradiation experiments

    NASA Astrophysics Data System (ADS)

    Fiege, K.; Bennett, C.; Guglielmino, M.; Orlando, T. M.; Trieloff, M.; Srama, R.

    2015-12-01

    The chemical and mineralogical characterization of meteorites and their parent asteroids provides us with information about the processes and conditions during the formation of the inner Solar System. However, linking meteorites to their parent bodies is problematic. Astronomical observations aim to reconstruct the surface properties of these bodies primarily by visible and infrared spectra, but space weathering severely modifies the optical, compositional and physical properties of thin surface layers and thus precludes proper identification of chemistry and mineralogy. The effects of space weathering have been experimentally studied mainly with respect to ion bombardment and sputtering. Other studies aimed to simulate the influence of micrometeoroid bombardment by using laser ablation techniques. However, there is sufficient evidence that laser ablation does not realistically lead to the same effects as produced during real micrometeorite impacts. We performed micrometeorite bombardment using a 2MV dust accelerator at the Institute for Space Systems at University of Stuttgart, Germany, capable of generating impact speeds up to 100 km s-1. These results are combined with energetic irradiation experiments at the Electron and Photon Induced Chemistry on Surfaces (EPICS) laboratory at Georgia Institute of Technology, USA. By simulating highly realistic irradiation conditions, we are able to investigate the processes of particle and solar wind irradiation on solid planetary surfaces and study the formation of e.g., nanophase iron in minerals, the effects on hydrous minerals regarding their volatile budgets, or possible OH-formation in nominally anhydrous minerals and relate these to their optical properties. Using a variety of minerals, this work aims to contribute to a better understanding of the general alteration mechanisms in space environments in dependence of weathering agent and available material. We here present the results of initial comparison analysis and

  6. Utility of ketone measurement in the prevention, diagnosis and management of diabetic ketoacidosis.

    PubMed

    Misra, S; Oliver, N S

    2015-01-01

    Ketone measurement is advocated for the diagnosis of diabetic ketoacidosis and assessment of its severity. Assessing the evidence base for ketone measurement in clinical practice is challenging because multiple methods are available but there is a lack of consensus about which is preferable. Evaluating the utility of ketone measurement is additionally problematic because of variability in the biochemical definition of ketoacidosis internationally and in the proposed thresholds for ketone measures. This has led to conflicting guidance from expert bodies on how ketone measurement should be used in the management of ketoacidosis. The development of point-of-care devices that can reliably measure the capillary blood ketone β-hydroxybutyrate (BOHB) has widened the spectrum of applications of ketone measurement, but whether the evidence base supporting these applications is robust enough to warrant their incorporation into routine clinical practice remains unclear. The imprecision of capillary blood ketone measures at higher values, the lack of availability of routine laboratory-based assays for BOHB and the continued cost-effectiveness of urine ketone assessment prompt further discussion on the role of capillary blood ketone assessment in ketoacidosis. In the present article, we review the various existing methods of ketone measurement, the precision of capillary blood ketone as compared with other measures, its diagnostic accuracy in predicting ketoacidosis and other clinical applications including prevention, assessment of severity and resolution of ketoacidosis. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  7. Ketones: metabolism's ugly duckling.

    PubMed

    VanItallie, Theodore B; Nufert, Thomas H

    2003-10-01

    Ketones were first discovered in the urine of diabetic patients in the mid-19th century; for almost 50 years thereafter, they were thought to be abnormal and undesirable by-products of incomplete fat oxidation. In the early 20th century, however, they were recognized as normal circulating metabolites produced by liver and readily utilized by extrahepatic tissues. In the 1920s, a drastic "hyperketogenic" diet was found remarkably effective for treatment of drug-resistant epilepsy in children. In 1967, circulating ketones were discovered to replace glucose as the brain's major fuel during the marked hyperketonemia of prolonged fasting. Until then, the adult human brain was thought to be entirely dependent upon glucose. During the 1990s, diet-induced hyperketonemia was found therapeutically effective for treatment of several rare genetic disorders involving impaired neuronal utilization of glucose or its metabolic products. Finally, growing evidence suggests that mitochondrial dysfunction and reduced bioenergetic efficiency occur in brains of patients with Parkinson's disease (PD) and Alzheimer's disease (AD). Because ketones are efficiently used by mitochondria for ATP generation and may also help protect vulnerable neurons from free radical damage, hyperketogenic diets should be evaluated for ability to benefit patients with PD, AD, and certain other neurodegenerative disorders.

  8. Energetics of median and paired fin swimming, body and caudal fin swimming, and gait transition in parrotfish (Scarus schlegeli) and triggerfish (Rhinecanthus aculeatus).

    PubMed

    Korsmeyer, Keith E; Steffensen, John Fleng; Herskin, Jannik

    2002-05-01

    To determine the energetic costs of rigid-body, median or paired-fin (MPF) swimming versus undulatory, body-caudal fin (BCF) swimming, we measured oxygen consumption as a function of swimming speed in two MPF swimming specialists, Schlegel's parrotfish and Picasso triggerfish. The parrotfish swam exclusively with the pectoral fins at prolonged swimming speeds up to 3.2 total lengths per second (L s(-1); 30 min critical swimming speed, U(crit)). At higher speeds, gait transferred to a burst-and-coast BCF swimming mode that resulted in rapid fatigue. The triggerfish swam using undulations of the soft dorsal and anal fins up to 1.5 L s(-1), beyond which BCF undulations were recruited intermittently. BCF swimming was used continuously above 3.5 L s(-1), and was accompanied by synchronous undulations of the dorsal and anal fins. The triggerfish were capable of high, prolonged swimming speeds of up to 4.1 L s(-1) (30 min U(crit)). In both species, the rates of increase in oxygen consumption with swimming speed were higher during BCF swimming than during rigid-body MPF swimming. Our results indicate that, for these species, undulatory swimming is energetically more costly than rigid-body swimming, and therefore support the hypothesis that MPF swimming is more efficient. In addition, use of the BCF gait at higher swimming speed increased the cost of transport in both species beyond that predicted for MPF swimming at the same speeds. This suggests that, unlike for terrestrial locomotion, gait transition in fishes does not occur to reduce energetic costs, but to increase recruitable muscle mass and propulsive surfaces. The appropriate use of the power and exponential functions to model swimming energetics is also discussed.

  9. Multi-body forces and the energetics of transition metals, alloys, and semiconductors. Annual progress report, (1991--1992)

    SciTech Connect

    Carlsson, A.E.

    1992-11-01

    Progress over the past year is divided into 3 areas: potential-energy functions for transition-metal aluminides; electronic structure and energetics of complex structures and quasicrystals; and ceramic materials (PdO, PtO).

  10. Novel ketone body therapy for managing Alzheimer's disease: An Editorial Highlight for Effects of a dietary ketone ester on hippocampal glycolytic and tricarboxylic acid cycle intermediates and amino acids in a 3xTgAD mouse model of Alzheimer's disease.

    PubMed

    Puchowicz, Michelle A; Seyfried, Thomas N

    2017-03-15

    Read the highlighted article 'Effects of a dietary ketone ester on hippocampal glycolytic and tricarboxylic acid cycle intermediates and amino acids in a 3xTgAD mouse model of Alzheimer's disease' on doi: 10.1111/jnc.13958.

  11. THE EVOLUTION OF FEMALE BODY SIZE IN RED-WINGED BLACKBIRDS: THE EFFECTS OF TIMING OF BREEDING, SOCIAL COMPETITION, AND REPRODUCTIVE ENERGETICS.

    PubMed

    Langston, Nancy E; Freeman, Scott; Rohwer, Sievert; Gori, David

    1990-11-01

    We examined opposing selective forces on female body size in the sexually dimorphic red-winged blackbird: social competition favoring larger females, and energetic advantages favoring smaller females. Downhower proposed that selection might drive female birds to be smaller than the optimum for survival, if smaller females were able to exceed their energetic requirements for self-maintenance earlier in the season and therefore breed earlier. Since in most birds the earliest breeders fledge the most young, this could favor the evolution of smaller female size, and therefore contribute to the magnitude of sexual size dimorphism in these birds. We tested this hypothesis in 1987 and 1988 by comparing the size and breeding date of female red-winged blackbirds. Consistent with our preditions, early-nesting females had much higher nesting success, but contrary to prediction, larger females bred earlier. We then examined the effects of female size on competition. If large females have an advantage in social competition, and if competition influences breeding date and reproductive success, then larger females might breed earlier. Primary females, the first females to arrive and nest on a territory, were more aggressive than lower ranked females; more aggressive females settled on better territories and laid earlier than less aggressive females; and larger females were more aggressive. Social competition between females may therefore favor large females. Finally, we tested the prediction that selection favoring large females might be limited by energetic constraints on large females. We found that large females had less fat than small females during breeding, and that the levels of fat that females of a given size carried affected breeding date and egg size. Therefore, social competition may favor large females, but reproductive energetics favoring smaller females may constrain selection for large female body size. © 1990 The Society for the Study of Evolution.

  12. [Effect of high-carbohydrate diet in the form of sugar beet on glucose and ketone body levels in the blood serum of highly pregnant and freshly lactating cows].

    PubMed

    Piatkowski, B; Voigt, J; Girschewski, H

    1977-12-01

    In an experiment using 24 high-yielding cows (3rd and 6th lactations), group II was fed sugar beet as carbohydrate source (2 kg DM per animal and day) for 4 weeks before and for 4 weeks after parturition, whilst group I was given the equivalent amount of dried spent beet pulp. Sugar beet feeding during the dry period caused the glucose level in the blood to rise significantly from 48 to 55 mg/100 ml. On the 21st day of lactation the glucose concentration in group II (27 mg) had declined more strongly than in group I (37 mg). Feeding large amounts of easily soluble carbohydrates during the dry period obviously inhibits gluconeogenesis during early lactation. The ketone body level of group II was found to rise to 14 mg/100 ml by the 21st day of lactation (group I--4 mg), a level indicative of ketosis. The ketogenous action (strong formation of butyric acid in the rumen) of sugar beet enhances this effect, too. The daily milk yield did not vary much coming to 26.8 and 27.8 kg in the control and in the experimental group, respectively. The results allow to conclude that feeding fresh sugar beet to high-yielding cows just before and shortly after parturition is not advisable.

  13. Preliminary study to compare body residues and sublethal energetic responses in benthic invertebrates exposed to sediment-bound 2,4,5-trichlorophenol

    SciTech Connect

    Penttinen, O.P.; Kukkonen, J.; Pellinen, J.

    1996-02-01

    Relationships between concentration of 2,4,5-trichlorophenol (TCP) in sediment, body residues of the chemical, and sublethal biological effects in three benthic invertebrates were studied. Uncontaminated lake sediment was spiked with four concentrations (23--85 {micro}g/g dry sediment) of TCP. Chironomid larvae (Chironomus riparius), oligochaete worms (Lumbriculus variegatus), and sphaeriid bivalves (Sphaerium corneum) were exposed to the sediment. The effect of chlorophenol on the rate of heat dissipation of animals was monitored by direct microcalorimetry. It appeared that both the behavior of the animals and their body residues explained the energetic response. Valve closure behavior of S. corneum reduced the accumulation of toxicant (< 0.3 {micro}mol/g) but was observed as a complex energetic response. Heat dissipation of L. variegatus was at the same level in control animals and those with high body residues of TCP (> 1.5 {micro}mol/g). Regardless of the amount of TCP accumulated to C. riparius (0.1--0.6 {micro}mol/g), the rate of heat dissipation was almost two times higher than that of the control animals, probably reflecting uncoupling of oxidative phosphorylation, which is the primary mode of toxic action of chlorophenols. However, when a threshold concentration was exceeded there was no concentration-response dependence until acute toxicity appears.

  14. Novel ketone diet enhances physical and cognitive performance

    PubMed Central

    Murray, Andrew J.; Knight, Nicholas S.; Cole, Mark A.; Cochlin, Lowri E.; Carter, Emma; Tchabanenko, Kirill; Pichulik, Tica; Gulston, Melanie K.; Atherton, Helen J.; Schroeder, Marie A.; Deacon, Robert M. J.; Kashiwaya, Yoshihiro; King, M. Todd; Pawlosky, Robert; Rawlins, J. Nicholas P.; Tyler, Damian J.; Griffin, Julian L.; Robertson, Jeremy; Veech, Richard L.; Clarke, Kieran

    2016-01-01

    Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low-carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson’s disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palm oil (P < 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [31P]-NMR spectroscopy. The novel ketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.—Murray, A. J., Knight, N. S., Cole, M. A., Cochlin, L. E., Carter, E., Tchabanenko, K., Pichulik, T., Gulston, M. K., Atherton, H. J., Schroeder, M. A., Deacon, R. M. J., Kashiwaya, Y., King, M. T., Pawlosky, R., Rawlins, J. N. P., Tyler, D. J., Griffin, J. L., Robertson, J., Veech, R. L., Clarke, K. Novel ketone diet enhances physical and cognitive performance. PMID:27528626

  15. Novel ketone diet enhances physical and cognitive performance.

    PubMed

    Murray, Andrew J; Knight, Nicholas S; Cole, Mark A; Cochlin, Lowri E; Carter, Emma; Tchabanenko, Kirill; Pichulik, Tica; Gulston, Melanie K; Atherton, Helen J; Schroeder, Marie A; Deacon, Robert M J; Kashiwaya, Yoshihiro; King, M Todd; Pawlosky, Robert; Rawlins, J Nicholas P; Tyler, Damian J; Griffin, Julian L; Robertson, Jeremy; Veech, Richard L; Clarke, Kieran

    2016-12-01

    Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low-carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson's disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palm oil (P < 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [(31)P]-NMR spectroscopy. The novel ketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.-Murray, A. J., Knight, N. S., Cole, M. A., Cochlin, L. E., Carter, E., Tchabanenko, K., Pichulik, T., Gulston, M. K., Atherton, H. J., Schroeder, M. A., Deacon, R. M. J., Kashiwaya, Y., King, M. T., Pawlosky, R., Rawlins, J. N. P., Tyler, D. J., Griffin, J. L., Robertson, J., Veech, R. L., Clarke, K. Novel ketone diet enhances physical and cognitive performance.

  16. Cerebral metabolic adaptation and ketone metabolism after brain injury.

    PubMed

    Prins, Mayumi L

    2008-01-01

    The developing central nervous system has the capacity to metabolize ketone bodies. It was once accepted that on weaning, the 'post-weaned/adult' brain was limited solely to glucose metabolism. However, increasing evidence from conditions of inadequate glucose availability or increased energy demands has shown that the adult brain is not static in its fuel options. The objective of this review is to summarize the body of literature specifically regarding cerebral ketone metabolism at different ages, under conditions of starvation and after various pathologic conditions. The evidence presented supports the following findings: (1) there is an inverse relationship between age and the brain's capacity for ketone metabolism that continues well after weaning; (2) neuroprotective potentials of ketone administration have been shown for neurodegenerative conditions, epilepsy, hypoxia/ischemia, and traumatic brain injury; and (3) there is an age-related therapeutic potential for ketone as an alternative substrate. The concept of cerebral metabolic adaptation under various physiologic and pathologic conditions is not new, but it has taken the contribution of numerous studies over many years to break the previously accepted dogma of cerebral metabolism. Our emerging understanding of cerebral metabolism is far more complex than could have been imagined. It is clear that in addition to glucose, other substrates must be considered along with fuel interactions, metabolic challenges, and cerebral maturation.

  17. Cerebral metabolic adaptation and ketone metabolism after brain injury

    PubMed Central

    Prins, Mayumi L

    2010-01-01

    The developing central nervous system has the capacity to metabolize ketone bodies. It was once accepted that on weaning, the ‘post-weaned/adult’ brain was limited solely to glucose metabolism. However, increasing evidence from conditions of inadequate glucose availability or increased energy demands has shown that the adult brain is not static in its fuel options. The objective of this review is to summarize the body of literature specifically regarding cerebral ketone metabolism at different ages, under conditions of starvation and after various pathologic conditions. The evidence presented supports the following findings: (1) there is an inverse relationship between age and the brain’s capacity for ketone metabolism that continues well after weaning; (2) neuroprotective potentials of ketone administration have been shown for neurodegenerative conditions, epilepsy, hypoxia/ischemia, and traumatic brain injury; and (3) there is an age-related therapeutic potential for ketone as an alternative substrate. The concept of cerebral metabolic adaptation under various physiologic and pathologic conditions is not new, but it has taken the contribution of numerous studies over many years to break the previously accepted dogma of cerebral metabolism. Our emerging understanding of cerebral metabolism is far more complex than could have been imagined. It is clear that in addition to glucose, other substrates must be considered along with fuel interactions, metabolic challenges, and cerebral maturation. PMID:17684514

  18. Apparent changes in body insulation of juvenile king penguins suggest an energetic challenge during their early life at sea.

    PubMed

    Enstipp, Manfred R; Bost, Charles-André; Le Bohec, Céline; Bost, Caroline; Le Maho, Yvon; Weimerskirch, Henri; Handrich, Yves

    2017-07-15

    Little is known about the early life at sea of marine top predators, like deep-diving king penguins (Aptenodytes patagonicus), although this dispersal phase is probably a critical phase in their life. Apart from finding favourable foraging sites, they have to develop effective prey search patterns as well as physiological capacities that enable them to capture sufficient prey to meet their energetic needs. To investigate the ontogeny of their thermoregulatory responses at sea, we implanted 30 juvenile king penguins and 8 adult breeders with a small data logger that recorded pressure and subcutaneous temperature continuously for up to 2.5 years. We found important changes in the development of peripheral temperature patterns of foraging juvenile king penguins throughout their first year at sea. Peripheral temperature during foraging bouts fell to increasingly lower levels during the first 6 months at sea, after which it stabilized. Most importantly, these changes re-occurred during their second year at sea, after birds had fasted for ∼4 weeks on land during their second moult. Furthermore, similar peripheral temperature patterns were also present in adult birds during foraging trips throughout their breeding cycle. We suggest that rather than being a simple consequence of concurrent changes in dive effort or an indication of a physiological maturation process, these seasonal temperature changes mainly reflect differences in thermal insulation. Heat loss estimates for juveniles at sea were initially high but declined to approximately half after ∼6 months at sea, suggesting that juvenile king penguins face a strong energetic challenge during their early oceanic existence. © 2017. Published by The Company of Biologists Ltd.

  19. Effects of independently altering body weight and mass on the energetic cost of a human running model.

    PubMed

    Ackerman, Jeffrey; Seipel, Justin

    2016-03-21

    The mechanisms underlying the metabolic cost of running, and legged locomotion in general, remain to be well understood. Prior experimental studies show that the metabolic cost of human running correlates well with the vertical force generated to support body weight, the mechanical work done, and changes in the effective leg stiffness. Further, previous work shows that the metabolic cost of running decreases with decreasing body weight, increases with increasing body weight and mass, and does not significantly change with changing body mass alone. In the present study, we seek to uncover the basic mechanism underlying this existing experimental data. We find that an actuated spring-mass mechanism representing the effective mechanics of human running provides a mechanistic explanation for the previously reported changes in the metabolic cost of human running if the dimensionless relative leg stiffness (effective stiffness normalized by body weight and leg length) is regulated to be constant. The model presented in this paper provides a mechanical explanation for the changes in metabolic cost due to changing body weight and mass which have been previously measured experimentally and highlights the importance of active leg stiffness regulation during human running.

  20. A mathematical high bar-human body model for analysing and interpreting mechanical-energetic processes on the high bar.

    PubMed

    Arampatzis, A; Brüggemann, G P

    1998-12-01

    The aims of this study were: 1. To study the transfer of energy between the high bar and the gymnast. 2. To develop criteria from the utilisation of high bar elasticity and the utilisation of muscle capacity to assess the effectiveness of a movement solution. 3. To study the influence of varying segment movement upon release parameters. For these purposes a model of the human body attached to the high bar (high bar-human body model) was developed. The human body was modelled using a 15-segment body system. The joint-beam element method (superelement) was employed for modelling the high bar. A superelement consists of four rigid segments connected by joints (two Cardan joints and one rotational-translational joint) and springs (seven rotation springs and one tension-compression spring). The high bar was modelled using three superelements. The input data required for the high bar human body model were collected with video-kinematographic (50 Hz) and dynamometric (500 Hz) techniques. Masses and moments of inertia of the 15 segments were calculated using the data from the Zatsiorsky et al. (1984) model. There are two major phases characteristic of the giant swing prior to dismounts from the high bar. In the first phase the gymnast attempts to supply energy to the high bar-humanbody system through muscle activity and to store this energy in the high bar. The difference between the energy transferred to the high bar and the reduction in the total energy of the body could be adopted as a criterion for the utilisation of high bar elasticity. The energy previously transferred into the high bar is returned to the body during the second phase. An advantageous increase in total body energy at the end of the exercise could only be obtained through muscle energy supply. An index characterising the utilisation of muscle capacity was developed out of the difference between the increase in total body energy and the energy returned from the high bar. A delayed and initially slow but

  1. Volatilization of ketones from water

    USGS Publications Warehouse

    Rathbun, R.E.; Tai, D.Y.

    1982-01-01

    The overall mass-transfer coefficients for the volatilization from water of acetone, 2-butanone, 2-pentanone, 3-pentanone, 4-methyl-2-pentanone, 2-heptanone, and 2-octanone were measured simultaneously with the oxygen-absorption coefficient in a laboratory stirred water bath. The liquid-film and gas-film coefficients of the two-film model were determined for the ketones from the overall coefficients, and both film resistances were important for volatilization of the ketones.The liquid-film coefficients for the ketones varied with the 0.719 power of the molecular-diffusion coefficient, in agreement with the literature. The liquid-film coefficients showed a variable dependence on molecular weight, with the dependence ranging from the −0.263 power for acetone to the −0.378 power for 2-octanone. This is in contrast with the literature where a constant −0.500 power dependence on the molecular weight is assumed.The gas-film coefficients for the ketones showed no dependence on molecular weight, in contrast with the literature where a −0.500 power is assumed.

  2. Bacterial production of methyl ketones

    DOEpatents

    Beller, Harry R.; Goh, Ee-Been

    2017-01-31

    The present invention relates to methods and compositions for increasing production of methyl ketones in a genetically modified host cell that overproduces .beta.-ketoacyl-CoAs through a re-engineered .beta.-oxidation pathway and overexpresses FadM.

  3. Stereoselective titanium-mediated aldol reactions of a chiral lactate-derived ethyl ketone with ketones.

    PubMed

    Alcoberro, Sandra; Gómez-Palomino, Alejandro; Solà, Ricard; Romea, Pedro; Urpí, Fèlix; Font-Bardia, Mercè

    2014-01-17

    Aldol reactions of titanium enolates of lactate-derived ethyl ketone 1 with other ketones proceed in a very efficient and stereocontrolled manner provided that a further equivalent of TiCl4 is added to the reacting mixture. The scope of these reactions encompasses simple ketones such as acetone or cyclohexanone as well as other ketones that contain potential chelating groups such as pyruvate esters or α- and β-hydroxy ketones.

  4. Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure

    PubMed Central

    Bedi, Kenneth C.; Snyder, Nathaniel W; Brandimarto, Jeffrey; Aziz, Moez; Mesaros, Clementina; Worth, Andrew J.; Wang, Linda L.; Javaheri, Ali; Blair, Ian A.; Margulies, Kenneth; Rame, J. Eduardo

    2016-01-01

    Background The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of HF there is a switch from a predominance of fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but inclusion of diabetics and nondiabetics obscures the distinction of adapations to metabolic derangements from adaptations to heart failure per se. Methods and Results We performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in non-diabetic, lean, predominantly non-ischemic advanced HF patients at the time of heart transplantation or LVAD implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long-chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-CoA species incorporated into Krebs cycle, while the myocardial concentration of acetyl-CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic β-hydroxybutyryl CoA, in association with increased myocardial utilization of β-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl-CoA: 3oxoacid-CoA transferase (SCOT), the rate limiting enzyme for myocardial oxidation of βOHB and acetoacetate. Conclusions These findings indicate increased ketone utilization in the severely failing human heart independent of diabetes, support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart. PMID:26819374

  5. Evidence for Intramyocardial Disruption of Lipid Metabolism and Increased Myocardial Ketone Utilization in Advanced Human Heart Failure.

    PubMed

    Bedi, Kenneth C; Snyder, Nathaniel W; Brandimarto, Jeffrey; Aziz, Moez; Mesaros, Clementina; Worth, Andrew J; Wang, Linda L; Javaheri, Ali; Blair, Ian A; Margulies, Kenneth B; Rame, J Eduardo

    2016-02-23

    The failing human heart is characterized by metabolic abnormalities, but these defects remains incompletely understood. In animal models of heart failure there is a switch from a predominance of fatty acid utilization to the more oxygen-sparing carbohydrate metabolism. Recent studies have reported decreases in myocardial lipid content, but the inclusion of diabetic and nondiabetic patients obscures the distinction of adaptations to metabolic derangements from adaptations to heart failure per se. We performed both unbiased and targeted myocardial lipid surveys using liquid chromatography-mass spectroscopy in nondiabetic, lean, predominantly nonischemic, advanced heart failure patients at the time of heart transplantation or left ventricular assist device implantation. We identified significantly decreased concentrations of the majority of myocardial lipid intermediates, including long-chain acylcarnitines, the primary subset of energetic lipid substrate for mitochondrial fatty acid oxidation. We report for the first time significantly reduced levels of intermediate and anaplerotic acyl-coenzyme A (CoA) species incorporated into the Krebs cycle, whereas the myocardial concentration of acetyl-CoA was significantly increased in end-stage heart failure. In contrast, we observed an increased abundance of ketogenic β-hydroxybutyryl-CoA, in association with increased myocardial utilization of β-hydroxybutyrate. We observed a significant increase in the expression of the gene encoding succinyl-CoA:3-oxoacid-CoA transferase, the rate-limiting enzyme for myocardial oxidation of β-hydroxybutyrate and acetoacetate. These findings indicate increased ketone utilization in the severely failing human heart independent of diabetes mellitus, and they support the role of ketone bodies as an alternative fuel and myocardial ketone oxidation as a key metabolic adaptation in the failing human heart. © 2016 American Heart Association, Inc.

  6. Ketone production in ultra marathon runners.

    PubMed

    Weibel, J; Glonek, T

    2007-12-01

    The aim of this study was to determine the magnitude of ketone production in ultra marathon runners and what affect if any this has on performance. Participants in the Cliff Young Australian Six Day Race (n=31) provided a prerace urine sample and, then, random urine samples throughout the duration of the event, ranging from 4-20 samples each. Based on urinalysis results, participants were divided into two groups: those who formed ketones (ketone group), and those who did not form ketones or formed ketones only once during a race at the lowest recordable value (non-ketone group). The average ketone level of the 22 athletes in the ketone group (value+/-standard deviation: 5.67+/-5.59 mg/dL) was statistically different from 9 athletes who were in the non-ketone group (0.18+/-0.14 mg/dL) (P<0.05). The average distances run for the two groups were 498.09+/-153.99 and 535.6+/-181.08 km, respectively (P=0.56). When average ketone value was compared, excluding runners who did not complete the race, the ketone group (5.88+/-1.37) remained statistically different from the non-ketone group (0.2+/-0.45) (P<0.05). The average distances for those athletes who completed the race were 583.9+/-116.09 and 557.8+/-85.82 km, respectively (P=0.52). We conclude that although two runner sub-populations were revealed, runners who produce ketones and runners who do not make ketones, the level of ketones produced did not affect overall distance run, which is the performance criterion of the race. The nature of this extreme event has illuminated a physiologic difference among ultra marathon runners, and although this difference does not appear to affect race performance, the long-term health consequences are unknown and additional rigorous research is warranted.

  7. The water hexamer: three-body interactions, structures, energetics, and OH-stretch spectroscopy at finite temperature.

    PubMed

    Tainter, C J; Skinner, J L

    2012-09-14

    Using a newly developed and recently parameterized classical empirical simulation model for water that involves explicit three-body interactions, we determine the eleven most stable isomers of the water hexamer. We find that the lowest energy isomer is one of the cage structures, in agreement with far-IR and microwave experiments. The energy ordering for the binding energies is cage > glove > book > bag > chair > boat > chaise, and energies relative to the cage are in good agreement with CCSD(T) calculations. The three-body contributions to the cage, book, and chair are also in reasonable agreement with CCSD(T) results. The energy of each isomer results from a delicate balance involving the number of hydrogen bonds, the strain of these hydrogen bonds, and cooperative and anti-cooperative three-body interactions, whose contribution we can understand simply from the form of the three-body interactions in the simulation model. Oxygen-oxygen distances in the cage and book isomers are in good agreement with microwave experiments. Hydrogen-bond distances depend on both donor and acceptor, which can again be understood from the three-body model. Fully anharmonic OH-stretch spectra are calculated for these low-energy structures, and compared with shifted harmonic results from ab initio and density functional theory calculations. Replica-exchange molecular dynamics simulations were performed from 40 to 194 K, which show that the cage isomer has the lowest free energy from 0 to 70 K, and the book isomer has the lowest free energy from 70 to 194 K. OH-stretch spectra were calculated between 40 and 194 K, and results at 40, 63, and 79 K were compared to recent experiments, leading to re-assignment of the peaks in the experimental spectra. We calculate local OH-stretch cumulative spectral densities for different donor-acceptor types and compare to analogous results for liquid water.

  8. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer.

    PubMed

    Poff, A M; Ari, C; Arnold, P; Seyfried, T N; D'Agostino, D P

    2014-10-01

    Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of β-hydroxybutyrate (βHB). Adult male inbred VM mice were implanted subcutaneously with firefly luciferase-tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies βHB and acetoacetate. Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood βHB and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51 and 69%, respectively (p < 0.05). Ketone administration elicited anticancer effects in vitro and in vivo independent of glucose levels or calorie restriction. The use of supplemental ketone precursors as a cancer treatment should be further investigated in animal models to determine potential for future clinical use.

  9. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer

    PubMed Central

    Poff, AM; Ari, C; Arnold, P; Seyfried, TN; D’Agostino, DP

    2014-01-01

    Cancer cells express an abnormal metabolism characterized by increased glucose consumption owing to genetic mutations and mitochondrial dysfunction. Previous studies indicate that unlike healthy tissues, cancer cells are unable to effectively use ketone bodies for energy. Furthermore, ketones inhibit the proliferation and viability of cultured tumor cells. As the Warburg effect is especially prominent in metastatic cells, we hypothesized that dietary ketone supplementation would inhibit metastatic cancer progression in vivo. Proliferation and viability were measured in the highly metastatic VM-M3 cells cultured in the presence and absence of β-hydroxybutyrate (βHB). Adult male inbred VM mice were implanted subcutaneously with firefly luciferase-tagged syngeneic VM-M3 cells. Mice were fed a standard diet supplemented with either 1,3-butanediol (BD) or a ketone ester (KE), which are metabolized to the ketone bodies βHB and acetoacetate. Tumor growth was monitored by in vivo bioluminescent imaging. Survival time, tumor growth rate, blood glucose, blood βHB and body weight were measured throughout the survival study. Ketone supplementation decreased proliferation and viability of the VM-M3 cells grown in vitro, even in the presence of high glucose. Dietary ketone supplementation with BD and KE prolonged survival in VM-M3 mice with systemic metastatic cancer by 51 and 69%, respectively (p < 0.05). Ketone administration elicited anticancer effects in vitro and in vivo independent of glucose levels or calorie restriction. The use of supplemental ketone precursors as a cancer treatment should be further investigated in animal models to determine potential for future clinical use. PMID:24615175

  10. Thermoregulation and energetics in hibernating black bears: metabolic rate and the mystery of multi-day body temperature cycles.

    PubMed

    Tøien, Øivind; Blake, John; Barnes, Brian M

    2015-05-01

    Black bears overwintering in outdoor hibernacula in Alaska decrease metabolism to as low as 25 % basal rates, while core body temperature (T(b)) decreases from 37 to 38 °C to a mid-hibernation average of 33 °C. T b develops cycles of 1.6-7.3 days length within a 30-36 °C range, with no circadian component. We do not know the mechanism or function underlying behind the T(b) cycles, although bears avoid T(b) of <30 °C and shorter cycles are predicted from higher rates of heat loss in colder conditions. To test this we manipulated den temperatures (T(den)) of 12 hibernating bears with body mass (BM) from 35.5 to 116.5 kg while recording T(b), metabolic rate (M), and shivering. T b cycle length (0.8-11.2 days) shortened as T den decreased (partial R(2) = 0.490, p < 0.001). Large bears with low thermal conductance (TC) showed more variation in T b cycle length with changes in T(den) than did smaller bears with high TC. Minimum T b across cycles was not consistent. At low T(den) bears shivered both during rising and decreasing phases of T(b) cycles, with minimum shivering during the fastest drop in T(b). At higher T den the T b pattern was more irregular. Mean M through T(b) cycles was negatively correlated to T den below lower critical temperatures (1.4-10.4 °C). Minimum M (0.3509 W/kg ± 0.0121 SE) during mid-hibernation scaled to BM [M (W) = 1.217 × BM (kg)(0.6979), R(2) = 0.855, p < 0.001]. Hibernating thermal conductance (TC) was negatively correlated to BM (R(2) = 0.721, p < 0.001); bears with high TC had the same T(b) cycle length as bears with low TC except at high T(den), thus not supporting the hypothesis that cooling rate alone determines T(b) cycle length. We conclude that T(b) cycling is effected by control of thermoregulatory heat production, and T(b) cycling may not be present when hibernating bears use passive thermoregulation. More intense shivering in the rising phase of cycles may contribute to the prevention of muscle disuse atrophy. Bears

  11. Energetic composites

    DOEpatents

    Danen, Wayne C.; Martin, Joe A.

    1993-01-01

    A method for providing chemical energy and energetic compositions of matter consisting of thin layers of substances which will exothermically react with one another. The layers of reactive substances are separated by thin layers of a buffer material which prevents the reactions from taking place until the desired time. The reactions are triggered by an external agent, such as mechanical stress or an electric spark. The compositions are known as metastable interstitial composites (MICs). This class of compositions includes materials which have not previously been capable of use as energetic materials. The speed and products of the reactions can be varied to suit the application.

  12. Energetic composites

    DOEpatents

    Danen, W.C.; Martin, J.A.

    1993-11-30

    A method for providing chemical energy and energetic compositions of matter consisting of thin layers of substances which will exothermically react with one another. The layers of reactive substances are separated by thin layers of a buffer material which prevents the reactions from taking place until the desired time. The reactions are triggered by an external agent, such as mechanical stress or an electric spark. The compositions are known as metastable interstitial composites (MICs). This class of compositions includes materials which have not previously been capable of use as energetic materials. The speed and products of the reactions can be varied to suit the application. 3 figures.

  13. EXTRACTION OF TETRAVALENT PLUTONIUM VALUES WITH METHYL ETHYL KETONE, METHYL ISOBUTYL KETONE ACETOPHENONE OR MENTHONE

    DOEpatents

    Seaborg, G.T.

    1961-08-01

    A process is described for extracting tetravalent plutonium from an aqueous acid solution with methyl ethyl ketone, methyl isobutyl ketone, or acetophenone and with the extraction of either tetravalent or hexavalent plutonium into menthone. (AEC)

  14. Energetics of tropical hibernation.

    PubMed

    Dausmann, K H; Glos, J; Heldmaier, G

    2009-04-01

    In this field study, the energetic properties of tropical hibernation were investigated by measuring oxygen consumption and body temperature of the Malagasy primate Cheirogaleus medius in their natural hibernacula. These lemurs use tree holes with extremely varying insulation capacities as hibernacula. In poorly insulated tree holes, tree hole temperature and body temperature fluctuated strongly each day (between 12.8 and 34.4 degrees C). The metabolic rate under these conditions also showed large daily fluctuations between about 29.0 ml O(2)/h and 97.9 ml O(2)/h in parallel with changes in body temperature. In well insulated tree holes in very large trees on the other hand, tree hole temperature and body temperature remained relatively constant at about 25 degrees C. Lemurs hibernating in these tree holes showed a more constant metabolic rate at an intermediate level, but hibernation was interrupted by repeated arousals with peak metabolic rates up to 350 ml O(2)/h. The occurrence of these spontaneous arousals proved that the ability for thermoregulation persists during hibernation. Arousals were energetically costly, but much less so than in temperate and arctic hibernators. Despite the decisive influence of tree hole properties on the pattern of body temperature and metabolic rate during hibernation, the choice of the hibernaculum does not seem to be of energetic importance. The overall energetic savings by tropical hibernation amounted to about 70% as compared to the active season (31.5 vs. 114.3 kJ/d). Therefore, tropical hibernation in C. medius is an effective, well-regulated adaptive response to survive unfavourable seasons.

  15. Impaired control of body cooling during heterothermia represents the major energetic constraint in an aging non-human primate exposed to cold.

    PubMed

    Terrien, Jeremy; Zahariev, Alexandre; Blanc, Stephane; Aujard, Fabienne

    2009-10-23

    Daily heterothermia is used by small mammals for energy and water savings, and seems to be preferentially exhibited during winter rather than during summer. This feature induces a trade-off between the energy saved during daily heterothermia and the energy cost of arousal, which can impact energy balance and survival under harsh environmental conditions. Especially, aging may significantly affect such trade off during cold-induced energy stress, but direct evidences are still lacking. We hypothesized that aging could alter the energetics of daily heterothermia, and that the effects could differ according to season. In the gray mouse lemur (Microcebus murinus), a non-human primate species which exhibits daily heterothermia, we investigated the effects of exposures to 25 and 12 degrees C on body composition, energy balance, patterns of heterothermia and water turnover in adult (N = 8) and aged animals (N = 7) acclimated to winter-like or summer-like photoperiods. Acclimation to summer prevented animals from deep heterothermia, even during aging. During winter, adult animals at 12 degrees C and aged animals at 25 degrees C exhibited low levels of energy expenditure with minor modulations of heterothermia. The major effects of cold were observed during winter, and were particularly pronounced in aged mouse lemurs which exhibited deep heterothermia phases. Body composition was not significantly affected by age and could not explain the age-related differences in heterothermia patterns. However, aging was associated with increased levels of energy expenditure during cold exposure, in concomitance with impaired energy balance. Interestingly, increased energy expenditure and depth of heterothermia phases were strongly correlated. In conclusion, it appeared that the exhibition of shallow heterothermia allowed energy savings during winter in adult animals only. Aged animals exhibited deep heterothermia and increased levels of energy expenditure, impairing energy balance

  16. Breath ketone testing: a new biomarker for diagnosis and therapeutic monitoring of diabetic ketosis.

    PubMed

    Qiao, Yue; Gao, Zhaohua; Liu, Yong; Cheng, Yan; Yu, Mengxiao; Zhao, Lingling; Duan, Yixiang; Liu, Yu

    2014-01-01

    Acetone, β -hydroxybutyric acid, and acetoacetic acid are three types of ketone body that may be found in the breath, blood, and urine. Detecting altered concentrations of ketones in the breath, blood, and urine is crucial for the diagnosis and treatment of diabetic ketosis. The aim of this study was to evaluate the advantages of different detection methods for ketones, and to establish whether detection of the concentration of ketones in the breath is an effective and practical technique. We measured the concentrations of acetone in the breath using gas chromatography-mass spectrometry and β -hydroxybutyrate in fingertip blood collected from 99 patients with diabetes assigned to groups 1 (-), 2 (±), 3 (+), 4 (++), or 5 (+++) according to urinary ketone concentrations. There were strong relationships between fasting blood glucose, age, and diabetic ketosis. Exhaled acetone concentration significantly correlated with concentrations of fasting blood glucose, ketones in the blood and urine, LDL-C, creatinine, and blood urea nitrogen. Breath testing for ketones has a high sensitivity and specificity and appears to be a noninvasive, convenient, and repeatable method for the diagnosis and therapeutic monitoring of diabetic ketosis.

  17. Breath Ketone Testing: A New Biomarker for Diagnosis and Therapeutic Monitoring of Diabetic Ketosis

    PubMed Central

    Qiao, Yue; Gao, Zhaohua; Liu, Yong; Cheng, Yan; Yu, Mengxiao; Zhao, Lingling

    2014-01-01

    Background. Acetone, β-hydroxybutyric acid, and acetoacetic acid are three types of ketone body that may be found in the breath, blood, and urine. Detecting altered concentrations of ketones in the breath, blood, and urine is crucial for the diagnosis and treatment of diabetic ketosis. The aim of this study was to evaluate the advantages of different detection methods for ketones, and to establish whether detection of the concentration of ketones in the breath is an effective and practical technique. Methods. We measured the concentrations of acetone in the breath using gas chromatography-mass spectrometry and β-hydroxybutyrate in fingertip blood collected from 99 patients with diabetes assigned to groups 1 (−), 2 (±), 3 (+), 4 (++), or 5 (+++) according to urinary ketone concentrations. Results. There were strong relationships between fasting blood glucose, age, and diabetic ketosis. Exhaled acetone concentration significantly correlated with concentrations of fasting blood glucose, ketones in the blood and urine, LDL-C, creatinine, and blood urea nitrogen. Conclusions. Breath testing for ketones has a high sensitivity and specificity and appears to be a noninvasive, convenient, and repeatable method for the diagnosis and therapeutic monitoring of diabetic ketosis. PMID:24900994

  18. A Convergent Radical Based Route to Trifluoromethyl Ketones and to α,β-Unsaturated Trifluoromethyl Ketones.

    PubMed

    Anthore, Lucile; Zard, Samir Z

    2015-06-19

    A convergent synthesis of trifluoromethyl ketones and α,β-unsaturated trifluoromethyl ketones is described, starting with aliphatic iodides and dithiocarbonates (xanthates) and exploiting both the α- and β-fragmentations of a sulfonyl radical. The transformation initially furnishes the ketones in a masked enol carbonate form, from which they can be easily regenerated.

  19. The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer.

    PubMed

    Meidenbauer, Joshua J; Mukherjee, Purna; Seyfried, Thomas N

    2015-01-01

    Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg effect), which is the common metabolic malady of most cancers including brain tumors. The KD targets tumor energy metabolism by lowering blood glucose and elevating blood ketones (β-hydroxybutyrate). Brain tumor cells, unlike normal brain cells, cannot use ketone bodies effectively for energy when glucose becomes limiting. Although plasma levels of glucose and ketone bodies have been used separately to predict the therapeutic success of metabolic therapy, daily glucose levels can fluctuate widely in brain cancer patients. This can create difficulty in linking changes in blood glucose and ketones to efficacy of metabolic therapy. A program was developed (Glucose Ketone Index Calculator, GKIC) that tracks the ratio of blood glucose to ketones as a single value. We have termed this ratio the Glucose Ketone Index (GKI). The GKIC was used to compute the GKI for data published on blood glucose and ketone levels in humans and mice with brain tumors. The results showed a clear relationship between the GKI and therapeutic efficacy using ketogenic diets and calorie restriction. The GKIC is a simple tool that can help monitor the efficacy of metabolic therapy in preclinical animal models and in clinical trials for malignant brain cancer and possibly other cancers that express aerobic fermentation.

  20. Mild electrophilic trifluoromethylthiolation of ketones with trifluoromethanesulfanamide.

    PubMed

    Wu, Wei; Zhang, Xuxue; Liang, Fang; Cao, Song

    2015-07-07

    A straightforward and convenient approach for trifluoromethylthiolation of various acyclic and cyclic ketones with PhNHSCF3 is described. The reaction proceeds smoothly in the presence of acetyl chloride at room temperature and affords α-trifluoromethylthiolated ketones in fair to good yields.

  1. Storage stability of ketones on carbon adsorbents.

    PubMed

    Prado, C; Alcaraz, M J; Fuentes, A; Garrido, J; Periago, J F

    2006-09-29

    Activated coconut carbon constitutes the more widely used sorbent for preconcentration of volatile organic compounds in sampling workplace air. Water vapour is always present in the air and its adsorption on the activated carbon surface is a serious drawback, mainly when sampling polar organic compounds, such as ketones. In this case, the recovery of the compounds diminishes; moreover, ketones can be decomposed during storage. Synthetic carbons contain less inorganic impurities and have a lower capacity for water adsorption than coconut charcoal. The aim of this work was to evaluate the storage stability of various ketones (acetone, 2-butanone, 4-methyl-2-pentanone and cyclohexanone) on different activated carbons and to study the effect of adsorbed water vapour under different storage conditions. The effect of storage temperature on extraction efficiencies was significant for each ketone in all the studied sorbents. Recovery was higher when samples were stored at 4 degrees C. The results obtained for storage stability of the studied ketones showed that the performance of synthetic carbons was better than for the coconut charcoals. The water adsorption and the ash content of the carbons can be a measure of the reactive sites that may chemisorb ketones or catalize their decomposition. Anasorb 747 showed good ketone stability at least for 7 days, except for cyclohexanone. After 30-days storage, the stability of the studied ketones was excellent on Carboxen 564. This sorbent had a nearly negligible ash content and the adsorbed water was much lower than for the other sorbents tested.

  2. Flare energetics

    NASA Technical Reports Server (NTRS)

    Wu, S. T.; Dejager, C.; Dennis, B. R.; Hudson, H. S.; Simnett, G. M.; Strong, K. T.; Bentley, R. D.; Bornmann, P. L.; Bruner, M. E.; Cargill, P. J.

    1986-01-01

    In this investigation of flare energetics, researchers sought to establish a comprehensive and self-consistent picture of the sources and transport of energy within a flare. To achieve this goal, they chose five flares in 1980 that were well observed with instruments on the Solar Maximum Mission, and with other space-borne and ground-based instruments. The events were chosen to represent various types of flares. Details of the observations available for them and the corresponding physical parameters derived from these data are presented. The flares were studied from two perspectives, the impulsive and gradual phases, and then the results were compared to obtain the overall picture of the energics of these flares. The role that modeling can play in estimating the total energy of a flare when the observationally determined parameters are used as the input to a numerical model is discussed. Finally, a critique of the current understanding of flare energetics and the methods used to determine various energetics terms is outlined, and possible future directions of research in this area are suggested.

  3. Energetic powder

    DOEpatents

    Jorgensen, Betty S.; Danen, Wayne C.

    2003-12-23

    Fluoroalkylsilane-coated metal particles. The particles have a central metal core, a buffer layer surrounding the core, and a fluoroalkylsilane layer attached to the buffer layer. The particles may be prepared by combining a chemically reactive fluoroalkylsilane compound with an oxide coated metal particle having a hydroxylated surface. The resulting fluoroalkylsilane layer that coats the particles provides them with excellent resistance to aging. The particles can be blended with oxidant particles to form energetic powder that releases chemical energy when the buffer layer is physically disrupted so that the reductant metal core can react with the oxidant.

  4. Ketones block amyloid entry and improve cognition in an Alzheimer's model.

    PubMed

    Yin, Jun Xiang; Maalouf, Marwan; Han, Pengcheng; Zhao, Minglei; Gao, Ming; Dharshaun, Turner; Ryan, Christopher; Whitelegge, Julian; Wu, Jie; Eisenberg, David; Reiman, Eric M; Schweizer, Felix E; Shi, Jiong

    2016-03-01

    Sporadic Alzheimer's disease (AD) is responsible for 60%-80% of dementia cases, and the most opportune time for preventive intervention is in the earliest stage of its preclinical phase. As traditional mitochondrial energy substrates, ketone bodies (ketones, for short), beta-hydroxybutyrate, and acetoacetate, have been reported to provide symptomatic improvement and disease-modifying activity in epilepsy and neurodegenerative disorders. Recently, ketones are thought as more than just metabolites and also as endogenous factors protecting against AD. In this study, we discovered a novel neuroprotective mechanism of ketones in which they blocked amyloid-β 42, a pathologic hallmark protein of AD, entry into neurons. The suppression of intracellular amyloid-β 42 accumulation rescued mitochondrial complex I activity, reduced oxidative stress, and improved synaptic plasticity. Most importantly, we show that peripheral administration of ketones significantly reduced amyloid burden and greatly improved learning and memory ability in a symptomatic mouse model of AD. These observations provide us insights to understand and to establish a novel therapeutic use of ketones in AD prevention. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Homologation Reaction of Ketones with Diazo Compounds.

    PubMed

    Candeias, Nuno R; Paterna, Roberta; Gois, Pedro M P

    2016-03-09

    This review covers the addition of diazo compounds to ketones to afford homologated ketones, either in the presence or in the absence of promoters or catalysts. Reactions with diazoalkanes, aryldiazomethanes, trimethylsilyldiazomethane, α-diazo esters, and disubstituted diazo compounds are covered, commenting on the complex regiochemistry of the reaction and the nature of the catalysts and promoters. The recent reports on the enantioselective version of ketone homologation reactions are gathered in one section, followed by reports on the use of cyclic ketones ring expansion in total synthesis. Although the first reports of this reaction appeared in the literature almost one century ago, the recent achievements, in particular, for the asymmetric version, forecast the development of new breakthroughs in the synthetically valuable field of diazo chemistry.

  6. Iodine promoted α-hydroxylation of ketones.

    PubMed

    Siddaraju, Yogesh; Prabhu, Kandikere Ramaiah

    2015-06-28

    A novel method for α-hydroxylation of ketones using substoichiometric amount of iodine under metal-free conditions is described. This method has been successfully employed in synthesizing a variety of heterocyclic compounds, which are useful precursors. α-Hydroxylation of diketones and triketones are illustrated. This strategy provides a novel, efficient, mild and inexpensive method for α-hydroxylation of aryl ketones using a sub-stoichiometric amount of molecular iodine.

  7. Rhodium-catalyzed acyl-transfer reaction between benzyl ketones and thioesters: synthesis of unsymmetric ketones by ketone CO-C bond cleavage and intermolecular rearrangement.

    PubMed

    Arisawa, Mieko; Kuwajima, Manabu; Toriyama, Fumihiko; Li, Guangzhe; Yamaguchi, Masahiko

    2012-07-20

    In the presence of catalytic amounts of RhH(CO)(PPh3)3 and 1,2-bis(diphenylphosphino)benzene (dppBz), acyl groups were transferred between benzyl ketones and thioesters/aryl esters. The rhodium complex catalyzed the cleavage of ketone CO-C bonds and intermolecular rearrangement giving unsymmetric ketones. The acyl-transfer reaction also occurred with 1-(p-chlorophenyl)-3-(p-cyanophenyl)propane-2-one giving unsymmetric ketones.

  8. Microbial production of natural raspberry ketone.

    PubMed

    Beekwilder, Jules; van der Meer, Ingrid M; Sibbesen, Ole; Broekgaarden, Mans; Qvist, Ingmar; Mikkelsen, Joern D; Hall, Robert D

    2007-10-01

    Raspberry ketone is an important compound for the flavour industry. It is frequently used in products such as soft drinks, sweets, puddings and ice creams. The compound can be produced by organic synthesis. Demand for "natural" raspberry ketone is growing considerably. However, this product is extremely expensive. Consequently, there is a remaining desire to better understand how raspberry ketone is synthesized in vivo, and which genes and enzymes are involved. With this information we will then be in a better position to design alternative production strategies such as microbial fermentation. This article focuses on the identification and application of genes potentially linked to raspberry ketone synthesis. We have isolated candidate genes from both raspberry and other plants, and these have been introduced into bacterial and yeast expression systems. Conditions have been determined that result in significant levels of raspberry ketone, up to 5 mg/L. These results therefore lay a strong foundation for a potentially renewable source of "natural" flavour compounds making use of plant genes.

  9. The promising potential role of ketones in inflammatory dermatologic disease: a new frontier in treatment research.

    PubMed

    Fomin, Daren A; McDaniel, Brianna; Crane, Jonathan

    2017-01-24

    The ketogenic diet has been shown to be beneficial for numerous diseases across different organ systems, but a dearth of information exists regarding these benefits for skin disease. Here, we searched the literature for known mechanisms behind inflammation in dermatologic disease and correlated that with suggested mechanisms of anti-inflammatory activity of ketones and a ketogenic state in the human body to observe how ketones and ketosis might aid in the treatment of inflammatory skin diseases based on these mechanisms. Specifically, we found that ketones modulate the NRPL3 inflammasome, augment anti-oxidation against reactive oxygen species through various direct and indirect means, and may influence mTOR activity, which are all involved in inflammatory dermatologic diseases to an extent. This evidence shows that ketones and the ketogenic diet may have a promising role in the dermatologist's disease treatment repertoire. Our goal is to provide a novel direction for research in the role of a ketogenic diet and even exogenous ketone therapy in the treatment of inflammatory dermatologic disease.

  10. Nile red detection of bacterial hydrocarbons and ketones in a high-throughput format.

    PubMed

    Pinzon, Neissa M; Aukema, Kelly G; Gralnick, Jeffrey A; Wackett, Lawrence P

    2011-01-01

    A method for use in high-throughput screening of bacteria for the production of long-chain hydrocarbons and ketones by monitoring fluorescent light emission in the presence of Nile red is described. Nile red has previously been used to screen for polyhydroxybutyrate (PHB) and fatty acid esters, but this is the first report of screening for recombinant bacteria making hydrocarbons or ketones. The microtiter plate assay was evaluated using wild-type and recombinant strains of Shewanella oneidensis and Escherichia coli expressing the enzyme OleA, previously shown to initiate hydrocarbon biosynthesis. The strains expressing exogenous Stenotrophomonas maltophilia oleA, with increased levels of ketone production as determined by gas chromatography-mass spectrometry, were distinguished with Nile red fluorescence. Confocal microscopy images of S. oneidensis oleA-expressing strains stained with Nile red were consistent with a membrane localization of the ketones. This differed from Nile red staining of bacterial PHB or algal lipid droplets that showed intracellular inclusion bodies. These results demonstrated the applicability of Nile red in a high-throughput technique for the detection of bacterial hydrocarbons and ketones. © 2011 Pinzon et al.

  11. Comparison of Properties among Dendritic and Hyperbranched Poly(ether ether ketone)s and Linear Poly(ether ketone)s.

    PubMed

    Morikawa, Atsushi

    2016-02-16

    Poly(ether ether ketone) dendrimers and hyperbranched polymers were prepared from 3,5-dimethoxy-4'-(4-fluorobenzoyl)diphenyl ether and 3,5-dihydroxy-4'-(4-fluorobenzoyl)diphenyl ether through aromatic nucleophilic substitution reactions. 1-(tert-Butyldimethylsiloxy)-3,5-bis(4-fluorobenzoyl)benzene was polycondensed with bisphenols, followed by cleavage of the protective group to form linear poly(ether ketone)s having the same hydroxyl groups in the side chains as the chain ends of the dendrimer and hyperbranched polymers. Their properties, such as solubilities, reduced viscosities, and thermal properties, were compared with one another. Similar comparisons were also carried out among the corresponding methoxy group polymers, and the size of the molecules was shown to affect the properties.

  12. [Changes of the storage stability of ketones collected on activated coconut carbon in environmental ketone measurement].

    PubMed

    Sakamroto, Takayuki; Hinoue, Mitsuo; Yoshikawa, Masahiro

    2011-06-01

    The storage stability for six ketones was studied on four activated coconut carbons commonly used for air sampling in Japan. As the ratios of the enol form of cyclohexanone and methyl ethyl ketone are high, the ketones showed drastic losses during storage (storage stability), which could be attributed to catalytic oxidation and chemisorption. Moreover, adsorbed water caused a further decrease in recoveries of the ketones from the carbons. Because keto-enol tautomerism and hydration are catalyzed by acid or base, the relationships between the recoveries of the ketones from the carbons and pH in the aqueous solution of the carbons and the ignition residue of the carbons were investigated. As a result, the intensity of acidity or basicity of the carbons correlated with the loss of the ketones during storage, but the ignition residue of the carbons did not. Therefore, these results lead us to the conclusion that a more neutral coconut carbon is more suitable for the collection of aliphatic ketones, and activated coconut carbons are not suitable for cyclohexanone.

  13. Aromatic ketones with terminal vinyl groups

    SciTech Connect

    Uvarova, L.R.; Burykina, L.K.; Zubareva, M.M.; Polyanskii, I.D.

    1988-12-20

    The Friedel-Crafts acylation of a hydrocarbon by an acylating agent containing bromoalkyl substituents gave a series of new ketones. Their subsequent dehydrobromination with potassium tert-butoxide gave high yields of aromatic ketones containing terminal vinyl groups. The reaction was conducted both with /beta/-bromoethylbenzene and with 4-(/beta/-bromoethyl)-benzoyl chloride and also with both compounds simultaneously. The structures of the synthesized compounds were confirmed by the PMR, IR, UV, and mass spectra and also by the data from elemental analysis.

  14. Stereoselective Formation of Fully Substituted Ketone Enolates.

    PubMed

    Haimov, Elvira; Nairoukh, Zackaria; Shterenberg, Alexander; Berkovitz, Tiran; Jamison, Timothy F; Marek, Ilan

    2016-04-25

    The application of stereochemically defined acyclic fully substituted enolates of ketones to the enantioselective synthesis of quaternary carbon stereocenters would be highly valuable. Herein, we describe an approach leading to the formation of several new stereogenic centers through a combined metalation-addition of a carbonyl-carbamoyl transfer to reveal in situ stereodefined α,α-disubstituted enolates of ketone as a single stereoisomer. This approach could produce a series of aldol and Mannich products from enol carbamate with excellent diastereomeric ratios.

  15. Highly Concentrated Catalytic Asymmetric Allylation of Ketones

    PubMed Central

    Wooten, Alfred J.; Kim, Jeung Gon; Walsh, Patrick J.

    2008-01-01

    We report the catalytic asymmetric allylation of ketones under highly concentrated reaction conditions with a catalyst generated from titanium tetraisopropoxide and BINOL (1:2 ratio) in the presence of isopropanol. This catalyst promotes the addition of tetraallylstannane to a variety of ketones to produce tertiary homoallylic alcohols in excellent yield (80–99%) with high enantioselectivities (79–95%). The resulting homoallylic alcohols can also be epoxidized in situ using tert-butyl hydroperoxide (TBHP) to afford cyclic epoxy alcohols in high yield (84–87%). PMID:17249767

  16. Highly concentrated catalytic asymmetric allylation of ketones.

    PubMed

    Wooten, Alfred J; Kim, Jeung Gon; Walsh, Patrick J

    2007-02-01

    [reaction: see text] We report the catalytic asymmetric allylation of ketones under highly concentrated reaction conditions with a catalyst generated from titanium tetraisopropoxide and BINOL (1:2 ratio) in the presence of isopropanol. This catalyst promotes the addition of tetraallylstannane to a variety of ketones to produce tertiary homoallylic alcohols in excellent yield (80-99%) with high enantioselectivities (79-95%). The resulting homoallylic alcohols can also be epoxidized in situ using tert-butyl hydroperoxide (TBHP) to afford cyclic epoxy alcohols in high yield (84-87%).

  17. Safety assessment of MIBK (methyl isobutyl ketone).

    PubMed

    Johnson, Wilbur

    2004-01-01

    MIBK (Methyl Isobutyl Ketone) is an aliphatic ketone that functions as both a denaturant and solvent in cosmetic products. Current use in cosmetic products is very limited, but MIBK is reported to be used in one nail correction pen (volume = 3 ml) at a concentration of 21%. The maximum percutaneous absorption rate in guinea pigs is 1.1 micromol/min/cm2 at 10 to 45 min. Metabolites include 4-hydroxy-4-methyl-2-pentanone (oxidation product) and 4-methyl-2-pentanol (4-MPOL) (reduction product). Values for the serum half-life and total clearance time of MIBK in animals were 66 min and 6 h, respectively. In clinical tests, most of the absorbed MIBK had been eliminated from the body 90 min post exposure. MIBK was not toxic via the oral or dermal route of exposure in acute, short-term, or subchronic animal studies, except that nephrotoxicity was observed in rats dosed with 1 g/kg in a short-term study. MIBK was an ocular and skin irritant in animal tests. Ocular irritation was noted in 12 volunteers exposed to 200 ppm MIBK for 15 min in a clinical test. A depression of the vestibulo-oculomotor reflex was seen with intravenous infusion of MIBK (in an emulsion) at 30 microM/kg/min in female rats. The no-observed-effect level in rats exposed orally to MIBK was 50 mg/kg. Both gross and microscopic evidence of lung damage were reported in acute inhalation toxicity studies in animals. Short-term and subchronic inhalation exposures (as low as 100 ppm) produced effects in the kidney and liver that were species and sex dependent. Dermal doses of 300 or 600 mg/kg for 4 months in rats produced reduced mitotic activity in hair follicles, increased thickness of horny and granular cell layers of the epidermis, a decrease in the number of reactive centers in follicles (spleen), an increase in the number of iron-containing pigments in the area of the red pulp (spleen), and a reduction in the lipid content of the cortical layer of the adrenal glands. Neuropathological changes in the most

  18. The Conversion of Carboxylic Acids to Ketones: A Repeated Discovery

    ERIC Educational Resources Information Center

    Nicholson, John W.; Wilson, Alan D.

    2004-01-01

    The conversion of carboxylic acids to ketones is a useful chemical transformation with a long history. Several chemists have claimed that they discovered the conversion of carboxylic acids to ketones yet in fact the reaction is actually known for centuries.

  19. The Conversion of Carboxylic Acids to Ketones: A Repeated Discovery

    ERIC Educational Resources Information Center

    Nicholson, John W.; Wilson, Alan D.

    2004-01-01

    The conversion of carboxylic acids to ketones is a useful chemical transformation with a long history. Several chemists have claimed that they discovered the conversion of carboxylic acids to ketones yet in fact the reaction is actually known for centuries.

  20. Asymmetric Michael addition of ketones to nitroolefins: pyrrolidinyl-oxazole-carboxamides as new efficient organocatalysts.

    PubMed

    Kamal, Ahmed; Sathish, Manda; Srinivasulu, Vunnam; Chetna, Jadala; Chandra Shekar, Kunta; Nekkanti, Shalini; Tangella, Yellaiah; Shankaraiah, Nagula

    2014-10-28

    Chiral pyrrolidinyl-oxazole-carboxamides were synthesized and used as efficient new organocatalysts for the asymmetric Michael addition of ketones with nitroalkenes under solvent-free conditions. Gratifyingly, the corresponding Michael adducts were obtained in higher yields (up to 99%) and excellent stereoselectivities (up to >99/1 dr and 99% ee). Transition state models have been proposed to account for the high enantio- and diastereoselectivity of these Michael addition reactions and also the energetics have been investigated using density functional methods. These results support the preferential formation of syn-products by the approach of trans-β-nitrostyrene through the re-face of anti-enamine.

  1. 40 CFR 721.4568 - Methylpolychloro aliphatic ketone.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Methylpolychloro aliphatic ketone. 721... Substances § 721.4568 Methylpolychloro aliphatic ketone. (a) Chemical substance and significant new uses... ketone (PMN No. P-91-1321) is subject to reporting under this section for the significant new uses...

  2. Vapor pressures and gas-film coefficients for ketones

    USGS Publications Warehouse

    Rathbun, R.E.; Tai, D.Y.

    1987-01-01

    Comparison of handbook vapor pressures for seven ketones with more recent literature data showed large differences for four of the ketones. Gas-film coefficients for the volatilization of these ketones from water determined by two different methods were in reasonable agreement. ?? 1987.

  3. 40 CFR 721.4925 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Methyl n-butyl ketone. 721.4925... Substances § 721.4925 Methyl n-butyl ketone. (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance methyl n-butyl ketone, CAS Number 591-78-6, is subject to reporting...

  4. 40 CFR 721.4925 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Methyl n-butyl ketone. 721.4925... Substances § 721.4925 Methyl n-butyl ketone. (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance methyl n-butyl ketone, CAS Number 591-78-6, is subject to reporting...

  5. 40 CFR 721.4925 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Methyl n-butyl ketone. 721.4925... Substances § 721.4925 Methyl n-butyl ketone. (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance methyl n-butyl ketone, CAS Number 591-78-6, is subject to reporting...

  6. 40 CFR 721.4925 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Methyl n-butyl ketone. 721.4925... Substances § 721.4925 Methyl n-butyl ketone. (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance methyl n-butyl ketone, CAS Number 591-78-6, is subject to reporting...

  7. 40 CFR 721.4925 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Methyl n-butyl ketone. 721.4925... Substances § 721.4925 Methyl n-butyl ketone. (a) Chemical substance and significant new use subject to reporting. (1) The chemical substance methyl n-butyl ketone, CAS Number 591-78-6, is subject to reporting...

  8. Thiourea-Catalyzed Enantioselective Cyanosilylation of Ketones

    PubMed Central

    Fuerst, Douglas E.; Jacobsen, Eric N.

    2011-01-01

    The new chiral amino thiourea catalyst 3d promotes the highly enantioselective cyanosilylation of a wide variety of ketones. The hindered tertiary amine substituent plays a crucial role both with regard to stereoinduction and reactivity, suggesting a cooperative mechanism involving electrophile activation by thiourea and nucleophile activation by the amine. PMID:15969569

  9. Stereoselective Borylative Ketone-Diene Coupling

    PubMed Central

    Cho, Hee Yeon; Yu, Zhiyong; Morken, James P.

    2011-01-01

    In the presence of catalytic Ni(cod)2 and P(t-Bu)3, ketones, dienes, and B2(pin)2 undergo a stereoselective multicomponent coupling reaction. Upon oxidation, the reaction furnishes 1,3-diols as the major reaction product. PMID:21905748

  10. Stereoselective borylative ketone-diene coupling.

    PubMed

    Cho, Hee Yeon; Yu, Zhiyong; Morken, James P

    2011-10-07

    In the presence of catalytic Ni(cod)(2) and P(t-Bu)(3), ketones, dienes, and B(2)(pin)(2) undergo a stereoselective multicomponent coupling reaction. Upon oxidation, the reaction furnishes 1,3-diols as the major reaction product. © 2011 American Chemical Society

  11. Understanding the energetic costs of living in saline environments: effects of salinity on basal metabolic rate, body mass and daily energy consumption of a long-distance migratory shorebird.

    PubMed

    Gutiérrez, Jorge S; Masero, José A; Abad-Gómez, José M; Villegas, Auxiliadora; Sánchez-Guzmán, Juan M

    2011-03-01

    Many migratory vertebrates typically move between habitats with varying salinities during the annual cycle. These organisms clearly exhibit a remarkable phenotypic flexibility in their 'osmoregulatory machinery', but the metabolic consequences of salinity acclimatization are still not well understood. We investigated the effects of salinity on basal metabolic rate (BMR), body mass and daily energy consumption of a long-distance migratory shorebird, the dunlin (Calidris alpina), outside the breeding season. Mass-corrected BMR and daily energy consumption increased significantly by 17 and 20% between freshwater (0.3‰ NaCl) and saltwater (33.0-35.0‰ NaCl), respectively. Body mass in both captive and wild dunlins was lower (9-16%) in saline than in freshwater environments. These changes on BMR and body mass were quickly reversed by returning the birds to freshwater, suggesting that metabolic adjustment to saltwater and metabolic readjustment to freshwater are both processes that occur in a few days. Our findings support empirically that the processes of developing and maintaining an active osmoregulatory machinery are energetically expensive, and they could help to explain diet and/or habitat selection patterns along the flyway. Finally, we discuss whether body mass loss in saltwater may be a strategy to reduce maintenance cost in osmotically stressful conditions such as overwintering in marine habitats, and raise some methodological implications for studies of BMR-related outcomes using captive birds captured in saline environments.

  12. A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat.

    PubMed

    Kashiwaya, Yoshihiro; Pawlosky, Robert; Markis, William; King, M Todd; Bergman, Christian; Srivastava, Shireesh; Murray, Andrew; Clarke, Kieran; Veech, Richard L

    2010-08-20

    Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD(+)]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.

  13. nBu4NI-catalyzed oxidative imidation of ketones with imides: synthesis of α-amino ketones.

    PubMed

    Lv, Yunhe; Li, Yan; Xiong, Tao; Lu, Yu; Liu, Qun; Zhang, Qian

    2014-03-04

    nBu4NI-Catalyzed oxidative imidation of ketones and imides for the synthesis of α-amino ketones were realized for the first time. The methodology is characterized by its wide substrate scope even for acetone with readily available phthalimide, saccharin and succinimide, which opens a new pathway for direct imidation of ketones.

  14. Thermochemistry and bond dissociation energies of ketones.

    PubMed

    Hudzik, Jason M; Bozzelli, Joseph W

    2012-06-14

    Ketones are a major class of organic chemicals and solvents, which contribute to hydrocarbon sources in the atmosphere, and are important intermediates in the oxidation and combustion of hydrocarbons and biofuels. Their stability, thermochemical properties, and chemical kinetics are important to understanding their reaction paths and their role as intermediates in combustion processes and in atmospheric chemistry. In this study, enthalpies (ΔH°(f 298)), entropies (S°(T)), heat capacities (C(p)°(T)), and internal rotor potentials are reported for 2-butanone, 3-pentanone, 2-pentanone, 3-methyl-2-butanone, and 2-methyl-3-pentanone, and their radicals corresponding to loss of hydrogen atoms. A detailed evaluation of the carbon-hydrogen bond dissociation energies (C-H BDEs) is also performed for the parent ketones for the first time. Standard enthalpies of formation and bond energies are calculated at the B3LYP/6-31G(d,p), B3LYP/6-311G(2d,2p), CBS-QB3, and G3MP2B3 levels of theory using isodesmic reactions to minimize calculation errors. Structures, moments of inertia, vibrational frequencies, and internal rotor potentials are calculated at the B3LYP/6-31G(d,p) density functional level and are used to determine the entropies and heat capacities. The recommended ideal gas-phase ΔH°(f 298), from the average of the CBS-QB3 and G3MP2B3 levels of theory, as well as the calculated values for entropy and heat capacity are shown to compare well with the available experimental data for the parent ketones. Bond energies for primary, secondary, and tertiary radicals are determined; here, we find the C-H BDEs on carbons in the α position to the ketone group decrease significantly with increasing substitution on these α carbons. Group additivity and hydrogen-bond increment values for these ketone radicals are also determined.

  15. Fe/Cu-Mediated One-Pot Ketone Synthesis.

    PubMed

    Kumar, Vemula Praveen; Babu, Vaddela Sudheer; Yahata, Kenzo; Kishi, Yoshito

    2017-05-19

    An Fe/Cu-mediated one-pot ketone synthesis was reported. Unlike Ni- and Pd-mediated one-pot ketone syntheses, the reported Fe/Cu-mediated method allowed selective activation and coupling of alkyl iodides over vinyl iodides. The newly developed one-pot ketone synthesis was applied to a synthesis of vinyl iodide/ketone 13, the left half of halichondrin B, as well as vinyl iodide/ketone 8a, the C20-C26 building block of halichondrins.

  16. Body size as a latent variable in a structural equation model: thermal acclimation and energetics of the leaf-eared mouse.

    PubMed

    Nespolo, Roberto F; Arim, Matías; Bozinovic, Francisco

    2003-07-01

    Body size is one of the most important determinants of energy metabolism in mammals. However, the usual physiological variables measured to characterize energy metabolism and heat dissipation in endotherms are strongly affected by thermal acclimation, and are also correlated among themselves. In addition to choosing the appropriate measurement of body size, these problems create additional complications when analyzing the relationships among physiological variables such as basal metabolism, non-shivering thermogenesis, thermoregulatory maximum metabolic rate and minimum thermal conductance, body size dependence, and the effect of thermal acclimation on them. We measured these variables in Phyllotis darwini, a murid rodent from central Chile, under conditions of warm and cold acclimation. In addition to standard statistical analyses to determine the effect of thermal acclimation on each variable and the body-mass-controlled correlation among them, we performed a Structural Equation Modeling analysis to evaluate the effects of three different measurements of body size (body mass, m(b); body length, L(b) and foot length, L(f)) on energy metabolism and thermal conductance. We found that thermal acclimation changed the correlation among physiological variables. Only cold-acclimated animals supported our a priori path models, and m(b) appeared to be the best descriptor of body size (compared with L(b) and L(f)) when dealing with energy metabolism and thermal conductance. However, while m(b) appeared to be the strongest determinant of energy metabolism, there was an important and significant contribution of L(b) (but not L(f)) to thermal conductance. This study demonstrates how additional information can be drawn from physiological ecology and general organismal studies by applying Structural Equation Modeling when multiple variables are measured in the same individuals.

  17. Ketone esters increase brown fat in mice and overcome insulin resistance in other tissues in the rat

    PubMed Central

    Veech, Richard L.

    2013-01-01

    Brown adipose tissue (BAT) is classically activated by sympathetic nervous stimulation resulting from exposure to cold. Feeding a high-fat diet also induces development of brown fat, but is decreased by caloric restriction. Blood ketone bodies, which function as alternative energy substrates to glucose, are increased during caloric restriction. Here we discuss the unexpected observation that feeding an ester of ketone bodies to the mouse, which increases blood ketone body concentrations, results in an activation of brown fat. The mechanism of this activation of brown fat is similar to that occurring from cold exposure in that cyclic adenosine monophosphate (AMP) levels are increased as are levels of the transcription factor cyclic AMP–responsive element–binding protein, which is also increased by ketone ester feeding. Other effects of feeding ketone esters, in addition to their ability to induce brown fat, are discussed such as their ability to overcome certain aspects of insulin resistance and to ameliorate the accumulation of amyloid and phosphorylated tau protein in brain, and improve cognitive function, in a triple transgenic mouse model of Alzheimer’s disease. PMID:23909803

  18. Ketone esters increase brown fat in mice and overcome insulin resistance in other tissues in the rat.

    PubMed

    Veech, Richard L

    2013-10-01

    Brown adipose tissue (BAT) is classically activated by sympathetic nervous stimulation resulting from exposure to cold. Feeding a high-fat diet also induces development of brown fat, but is decreased by caloric restriction. Blood ketone bodies, which function as alternative energy substrates to glucose, are increased during caloric restriction. Here we discuss the unexpected observation that feeding an ester of ketone bodies to the mouse, which increases blood ketone body concentrations, results in an activation of brown fat. The mechanism of this activation of brown fat is similar to that occurring from cold exposure in that cyclic adenosine monophosphate (AMP) levels are increased as are levels of the transcription factor cyclic AMP-responsive element-binding protein, which is also increased by ketone ester feeding. Other effects of feeding ketone esters, in addition to their ability to induce brown fat, are discussed such as their ability to overcome certain aspects of insulin resistance and to ameliorate the accumulation of amyloid and phosphorylated tau protein in brain, and improve cognitive function, in a triple transgenic mouse model of Alzheimer's disease.

  19. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution.

    PubMed

    Cunnane, Stephen C; Crawford, Michael A

    2014-12-01

    The human brain confronts two major challenges during its development: (i) meeting a very high energy requirement, and (ii) reliably accessing an adequate dietary source of specific brain selective nutrients needed for its structure and function. Implicitly, these energetic and nutritional constraints to normal brain development today would also have been constraints on human brain evolution. The energetic constraint was solved in large measure by the evolution in hominins of a unique and significant layer of body fat on the fetus starting during the third trimester of gestation. By providing fatty acids for ketone production that are needed as brain fuel, this fat layer supports the brain's high energy needs well into childhood. This fat layer also contains an important reserve of the brain selective omega-3 fatty acid, docosahexaenoic acid (DHA), not available in other primates. Foremost amongst the brain selective minerals are iodine and iron, with zinc, copper and selenium also being important. A shore-based diet, i.e., fish, molluscs, crustaceans, frogs, bird's eggs and aquatic plants, provides the richest known dietary sources of brain selective nutrients. Regular access to these foods by the early hominin lineage that evolved into humans would therefore have helped free the nutritional constraint on primate brain development and function. Inadequate dietary supply of brain selective nutrients still has a deleterious impact on human brain development on a global scale today, demonstrating the brain's ongoing vulnerability. The core of the shore-based paradigm of human brain evolution proposes that sustained access by certain groups of early Homo to freshwater and marine food resources would have helped surmount both the nutritional as well as the energetic constraints on mammalian brain development.

  20. Nile Red Detection of Bacterial Hydrocarbons and Ketones in a High-Throughput Format

    SciTech Connect

    Pinzon, NM; Aukema, KG; Gralnick, JA; Wackett, LP

    2011-06-28

    A method for use in high-throughput screening of bacteria for the production of long-chain hydrocarbons and ketones by monitoring fluorescent light emission in the presence of Nile red is described. Nile red has previously been used to screen for polyhydroxybutyrate (PHB) and fatty acid esters, but this is the first report of screening for recombinant bacteria making hydrocarbons or ketones. The microtiter plate assay was evaluated using wild-type and recombinant strains of Shewanella oneidensis and Escherichia coli expressing the enzyme OleA, previously shown to initiate hydrocarbon biosynthesis. The strains expressing exogenous Stenotrophomonas maltophilia oleA, with increased levels of ketone production as determined by gas chromatography-mass spectrometry, were distinguished with Nile red fluorescence. Confocal microscopy images of S. oneidensis oleA-expressing strains stained with Nile red were consistent with a membrane localization of the ketones. This differed from Nile red staining of bacterial PHB or algal lipid droplets that showed intracellular inclusion bodies. These results demonstrated the applicability of Nile red in a high-throughput technique for the detection of bacterial hydrocarbons and ketones. IMPORTANCE In recent years, there has been renewed interest in advanced biofuel sources such as bacterial hydrocarbon production. Previous studies used solvent extraction of bacterial cultures followed by gas chromatography-mass spectrometry (GC-MS) to detect and quantify ketones and hydrocarbons (Beller HR, Goh EB, Keasling JD, Appl. Environ. Microbiol. 76: 1212-1223, 2010; Sukovich DJ, Seffernick JL, Richman JE, Gralnick JA, Wackett LP, Appl. Environ. Microbiol. 76: 3850-3862, 2010). While these analyses are powerful and accurate, their labor-intensive nature makes them intractable to high-throughput screening; therefore, methods for rapid identification of bacterial strains that are overproducing hydrocarbons are needed. The use of high

  1. Mass and Ion Transport in Ketones and Ketone Electrolytes: Comparison with Acetate Systems.

    PubMed

    Bopege, Dharshani N; Petrowsky, Matt; Johnson, Matthew B; Frech, Roger

    2013-03-01

    Self-diffusion coefficient measurements were performed for pure n-alkyl ketone liquids using the pulsed field gradient NMR spin-echo technique. Ionic conductivities and dielectric constants of 0.0055 mol·L(-1) tetrabutylammonium trifluoromethanesulfonate in 2-pentanone, 2-hexanone, 2-heptanone, 2-octanone, 2-nonanone, and 2-decanone were also measured. The temperature-dependent conductivities and diffusion coefficients over the range 5-80 °C can be described using the compensated Arrhenius formalism. Compensated Arrhenius equation plots were used to calculate the average activation energy for both sets of data. The average activation energy from conductivity data is approximately equal to that from diffusion data. The data for the pure ketones and ketone-based electrolytes are compared with analogous data for pure n-alkyl acetates and n-alkyl acetate-based electrolytes.

  2. A bio-catalytic approach to aliphatic ketones.

    PubMed

    Xiong, Mingyong; Deng, Jin; Woodruff, Adam P; Zhu, Minshan; Zhou, Jun; Park, Sun Wook; Li, Hui; Fu, Yao; Zhang, Kechun

    2012-01-01

    Depleting oil reserves and growing environmental concerns have necessitated the development of sustainable processes to fuels and chemicals. Here we have developed a general metabolic platform in E. coli to biosynthesize carboxylic acids. By engineering selectivity of 2-ketoacid decarboxylases and screening for promiscuous aldehyde dehydrogenases, synthetic pathways were constructed to produce both C5 and C6 acids. In particular, the production of isovaleric acid reached 32 g/L (0.22 g/g glucose yield), which is 58% of the theoretical yield. Furthermore, we have developed solid base catalysts to efficiently ketonize the bio-derived carboxylic acids such as isovaleric acid and isocaproic acid into high volume industrial ketones: methyl isobutyl ketone (MIBK, yield 84%), diisobutyl ketone (DIBK, yield 66%) and methyl isoamyl ketone (MIAK, yield 81%). This hybrid "Bio-Catalytic conversion" approach provides a general strategy to manufacture aliphatic ketones, and represents an alternate route to expanding the repertoire of renewable chemicals.

  3. A Bio-Catalytic Approach to Aliphatic Ketones

    PubMed Central

    Xiong, Mingyong; Deng, Jin; Woodruff, Adam P.; Zhu, Minshan; Zhou, Jun; Park, Sun Wook; Li, Hui; Fu, Yao; Zhang, Kechun

    2012-01-01

    Depleting oil reserves and growing environmental concerns have necessitated the development of sustainable processes to fuels and chemicals. Here we have developed a general metabolic platform in E. coli to biosynthesize carboxylic acids. By engineering selectivity of 2-ketoacid decarboxylases and screening for promiscuous aldehyde dehydrogenases, synthetic pathways were constructed to produce both C5 and C6 acids. In particular, the production of isovaleric acid reached 32 g/L (0.22 g/g glucose yield), which is 58% of the theoretical yield. Furthermore, we have developed solid base catalysts to efficiently ketonize the bio-derived carboxylic acids such as isovaleric acid and isocaproic acid into high volume industrial ketones: methyl isobutyl ketone (MIBK, yield 84%), diisobutyl ketone (DIBK, yield 66%) and methyl isoamyl ketone (MIAK, yield 81%). This hybrid “Bio-Catalytic conversion” approach provides a general strategy to manufacture aliphatic ketones, and represents an alternate route to expanding the repertoire of renewable chemicals. PMID:22416247

  4. Synthesis of methyl ketones by metabolically engineered Escherichia coli.

    PubMed

    Park, John; Rodríguez-Moyá, María; Li, Mai; Pichersky, Eran; San, Ka-Yiu; Gonzalez, Ramon

    2012-11-01

    Methyl ketones are a group of highly reduced platform chemicals with widespread applications in the fragrance, flavor and pharmacological industries. Current methods for the industrial production of methyl ketones include oxidation of hydrocarbons, but recent advances in the characterization of methyl ketone synthases from wild tomato have sparked interest towards the development of microbial platforms for the industrial production of methyl ketones. A functional methyl ketone biosynthetic pathway was constructed in Escherichia coli by over-expressing two genes from Solanum habrochaites: shmks2, encoding a 3-ketoacyl-ACP thioesterase, and shmks1, encoding a beta-decarboxylase. These enzymes enabled methyl ketone synthesis from 3-ketoacyl-ACP, an intermediate in the fatty acid biosynthetic cycle. The production of 2-nonanone, 2-undecanone, and 2-tridecanone by MG1655 pTH-shmks2-shmks1 was initially detected by nuclear magnetic resonance and gas chromatography-mass spectrometry analyses at levels close to 6 mg/L. The deletion of major fermentative pathways leading to ethanol (adhE), lactate (ldhA), and acetate (pta, poxB) production allowed for the carbon flux to be redirected towards methyl ketone production, doubling total methyl ketone concentration. Variations in methyl ketone production observed under different working volumes in flask experiments led to a more detailed analysis of the effects of oxygen availability on methyl ketone concentration in order to determine optimal levels of oxygen. The methyl ketone concentration achieved with MG1655 ∆adhE ∆ldhA ∆poxB ∆pta pTrcHis2A-shmks2-shmks1, the best performer strain in this study, was approximately 500 mg/L, the highest reported for an engineered microorganism. Through the establishment of optimal operating conditions and by executing rational metabolic engineering strategies, we were able to increase methyl ketone concentrations by almost 75-fold from the initial confirmatory levels.

  5. Poly (Aryl Ether Ketones) Bearing Alkylated Side Chains

    NASA Technical Reports Server (NTRS)

    Cassidy, Patrick E. (Inventor); Fitch, John W., III (Inventor); Gronewald, Scott D. (Inventor); St.Clair, Ann K. (Inventor); Stoakley, Diane M. (Inventor)

    2002-01-01

    This invention relates generally to poly(aryl ether ketones) bearing alkylated side chains. It relates particularly to soluble, thermally stable. low dielectric poly(aryl ether ketones) with alkylated side chains and especially to films and coatings thereof. These poly(aryl ether ketones) have a structural formula wherein Y is selected from the group consisting of CF3 and CH3; and wherein R is C(sub n)H(sub (2n+1)) and n = 11-18.

  6. Application of aryloximes as solid-phase ketone linkers.

    PubMed

    Lepore, Salvatore D; Wiley, Michael R

    2003-01-09

    In both solution and the solid phase, a variety of ketone oxime anions have been treated with 4-substituted-2-fluorobenzonitriles to give the corresponding nucleophilic aromatic substitution aryloxime adducts. Under aqueous acidic conditions, these adducts underwent cyclization to give the corresponding ketones. Suzuki and amide coupling reactions were also successfully performed on two resin-bound oximes followed by subsequent cyclorelease to give ketone product in good yields and purities. [reaction--see text

  7. Analysis of the energetic metabolism in cyclic Bedouin goats (Capra hircus): Nychthemeral and seasonal variations of some haematochemical parameters in relation with body and ambient temperatures.

    PubMed

    Malek, Mouna; Amirat, Zaina; Khammar, Farida; Khaldoun, Mounira

    2016-08-01

    Several studies have examined changes in some haematochemical parameters as a function of the different physiological status (cyclic, pregnant and lactating) of goats, but no relevant literature has exhaustively investigated these variations from anestrous to estrous stages in cyclic goats. In this paper, we report nychthemeral and seasonal variations in ambient and body temperatures, and in some haematochemical parameters (glycemia, cholesterolemia, triglyceridemia, creatininemia and uremia) measured during summer, winter and spring, in seven (7) experimental cyclic female Bedouin goats (Capra hircus) living in the Béni-Abbès region (Algerian Sahara desert). Cosinor rhythmometry procedure was used to determine the rhythmic parameters of ambient temperature and haematochemical parameters. To determine the effect of time of day on the rhythmicity of the studied parameters, as well as their seasonality, repeated measure analysis of variance (ANOVA) was applied. The results showed that in spite of the nychthemeral profile presented by the ambient temperature for each season, the body temperature remained in a narrow range, thus indicating a successful thermoregulation. The rhythmometry analysis showed a circadian rhythmicity of ambient temperature and haematochemical parameters with diurnal acrophases. A statistically significant effect of the time of day was shown on all studied haematochemical parameters, except on creatininemia. It was also found that only uremia, cholesterolemia and triglyceridemia followed the seasonal sexual activity of the studied ruminant. This study demonstrated the good physiological adaptation developed by this breed in response to the harsh climatic conditions of its natural environment.

  8. Ketone Body Metabolic Enzyme OXCT1 Regulates Prostate Cancer Chemoresistance

    DTIC Science & Technology

    2014-10-01

    Cancer Chemoresistance PRINCIPAL INVESTIGATOR: Dr. Qiong Liu CONTRACTING ORGANIZATION: Oregon Health & Science University...Portland, Oregon , 97239 REPORT DATE: October 2014 TYPE OF REPORT: Annual Progress Report...ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Oregon Health & Science University 3303 SW Bond Ave Portland

  9. Liver-derived ketone bodies are necessary for food anticipation.

    PubMed

    Chavan, Rohit; Feillet, Céline; Costa, Sara S Fonseca; Delorme, James E; Okabe, Takashi; Ripperger, Jürgen A; Albrecht, Urs

    2016-02-03

    The circadian system has endowed animals with the ability to anticipate recurring food availability at particular times of day. As daily food anticipation (FA) is independent of the suprachiasmatic nuclei, the central pacemaker of the circadian system, questions arise of where FA signals originate and what role components of the circadian clock might play. Here we show that liver-specific deletion of Per2 in mice abolishes FA, an effect that is rescued by viral overexpression of Per2 in the liver. RNA sequencing indicates that Per2 regulates β-hydroxybutyrate (βOHB) production to induce FA leading to the conclusion that liver Per2 is important for this process. Unexpectedly, we show that FA originates in the liver and not in the brain. However, manifestation of FA involves processing of the liver-derived βOHB signal in the brain, indicating that the food-entrainable oscillator is not located in a single tissue but is of systemic nature.

  10. Rhodium-catalyzed Asymmetric Hydrogenation of α-Dehydroamino Ketones: A General Approach to Chiral α-amino Ketones.

    PubMed

    Gao, Wenchao; Wang, Qingli; Xie, Yun; Lv, Hui; Zhang, Xumu

    2016-01-01

    Rhodium/DuanPhos-catalyzed asymmetric hydrogenation of aliphatic α-dehydroamino ketones has been achieved and afforded chiral α-amino ketones in high yields and excellent enantioselectives (up to 99 % ee), which could be reduced further to chiral β-amino alcohols by LiAlH(tBuO)3 with good yields. This protocol provides a readily accessible route for the synthesis of chiral α-amino ketones and chiral β-amino alcohols.

  11. Fluorinated Poly(Phenylene Ether Ketones)

    NASA Technical Reports Server (NTRS)

    St. Clair, Anne K.; Cassidy, Patrick E.; Tullos, Gordon L.

    1994-01-01

    Fluorinated poly(phenylene ether ketones) are colorless, transparent, low-dielectric-constant, highly thermally stable polymers. Particularly suitable for use as film and coating materials in electronic and thermal-control applications such as; passivant insulating coats and interlevel dielectrics in microelectronic circuits, or as protective transparent coats on solar cells or mirrors. Solubility and transparency of 12F-PEK along with its lower dielectric constant and other properties make it more useful as dielectric film and coating material in many applications.

  12. Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

    PubMed

    Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

    2016-03-01

    Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. © 2016 New York Academy of Sciences.

  13. IRIS Toxicological Review of Methyl Ethyl Ketone (2003 Final)

    EPA Science Inventory

    EPA announced the release of the final report, Toxicological Review of Methyl Ethyl Ketone: in support of the Integrated Risk Information System (IRIS). The updated Summary for Methyl Ethyl Ketone and accompanying toxicological review have been added to the IRIS Database....

  14. Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors

    PubMed Central

    Kim, Do Young; Vallejo, Johana; Rho, Jong M

    2010-01-01

    Abstract Ketones have previously shown beneficial effects in models of neurodegenerative disorders, particularly against associated mitochondrial dysfunction and cognitive impairment. However, evidence of a synaptic protective effect of ketones remains lacking. We tested the effects of ketones on synaptic impairment induced by mitochondrial respiratory complex (MRC) inhibitors using electrophysiological, reactive oxygen species (ROS) imaging and biochemical techniques. MRC inhibitors dose-dependently suppressed both population spike (PS) and field potential amplitudes in the CA1 hippocampus. Pre-treatment with ketones strongly prevented changes in the PS, whereas partial protection was seen in the field potential. Rotenone (Rot; 100 nmol/L), a MRC I inhibitor, suppressed synaptic function without altering ROS levels and PS depression by Rot was unaffected by antioxidants. In contrast, antioxidant-induced PS recovery against the MRC II inhibitor 3-nitropropionic acid (3-NP; 1 mmol/L) was similar to the synaptic protective effects of ketones. Ketones also suppressed ROS generation induced by 3-NP. Finally, ketones reversed the decreases in ATP levels caused by Rot and 3-NP. In summary, our data demonstrate that ketones can preserve synaptic function in CA1 hippocampus induced by MRC dysfunction, likely through an antioxidant action and enhanced ATP generation. PMID:20374433

  15. 27 CFR 21.117 - Methyl isobutyl ketone.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Methyl isobutyl ketone. 21.117 Section 21.117 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....117 Methyl isobutyl ketone. (a) Acidity (as acetic acid). 0.02 percent by weight, maximum. (b) Color...

  16. 27 CFR 21.117 - Methyl isobutyl ketone.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Methyl isobutyl ketone. 21.117 Section 21.117 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....117 Methyl isobutyl ketone. (a) Acidity (as acetic acid). 0.02 percent by weight, maximum. (b) Color...

  17. Tandem Reaction of Enynyl Acetate: Precursor of Allenyl Ketones.

    PubMed

    Okamoto, Noriko; Sueda, Takuya; Yanada, Reiko

    2016-01-01

    Deacetylation of enynyl acetates under basic conditions allows convenient access to reactive allenyl ketones, which can then undergo 1,4-addition of nucleophiles to furnish β,γ-unsaturated ketones. Benzofuran and indole derivatives have also been obtained from enynyl acetates with an o-hetero-atom-substituted aryl group via intramolecular 1,4-addition.

  18. 27 CFR 21.117 - Methyl isobutyl ketone.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Methyl isobutyl ketone. 21.117 Section 21.117 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....117 Methyl isobutyl ketone. (a) Acidity (as acetic acid). 0.02 percent by weight, maximum. (b) Color...

  19. 27 CFR 21.117 - Methyl isobutyl ketone.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Methyl isobutyl ketone. 21.117 Section 21.117 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....117 Methyl isobutyl ketone. (a) Acidity (as acetic acid). 0.02 percent by weight, maximum. (b) Color...

  20. IRIS TOXICOLOGICAL REVIEW OF METHYL ETHYL KETONE (2003 Final)

    EPA Science Inventory

    EPA is announcing the release of the final report, "Toxicological Review of Methyl Ethyl Ketone: in support of the Integrated Risk Information System (IRIS)". The updated Summary for Methyl Ethyl Ketone and accompanying Quickview have also been added to the IRIS Database.

  1. One-Step Conversion of Methyl Ketones to Acyl Chlorides.

    PubMed

    Zaragoza, Florencio

    2015-10-16

    Treatment of aromatic and heteroaromatic methyl ketones with sulfur monochloride and catalytic amounts of pyridine in refluxing chlorobenzene leads to the formation of acyl chlorides. Both electron-rich and electron-poor aryl methyl ketones can be used as starting materials. The resulting C1-byproduct depends on the precise reaction conditions chosen.

  2. Deaminative and decarboxylative catalytic alkylation of amino acids with ketones.

    PubMed

    Kalutharage, Nishantha; Yi, Chae S

    2013-12-16

    It cuts two ways: The cationic [Ru-H] complex catalyzes selective coupling of α- and β-amino acids with ketones to form α-alkylated ketone products. The reaction involves CC and CN bond cleavage which result in regio- and stereoselective alkylation using amino acids. A broad substrate scope and high functional-group tolerance is demonstrated.

  3. IRIS Toxicological Review of Methyl Ethyl Ketone (2003 Final)

    EPA Science Inventory

    EPA announced the release of the final report, Toxicological Review of Methyl Ethyl Ketone: in support of the Integrated Risk Information System (IRIS). The updated Summary for Methyl Ethyl Ketone and accompanying toxicological review have been added to the IRIS Database....

  4. Production of methyl-vinyl ketone from levulinic acid

    DOEpatents

    Dumesic, James A.; West; Ryan M.

    2011-06-14

    A method for converting levulinic acid to methyl vinyl ketone is described. The method includes the steps of reacting an aqueous solution of levulinic acid, over an acid catalyst, at a temperature of from room temperature to about 1100 K. Methyl vinyl ketone is thereby formed.

  5. 27 CFR 21.118 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Methyl n-butyl ketone. 21.118 Section 21.118 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....118 Methyl n-butyl ketone. (a) Acidity (as acetic acid). 0.02 percent by weight, maximum. (b)...

  6. 27 CFR 21.118 - Methyl n-butyl ketone.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Methyl n-butyl ketone. 21.118 Section 21.118 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU....118 Methyl n-butyl ketone. (a) Acidity (as acetic acid). 0.02 percent by weight, maximum. (b) Color...

  7. Solar Energetic Particles

    NASA Astrophysics Data System (ADS)

    Király, Péter

    Energetic particles recorded in the Earth environment and in interplanetary space have a multitude of origins, i.e. acceleration and propagation histories. At early days practically all sufficiently energetic particles were considered to have come either from solar flares or from interstellar space. Later on, co-rotating interplanetary shocks, the termination shock of the supersonic solar wind, planetary bow shocks and magnetospheres, and also coronal mass ejections (CME) were recognized as energetic particle sources. It was also recognized that less energetic (suprathermal) particles of solar origin and pick-up ions have also a vital role in giving rise to energetic particles in interplanetary disturbances. The meaning of the term "solar energetic particles" (SEP) is now somewhat vague, but essentially it refers to particles produced in disturbances fairly directly related to solar processes. Variation of intensity fluctuations with energy and with the phase of the solar cycle will be discussed. Particular attention will be given to extremes of time variation, i.e. to very quiet periods and to large events. While quiet-time fluxes are expected to shed light on some basic coronal processes, large events dominate the fluctuation characteristics of cumulated fluence, and the change of that fluctuation with energy and with the phase of the solar cycle may also provide important clues. Mainly ISEE-3 and long-term IMP-8 data will be invoked. Energetic and suprathermal particles that may never escape into interplanetary space may play an important part in heating the corona of the sun.

  8. Anticonvulsant properties of an oral ketone ester in a pentylenetetrazole-model of seizure.

    PubMed

    Viggiano, Andrea; Pilla, Raffaele; Arnold, Patrick; Monda, Marcellino; D'Agostino, Dominic; Coppola, Giangennaro

    2015-08-27

    The ketogenic diet is known to have an anti-epileptic effect; in fact it is currently used to treat drug resistant epilepsies. The efficacy of this diet is thought to be correlated to the elevation of blood ketone bodies. Because of problems with compliance to this diet, there is an interest in evaluating alternative pharmacological treatments that can have anti-seizure effects by elevating ketone bodies. In the present experiment, an orally administered synthetic ketone ester (R,S - 1,3-butanediol acetoacetate diester, or BD-AcAc2) was evaluated for its anti-seizure efficacy in a rat model. The threshold for seizure induction with progressive intravenous infusion of pentylenetrazole (PTZ) was evaluated in anesthetized Wistar rats two hours after a single 1 ml intragastric administration of BD-AcAc2 (i.e. 4 g/kg b.w., treated group) or water (control group). After correction for the dose of anesthetic, the results showed that the administration of BD-AcAc2 induced an elevation of the PTZ threshold (140 ± 11 mg/kg for the treated group, 122 ± 6 mg/kg for the control group), along with an increased level of blood β-hydroxybutyrate (2.7 ± 0.3mM for the treated group, 1.4 ± 0.1mM for the control group). This result suggests that ketone esters may pave the road towards the establishment of a "ketogenic diet in a pill".

  9. Chapter 4: Measuring Energetics of Biological Processes

    USDA-ARS?s Scientific Manuscript database

    Measurement of the energetics of biological processes is the key component in understanding the thermodynamic responses of homoeothermic animals to the environment. For these animals to achieve body temperature control, they must adapt to thermal-environmental conditions and variations caused by wea...

  10. Conductivity enhancement of sulfonated poly(ether ketone ketone) blends using electric field structuring techniques

    NASA Astrophysics Data System (ADS)

    Gasa, Jeffrey V.; Shaw, Montgomery T.

    2004-03-01

    Binary blends composed of an ion-containing polymer and a secondary component were cast under an applied elec. field to produce membranes with anisotropic morphologies. The ion-containing polymer was sulfonated poly(ether ketone ketone) (SPEKK) and the secondary component was either poly(ether imide) (PEI) or styrene-acrylonitrile (SAN) copolymer. A range of compositions and sulfonation levels were studied using this blend system. Optical and SEM micrographs of the resulting membranes showed columnar structures that were oriented along the direction of the field. It was found that electric field alignment only occurs when SPEKK is the dispersed phase but not when it is the matrix. The results show that the conductivities of the membranes that were cast under an electric field were significantly higher than those of the membranes cast without electric field. The conductivity measurements were interpreted in terms of a composite equation with structure-dependent parameters.

  11. A sulfonated poly (aryl ether ether ketone ketone) isomer: synthesis and DMFC performance

    SciTech Connect

    Kim, Yu Seung; Liu, Baijun; Hu, Wei; Jiang, Zhenhua; Robertson, Gilles; Guiver, Michael

    2009-01-01

    A sulfonated poly(aryl ether ether ketone ketone) (PEEKK) having a well-defined rigid homopolymer-like chemical structure was synthesized from a readily-prepared PEEKK post-sulfonation with concentrated sulfuric acid at room temperature within several hours. The polymer electrolyte membrane (PEM) cast from the resulting polymer exhibited an excellent combination of thermal resistance, oxidative and dimensional stability, low methanol fuel permeability and high proton conductivity. Furthermore, membrane electrode assemblies (MEAs) were successfully fabricated and good direct methanol fuel cell (DMFC) performance was observed. At 2 M MeOH feed, the current density at 0.5 V reached 165 mA/cm, which outperformed our reported analogues and eveluated Nafion membranes.

  12. Synthesis of Energetic Polymers.

    DTIC Science & Technology

    1981-10-15

    POLYMERS Summary Report 15 July 1980 to 14 July 1981 COctober 15, 1981 By: G. E. Manser and D. L. Ross Prepared for: ) OFFICE OF NAVAL RESEARCH 800 N...OF ENERGETIC POLYMERS Summary Report 15 July 1980 to 14 July 1981 iOctober 15, 1981 By: G. E. Manser and D. L. Ross Prepared for: OFFICE OF NAVAL...necessary and identify by block number) Three general synthetic routes to the preparation of energetic oxetanes and tetrahydrofurans were investigated during

  13. Intermittent trickling bed filter for the removal of methyl ethyl ketone and methyl isobutyl ketone.

    PubMed

    Farnazo, Danvir Mark C; Nisola, Grace M; Han, Mideok; Yoo, Namjong; Chung, Wook-Jin

    2012-05-01

    Biodegradations of methyl ethyl ketone and methyl isobutyl ketone were performed in intermittent biotrickling filter beds (ITBF) operated at two different trickling periods: 12 h/day (ITBF-12) and 30 min/day (ITBF-0.5). Ralstonia sp. MG1 was able to degrade both ketones as evidenced by growth kinetic experiments. Results show that trickling period is an important parameter to achieve high removal performance and to maintain the robustness of Ralstonia sp. MG1. Overall, ITBF-12 outperformed ITBF-0.5 regardless of the target compound. ITBF-12 had high performance recovery at various inlet gas concentrations. The higher carbon dioxide production rates in ITBF-12 suggest higher microbial activity than in ITBF-0.5. Additionally, lower concentrations of absorbed volatile organic compound (VOC) in trickling solutions of ITBF-12 systems also indicate VOC removal through biodegradation. Pressure drop levels in ITBF-12 were relatively higher than in ITBF-0.5 systems, which can be attributed to the decrease in packed bed porosity as Ralstonia sp. MG1 grew well in ITBF-12. Nonetheless, the obtained pressure drop levels did not have any adverse effect on the performance of ITBF-12. Biokinetic constants were also obtained which indicated that ITBF-12 performed better than ITBF-0.5 and other conventional biotrickling filter systems.

  14. Olfactory Psychometric Functions for Homologous 2-Ketones

    PubMed Central

    Cometto-Muñiz, J. Enrique; Abraham, Michael H.

    2009-01-01

    We measured concentration-detection (i.e., psychometric) odor functions for the homologous ketones propanone (acetone), 2-pentanone, 2-heptanone, and 2-nonanone. Under a forced-choice procedure, stimuli were presented via an 8-channel air-dilution olfactometer that allowed natural sampling of the odorant and whose output was quantified by gas chromatography. Subjects (17 to 22 per compound) comprised young adults from both genders, all normosmics and nonsmokers. A sigmoid (logistic) equation tightly fitted group and individual functions. The odor detection threshold (ODT) was the concentration detectable at halfway (P=0.5) between chance (P=0.0) and perfect (P=1.0) detection. Odor sensitivity increased (i.e., thresholds decreased) from acetone to heptanone, remaining constant for nonanone. This relative trend was also observed in previous work and in odor thresholds compilations, but the absolute ODTs obtained here were consistently at the lower end of those reported before. Interindividual variability of ODTs was about one order of magnitude. These odor functions measured behaviorally in humans were obtained at vapor concentrations 1,000 times lower than functions measured via activation, with similar 2-ketones, of receptor neurons converging into individual olfactory glomeruli of mice, visualized with calcium sensitive dyes. Odorant concentrations presented as vapors (as in behavioral studies) and those presented as liquids (as in cellular/tissue studies) can be rendered equivalent via liquid-vapor partition coefficients and, then, compared in relative olfactory potency. These comparisons can reveal how sensitivity is progressively shaped across levels of the neural pathway. PMID:19428635

  15. Olfactory psychometric functions for homologous 2-ketones.

    PubMed

    Cometto-Muñiz, J Enrique; Abraham, Michael H

    2009-07-19

    We measured concentration-detection (i.e., psychometric) odor functions for the homologous ketones propanone (acetone), 2-pentanone, 2-heptanone, and 2-nonanone. Under a forced-choice procedure, stimuli were presented via an 8-channel air-dilution olfactometer that allowed natural sampling of the odorant and whose output was quantified by gas chromatography. Subjects (17-22 per compound) comprised young adults from both genders, all normosmics and nonsmokers. A sigmoid (logistic) equation tightly fitted group and individual functions. The odor detection threshold (ODT) was the concentration detectable at halfway (P=0.5) between chance (P=0.0) and perfect (P=1.0) detection. Odor sensitivity increased (i.e., thresholds decreased) from acetone to heptanone, remaining constant for nonanone. This relative trend was also observed in previous work and in odor thresholds compilations, but the absolute ODTs obtained here were consistently at the lower end of those reported before. Interindividual variability of ODTs was about 1 order of magnitude. These odor functions measured behaviorally in humans were obtained at vapor concentrations 1000 times lower than functions measured via activation, with similar 2-ketones, of receptor neurons converging into individual olfactory glomeruli of mice, visualized with calcium sensitive dyes. Odorant concentrations presented as vapors (as in behavioral studies) and those presented as liquids (as in cellular/tissue studies) can be rendered equivalent via liquid-vapor partition coefficients and, then, compared in relative olfactory potency. These comparisons can reveal how sensitivity is progressively shaped across levels of the neural pathway.

  16. Engineering of bacterial methyl ketone synthesis for biofuels.

    PubMed

    Goh, Ee-Been; Baidoo, Edward E K; Keasling, Jay D; Beller, Harry R

    2012-01-01

    We have engineered Escherichia coli to overproduce saturated and monounsaturated aliphatic methyl ketones in the C₁₁ to C₁₅ (diesel) range; this group of methyl ketones includes 2-undecanone and 2-tridecanone, which are of importance to the flavor and fragrance industry and also have favorable cetane numbers (as we report here). We describe specific improvements that resulted in a 700-fold enhancement in methyl ketone titer relative to that of a fatty acid-overproducing E. coli strain, including the following: (i) overproduction of β-ketoacyl coenzyme A (CoA) thioesters achieved by modification of the β-oxidation pathway (specifically, overexpression of a heterologous acyl-CoA oxidase and native FadB and chromosomal deletion of fadA) and (ii) overexpression of a native thioesterase (FadM). FadM was previously associated with oleic acid degradation, not methyl ketone synthesis, but outperformed a recently identified methyl ketone synthase (Solanum habrochaites MKS2 [ShMKS2], a thioesterase from wild tomato) in β-ketoacyl-CoA-overproducing strains tested. Whole-genome transcriptional (microarray) studies led to the discovery that FadM is a valuable catalyst for enhancing methyl ketone production. The use of a two-phase system with decane enhanced methyl ketone production by 4- to 7-fold in addition to increases from genetic modifications.

  17. Engineering of Bacterial Methyl Ketone Synthesis for Biofuels

    PubMed Central

    Goh, Ee-Been; Baidoo, Edward E. K.; Keasling, Jay D.

    2012-01-01

    We have engineered Escherichia coli to overproduce saturated and monounsaturated aliphatic methyl ketones in the C11 to C15 (diesel) range; this group of methyl ketones includes 2-undecanone and 2-tridecanone, which are of importance to the flavor and fragrance industry and also have favorable cetane numbers (as we report here). We describe specific improvements that resulted in a 700-fold enhancement in methyl ketone titer relative to that of a fatty acid-overproducing E. coli strain, including the following: (i) overproduction of β-ketoacyl coenzyme A (CoA) thioesters achieved by modification of the β-oxidation pathway (specifically, overexpression of a heterologous acyl-CoA oxidase and native FadB and chromosomal deletion of fadA) and (ii) overexpression of a native thioesterase (FadM). FadM was previously associated with oleic acid degradation, not methyl ketone synthesis, but outperformed a recently identified methyl ketone synthase (Solanum habrochaites MKS2 [ShMKS2], a thioesterase from wild tomato) in β-ketoacyl-CoA-overproducing strains tested. Whole-genome transcriptional (microarray) studies led to the discovery that FadM is a valuable catalyst for enhancing methyl ketone production. The use of a two-phase system with decane enhanced methyl ketone production by 4- to 7-fold in addition to increases from genetic modifications. PMID:22038610

  18. Direct α-alkylation of ketones with alcohols in water.

    PubMed

    Xu, Guoqiang; Li, Qiong; Feng, Jiange; Liu, Qiang; Zhang, Zuojun; Wang, Xicheng; Zhang, Xiaoyun; Mu, Xindong

    2014-01-01

    The direct α-alkylation of ketones with alcohols has emerged as a new green protocol to construct C-C bonds with H2 O as the sole byproduct. In this work, a very simple and convenient Pd/C catalytic system for the direct α-alkylation of ketones with primary alcohols in pure water is developed. Based on this catalytic system, aqueous mixtures of dilute acetone, 1-butanol, and ethanol (mimicking ABE fermentation products) can be directly transformed into C5 -C11 or longer-chain ketones and alcohols, which are precursors to fuels. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Substrate-controlled Michael additions of chiral ketones to enones.

    PubMed

    Fàbregas, Mireia; Gómez-Palomino, Alejandro; Pellicena, Miquel; Reina, Daniel F; Romea, Pedro; Urpí, Fèlix; Font-Bardia, Mercè

    2014-12-05

    Substrate-controlled Michael additions of the titanium(IV) enolate of lactate-derived ketone 1 to acyclic α,β-unsaturated ketones in the presence of a Lewis acid (TiCl4 or SnCl4) provide the corresponding 2,4-anti-4,5-anti dicarbonyl compounds in good yields and excellent diastereomeric ratios. Likely, the nucleophilic species involved in such additions are bimetallic enolates that may add to enones through cyclic transition states. Finally, further studies indicate that a structurally related β-benzyloxy chiral ketone can also participate in such stereocontrolled conjugate additions.

  20. The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury.

    PubMed

    Prins, Mayumi L; Matsumoto, Joyce H

    2014-12-01

    The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone bodies are the only known natural alternative substrate to glucose for cerebral energy metabolism. While it has been demonstrated that other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the brain, ketones are the only endogenous fuel that can contribute significantly to cerebral metabolism. Preclinical studies employing both pre- and postinjury implementation of the ketogenic diet have demonstrated improved structural and functional outcome in traumatic brain injury (TBI) models, mild TBI/concussion models, and spinal cord injury. Further clinical studies are required to determine the optimal method to induce cerebral ketone metabolism in the postinjury brain, and to validate the neuroprotective benefits of ketogenic therapy in humans. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

  1. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease.

    PubMed

    Newport, Mary T; VanItallie, Theodore B; Kashiwaya, Yoshihiro; King, Michael Todd; Veech, Richard L

    2015-01-01

    Providing ketone bodies to the brain can bypass metabolic blocks to glucose utilization and improve function in energy-starved neurons. For this, plasma ketones must be elevated well above the ≤ 0.2 mM default concentrations normally prevalent. Limitations of dietary methods currently used to produce therapeutic hyperketonemia have stimulated the search for better approaches. Described herein is a new way to produce therapeutic hyperketonemia, entailing prolonged oral administration of a potent ketogenic agent--ketone monoester (KME)--to a patient with Alzheimer's disease dementia and a pretreatment Mini-Mental State Examination score of 12. The patient improved markedly in mood, affect, self-care, and cognitive and daily activity performance. The KME was well tolerated throughout the 20-month treatment period. Cognitive performance tracked plasma β-hydroxybutyrate concentrations, with noticeable improvements in conversation and interaction at the higher levels, compared with predose levels. KME-induced hyperketonemia is robust, convenient, and safe, and the ester can be taken as an oral supplement without changing the habitual diet. Published by Elsevier Inc.

  2. The collective therapeutic potential of cerebral ketone metabolism in traumatic brain injury

    PubMed Central

    Prins, Mayumi L.; Matsumoto, Joyce H.

    2014-01-01

    The postinjury period of glucose metabolic depression is accompanied by adenosine triphosphate decreases, increased flux of glucose through the pentose phosphate pathway, free radical production, activation of poly-ADP ribose polymerase via DNA damage, and inhibition of glyceraldehyde dehydrogenase (a key glycolytic enzyme) via depletion of the cytosolic NAD pool. Under these post-brain injury conditions of impaired glycolytic metabolism, glucose becomes a less favorable energy substrate. Ketone bodies are the only known natural alternative substrate to glucose for cerebral energy metabolism. While it has been demonstrated that other fuels (pyruvate, lactate, and acetyl-L-carnitine) can be metabolized by the brain, ketones are the only endogenous fuel that can contribute significantly to cerebral metabolism. Preclinical studies employing both pre- and postinjury implementation of the ketogenic diet have demonstrated improved structural and functional outcome in traumatic brain injury (TBI) models, mild TBI/concussion models, and spinal cord injury. Further clinical studies are required to determine the optimal method to induce cerebral ketone metabolism in the postinjury brain, and to validate the neuroprotective benefits of ketogenic therapy in humans. PMID:24721741

  3. Research in Energetic Compounds.

    DTIC Science & Technology

    1986-02-01

    2,2-dinitro-l,3- propanediol in base functioning as an in-situ source of dinitromethane, would give 3,3,5,5-tetrafluoro-4,4- dinitropimelic acid. The...3-chloro-3,3-difluoropropionate were also studied. However, 2,2-d initro- 1,3- propanediol (A-Diol) failed to give stable adducts, possibly because it...deformylated 2-fluoro-2-nitro- I ,3- propanediol reacted with 2-chloro-2,2-difluoroethyl isopropyl ketone to give the corresponding difunctional adduct 2,14

  4. Direct β-functionalization of cyclic ketones with aryl ketones via the merger of photoredox and organocatalysis.

    PubMed

    Petronijević, Filip R; Nappi, Manuel; MacMillan, David W C

    2013-12-11

    The direct β-coupling of cyclic ketones with aryl ketones has been achieved via the synergistic combination of photoredox catalysis and organocatalysis. Diaryl oxymethyl or aryl-alkyl oxymethyl radicals, transiently generated via single-electron reduction of ketone precursors, readily merge with β-enaminyl radical species, generated by photon-induced enamine oxidation, to produce γ-hydroxyketone adducts. Experimental evidence indicates that two discrete reaction pathways can be operable in this process depending upon the nature of the ketyl radical precursor and the photocatalyst.

  5. Direct β-Functionalization of Cyclic Ketones with Aryl Ketones via the Merger of Photoredox and Organocatalysis

    PubMed Central

    Petronijević, Filip R.; Nappi, Manuel

    2014-01-01

    The direct β-coupling of cyclic ketones with aryl ketones has been achieved via the synergistic combination of photoredox catalysis and organocatalysis. Diaryl oxymethyl or aryl–alkyl oxymethyl radicals, transiently generated via single-electron reduction of ketone precursors, readily merge with β-enaminyl radical species – generated by photon-induced enamine oxidation – to produce γ-hydroxyketone adducts. Experimental evidence indicates that two discrete reaction pathways can be operable in this process depending upon the nature of the ketyl radical precursor and the photocatalyst. PMID:24237366

  6. Asymmetric organocatalytic Michael addition of ketones to vinyl sulfone.

    PubMed

    Zhu, Qiang; Cheng, Lili; Lu, Yixin

    2008-12-21

    Highly enantioselective organocatalytic Michael addition of ketones to vinyl sulfone catalyzed by a cinchona alkaloid-derived primary amine is reported for the first time; the described synthetic methodology was applied to the synthesis of sodium cyclamate.

  7. Synthesis and Applications of Hajos-Parrish Ketone Isomers.

    PubMed

    Eagan, James M; Hori, Masahiro; Wu, Jianbin; Kanyiva, Kyalo Stephen; Snyder, Scott A

    2015-06-26

    Numerous natural products possess ring systems and functionality for which Hajos-Parrish ketone isomers with a transposed methyl group (termed "iso-Hajos-Parrish ketones") would be of value. However, such building blocks have not been exploited to the same degree as the more typical Hajos-Parrish hydrindane. An efficient three-step synthesis of such materials was fueled by a simple method for the rapid preparation of highly functionalized cyclopentenones, several of which are new chemical entities that would be challenging to access through other approaches. Furthermore, one iso-Hajos-Parrish ketone was converted into two distinct natural product analogues and one natural product. As one indication of the value of these new building blocks, that latter target was obtained in 10 steps, having previously been accessed in 18 steps using the Hajos-Parrish ketone. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Enantioselective rhodium(I)-catalyzed hydrogenation of trifluoromethyl ketones.

    PubMed

    Kuroki, Y; Sakamaki, Y; Iseki, K

    2001-02-08

    [figure: see text] The asymmetric hydrogenation of trifluoromethyl ketones to yield chiral alpha-trifluoromethyl alcohols with enantiomeric excesses up to 98% was achieved in the presence of chiral rhodium-(amidephosphine-phosphinite) complexes.

  9. Bleaching of kraft plus using dioxiranes: Structural effect of ketones

    SciTech Connect

    Chen, J.; Wearing, J.T.

    1996-10-01

    Recent developments in totally chlorine-free (TCF) bleaching of kraft pulps have led to a new finding showing that dimethyldioxirane (DMD), formed by reaction of peroxymonosulphate with acetone, is a very effective and selective bleaching agent. Because of the high volatility of acetone, careful design and special equipment are needed for the DMD bleaching process in order to meet operational safety, health and emission control requirements. Other ketones are considered as alternatives to acetone for dioxirane bleaching; however, the use of alternative ketones exhibits different responses in bleaching compared to acetone. This paper examines the bleaching performance of a number of selected ketones in light of different chemical structures and properties of the ketones as well as bleaching variables.

  10. Inhibition of serine proteases by peptidyl fluoromethyl ketones

    SciTech Connect

    Imperiali, B.; Abeles, R.H.

    1986-07-01

    Peptidyl fluoromethyl ketones that are specific inhibitors of the serine proteases ..cap alpha..-chymotrypsin and porcine pancreatic elastase were synthesized. By analogy with the corresponding aldehydes it is assumed that the fluoromethyl ketones react with the ..gamma..-OH group of the active site serine to form a stable hemiacetal. /sup 19/F NMR studies of the chymotrypsin-bound trifluoromethyl ketone inhibitors Ac-Leu-ambo-Phe-CF/sub 3//sup 1/ and Ac-ambo-Phe-CF/sub 3/ clearly indicate that the carbonyl carbon is tetrahedral at the active site of the enzyme. The inhibitor is bound as either the stable hydrat or the hemiacetal, involving the active site serine. The effect of varying the number of amino acid residues in the peptidyl portion of the inhibitor and the number of fluorines in the fluoromethyl ketone moiety is examined. In the series of trifluoromethyl ketone elastase inhibitors, the lowering of K/sub i/ concomitant with the change from a dipeptide analogue to a tetrapeptide analogue correlates well with the variation in V/K for hydrolysis of the corresponding amide substrates. This trend is indicative of the inhibitors acting as transition-state analogues. In addition to chain length, the number of fluorine substituents also affects the K/sub i/. In the case of chymotrypsin, the K/sub i/ for Ac-Leu-ambo-Phe-CF/sub 3/ is 30-fold lower than that for Ac-Leu-ambo-Phe-CF/sub 2/H. With elastase this trend is not as profound. In all cases, however, the difluoro- and trifluoromethyl ketones are better inhibitors than the monofluoromethyl and nonfluorinated analogues. This improvement must be associated with both the degree of hydration of the fluoromethyl ketones and the significant effect that fluorine substitution has on lowering the first pK/sub a/ of the hemiacetal hydroxyl. The monofluoromethyl ketone inhibitor of chymotrypsin, Ac-Leu-ambo-Phe-CFH/sub 2/, is a weak competitive inhibitor.

  11. Cookoff of energetic materials

    SciTech Connect

    Baer, M.R.; Hobbs, M.L.; Gross, R.J.; Schmitt, R.G.

    1998-09-01

    An overview of cookoff modeling at Sandia National Laboratories is presented aimed at assessing the violence of reaction following cookoff of confined energetic materials. During cookoff, the response of energetic materials is known to involve coupled thermal/chemical/mechanical processes which induce thermal damage to the energetic material prior to the onset of ignition. These damaged states enhance shock sensitivity and lead to conditions favoring self-supported accelerated combustion. Thus, the level of violence depends on the competition between pressure buildup and stress release due to the loss of confinement. To model these complex processes, finite element-based analysis capabilities are being developed which can resolve coupled heat transfer with chemistry, quasi-static structural mechanics and dynamic response. Numerical simulations that assess the level of violence demonstrate the importance of determining material damage in pre- and post-ignition cookoff events.

  12. Nanostructured Energetic Materials

    DTIC Science & Technology

    2006-11-01

    for the nanoenergetic composites prepared using mesoporous Fe2O3 gel, nanoparticles of WO3, MoO3, Bi2O3 , and CuO mixed with Al-nanoparticles and...used in the energetic composite. For example, in the energetic reactions of the composites containing Fe2O3, WO3, MoO3, Bi2O3 , and CuO, combined...MA), WO3 (Aldrich, WI), MoO3 and Bi2O3 (Accumet Materials, NY) and nanoparticles of Al (avg. size 80 nm with 2 nm passivation layer from

  13. INTENSE ENERGETIC GAS DISCHARGE

    DOEpatents

    Luce, J.S.

    1960-03-01

    A method and apparatus for initiating and sustaining an energetic gas arc discharge are described. A hollow cathode and a hollow anode are provided. By regulating the rate of gas flow into the interior of the cathode, the arc discharge is caused to run from the inner surface of the cathode with the result that adequate space-charge neutralization is provided inside the cathode but not in the main arc volume. Thus, the gas fed to the cathode is substantially completely ionized before it leaves the cathode, with the result that an energetic arc discharge can be maintained at lower operating pressures.

  14. Regulated workplace ketones and their interference in the PFBHA method for aldehydes.

    PubMed

    Lin, Y W; Hee, S S

    2000-11-01

    Ketones are the major positive interferences for an aldehyde dynamic air sampler that consists of 200-mg 20 percent (w/w) O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) on Tenax TA contained in a Pyrex tube 7-mm OD, 5-mm ID, and 70-mm in length, that utilizes a personal battery-powered pump at 10-50 mL/min. The ketone O-oxime derivatives were synthesized to allow absolute quantitation of O-oximes formed during sampling. Wet spiking allowed ketone recoveries to be found. Ketone vapors of known concentrations were generated statically in Tedlar gas bags. The O-oximes were desorbed with hexane, and an aliquot injected for gas chromatographic analysis on a nonpolar capillary column with mass spectrometric or electron capture detection. Gas phase recoveries up to 200 ppm-hour loadings exceeded 75 percent at 25 degrees C for chloroacetone, cyclohexanone, diacetone alcohol, diethyl ketone, dipropyl ketone, ethyl butyl ketone, methyl amyl ketone, methyl butyl ketone, 2-methylcyclohexanone, methyl ethyl ketone, methyl isobutyl ketone, methyl isopropyl ketone, and methyl propyl ketone. The recoveries for acetophenone, 2-chloroacetophenone, and ethyl amyl ketone were lower than 75 percent, and were caused by steric hindrance. Sampling for both aldehydes and ketones is recommended at 10 mL/min for TLV concentrations.

  15. Rotational Spectroscopy of Methyl Vinyl Ketone

    NASA Astrophysics Data System (ADS)

    Zakharenko, Olena; Motiyenko, R. A.; Aviles Moreno, Juan-Ramon; Huet, T. R.

    2015-06-01

    Methyl vinyl ketone, MVK, along with previously studied by our team methacrolein, is a major oxidation product of isoprene, which is one of the primary contributors to annual global VOC emissions. In this talk we present the analysis of the rotational spectrum of MVK recorded at room temperature in the 50 -- 650 GHz region using the Lille spectrometer. The spectroscopic characterization of MVK ground state will be useful in the detailed analysis of high resolution infrared spectra. Our study is supported by high level quantum chemical calculations to model the structure of the two stable s-trans and s-cis conformers and to obtain the harmonic force field parameters, internal rotation barrier heights, and vibrational frequencies. In the Doppler-limited spectra the splittings due to the internal rotation of methyl group are resolved, therefore for analysis of this molecule we used the Rho-Axis-Method Hamiltonian and RAM36 code to fit the rotational transitions. At the present time the ground state of two conformers is analyzed. Also we intend to study some low lying excited states. The analysis is in progress and the latest results will be presented. Support from the French Laboratoire d'Excellence CaPPA (Chemical and Physical Properties of the Atmosphere) through contract ANR-10-LABX-0005 of the Programme d'Investissements d'Avenir is acknowledged.

  16. Additional vinyl ketones and their pyranyl ketones in gonyleptid harvestmen (Arachnida: Opiliones) suggest these metabolites are widespread in this family.

    PubMed

    Wouters, Felipe C; Rocha, Daniele F O; Gonçalves, Caroline C S; Machado, Glauco; Marsaioli, Anita J

    2013-09-27

    Four species of gonyleptid harvestmen, Acanthogonyleptes pulcher, Gonyleptes saprophilus (Gonyleptinae), Sodreana barbiellini, and Sodreana leprevosti (Sodreaninae), were examined by GC-MS and ¹³H NMR. All of these species release vinyl ketones, and three of them produce the corresponding pyranyl ketones, which are presumed hetero-Diels-Alder (HDA) dimers. The vinyl ketones 5-methyl-1-hexen-3-one, rac-4-methyl-1-hexen-3-one, and (S)-4-methyl-1-hexen-3-one were synthesized. Natural 4-methyl-1-hexen-3-one is present as a single stereoisomer and has the R-configuration. Vinyl ketone dimers (HDA dimers) were also observed in the scent gland exudate and characterized by HRMS, ¹³C NMR, and ¹H NMR chemical shifts of the pyranyl moiety.

  17. ESR, electrochemical and cyclodextrin-inclusion studies of triazolopyridyl pyridyl ketones and dipyridyl ketones derivatives.

    PubMed

    Olea-Azar, C; Abarca, B; Norambuena, E; Opazo, L; Jullian, C; Valencia, S; Ballesteros, R; Chadlaoui, M

    2008-11-15

    The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic reduction of triazolopyridyl pyridyl ketones and dipyridyl ketones derivatives were measured in dimethylsulfoxide (DMSO). The hyperfine patterns indicate that the spin density delocalization is dependent of the rings presented in the molecule. The electrochemistry of these compounds was characterized using cyclic voltammetry, in DMSO as solvent. When one carbonyl is present in the molecule one step in the reduction mechanism was observed while two carbonyl are present two steps were detected. The first wave was assigned to the generation of the correspondent free radical species, and the second wave was assigned to the dianion derivatives. The phase-solubility measurements indicated an interaction between molecules selected and cyclodextrins in water. These inclusion complexes are 1:1 with betaCD, and HP-betaCD. The values of Ks showed a different kind of complexes depending on which rings are included. AM1 and DFT calculations were performed to obtain the optimized geometries, theoretical hyperfine constants, and spin distributions, respectively. The theoretical results are in complete agreement with the experimental ones.

  18. Benchtop Energetics Progress

    NASA Astrophysics Data System (ADS)

    Fajardo, Mario

    2011-06-01

    We have constructed an apparatus for investigating the reactive chemical dynamics of mg-scale energetic materials samples. We seek to advance the understanding of the reaction kinetics of energetic materials, and of the chemical influences on energetic materials sensitivity. We employ direct laser irradiation, and indirect laser-driven shock, techniques to initiate thin-film explosive samples contained in a high-vacuum chamber. Expansion of the reacting flow into vacuum quenches the chemistry and preserves reaction intermediates for interrogation via time-of-flight mass spectrometry (TOFMS). By rastering the sample coupon through the fixed laser beam focus, we generate hundreds of repetitive energetic events in a few minutes. A detonation wave passing through an organic explosive, such as pentaerythritol tetranitrate (PETN, C5H4N4O12) , is remarkably efficient in converting the solid explosive into final thermodynamically-stable gaseous products (e . g . N2, CO2, H2O...). Termination of a detonation at an explosive-to-vacuum interface produces an expanding pulse of hyperthermal molecular species, with leading-edge velocities ~10 km/s. In contrast, deflagration (subsonic combustion) of PETN in vacuum produces mostly reaction intermediates, such as NO and NO2, with much slower molecular velocities; consistent with expansion-quenched thermal decomposition of PETN. We propose to exploit these differences in product chemical identities and molecular species velocities to provide a chemically-based diagnostic for distinguishing between detonation and deflagration events. In this talk we also report recent progress towards the quantitative detection of hyperthermal neutral species produced by direct laser ablation of aluminum metal and of organic energetic materials, as a step towards demonstrating the ability to discriminate slow reaction intermediates from fast thermodynamically-stable final products. Work done in collaboration with Emily Fossum, Christopher Molek, and

  19. The partitioning of ketones between the gas and aqueous phases

    NASA Astrophysics Data System (ADS)

    Betterton, Eric A.

    Most ketones are not significantly hydrated; they therefore retain their chromophore and they could be photolytically degraded in solution yielding a variety of products including carboxylic acids, aldehydes and radicals. It is difficult to accurately model the partitioning of ketones between the gas phase and aqueous phase because of the lack suitable estimates of the Henry's Law constants; consequently the fate and environmental effects of ketones cannot be confidently predicted. Here we report the experimental determination of the Henry's Law constants of a series of ketones that has yielded a simple straight line equation to predict the Henry's Law constants of simple aliphatic ketones: log H ∗ =0.23Σσ ∗ + 1.51; where H ∗ is the effective Henry's Law constant (M atm -1, and Σσ ∗ is the Taft polar substituents constants. The results for 25°C are (M atm -1) CH 3COCH 3, 32; C 6H 5COCH 3, 110; CH 2ClCOCH 3, 59; CH 3COCOCH 3, 74; CF 3COCH 3, 138. Acetophenone appears to have an abnormally high H ∗. Most low molecular weight aliphatic ketones are predicted to characterized by H ∗⩾30 M atm -1 and therefore they are expected to be found in the aqueous phase at concentrations of ⩾5 - 0.5 μM (given a typical gas-phase concentration range of 1-10 ppbv). The expected rate of decomposition of ketones due to photolysis in hydrometers is briefly discussed.

  20. Mitochondrial Energetics and Therapeutics

    PubMed Central

    Wallace, Douglas C.; Fan, Weiwei; Procaccio, Vincent

    2011-01-01

    Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems approach, which, ironically, was first successfully applied over 80 years ago with the introduction of the ketogenic diet, is required. Analysis of the many ways that a shift from carbohydrate glycolytic metabolism to fatty acid and ketone oxidative metabolism may modulate metabolism, signal transduction pathways, and the epigenome gives us an appreciation of the ketogenic diet and the potential for bioenergetic therapeutics. PMID:20078222

  1. Stereoselective Reduction of Prochiral Ketones by Plant and Microbial Biocatalysts

    PubMed Central

    Javidnia, K.; Faghih-Mirzaei, E.; Miri, R.; Attarroshan, M.; Zomorodian, K.

    2016-01-01

    Chiral alcohols are the key chiral building blocks to many enantiomerically pure pharmaceuticals. The biocatalytic approach in asymmetric reduction of corresponding prochiral ketones to the preparation of these optically pure substances is one of the most promising routes. The stereoselective reduction of different kinds of prochiral ketones catalyzed by various plants and microorganisms was studied in this work. Benzyl acetoacetate, methyl 3-oxopentanoate, ethyl 3-oxopentanoate, and ethyl butyryl acetate were chosen as the model substrates for β-ketoesters. Benzoyl acetonitrile, 3-chloro propiophenone, and 1-acetyl naphthalene were chosen as aromatic aliphatic ketones. Finally, 2-methyl benzophenone and 4-chloro benzophenone were selected as diaryl ketones. Plant catalysis was conducted by Daucus carota, Brassica rapa, Brassica oleracea, Pastinaca sativa, and Raphnus sativus. For microbial catalysis, Aspergillus foetidus, Penicillum citrinum, Saccharomyces carlbergensis, Pichia fermentans, and Rhodotrula glutinis were chosen. Chiral alcohols were obtained in high yields and with optical purity. A superiority in the microorganisms' performance in the bioreduction of prochiral ketones was detected. Among microorganisms, Rhodotrula glutinis showed remarkable results with nearly all substrates and is proposed for future studies. PMID:27168684

  2. Ketone measurements using dipstick methodology in cats with diabetes mellitus.

    PubMed

    Zeugswetter, F; Pagitz, M

    2009-01-01

    To compare the results of urine and plasma ketone dip test in a group of diabetic cats with possible ketosis or ketoacidosis, using laboratory plasma beta-hydroxybutyrate measurements as the gold standard. According to clinical examinations, plasma beta-hydroxybutyrate measurements and venous blood gas analysis, 54 cats with diabetes mellitus were classified as non-ketotic (n=3), ketotic (n=40) or ketoacidotic (n=11). Plasma and urine acetoacetate concentrations were determined using urine reagent strips. Although there was a significant positive correlation between blood and urine ketone measurements (r=0.695, P<0.001), the results differed significantly (Z=-3.494, P<0.001). Using the differential positive rates, the best cut-off value to detect cats with ketoacidosis was 1.5 mmol/l for urine and 4 mmol/l for plasma. The sensitivity/specificity was 82/95 per cent for urine and 100/88 per cent for plasma, respectively. The urine and plasma ketone dip tests have a different diagnostic accuracy, and results have to be interpreted differently. Because of its high sensitivity, the plasma ketone dip test performs better than the urine ketone dip test to identify cats with impending or established ketoacidosis.

  3. Solar flare energetics

    NASA Astrophysics Data System (ADS)

    Lin, R. P.

    A review is presented regarding the current knowledge of the energetics of solar flares. Recent observations by the Solar Maximum Mission and by balloon-borne instrumentation indicate that the flare hard X-ray emission arises from nonthermal bremsstrahlung - the collisions of fast electrons into a cold ambient medium (Ee much greater than kT). Under this interpretation, most of the energy released for many flares is initially contained in the energetic electrons. These electrons can produce most of the observed flare phenomena via interactions with the solar atmosphere. In large flares a shock wave may result from explosive heating of the solar atmosphere by these electrons. This shock wave can accelerate nuclei to relativistic energies. It is argued that recent SMM observations of fast gamma-ray bursts are consistent with this picture of shock acceleration of nuclei.

  4. Solar flare energetics

    NASA Technical Reports Server (NTRS)

    Lin, R. P.

    1982-01-01

    A review is presented regarding the current knowledge of the energetics of solar flares. Recent observations by the Solar Maximum Mission and by balloon-borne instrumentation indicate that the flare hard X-ray emission arises from nonthermal bremsstrahlung - the collisions of fast electrons into a cold ambient medium (Ee much greater than kT). Under this interpretation, most of the energy released for many flares is initially contained in the energetic electrons. These electrons can produce most of the observed flare phenomena via interactions with the solar atmosphere. In large flares a shock wave may result from explosive heating of the solar atmosphere by these electrons. This shock wave can accelerate nuclei to relativistic energies. It is argued that recent SMM observations of fast gamma-ray bursts are consistent with this picture of shock acceleration of nuclei.

  5. Energetic inequivalence in eusocial insect colonies

    PubMed Central

    DeLong, John P.

    2011-01-01

    The energetic equivalence rule states that population-level metabolic rate is independent of average body size. This rule has been both supported and refuted by allometric studies of abundance and individual metabolic rate, but no study, to my knowledge, has tested the rule with direct measurements of whole-population metabolic rate. Here, I find a positive scaling of whole-colony metabolic rate with body size for eusocial insects. Individual metabolic rates in these colonies scaled with body size more steeply than expected from laboratory studies on insects, while population size was independent of body size. Using consumer-resource models, I suggest that the colony-level metabolic rate scaling observed here may arise from a change in the scaling of individual metabolic rate resulting from a change in the body size dependence of mortality rates. PMID:21367781

  6. Synthesis of Energetic Materials.

    DTIC Science & Technology

    1986-03-31

    1 ) ................... 2 2 GPC of Polyformal of Decafluorodiol ( 2 ) .......................... 4 3 GPC of Polyformal of...turn: ( 1 ) synthesis of energetic monomers and polymers, and ( 2 ) synthesis of polycyclic and adamantoid nitramines. Both tasks were continuations of...preparation of 2,2,3,3,4,4-hexafluoropentane-l,lidiol polyformal (FPF- 1 ) by the 2 step sequence shown below was reported. " HOCH2 (CF2 )3CH20H + (CH20) 3

  7. Free Volume in Glassy Poly(arylene Ether Ketone)s

    NASA Technical Reports Server (NTRS)

    Hinkley, J. A.; Eftekhari, A.; Crook, R. A.; Jensen, B. J.; Singh, J. J.

    1996-01-01

    Amorphous polyarylene ether ketones were examined in the glassy state by positron annihilation lifetime spectroscopy ( PALS ) and in the melt by standard rheological techniques. Specimens were well-characterized fractions of two isomeric structures. PALS clearly shows that the polymer with meta linkages in its backbone contains larger voids (greater than 0.25 nm radius). Thus despite their similar bulk densities, the two materials must pack very differently on a local scale. On the other hand, the free volumes inferred from the WLF treatment of melt viscosity data are practically identical in both materials ca. 4% at T(sub g). The comparison between techniques sheds some light on the distribution of free volume.

  8. Energetic component treatability study

    SciTech Connect

    Gildea, P.D.; Brandon, S.L.; Brown, B.G.

    1997-11-01

    The effectiveness of three environmentally sound processes for small energetic component disposal was examined experimentally in this study. The three destruction methods, batch reactor supercritical water oxidation, sodium hydroxide base hydrolysis and calcium carbonate cookoff were selected based on their potential for producing a clean solid residue and minimum release of toxic gases after component detonation. The explosive hazard was destroyed by all three processes. Batch supercritical water oxidation destroyed both the energetics and organics. Further development is desired to optimize process parameters. Sodium hydroxide base hydrolysis and calcium carbonate cookoff results indicated the potential for scrubbing gaseous detonation products. Further study and testing are needed to quantify the effectiveness of these later two processes for full-scale munition destruction. The preliminary experiments completed in this study have demonstrated the promise of these three processes as environmentally sound technologies for energetic component destruction. Continuation of these experimental programs is strongly recommended to optimize batch supercritical water oxidation processing, and to fully develop the sodium hydroxide base hydrolysis and calcium carbonate cookoff technologies.

  9. Pd-catalyzed enantioselective intramolecular α-arylation of α-substituted cyclic ketones: facile synthesis of functionalized chiral spirobicycles.

    PubMed

    Fan, Lulu; Takizawa, Shinobu; Takeuchi, Yoshiki; Takenaka, Kazuhiro; Sasai, Hiroaki

    2015-05-07

    Catalytic synthesis of chiral spirocyclic ketones was accomplished via the Pd-catalyzed intramolecular α-arylation of α-substituted cyclic ketones. The obtained spirocyclic ketone could be converted into a bifunctional organocatalyst.

  10. Mammalian energetics. Instantaneous energetics of puma kills reveal advantage of felid sneak attacks.

    PubMed

    Williams, Terrie M; Wolfe, Lisa; Davis, Tracy; Kendall, Traci; Richter, Beau; Wang, Yiwei; Bryce, Caleb; Elkaim, Gabriel Hugh; Wilmers, Christopher C

    2014-10-03

    Pumas (Puma concolor) live in diverse, often rugged, complex habitats. The energy they expend for hunting must account for this complexity but is difficult to measure for this and other large, cryptic carnivores. We developed and deployed a physiological SMART (species movement, acceleration, and radio tracking) collar that used accelerometry to continuously monitor energetics, movements, and behavior of free-ranging pumas. This felid species displayed marked individuality in predatory activities, ranging from low-cost sit-and-wait behaviors to constant movements with energetic costs averaging 2.3 times those predicted for running mammals. Pumas reduce these costs by remaining cryptic and precisely matching maximum pouncing force (overall dynamic body acceleration = 5.3 to 16.1g) to prey size. Such instantaneous energetics help to explain why most felids stalk and pounce, and their analysis represents a powerful approach for accurately forecasting resource demands required for survival by large, mobile predators.

  11. Synthesis and Applications of iso-Hajos–Parrish Ketones**

    PubMed Central

    Eagan, James M.; Hori, Masahiro; Wu, Jianbin; Kanyiva, Kyalo Stephen; Snyder, Scott A.

    2015-01-01

    Although numerous natural products possess ring systems and functionality for which “iso-Hajos–Parrish” ketones would be of value, such building blocks have not been exploited to the same degree as the more typical Hajos–Parrish hydrindane. Herein we outline an efficient three-step synthesis of such materials fueled by a simple method for the rapid preparation of highly functionalized cyclopentenones, several of which are new chemical entities that would be challenging to access through other approaches. We then show how one iso-Hajos–Parrish ketone can be converted into two distinct natural product analogs as well as one natural product. As one indication of the value of these new building blocks, that latter target was obtained in 10 steps, having previously been accessed in 18 steps using the Hajos–Parrish ketone. PMID:25974879

  12. Point-of-Care Glucose and Ketone Monitoring.

    PubMed

    Chong, Siew Kim; Reineke, Erica L

    2016-03-01

    Early and rapid identification of hypo- and hyperglycemia as well as ketosis is essential for the practicing veterinarian as these conditions can be life threatening and require emergent treatment. Point-of-care testing for both glucose and ketone is available for clinical use and it is important for the veterinarian to understand the limitations and potential sources of error with these tests. This article discusses the devices used to monitor blood glucose including portable blood glucose meters, point-of-care blood gas analyzers and continuous glucose monitoring systems. Ketone monitoring options discussed include the nitroprusside reagent test strips and the 3-β-hydroxybutyrate ketone meter. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A practical catalytic asymmetric addition of alkyl groups to ketones.

    PubMed

    García, Celina; LaRochelle, Lynne K; Walsh, Patrick J

    2002-09-18

    Many catalysts will promote the asymmetric addition of alkylzinc reagents to aldehydes. In contrast, there are no reports of additions to ketones that are both general and highly enantioselective. We describe herein a practical catalytic asymmetric addition of ethyl groups to ketones. The catalyst is derived from reaction of camphor sulfonyl chloride and trans-1,2-diaminocyclohexane. The resulting diketone is reduced with NaBH4 to give the C2-symmetric exo diastereomer. Use of this ligand with titanium tetraisopropoxide and dialkylzinc at room temperature results in enantioselective addition of the alkyl group to the ketone. The resulting tertiary alcohols are isolated with high enantiomeric excess (all cases give greater than 87% ee, except one). The reaction has been run with 37 mmol (5 g) 3-methylacetophenone and 2 mol % catalyst to afford 73% yield of the resulting tertiary alcohol with 99% ee.

  14. Modified nanocrystal cellulose/fluorene-containing sulfonated poly(ether ether ketone ketone) composites for proton exchange membranes

    NASA Astrophysics Data System (ADS)

    Wei, Yingcong; Shang, Yabei; Ni, Chuangjiang; Zhang, Hanyu; Li, Xiaobai; Liu, Baijun; Men, Yongfeng; Zhang, Mingyao; Hu, Wei

    2017-09-01

    Highly sulfonated poly(ether ether ketone ketone)s (SFPEEKKs) with sulfonation degrees of 2.34 (SFPEEKK5) and 2.48 (SFPEEKK10) were synthesized through the direct sulfonation of a fluorene-containing poly(ether ether ketone ketone) under a relatively mild reaction condition. Using the solution blending method, sulfonated nanocrystal cellulose (sNCC)-enhanced SFPEEKK composites (SFPEEKK/sNCC) were successfully prepared for investigation as proton exchange membranes. Transmission electron microscopy showed that sNCC was uniformly distributed in the composite membranes. The properties of the composite membranes, including thermal stability, mechanical properties, water uptake, swelling ratio, oxidative stability and proton conductivity were thoroughly evaluated. Results indicated that the insertion of sNCC could contribute to water management and improve the mechanical performance of the membranes. Notably, the proton conductivity of SFPEEKK5/sNCC-5 was as high as 0.242 S cm-1 at 80 °C. All data proved the potential of SFPEEKK/sNCC composites for proton exchange membranes in medium-temperature fuel cells.

  15. METHYL KETONE METABOLISM IN HYDROCARBON-UTILIZING MYCOBACTERIA

    PubMed Central

    Lukins, H. B.; Foster, J. W.

    1963-01-01

    Lukins, H. B. (University of Texas, Austin) and J. W. Foster. Methyl ketone metabolism in hydrocarbon-utilizing mycobacteria. J. Bacteriol. 85: 1074–1087. 1963.—Species of Mycobacterium especially M. smegmatis 422, produced the homologous methyl ketones during the oxidation of propane, n-butane, n-pentane, or n-hexane. A carrier-trapping experiment demonstrated the formation of 2-undecanone, as well as 1,11-undecanedioic acid, during the oxidation of undecane-1-C14. Aliphatic alkane-utilizing mycobacteria were able to grow at the expense of several aliphatic methyl ketones as sole sources of carbon. Other ketones which did not support growth were oxidized by resting bacterial suspensions. M. smegmatis 422 cells grown on propane or acetone were simultaneously adapted to oxidize both substrates, as well as n-propanol. n-Propanol cells were unadapted to propane or acetone. Acetone produced from propane in a medium enriched in D2O contained a negligible quantity of D, presumably eliminating propylene as an intermediate in the oxidation. Cells grown at the expense of alkanes or methyl ketones in the presence of O218 had a higher content of O18 than did cells grown on terminally oxidized compounds, e.g., primary alcohols or fatty acids. An oxygenase reaction is postulated for the attack on methyl ketones. Acetol was isolated and characterized as an oxidation product of acetone by M. smegmatis 422. Acetol-grown cells had a higher O18 content than did n-propanol cells, and its utilization appears to involve at least one oxygenase reaction. Acetol produced from acetone in the presence of O218 was not enriched in the isotope, indicating the occurrence of exchange reactions or of oxygenation reactions at a later stage in the assimilation of acetone and acetol. PMID:14043998

  16. Energetic cost of walking in fossil hominins.

    PubMed

    Vidal-Cordasco, M; Mateos, A; Zorrilla-Revilla, G; Prado-Nóvoa, O; Rodríguez, J

    2017-08-19

    Many biomechanical studies consistently show that a broader pelvis increases the reaction forces and bending moments across the femoral shaft, increasing the energetic costs of unloaded locomotion. However, a biomechanical model does not provide the real amount of metabolic energy expended in walking. The aim of this study is to test the influence of pelvis breadth on locomotion cost and to evaluate the locomotion efficiency of extinct Pleistocene hominins. The current study measures in vivo the influence of pelvis width on the caloric cost of locomotion, integrating anthropometry, body composition and indirect calorimetry protocols in a sample of 46 subjects of both sexes. We show that a broader false pelvis is substantially more efficient for locomotion than a narrower one and that the influence of false pelvis width on the energetic cost is similar to the influence of leg length. Two models integrating body mass, femur length and bi-iliac breadth are used to estimate the net and gross energetic costs of locomotion in a number of extinct hominins. The results presented here show that the locomotion of Homo was not energetically more efficient than that of Australopithecus and that the locomotion of extinct Homo species was not less efficient than that of modern Homo sapiens. The changes in the anatomy of the pelvis and lower limb observed with the appearance of Homo ergaster probably did not fully offset the increased expenditure resulting from a larger body mass. Moreover, the narrow pelvis in modern humans does not contribute to greater efficiency of locomotion. © 2017 Wiley Periodicals, Inc.

  17. Copper-catalyzed synthesis of α-trifluoromethylthio-substituted ketones.

    PubMed

    Huang, Yangjie; He, Xing; Lin, Xiaoxi; Rong, Mingguang; Weng, Zhiqiang

    2014-06-20

    The CF3S-substituted moiety serves as an important structural element in many bioactive molecules. A versatile copper catalyst that allowed for trifluoromethylthiolation of primary and secondary α-bromoketones is described. The reaction with readily available elemental sulfur and CF3SiMe3 afforded a broad scope and moderate to good yields of α-trifluoromethylthio-substituted ketones. This procedure represents a very operationally simple yet powerful strategy for the synthesis of α-trifluoromethylthio-substituted ketones, a useful and versatile class of synthetic synthons.

  18. Chromium(II)-catalyzed enantioselective arylation of ketones

    PubMed Central

    Wang, Gang; Sun, Shutao; Mao, Ying; Xie, Zhiyu

    2016-01-01

    The chromium-catalyzed enantioselective addition of carbo halides to carbonyl compounds is an important transformation in organic synthesis. However, the corresponding catalytic enantioselective arylation of ketones has not been reported to date. Herein, we report the first Cr-catalyzed enantioselective addition of aryl halides to both arylaliphatic and aliphatic ketones with high enantioselectivity in an intramolecular version, providing facile access to enantiopure tetrahydronaphthalen-1-ols and 2,3-dihydro-1H-inden-1-ols containing a tertiary alcohol. PMID:28144349

  19. Enantioselective Organocatalytic α-Fluorination of Cyclic Ketones

    PubMed Central

    Kwiatkowski, Piotr; Beeson, Teresa D.; Conrad, Jay C.

    2011-01-01

    The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides diastereo-, regio- and chemoselective catalyst control in fluorinations involving complex carbonyl systems. PMID:21247133

  20. Catalytic Intramolecular Ketone Alkylation with Olefins by Dual Activation.

    PubMed

    Lim, Hee Nam; Dong, Guangbin

    2015-12-07

    Two complementary methods for catalytic intramolecular ketone alkylation reactions with unactivated olefins, resulting in Conia-ene-type reactions, are reported. The transformations are enabled by dual activation of both the ketone and the olefin and are atom-economical as stoichiometric oxidants or reductants are not required. Assisted by Kool's aniline catalyst, the reaction conditions can be both pH- and redox-neutral. A broad range of functional groups are thus tolerated. Whereas the rhodium catalysts are effective for the formation of five-membered rings, a ruthenium-based system that affords the six-membered ring products was also developed.

  1. Induced axial chirality in biocatalytic asymmetric ketone reduction.

    PubMed

    Agudo, Rubén; Roiban, Gheorghe-Doru; Reetz, Manfred T

    2013-02-06

    Catalytic asymmetric reduction of prochiral ketones of type 4-alkylidene cyclohexanone with formation of the corresponding axially chiral R-configurated alcohols (up to 99% ee) was achieved using alcohol dehydrogenases, whereas chiral transition-metal catalysts fail. Reversal of enantioselectivity proved to be possible by directed evolution based on saturation mutagenesis (up to 98% ee (S)). Utilization of ketone with a vinyl bromide moiety allows respective R- and S-alcohols to be exploited as key compounds in Pd-catalyzed cascade reactions.

  2. Rhodium Catalyzed Intramolecular C-H Insertion of α-Aryl-α-diazo Ketones

    PubMed Central

    Taber, Douglass F.; Tian, Weiwei

    2011-01-01

    Direct diazo transfer proceeds smoothly with α-aryl ketones. The derived α-aryl-α-diazo ketones cyclize efficiently with Rh catalysis to give the corresponding α-aryl cyclopentanones. PMID:17385917

  3. Synthesis of Macrocyclic Ketones through Catalyst-Free Electrophilic Halogen-Mediated Semipinacol Rearrangement: Application to the Total Synthesis of (±)-Muscone.

    PubMed

    Liu, Yi; Yeung, Ying-Yeung

    2017-03-17

    A series of macrocycles were successfully prepared using electrophilic halogen-mediated semipinacol rearrangement under mild conditions. Although the expansion from small ring to medium ring is an energetically unfavorable process, the electrophilic halogenation was found to be powerful enough to override such an energy barrier. The rearranged products could further undergo Dowd-Beckwith rearrangement to give the corresponding one-carbon ring-expanded ketones. This approach has been applied to the total synthesis of the natural product (±)-muscone, which is widely used in modern perfumery and medicines, in a two-step sequence.

  4. Chemoselective synthesis of highly substituted 1,2-allenyl ketones, furans, and 2-alkynyl ketones from reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and electrophiles.

    PubMed

    Xu, Jianfeng; Zhu, Shugao; Wu, Luling; Huang, Xian

    2012-05-14

    A homo-Michael addition reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and the subsequent reaction with electrophiles such as PhSeBr, NFSI and NCS is reported. Based on the nature of electrophiles, this reaction may afford highly substituted 1,2-allenyl ketones or furans (E(+) = PhSe(+)) and 2-alkynyl ketones (E(+) = F(+), Cl(+), active halides) as the final products, respectively.

  5. Catalytic Asymmetric Methallylation of Ketones with an (H8-BINOLate)Ti-Based Catalyst

    PubMed Central

    Kim, Jeung Gon; Camp, Elizabeth H.; Walsh, Patrick J.

    2008-01-01

    The first catalytic asymmetric methallylation of ketones is reported. The catalyst, which is generated from titanium tetraisopropoxide, H8-BINOL, isopropanol, and tetramethallylstannane, reacts with ketones in acetonitrile to afford tertiary homoallylic alcohols in fair to excellent yields (55-99%) and fair to high enantioselectivities (46-90%). Ozonolysis of the resulting products provides access to chiral β-hydroxy ketones, which are not readily prepared from direct asymmetric aldol reaction of acetone with ketones. PMID:16986913

  6. Diene-ligated iridium catalyst for allylation reactions of ketones and imines.

    PubMed

    Barker, Timothy J; Jarvo, Elizabeth R

    2009-03-05

    [Ir(cod)Cl](2) is a highly reactive catalyst for allylation reactions of ketones using allylboronic ester. Mechanistic experiments are consistent with formation of a nucleophilic allyliridium(I) complex that is activated by the diene ligand toward attack of a ketone. Aryl and alkyl ketones react smoothly at room temperature. Aldimines also undergo allylation under these reaction conditions, requiring increased reaction times relative to the corresponding ketones.

  7. Tandem Aldol Condensation – Platinacycle-Catalyzed Addition Reactions of Aldehydes, Methyl Ketones and Arylboronic Acids

    PubMed Central

    Liao, Yuan-Xi; Hu, Qiao-Sheng

    2013-01-01

    Tandem aldol condensation of aldehydes with methyl ketones followed by anionic four-electron donor-based (Type I) platinacycle-catalyzed addition reactions of arylboronic acids to form β-arylated ketones is described. Good to excellent yields of β-arylated ketones were obtained for the tandem reactions of aromatic/aliphatic aldehydes, methyl ketones and arylboronic acids, and moderate yields were observed for the tandem reaction with α, β-unsaturated aldehydes as the aldehyde source. PMID:23335856

  8. Tandem Aldol Condensation - Platinacycle-Catalyzed Addition Reactions of Aldehydes, Methyl Ketones and Arylboronic Acids.

    PubMed

    Liao, Yuan-Xi; Hu, Qiao-Sheng

    2012-10-01

    Tandem aldol condensation of aldehydes with methyl ketones followed by anionic four-electron donor-based (Type I) platinacycle-catalyzed addition reactions of arylboronic acids to form β-arylated ketones is described. Good to excellent yields of β-arylated ketones were obtained for the tandem reactions of aromatic/aliphatic aldehydes, methyl ketones and arylboronic acids, and moderate yields were observed for the tandem reaction with α, β-unsaturated aldehydes as the aldehyde source.

  9. A One-Pot Synthesis of 2-Aminopyrimidines from Ketones, Arylacetylenes, and Guanidine.

    PubMed

    Schmidt, Elena Yu; Tatarinova, Inna V; Protsuk, Nadezhda I; Ushakov, Igor' A; Trofimov, Boris A

    2017-01-06

    The three-component reaction of ketones, arylacetylenes, and guanidine catalyzed by the KOBu(t)/DMSO system leads to 2-aminopyrimidines in up to 80% yield. Depending on structure of the starting ketones, the aromatization of intermediate dihydropyrimidines occurs either with loss of hydrogen molecules or methylbenzenes. The latter process takes place in the ketones, in which one of the substituents is not a methyl group. The reaction conditions are tolerable for dialkyl-, aryl(hetaryl) alkyl-, and cycloalkyl ketones.

  10. Nonadiabatic reaction of energetic molecules.

    PubMed

    Bhattacharya, Atanu; Guo, Yuanqing; Bernstein, Elliot R

    2010-12-21

    Energetic materials store a large amount of chemical energy that can be readily converted into mechanical energy via decomposition. A number of different ignition processes such as sparks, shocks, heat, or arcs can initiate the excited electronic state decomposition of energetic materials. Experiments have demonstrated the essential role of excited electronic state decomposition in the energy conversion process. A full understanding of the mechanisms for the decomposition of energetic materials from excited electronic states will require the investigation and analysis of the specific topography of the excited electronic potential energy surfaces (PESs) of these molecules. The crossing of multidimensional electronic PESs creates a funnel-like topography, known as conical intersections (CIs). CIs are well established as a controlling factor in the excited electronic state decomposition of polyatomic molecules. This Account summarizes our current understanding of the nonadiabatic unimolecular chemistry of energetic materials through CIs and presents the essential role of CIs in the determination of decomposition pathways of these energetic systems. Because of the involvement of more than one PES, a decomposition process involving CIs is an electronically nonadiabatic mechanism. Based on our experimental observations and theoretical calculations, we find that a nonadiabatic reaction through CIs dominates the initial decomposition process of energetic materials from excited electronic states. Although the nonadiabatic behavior of some polyatomic molecules has been well studied, the role of nonadiabatic reactions in the excited electronic state decomposition of energetic molecules has not been well investigated. We use both nanosecond energy-resolved and femtosecond time-resolved spectroscopic techniques to determine the decomposition mechanism and dynamics of energetic species experimentally. Subsequently, we employ multiconfigurational methodologies (such as, CASSCF

  11. Catalyst-free dehydrative α-alkylation of ketones with alcohols: green and selective autocatalyzed synthesis of alcohols and ketones.

    PubMed

    Xu, Qing; Chen, Jianhui; Tian, Haiwen; Yuan, Xueqin; Li, Shuangyan; Zhou, Chongkuan; Liu, Jianping

    2014-01-03

    Direct dehydrative α-alkylation reactions of ketones with alcohols are now realized under simple, practical, and green conditions without using external catalysts. These catalyst-free autocatalyzed alkylation methods can efficiently afford useful alkylated ketone or alcohol products in a one-pot manner and on a large scale by CC bond formation of the in situ generated intermediates with subsequent controllable and selective Meerwein-Pondorf-Verley-Oppenauer-type redox processes. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Energetic charged particle interactions at icy satellites

    NASA Astrophysics Data System (ADS)

    Nordheim, T.; Hand, K. P.; Paranicas, C.; Howett, C.; Hendrix, A. R.

    2016-12-01

    Satellites embedded within planetary magnetospheres are typically exposed to bombardment by charged particles, from thermal plasma to more energetic particles at radiation belt energies. At many planetary satellites, energetic charged particles are typically unimpeded by patchy atmospheres or induced satellite magnetic fields and instead are stopped in the surface itself. Most of these primaries have ranges in porous water ice that are at most centimeters, but some of their secondary photons, emitted during the deceleration process, can reach meter depths [Paranicas et al., 2002, 2004; Johnson et al., 2004]. Examples of radiation-induced surface alteration includes sputtering, radiolysis and grain sintering, processes that are capable of significantly altering the physical properties of surface material. Thus, accurate characterization of energetic charged particle weathering at icy satellites is crucial to a more comprehensive understanding of these bodies. At Saturn's inner mid-size moons remote sensing observations by several instruments onboard the Cassini spacecraft have revealed distinct weathering patterns which have been attributed to energetic electron bombardment of the surface [Howett et al., 2011, 2012, 2014; Schenk et al., 2011; Paranicas et al., 2014]. In the Jovian system, radiolytic production of oxidants has been invoked as a potential source of energy for life which may reside in the sub-surface ocean of its satellite Europa [Johnson et al., 2003; Hand et al., 2007; Vance et al., 2016]. Here we will discuss the near-surface energetic charged particle environment of icy satellites, with particular emphasis on comparative studies between the Saturnian and Jovian systems and interpretation of remote sensing observations by instruments onboard missions such as Cassini and Galileo. In addition, we will discuss implications for surface sampling by future lander missions (e.g. the proposed Europa lander now under study).

  13. Current energetic particle sensors

    NASA Astrophysics Data System (ADS)

    Fennell, J. F.; Blake, J. B.; Claudepierre, S.; Mazur, J.; Kanekal, S.; O'Brien, P.; Baker, D.; Crain, W.; Mabry, D.; Clemmons, J.

    2016-09-01

    Several energetic particle sensors designed to make measurements in the current decade are described and their technology and capabilities discussed and demonstrated. Most of these instruments are already on orbit or approaching launch. These include the Magnetic Electron Ion Spectrometers (MagEIS) and the Relativistic Electron Proton Telescope (REPT) that are flying on the Van Allen Probes, the Fly's Eye Electron Proton Spectrometers (FEEPS) flying on the Magnetospheric Multiscale (MMS) mission, and Dosimeters flying on the AC6 Cubesat mission. We focus mostly on the electron measurement capability of these sensors while providing summary comments of their ion measurement capabilities if they have any.

  14. 40 CFR 721.10413 - Fluorinated dialkyl ketone (generic) (P-10-135).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Fluorinated dialkyl ketone (generic... Specific Chemical Substances § 721.10413 Fluorinated dialkyl ketone (generic) (P-10-135). (a) Chemical... as fluorinated dialkyl ketone (PMN P-10-135) is subject to reporting under this section for the...

  15. 40 CFR 721.10417 - Biphenyl alkyl morpholino ketone (generic) (P-11-338).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Biphenyl alkyl morpholino ketone... Specific Chemical Substances § 721.10417 Biphenyl alkyl morpholino ketone (generic) (P-11-338). (a... generically as biphenyl alkyl morpholino ketone (PMN P-11-338) is subject to reporting under this section for...

  16. 40 CFR 721.10417 - Biphenyl alkyl morpholino ketone (generic) (P-11-338).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Biphenyl alkyl morpholino ketone... Specific Chemical Substances § 721.10417 Biphenyl alkyl morpholino ketone (generic) (P-11-338). (a... generically as biphenyl alkyl morpholino ketone (PMN P-11-338) is subject to reporting under this section for...

  17. 40 CFR 721.10413 - Fluorinated dialkyl ketone (generic) (P-10-135).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Fluorinated dialkyl ketone (generic... Specific Chemical Substances § 721.10413 Fluorinated dialkyl ketone (generic) (P-10-135). (a) Chemical... as fluorinated dialkyl ketone (PMN P-10-135) is subject to reporting under this section for the...

  18. 40 CFR 721.10413 - Fluorinated dialkyl ketone (generic) (P-10-135).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Fluorinated dialkyl ketone (generic... Specific Chemical Substances § 721.10413 Fluorinated dialkyl ketone (generic) (P-10-135). (a) Chemical... as fluorinated dialkyl ketone (PMN P-10-135) is subject to reporting under this section for the...

  19. Acyl hydrazides as acyl donors for the synthesis of diaryl and aryl alkyl ketones.

    PubMed

    Akhbar, Ahmed R; Chudasama, Vijay; Fitzmaurice, Richard J; Powell, Lyn; Caddick, Stephen

    2014-01-21

    In this communication we describe a novel strategy for the formation of valuable diaryl and aryl alkyl ketones from acyl hydrazides. A wide variety of ketones are prepared and the mild reaction conditions allow for the use of a range of functionalities, especially in the synthesis of diaryl ketones.

  20. 40 CFR 721.10417 - Biphenyl alkyl morpholino ketone (generic) (P-11-338).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Biphenyl alkyl morpholino ketone... Specific Chemical Substances § 721.10417 Biphenyl alkyl morpholino ketone (generic) (P-11-338). (a... generically as biphenyl alkyl morpholino ketone (PMN P-11-338) is subject to reporting under this section for...

  1. Diversity-oriented synthesis of chromenes via metal-free domino reactions from ketones and phenols.

    PubMed

    Xue, Wei-Jian; Li, Qi; Gao, Fang-fang; Zhu, Yan-ping; Wang, Jun-gang; Zhang, Wei; Wu, An-Xin

    2012-08-13

    Functionalized chromenes have been synthesized via highly selective metal-free domino reactions from ketones and phenols. 2H-Chromenes, 4H-chromenes, spiran and benzocyclopentane can be respectively prepared starting from the corresponding cyclic ketones, aryl methyl ketones, acetone, and 3-pentanone.

  2. Crystal morphology and phase identifications in poly(aryl ether ketones)s and their copolymers

    SciTech Connect

    Ho, R.M.; Cheng, S.Z.D.; Hsiao, B.S.

    1995-12-01

    A series of poly(aryl ether ketone ketone)s prepared from diphenyl ether (DPE) and terephthalic acid M or isophthalic acid (T) have been investigated. PEKK(T) has been reported to exhibit two polymorphism (form I and form II) based on wide angle X-ray diffraction (WAXD) and electron diffraction (ED) experiments.

  3. The energetic basis of acoustic communication.

    PubMed

    Gillooly, James F; Ophir, Alexander G

    2010-05-07

    Animals produce a tremendous diversity of sounds for communication to perform life's basic functions, from courtship and parental care to defence and foraging. Explaining this diversity in sound production is important for understanding the ecology, evolution and behaviour of species. Here, we present a theory of acoustic communication that shows that much of the heterogeneity in animal vocal signals can be explained based on the energetic constraints of sound production. The models presented here yield quantitative predictions on key features of acoustic signals, including the frequency, power and duration of signals. Predictions are supported with data from nearly 500 diverse species (e.g. insects, fishes, reptiles, amphibians, birds and mammals). These results indicate that, for all species, acoustic communication is primarily controlled by individual metabolism such that call features vary predictably with body size and temperature. These results also provide insights regarding the common energetic and neuromuscular constraints on sound production, and the ecological and evolutionary consequences of producing these sounds.

  4. 21 CFR 862.1435 - Ketones (nonquantitative) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ketones (nonquantitative) test system. 862.1435 Section 862.1435 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  5. Chiral Ketone and Iminium Catalysts for Olefin Epoxidation

    NASA Astrophysics Data System (ADS)

    Wong, O. Andrea; Shi, Yian

    Organo-catalyzed asymmetric epoxidation has received much attention in the past 30 years and significant progress has been made for various types of olefins. This review will cover the advancement made in the field of chiral ketone and chiral iminium salt-catalyzed epoxidations.

  6. Process for conversion of levulinic acid to ketones

    DOEpatents

    Dagle, Vanessa M.; Dagle, Robert A.

    2017-05-30

    A method for generating desired platform chemicals from feedstocks such as cellulosic biomass feedstocks containing levulinic acid by decarboxylating a feed stock comprising levulinic acid to generate ketones. This is done by passing a feed stock comprising levulinic acid in a gas phase over a non-precious metal catalyst on a neutral support.

  7. Organocatalytic enantioselective indole alkylations of alpha,beta-unsaturated ketones.

    PubMed

    Chen, Wei; Du, Wei; Yue, Lei; Li, Rui; Wu, Yong; Ding, Li-Sheng; Chen, Ying-Chun

    2007-03-07

    The C3-selective enantioselective Michael-type Friedel-Crafts alkylations of indoles with nonchelating alpha,beta-unsaturated alkyl ketones, catalysed by a chiral primary amine derived from natural cinchonine, were investigated. The reactions, in the presence of 30 mol% catalyst, were smoothly conducted at 0 to -20 degrees C. Moderate to good ee (47-89%) has been achieved.

  8. Multicentric evaluation of eight glucose and four ketone blood meters.

    PubMed

    Guimont, Marie-Christine; Desjobert, Hélène; Fonfrède, Michèle; Vitoux, Dominique; Benoist, Jean-Francois; Launay, Jean-Marie; Peoc'h, Katell; Lefèvre, Guillaume

    2015-12-01

    High precision meters for blood glycemia are mandatory for monitoring glucose status in patients, avoiding both hypo- and hyper-glycemia. Health care providers routinely used in both out- and in-patients point-of-care measurements of glucose and ketone. These measurements, frequently used for medical decisions, are known to be less accurate than those performed in laboratories. Our aim was to evaluate, within the frame of an Assistance Publique-Hôpitaux de Paris (AP-HP) multicentric study, the performances of eight glucose and four ketone meters, either connected or non-connected to a laboratory software. Glucose meter accuracy, precision, correlation with plasma glucose determined in central laboratories and hematocrit interferences were determined according to the ISO 15197:2003 norm. The same norm was applied for the determination of accuracy, precision and recovery of ketone meters for B-hydroxybutyrate measurements. Among those meters, seven were considered as acceptable for glucose measurement and two for ketone measurement. Since all meters do not fit clinically relevant criteria, meters' performances have to be evaluated before use in clinical practice. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  9. Photoreactivity of. cap alpha. -fluorinated phenyl alkyl ketones

    SciTech Connect

    Wagner, P.J.; Thomas, M.J.; Puchalski, A.E.

    1986-11-26

    The photoreactivities of the mono-, di-, and tri-..cap alpha..-fluorinated acetophenones have been compared to that of acetophenone itself. All four ketones have similar triplet excitation energies; the three fluorinated ketones have reduction potentials 0.5-0.7 eV lower than that of acetophenone. Triplet reactivity toward alkylbenzenes keeps increasing with fluorine substitution, since the rate-determining step becomes charge-transfer complexation as the ketone reduction potential decreases. The primary/tertiary C-H selectivity toward p-cymene increases with the number of fluorines. Triplet reactivity toward cyclopentane also is increased by fluorination but peaks at two fluorines, since the lowest triplet switches from n,..pi..* to ..pi..,..pi..* with two or three fluorines and ..pi..,..pi..* triplets are unreactive in simple hydrogen atom abstraction. In contrast, ..cap alpha..-fluorination of valerophenone does not significantly increase the rate of triplet ..gamma..-hydrogen abstraction. The inductive effect on reactivity apparently is offset by a conformational effect. The ..cap alpha..-fluorinated phenones give predominantly cyclobutanols instead of Norrish type II elimination. ..cap alpha..-Fluoroacetophenone forms predominantly acetophenone and HF when irradiated with 2-propanol, in what appears to be a short chain process involving electron transfer to ketone followed by fluoride ion loss. Finally, the radical coupling products in these reactions are formed in varying yields, depending on solvent and additives.

  10. Ketonization of Cuphea oil for the production of 2-undecanone

    USDA-ARS?s Scientific Manuscript database

    The objective of this work was to demonstrate the viability of the cross ketonization reaction with the triacylglycerol from Cuphea sp. and acetic acid in a fixed-bed plug-flow reactor. The seed oil from Cuphea sp. contains up to 71% decanoic acid and the reaction of this fatty acid residue with ac...

  11. Energetics of Nanomaterials

    SciTech Connect

    Alexandra Navrotsky; Brian Woodfield; Juliana Boerio-Goates; Frances Hellman

    2005-01-28

    This project, "Energetics of Nanomaterials," represents a three-year collaboration among Alexandra Navrotsky (UC Davis), Brian Woodfield and Juliana Boerio-Goates (BYU), and Frances Hellman (UC Berkeley). It's purpose has been to explore the differences between bulk materials, nanoparticles, and thin films in term of their thermodynamic properties, with an emphasis on heat capaacities and entropies, as well as enthalpies. the three groups have brought very different expertise and capabilities to the project. Navrotsky is a solid-state chemist and geochemist, with a unique Thermochemistry Facility emphasizing enthalpy of formation measurements by high temperature oxide melt and room temperatue acid solution calorimetry. Boerio-Goates and Woodfield are calorimetry. Hellman is a physicist with expertise in magnetism and heat capacity measurements using microscale "detector on a chip" calorimetric technology that she pioneered. The overarching question of our work is "How does the free energy play out in nanoparticles?", or "How do differences in free energy affect overall nanoparticle behavior?" Because the free energy represents the temperature-dependent balance between the enthalpy of a system and its entropy, there are two separate, but related, components to the experimental investigations: Solution calorimetric measurements provide the energetics and two types of heat capacity measurements the entropy. We use materials that are well characterized in other ways (structurally, magnetically, and chemically), and samples are shared across the collaboration.

  12. Dielectric behavior of some small ketones as ideal polar molecules.

    PubMed

    Shikata, Toshiyuki; Yoshida, Nao

    2012-05-17

    The dielectric behaviors of some small symmetric ketone molecules, including acetone, 3-pentanone, cyclopentanone, 4-heptanone, and cyclohexanone, were investigated as a function of temperature (T) over a wide frequency range from 50 MHz (3.14 × 10(8) s(-1), in angular frequency) to 3 THz (1.88 × 10(13) s(-1)). The temperature dependencies of the rotational diffusion times (τ(r)) determined using (17)O NMR spin-lattice relaxation time (T(1)) measurements and viscosities of the ketones were also examined. The obtained temperature dependencies of the parameters for the ketones were compared with those of ideal polar molecules, which obey the Stokes-Einstein-Debye (SED) relationship without the formation of intermolecular dimeric associations and without orientational correlations between dipoles (molecular axes), that is, free rotation. Kirkwood correlation factors (g(K)) of only acetone and 3-pentanone were close to unity over a wide temperature range, whereas those of other ketones were obviously less than unity. These results revealed that no correlations exist between the rotational motions of dipoles in acetone and 3-pentanone, as expected in ideal polar molecules. However, other ketones exhibited orientational correlations in their dipoles because of dipole-dipole interactions via antiparallel configurations. Furthermore, because acetone and 3-pentanone satisfied the SED relationship and because their microscopic dielectric relaxation times (τ(μ)), which were calculated from the determined dielectric relaxation times (τ(D)) via the relationship τ(μ) = τ(D)g(K)(-1), were identical to 3τ(r) and were proportional to Vη(k(B)T)(-1) over the wide temperature range examined, where V, k(B), and η represent the effective molecular volume, Boltzmann's constant, and the viscosity of the liquid molecules, respectively, these two ketone molecules behave as ideal polar molecules. In addition, other ketones not significantly larger than acetone and 3-pentanone in

  13. Studies on elimination pathways of β-halovinyl ketones leading to allenyl and propargyl ketones and furans under the action of mild bases.

    PubMed

    Kim, Hun Young; Li, Jian-Yuan; Oh, Kyungsoo

    2012-12-21

    The elimination pathway of stereochemically defined β-halovinyl ketones has been investigated using a mild base, NEt(3), leading to the formation of allenyl ketones and propargyl ketones. A preferential α-vinyl enolization of (E)-β-chlorovinyl ketones has been observed where a nonplanar s-cis conformation is proposed as a dominant conformation as opposed to a planar s-cis conformation of (Z)-β-chlorovinyl ketones. Other eliminative pathways, such as concerted syn- and anti-E2 as well as γ-deprotonation, are excluded on the basis of the deuterium isotope studies. The synthetic utility of the elimination reaction of β-chlorovinyl ketones was further demonstrated for a one-pot synthesis of 2,5-disubstituted furans in the presence of 1 mol % CuCl.

  14. Ultrafast Vibrational Spectroscopy of Inhomogeneous Energetic Materials and Energetic Interfaces

    DTIC Science & Technology

    2005-12-01

    nanocomposite energetic materials and fast mechanical processes at a molecular level. We are attacking these difficult problems using three parallel...not changed) The goal of this project remains the development of a fundamental understanding of nanocomposite energetic materials and fast mechanical...nanoparticle rocket propellants, we are thinking this type of mechanism might explain some anomalies observed in flame propagation of burning nanocomposites

  15. Regiodivergent halogenation of (E)-β-chlorovinyl ketones via soft α-vinyl enolization strategy.

    PubMed

    Kim, Hun Young; Lee, Seokwoo; Kim, Sanghee; Oh, Kyungsoo

    2015-02-06

    The soft α-vinyl enolization of (E)-β-chlorovinyl ketones was investigated in the presence of various halogen electrophiles. Depending on the nature of halogen electrophiles, the selective formation of three products, namely α,α-dichloropropargyl ketones, α,γ-dihaloallenyl ketones, and 3-halofurans, was observed. The observed regiodivergent nucleophilic pathways of (E)-β-chlorovinyl ketones demonstrate the diversity-oriented synthesis strategy in which the nucleophilic reactivity of (E)-β-chlorovinyl ketones can be selectively modulated by the choice of suitable hard and soft electrophiles.

  16. Spider monkeys (Ateles geoffroyi) are less sensitive to the odor of aliphatic ketones than to the odor of other classes of aliphatic compounds.

    PubMed

    Eliasson, Moa; Hernandez Salazar, Laura Teresa; Laska, Matthias

    2015-10-01

    Aliphatic ketones are widely present in body-borne and food odors of primates. Therefore, we used an operant conditioning paradigm and determined olfactory detection thresholds in four spider monkeys for a homologous series of aliphatic 2-ketones (2-butanone to 2-nonanone) and two of their isomers (3- and 4-heptanone). We found that, with the exception of the two shortest-chained ketones, all animals detected concentrations <1 ppm (parts per million), and with five odorants individual animals even reached threshold values <0.1 ppm. Further, we found a significant correlation between olfactory sensitivity of the spider monkeys and carbon chain length of the 2-ketones which can best be described as a U-shaped function. In contrast, no significant correlation was found between olfactory sensitivity and position of the functional carbonyl group. Across-odorant and across-species comparisons revealed the following: spider monkeys are significantly less sensitive to the odors of aliphatic ketones than to the odor of other classes of aliphatic compounds (1-alcohols, n-aldehydes, n-acetic esters, and n-carboxylic acids) sharing the same carbon length. Spider monkeys do not differ significantly in their olfactory sensitivity for aliphatic ketones from squirrel monkeys and pigtail macaques, but are significantly less sensitive to these odorants compared to human subjects and mice. These findings support the notion that neuroanatomical and genetic properties do not allow for reliable predictions with regard to a species' olfactory sensitivity. Further, we conclude that the frequency of occurrence of a class of odorants in a species' chemical environment does not allow for reliable predictions of the species' olfactory sensitivity.

  17. Molecular characterization of energetic materials

    NASA Astrophysics Data System (ADS)

    Saraf, Sanjeev R.

    2003-06-01

    Assessing hazards due to energetic or reactive chemicals is a challenging and complicated task and has received considerable attention from industry and regulatory bodies. Thermal analysis techniques, such as Differential Scanning Calorimeter (DSC), are commonly employed to evaluate reactivity hazards. A simple classification based on energy of reaction (-DeltaH), a thermodynamic parameter, and onset temperature (To), a kinetic parameter, is proposed with the aim of recognizing more hazardous compositions. The utility of other DSC parameter in predicting explosive properties is discussed. Calorimetric measurements to determine reactivity can be resource consuming, so computational methods to predict reactivity hazards present an attractive option. Molecular modeling techniques were employed to gain information at the molecular scale to predict calorimetric data. Molecular descriptors, calculated at density functional level of theory, were correlated with DSC data for mono nitro compounds applying Quantitative Structure Property Relationships (QSPR) and yielded reasonable predictions. Such correlations can be incorporated into a software program for a priori prediction of potential reactivity hazards. Estimations of potential hazards can greatly help to focus attention on more hazardous substances, such as hydroxylamine (HA), which was involved in two major industrial incidents in the past four years. A detailed discussion of HA investigation is presented.

  18. New energetic epoxy binders

    SciTech Connect

    Jain, S.R.; Amanulla, S.

    1996-07-01

    A new class of epoxy resins having N{single_bond}N bonds in the backbone has been synthesized with a view to explore their properties as energetic binders. The N-epoxidation of bis-dicarbonylhydrazones of adipic, azelaic and sebacic dihydrazides results in the formation of viscous resins having epoxide end groups. The resins have been characterized by the elemental and end group analyses, IR and NMR spectra. Relevant properties for their use as binders in solid propellants, such as thermal stability, heat of combustion, burn rate and performance parameters of AP-based propellant systems, have been evaluated. A significant increase in the burn rate of AP-based propellants noticed, is perhaps related to the exothermicity of the binder decomposition and the reactivity of N{single_bond}N bonds with perchloric acid formed during the combustion of AP.

  19. Energetics of Nanomaterials

    SciTech Connect

    Hellman, Frances

    2004-12-13

    This project, ''Energetics of Nanomaterials'', represents a three-year collaboration among Alexandra Navrotsky (University of California at Davis), Brian Woodfield and Juliana Boerio-Goates (Brigham Young University) and Frances Hellman (University of California at San Diego). Its purpose has been to explore the differences between bulk materials, nanoparticles, and thin films in terms of their thermodynamic properties, with an emphasis on heat capacities and entropies, as well as enthalpies. We used our combined experimental techniques to address the following questions: How does energy and entropy depend on particle size and crystal structure? Do entropic differences have their origins in changes in vibrational densities of states or configurational (including surface configuration) effects? Do material preparation and sample geometry, i.e., nanoparticles versus thin films, change these quantities? How do the thermodynamics of magnetic and structural transitions change in nanoparticles and thin films? Are different crystal structures stabilized for a given composition at the nanoscale, and are the responsible factors energetic, entropic, or both? How do adsorption energies (for water and other gases) depend on particle size and crystal structure in the nanoregime? What are the energetics of formation and strain energies in artificially layered thin films? Do the differing structures of grain boundaries in films and nanocomposites alter the energetics of nanoscale materials? Of the several directions we first proposed, we initially concentrated on a few systems: TiO(sub 2), CoO, and CoO-MgO. In these systems, we were able to clearly identify particle size-dependent effects on energy and vibrational entropy, and to separate out the effect of particle size and water content on the enthalpy of formation of the various TiO(sub 2) polymorphs. With CoO, we were able to directly compare nanoparticle films and bulk materials; this comparison is important because films can

  20. Utilization of FEP energetics

    NASA Technical Reports Server (NTRS)

    Frederking, T. H. K.; Abbassi, P.; Afifi, F.; Khandhar, P. K.; Ono, D. Y.; Chen, W. E. W.

    1987-01-01

    The research and development work on Fountain Effect Pump Systems (FEP systems) has been of interest in the competition between mechanical pumps for He II and FEP units. The latter do not have moving parts. In the course of the work, the energetics have been addressed using one part of a simple four-changes-of-state cycle. One option is the FEP ideal change of state at constant chemical potential (mu). The other option is the two-state sequence mu-P with a d mu=0 state change followed by an isobar. Questions of pump behavior, of flow rate response to temperature difference at the hot end, and related questions of thermodynamic cycle completion and heat transfer have been addressed. Porous media data obtained elucidate differences between vapor-liquid phase separation (VLPS) and Zero Net Mass Transfer (ZNMF).

  1. Energetic consequences of being a Homo erectus female.

    PubMed

    Aiello, Leslie C; Key, Cathy

    2002-01-01

    Body size is one of the most important characteristics of any animal because it affects a range of behavioral, ecological, and physiological traits including energy requirements, choice of food, reproductive strategies, predation risk, range size, and locomotor style. This article focuses on the implications of being large bodied for Homo erectus females, estimated to have been over 50% heavier than average australopithecine females. The energy requirements of these hominins are modeled using data on activity patterns, body mass, and life history from living primates. Particular attention is given to the inferred energetic costs of reproduction for Homo erectus females based on chimpanzee and human reproductive scheduling. Daily energy requirements during gestation and lactation would have been significantly higher for Homo erectus females, as would total energetic cost per offspring if the australopithecines and Homo erectus had similar reproductive schedules (gestation and lactation lengths and interbirth intervals). Shortening the interbirth interval could considerably reduce the costs per offspring to Homo erectus and have the added advantage of increasing reproductive output. The mother would, however, incur additional daily costs of caring for the dependent offspring. If Homo erectus females adopted this reproductive strategy, it would necessarily imply a revolution in the way in which females obtained and utilized energy to support their increased energetic requirements. This transformation is likely to have occurred on several levels involving cooperative economic division of labor, locomotor energetics, menopause, organ size, and other physiological mechanisms for reducing the energetic load on females.

  2. Low-temperature combustion chemistry of novel biofuels: resonance-stabilized QOOH in the oxidation of diethyl ketone.

    PubMed

    Scheer, Adam M; Welz, Oliver; Zádor, Judit; Osborn, David L; Taatjes, Craig A

    2014-07-14

    The Cl˙ initiated oxidation reactions of diethyl ketone (DEK; 3-pentanone; (CH3CH2)2C=O), 2,2,4,4-d4-diethyl ketone (d4-DEK; (CH3CD2)2C=O) and 1,1,1,5,5,5-d6-diethyl ketone (d6-DEK; (CD3CH2)2C=O) are studied at 8 Torr and 550-650 K using Cl2 as a source for the pulsed-photolytic generation of Cl˙. Products are monitored as a function of reaction time, mass, and photoionization energy using multiplexed photoionization mass spectrometry with tunable synchrotron radiation. Adding a large excess of O2 to the reacting flow allows determination of products resulting from oxidation of the initial primary (Rp) and secondary (Rs) radicals formed via the Cl˙ + DEK reaction. Because of resonance stabilization, the secondary DEK radical (3-oxopentan-2-yl) reaction with O2 has a shallow alkyl peroxy radical (RsO2) well and no energetically low-lying product channels. This leads to preferential back dissociation of RsO2 and a greater likelihood of consumption of Rs by competing radical-radical reactions. On the other hand, reaction of the primary DEK radical (3-oxopentan-1-yl) with O2 has several accessible bimolecular product channels. Vinyl ethyl ketone is observed from HO2-elimination from the DEK alkylperoxy radicals, and small-molecule products are identified from β-scission reactions and decomposition reactions of oxy radical secondary products. Although channels yielding OH + 3-, 4-, 5- and 6-membered ring cyclic ether products are possible in the oxidation of DEK, at the conditions of this study (8 Torr, 550-650 K) only the 5-membered ring, 2-methyltetrahydrofuran-3-one, is observed in significant quantities. Computation of relevant stationary points on the potential energy surfaces for the reactions of Rp and Rs with O2 indicates this cyclic ether is formed via a resonance-stabilized hydroperoxyalkyl radical (QOOH) intermediate, formed from isomerization of the RpO2 radical.

  3. Inhalation developmental toxicology studies: Teratology study of methyl ethyl ketone in mice: Final report

    SciTech Connect

    Mast, T.J.; Dill, J.A.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.; Westerberg, R.B.

    1989-02-01

    Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1) mice were exposed to 0, 400, 1000 or 3000 ppM MEK vapors, 7 h/day, 7 dy/wk. Ten virgin females and approx.30 plug-positive females per group were exposed concurrently for 10 consecutive days (6--15 dg for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 18 dg. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity, although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppM group. Mild developmental toxicity was evident at 3000-ppM as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes. 17 refs., 4 figs., 10 tabs.

  4. Electrical initiation of an energetic nanolaminate film

    DOEpatents

    Tringe, Joseph W.; Gash, Alexander E.; Barbee, Jr., Troy W.

    2010-03-30

    A heating apparatus comprising an energetic nanolaminate film that produces heat when initiated, a power source that provides an electric current, and a control that initiates the energetic nanolaminate film by directing the electric current to the energetic nanolaminate film and joule heating the energetic nanolaminate film to an initiation temperature. Also a method of heating comprising providing an energetic nanolaminate film that produces heat when initiated, and initiating the energetic nanolaminate film by directing an electric current to the energetic nanolaminate film and joule heating the energetic nanolaminate film to an initiation temperature.

  5. Photoreduction and ketone-sensitized reduction of alkaloids.

    PubMed

    Görner, Helmut; Miskolczy, Zsombor; Megyesi, Mónika; Biczók, László

    2011-01-01

    The photoprocesses of berberine, palmatine, coralyne, sanguinarine, flavopereirine and ellipticine were studied in several solvents. The quantum yields Φ(Δ) of singlet molecular oxygen formation of berberine, palmatine and sanguinarine are moderate in dichloromethane (0.2-0.6) and much smaller in acetonitrile or trifluoroethanol. For the other alkaloids examined, Φ(Δ) is rather independent of solvent polarity. The direct and ketone-sensitized photolysis, using steady-state irradiation at 313 nm or 248/308 nm laser pulses, was studied by absorption and fluorescence spectroscopy. Thereby, radicals were observed yielding eventually dihydro derivatives as major products, which are thermally back-converted on admission of oxygen. The quantum yield of conversion of alkaloids to dihydroalkaloids is enhanced in the presence of triethylamine. The reaction in the presence of ketones and electron or H-atom donors has a quantum yield of close to unity.

  6. A constitutive model of polyether-ether-ketone (PEEK).

    PubMed

    Chen, Fei; Ou, Hengan; Lu, Bin; Long, Hui

    2016-01-01

    A modified Johnson-Cook (JC) model was proposed to describe the flow behaviour of polyether-ether-ketone (PEEK) with the consideration of coupled effects of strain, strain rate and temperature. As compared to traditional JC model, the modified one has better ability to predict the flow behaviour at elevated temperature conditions. In particular, the yield stress was found to be inversely proportional to temperature from the predictions of the proposed model.

  7. Thiomethylation of ketones by sulphide-alkaline solutions and formaldehyde

    SciTech Connect

    Ulendeyeva, A.D.; Samigullin, I.I.; Nasteka, V.I.

    1993-12-31

    An investigation has been made of the thiomethylation of ketones by formaldehyde with mercaptides, sodium sulphide and their mixture. It is possible to regenerate 78-100 rel.% of the sulphide-alkaline solutions under mild conditions (20-50{degrees}C, atmospheric pressure) without feeding a catalyst, with the simultaneous production of ketosulphide concentrate - a less toxic product with properties of practical benefit. 7 refs., 2 figs., 2 tabs.

  8. Catalytic Leuckart-Wallach-type reductive amination of ketones.

    PubMed

    Kitamura, Masato; Lee, Donghyun; Hayashi, Shinnosuke; Tanaka, Shinji; Yoshimura, Masahiro

    2002-11-29

    A CpRh(III) complex catalyzes reductive amination of ketones using HCOONH(4) at 50-70 degrees C to give the corresponding primary amines in high yields. The reaction is clean and operationally simple and proceeds at a lower temperature and with higher chemoselectivity than the original Leuckart-Wallach reaction. The new method has been applied to the synthesis of alpha-amino acids directly from alpha-keto acids.

  9. Stab Sensitivity of Energetic Nanolaminates

    SciTech Connect

    Gash, A; Barbee, T; Cervantes, O

    2006-05-22

    This work details the stab ignition, small-scale safety, and energy release characteristics of bimetallic Al/Ni(V) and Al/Monel energetic nanolaminate freestanding thin films. The influence of the engineered nanostructural features of the energetic multilayers is correlated with both stab initiation and small-scale energetic materials testing results. Structural parameters of the energetic thin films found to be important include the bi-layer period, total thickness of the film, and presence or absence of aluminum coating layers. In general the most sensitive nanolaminates were those that were relatively thick, possessed fine bi-layer periods, and were not coated. Energetic nanolaminates were tested for their stab sensitivity as freestanding continuous parts and as coarse powders. The stab sensitivity of mock M55 detonators loaded with energetic nanolaminate was found to depend strongly upon both the particle size of the material and the configuration of nanolaminate material, in the detonator cup. In these instances stab ignition was observed with input energies as low as 5 mJ for a coarse powder with an average particle dimension of 400 {micro}m. Selected experiments indicate that the reacting nanolaminate can be used to ignite other energetic materials such as sol-gel nanostructured thermite, and conventional thermite that was either coated onto the multilayer substrate or pressed on it. These results demonstrate that energetic nanolaminates can be tuned to have precise and controlled ignition thresholds and can initiate other energetic materials and therefore are viable candidates as lead-free impact initiated igniters or detonators.

  10. Chiral N-phosphonyl imine chemistry: asymmetric synthesis of alpha-alkyl beta-amino ketones by reacting phosphonyl imines with ketone-derived enolates.

    PubMed

    Ai, Teng; Han, Jianlin; Chen, Zhong-Xiu; Li, Guigen

    2009-02-01

    A series of new chiral syn-alpha-branched beta-amino ketones has been synthesized by reacting chiral phosphonyl imines with ketone-derived enolates. The N-protection group on imine auxiliary was found to be crucial to the asymmetric induction. The absolute stereochemistry has been unambiguously determined by converting a product to a known sample.

  11. Nickel-Catalyzed Cycloadditions of Unsaturated Hydrocarbons, Aldehydes, and Ketones

    PubMed Central

    Tekavec, Thomas N.

    2014-01-01

    The nickel-catalyzed cycloaddition of unsaturated hydrocarbons and carbonyls is reported. Diynes and enynes were used as coupling partners. Carbonyl substrates include both aldehdyes and ketones. Reactions of diynes and aldehydes afforded the [3, 3] electrocyclic ring-opened tautomers, rather than pyrans, in high yields. The cycloaddition reaction of enynes and aldehydes afforded two distinct products. A new carbon–carbon bond is formed, prior to a competitive β-hydrogen elimination of a nickel alkoxide, between the carbonyl carbon and either one of the carbons of the olefin or the alkyne. The steric hindrance of the enyne greatly affected the chemoselectivity of the cycloaddition of enynes and aldehydes. In some cases, dihydropyran was also formed. The scope of the cycloaddition reaction was expanded to include the coupling of enynes and ketones. No β-hydrogen elimination was observed in cycloaddition reaction of enynes and ketones. Instead, C–O bond-forming reductive elimination occurred exclusively to afford dihydropyrans in excellent yields. In all cases, complete chemoselectivity was observed; only dihydropyrans where the carbonyl carbon forms a carbon–carbon bond with a carbon of the olefin, rather than of the alkyne, were observed. All cycloaddition reactions occur at room temperature and employ nickel catalysts bearing the hindered 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) or its saturated analogue, 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazolin-2-ylidene (SIPr). PMID:18318544

  12. Aqueous oxidation of phenylurea herbicides by triplet aromatic ketones.

    PubMed

    Canonica, Silvio; Hellrung, Bruno; Müller, Pavel; Wirz, Jakob

    2006-11-01

    Excited triplet states of dissolved natural organic matter (DOM) are important players for the transformation of organic chemical contaminants in sunlit natural waters. The present study focuses on kinetics and mechanistic aspects of the transformation of phenylurea herbicides induced by well-defined excited triplet states, which have been chosen to model DOM triplet states having oxidative character. The aromatic ketones benzophenone, 3'-methoxyacetophenone, and 2-acetonaphthone were used to photogenerate their triplet states and oxidize a series of eleven substituted phenylureas. Quenching of the excited triplet states by the phenylureas was measured using laser flash photolysis in the microsecond time domain, while the oxidation kinetics of the phenylureas was followed under steady-state irradiation. Second-order rate constants for quenching and oxidation were largely identical for a given pair of ketone and phenylurea. They reached the diffusion-controlled limit (approximately 4 x 10(9) M(-1) s(-1)) and decreased with increasing free energy of electron transfer from the phenylurea to the ketone triplet. These results confirm those already obtained using phenols as the substrates to be oxidized and suggest that oxidation rates are mainly determined by the bimolecular rate constant for electron transfer, a rule that can possibly be extended to various organic contaminants. A refined estimate of the effective reduction potential of DOM excited triplet states was also obtained.

  13. Solvation of Esters and Ketones in Supercritical CO2.

    PubMed

    Kajiya, Daisuke; Imanishi, Masayoshi; Saitow, Ken-ichi

    2016-02-04

    Vibrational Raman spectra for the C═O stretching modes of three esters with different functional groups (methyl, a single phenyl, and two phenyl groups) were measured in supercritical carbon dioxide (scCO2). The results were compared with Raman spectra for three ketones involving the same functional groups, measured at the same thermodynamic states in scCO2. The peak frequencies of the Raman spectra of these six solute molecules were analyzed by decomposition into the attractive and repulsive energy components, based on the perturbed hard-sphere theory. For all solute molecules, the attractive energy is greater than the repulsive energy. In particular, a significant difference in the attractive energies of the ester-CO2 and ketone-CO2 systems was observed when the methyl group is attached to the ester or ketone. This difference was significantly reduced in the solute systems with a single phenyl group and was completely absent in those with two phenyl groups. The optimized structures among the solutes and CO2 molecules based on quantum chemical calculations indicate that greater attractive energy is obtained for a system where the oxygen atom of the ester is solvated by CO2 molecules.

  14. Energetic Particles Investigation (EPI)

    NASA Astrophysics Data System (ADS)

    Fischer, H. M.; Mihalov, J. D.; Lanzerotti, L. J.; Wibberenz, G.; Rinnert, K.; Gliem, F. O.; Bach, J.

    1992-05-01

    The EPI instrument operates during the pre-entry phase of the Galileo Probe. The main objective is the study of the energetic particle population in the inner Jovian magnetosphere and in the upper atmosphere. This will be achieved through omnidirectional measurements of electrons, protons, alpha-particles and heavy ions (Z greater than 2) and recording intensity profiles with a spatial resolution of about 0.02 Jupiter radii. Sectored data will also be obtained for electrons, protons, and alpha-particles to determine directional anisotropies and particle pitch angle distributions. The detector assembly is a two-element telescope using totally depleted circular silicon surface-barrier detectors surrounded by cylindrical tungsten shielding. The lower energy threshold of the particle species investigated during the Probe's pre-entry phase is determined by the material thickness of the Probe's rear heat shield which is required for heat protection of the scientific payload during entry into the Jovian atmosphere. The EPI instrument is combined with the Lightning and Radio Emission Detector and both instruments share one interface of the Probe's power, command, and data unit.

  15. ENERGETICS, EPIGENETICS, MITOCHONDRIAL GENETICS

    PubMed Central

    Wallace, Douglas C.; Fan, Weiwei

    2011-01-01

    The epigenome has been hypothesized to provide the interface between the environment and the nuclear DNA (nDNA) genes. Key factors in the environment are the availability of calories and demands on the organism’s energetic capacity. Energy is funneled through glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), the cellular bioenergetic systems. Since there are thousands of bioenergetic genes dispersed across the chromosomes and mitochondrial DNA (mtDNA), both cis and trans regulation of the nDNA genes is required. The bioenergetic systems convert environmental calories into ATP, acetyl-Coenzyme A (acetyl-CoA), S-adenosyl-methionine (SAM), and reduced NAD+. When calories are abundant, ATP and acetyl-CoA phosphorylate and acetylate chromatin, opening the nDNA for transcription and replication. When calories are limiting, chromatin phosphorylation and acetylation are lost and gene expression is suppressed. DNA methylaton via SAM can also be modulated by mitochondrial function. Phosphorylation and acetylation are also pivotal to regulating cellular signal transduction pathways. Therefore, bioenergetics provides the interface between the environment and the epigenome. Consistent with this conclusion, the clinical phenotypes of bioenergetic diseases are strikingly similar to those observed in epigenetic diseases (Angelman, Rett, Fragile X Syndromes, the laminopathies, cancer, etc.), and an increasing number of epigenetic diseases are being associated with mitochondrial dysfunction. This bioenergetic-epigenomic hypothesis has broad implications for the etiology, pathophysiology, and treatment of a wide range of common diseases. PMID:19796712

  16. "Energetics of Nanomaterials"

    SciTech Connect

    Professor Alexandra Navrotsky

    2005-01-31

    This project represents a three-year collaboration among Alexandra Navrotsky, Brian Woodfield, Juliana Bocrio-Goates and Frances Hellman. It's purpose has been to explore the differences between bulk materials, nanoparticles, and thin films in terms of their thermodynamic properties, with an emphasis on heat capacities and entropies, as well as enthalpies. The three groups have brought very different expertise and capabilities to the project. Navrotsky is a solid-state chemist and geochemist, with a unique Thermochemistry Facility emphasizing enthalpy of formation measurements by high temperature oxide melt and room temperature acid solution calorimetry. Bocrio-Goates and Woodfield are physical chemists with unique capabilities in accurate cryogenic heat capacity measurements using adiabatic calorimetry. Hellman is a physicist with expertise in magnetism and heat capacity measurements using microscale ''detector on a chip'' calorimetric technology that she pioneered. The overarching question of the work is ''How does the free energy play out in nanoparticles''? or ''How do differences in free energy affect overall nanoparticle behavior''? Because the free energy represents the temperature-dependent balance between the enthalpy of a system and its entropy, there are two separate, but related, components to the experimental investigations: Solution calorimetric measurements provide the energetics and two types of heat capacity measurements the entropy. They use materials that are well characterized in other ways (structurally, magnetically, and chemically), and samples are shared across the collaboration.

  17. Energetic particles at Uranus

    NASA Technical Reports Server (NTRS)

    Cheng, Andrew F.; Krimigis, S. M.; Lanzerotti, L. J.

    1991-01-01

    The energetic particle measurements by the low-energy charged-particle and cosmic-ray instruments on the Voyager 2 spacecraft in the magnetosphere of Uranus are reviewed. Upstream events were observed outside the Uranian bow shock, probably produced by ion escape from the magnetosphere. Evidence of earthlike substorm activity was discovered within the Uranian magnetosphere. A proton injection event was observed within the orbit of Umbriel and proton events were observed in the magnetotail plasma-sheet boundary layer that are diagnostic of earthlike substorms. The magnetospheric composition is totally dominated by protons, with only a trace abundance of H(2+) and no evidence for He or heavy ions; the Uranian atmophere is argued to be the principal plasma source. Phase-space densities of medium energy protons show inward radial diffusion and are quantitatively similar to those observed at the earth, Jupiter, and Saturn. These findings and plasma wave data suggest the existence of structures analogous to the earth's plasmasphere and plasmapause.

  18. Voyager 2 Observes Energetic Electrons

    NASA Image and Video Library

    This animation shows the Voyager 2 observations of energetic electrons. Voyager 2 detected a dramatic drop of the flux of electrons as it left the sector region. The intense flux came back as soon ...

  19. Method for forming energetic nanopowders

    DOEpatents

    Lee, Kien-Yin; Asay, Blaine W.; Kennedy, James E.

    2013-10-15

    A method for the preparation of neat energetic powders, having nanometer dimensions, is described herein. For these neat powder, a solution of a chosen energetic material is prepared in an aprotic solvent and later combined with liquid hexane that is miscible with such solvent. The energetic material chosen is less soluble in the liquid hexane than in the aprotic solvent and the liquid hexane is cooled to a temperature that is below that of the solvent solution. In order to form a precipitate of said neat powders, the solvent solution is rapidly combined with the liquid hexane. When the resulting precipitate is collected, it may be dried and filtered to yield an energetic nanopowder material.

  20. Design of Energetic Ionic Liquids

    DTIC Science & Technology

    2009-05-12

    effectiveness of the FMO method in both providing accurate results and reducing computational requirements, timings were performed for the ionic liquid ...Technical Paper 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Design of Energetic Ionic Liquids 5b. GRANT NUMBER 5c...Design of Energetic Ionic Liquids challenge project is to address several key technical issues and challenges associated with the characterization

  1. Photodecomposition of energetic nitro compounds

    SciTech Connect

    Mialocq, J.C.

    1989-03-14

    The photodecomposition of energetic nitrocompounds depends on the excitation energy, the light intensity which determines the mono-, bi- or multiphotonic character of the initial process and their gaseous, liquid or solid state. The initial processes of the photodecomposition of nitromethane and nitroalcanes are reviewed and their relevance to the initiation of energetic nitrocompounds detonation is discussed. The case of nitramines (dimethylnitramine and tutorial) is also briefly introduced.

  2. Solar Energetic Particle Variations

    NASA Technical Reports Server (NTRS)

    Reames, D. V.

    2003-01-01

    In the largest solar energetic-particle (SEP) events, acceleration occurs at shock waves driven out from the Sun by coronal mass ejections (CMEs). In fact, the highest proton intensities directly measured near Earth at energies up to approximately 1 GeV occur at the time of passage of shocks, which arrive about a day after the CMEs leave the Sun. CME-driven shocks expanding across magnetic fields can fill over half of the heliosphere with SEPs. Proton-generated Alfven waves trap particles near the shock for efficient acceleration but also throttle the intensities at Earth to the streaming limit early in the events. At high energies, particles begin to leak from the shock and the spectrum rolls downward to form an energy-spectral 'knee' that can vary in energy from approximately 1 MeV to approximately 1 GeV in different events. All of these factors affect the radiation dose as a function of depth and latitude in the Earth's atmosphere and the risk to astronauts and equipment in space. SEP ionization of the polar atmosphere produces nitrates that precipitate to become trapped in the polar ice. Observations of nitrate deposits in ice cores reveal individual large SEP events and extend back approximately 400 years. Unlike sunspots, SEP events follow the approximately 80-100-year Gleissberg cycle rather faithfully and are now at a minimum in that cycle. The largest SEP event in the last 400 years appears to be related to the flare observed by Carrington in 1859, but the probability of SEP events with such large fluences falls off sharply because of the streaming limit.

  3. Aerobic dehydrogenative α-diarylation of benzyl ketones with aromatics through carbon-carbon bond cleavage.

    PubMed

    More, Nagnath Yadav; Jeganmohan, Masilamani

    2014-02-07

    Substituted benzyl ketones reacted with aromatics in the presence of K2S2O8 in CF3COOH at room temperature, yielding α-diaryl benzyl ketones through a carbon-carbon bond cleavage. In the reaction, two new carbon-carbon bonds were formed and one carbon-carbon bond was cleaved. It is very interesting that two different nucleophiles such as benzyl ketones and aromatics were coupled together without metal, which is unusual in organic synthesis.

  4. Enantioselective Pd-catalyzed allylation of acyclic α-fluorinated ketones.

    PubMed

    Wang, Wengui; Shen, Haiming; Wan, Xiao-Long; Chen, Qing-Yun; Guo, Yong

    2014-07-03

    Significant synthetic challenges remain for the asymmetric synthesis of tertiary α-fluoro ketones, which are potentially useful molecules for the development of drugs, agrochemicals, and functional materials. Herein, we describe the development of a method for the catalytic enantioselective synthesis of tertiary α-fluoro ketones via the Tsuji-Trost reaction of racemic acyclic α-fluorinated ketones. Enantioenriched acyclic α-cabonyl tertiary fluorides can be produced with the aid of a palladium/phosphinooxazoline catalyst.

  5. Regio- and Stereoselective Modification of Chiral α-Amino Ketones by Pd-Catalyzed Allylic Alkylation.

    PubMed

    Huwig, Kai; Schultz, Katharina; Kazmaier, Uli

    2015-07-27

    Chiral α-amino ketones are excellent nucleophiles for stereoselective palladium-catalyzed allylic alkylations. Both chiral as well as achiral allylic substrates can be applied, while the stereochemical outcome of the reaction is controlled by the chiral ketone enolate. The substituted amino ketones formed can be reduced stereoselectively, and up to five consecutive stereogenic centers can be obtained. This approach can be used for the synthesis of highly substituted piperidine derivatives.

  6. Exploring the clinical utility of blood ketone levels in the emergency department assessment of paediatric patients

    PubMed Central

    O'Donohoe, P B; Kessler, R; Beattie, T F

    2006-01-01

    Background Ketonuria (on standard urine testing) is a frequent finding in children presenting to emergency departments. With the advent of hand‐held ketone meters, blood ketone levels can now be rapidly quantified. Hypothesis Point of care testing (POCT) of blood ketone levels could provide clinically useful information on severity of illness in children and risk of hospital admission. Methods A prospective study using POCT of blood ketone levels in a convenience sample of children <13 years old, with a typical case mix of medical problems. Findings 186 children were studied. The range of ketone levels varied widely among this study population depending on the presenting complaint. Higher levels were noted in those presenting with anorexia or vomiting and fever. The median ketone level of the total study population was 0.2 (range 0–6.0, interquartile range 0.1–0.9) mmol/l. Ketone levels correlated poorly with discharge destination and duration of admission. However, receiver–operator characteristics for ketones as a predictor of admission were comparable to Pediatric Risk of Admission scores (area under the curve 0.64 and 0.72, respectively) and may represent an independent risk factor for admission. A ketone level >1.2 mmol/l has a positive predictive value of 66.7% for admission. Ketone levels correlated well with decreased oral intake (R2 = 0.25; p<0.001). Conclusions A strong association was found between ketone levels, decreased oral intake and fever. Although ketone levels do not correlate well with more traditional markers of illness severity, they can help to predict the requirement for admission to hospital when interpreted in the context of the presenting illness. They may have applications in both the emergency department and primary care settings. Further prospective testing is required to validate these findings. PMID:16988307

  7. Rhodium-Catalyzed Ketone Methylation Using Methanol Under Mild Conditions: Formation of α-Branched Products**

    PubMed Central

    Chan, Louis K M; Poole, Darren L; Shen, Di; Healy, Mark P; Donohoe, Timothy J

    2014-01-01

    The rhodium-catalyzed methylation of ketones has been accomplished using methanol as the methylating agent and the hydrogen-borrowing method. The sequence is notable for the relatively low temperatures that are required and for the ability of the reaction system to form α-branched products with ease. Doubly alkylated ketones can be prepared from methyl ketones and two different alcohols by using a sequential one-pot iridium- and rhodium-catalyzed process. PMID:24288297

  8. Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

    PubMed Central

    Mastracchio, Anthony; Warkentin, Alexander A.; Walji, Abbas M.; MacMillan, David W. C.

    2010-01-01

    The first enantioselective organocatalytic α-allylation of cyclic ketones has been accomplished via singly occupied molecular orbital catalysis. Geometrically constrained radical cations, forged from the one-electron oxidation of transiently generated enamines, readily undergo allylic alkylation with a variety of commercially available allyl silanes. A reasonable latitude in both the ketone and allyl silane components is readily accommodated in this new transformation. Moreover, three new oxidatively stable imidazolidinone catalysts have been developed that allow cyclic ketones to successfully participate in this transformation. The new catalyst platform has also been exploited in the first catalytic enantioselective α-enolation and α-carbooxidation of ketones. PMID:20921367

  9. Stereoselective synthesis of cyclohexanones via phase transfer catalyzed double addition of nucleophiles to divinyl ketones.

    PubMed

    Silvanus, Andrew C; Groombridge, Benjamin J; Andrews, Benjamin I; Kociok-Köhn, Gabriele; Carbery, David R

    2010-11-05

    Functionalized cyclohexanones are formed in excellent yield and diastereoselectivity from a phase transfer catalyzed double addition of active methylene pronucleophiles to nonsymmetrical divinyl ketones.

  10. Gallium (III) triflate catalyzed efficient Strecker reaction of ketones and their fluorinated analogs

    PubMed Central

    Prakash, G. K. Surya; Mathew, Thomas; Panja, Chiradeep; Alconcel, Steevens; Vaghoo, Habiba; Do, Clement; Olah, George A.

    2007-01-01

    The synthesis of α-aminonitriles and their fluorinated analogs has been carried out in high yield and purity by the Strecker reaction from the corresponding ketones and amines with trimethylsilyl cyanide using gallium triflate in dichloromethane. Monofluoro-, difluro-, or trifluoromethyl groups can be incorporated into the α-aminonitrile product by varying the nature of the fluorinated ketones. Study with various fluorinated and nonfluorinated ketones reveals that the choice of proper catalyst and the solvent system (suitable metal triflates as a catalyst and dichloromethane as a solvent) plays the key role in the direct Strecker reactions of ketones. PMID:17360416

  11. Palladium-catalysed mono-α-alkenylation of ketones with alkenyl tosylates.

    PubMed

    Wu, Yong; Fu, Wai Chung; Chiang, Chien-Wei; Choy, Pui Ying; Kwong, Fuk Yee; Lei, Aiwen

    2017-01-16

    The first example of palladium-catalysed selective mono-α-alkenylation of ketones with alkenyl tosylates is described. In the presence of a Pd/XPhos catalyst system (0.1-1.0 mol%), the reaction provides mono-α-alkenylated ketones in good yields and exhibits excellent substrate tolerance. Highly congested, tri- and tetra-substituted alkenyl tosylates react smoothly and even problematic heteroaryl and aliphatic ketones are applicable substrates. Notably, small β,γ-unsaturated ketones are successfully prepared using acetone as a simple three-carbon feedstock.

  12. [Pollution Characteristics of Aldehydes and Ketones Compounds in the Exhaust of Beijing Typical Restaurants].

    PubMed

    Cheng, Jing-chen; Cui, Tong; He, Wan-qing; Nie, Lei; Wang, Jun-ling; Pan, Tao

    2015-08-01

    Aldehydes and ketones compounds, as one of the components in the exhaust of restaurants, are a class of volatile organic compounds (VOCs) with strong chemical reactivity. However, there is no systematic study on aldehydes and ketones compounds in the exhaust of restaurants. To further clarify the food source emission levels of aldehydes and ketones compounds and controlling measures, to access city group catering VOCs emissions control decision-making basis, this study selected 8 Beijing restaurants with different types. The aldehydes and ketones compounds were sampled using DNPH-silica tube, and then ultra performance liquid chromatography was used for quantitative measurement. The aldehydes and ketones concentrations of reference volume condition from 8 restaurants in descending order were Roasted Duck restaurant, Chinese Style Barbecue, Home Dishes, Western Fast-food, School Canteen, Chinese Style Fast-food, Sichuan Cuisine, Huaiyang Cuisine. The results showed that the range of aldehydes and ketones compounds (C1-C9) concentrations of reference volume condition in the exhaust of restaurants was 115.47-1035.99 microg x m(-3). The composition of aldehydes and ketones compounds in the exhaust of sampled restaurants was obviously different. The percentages of C1-C3 were above 40% in the exhaust from Chinese style restaurants. Fast food might emit more C4-C9 aldehydes and ketones compounds. From the current situation of existing aldehydes and ketones compounds control, the removal efficiency of high voltage electrostatic purifiers widely used in Beijing is limited.

  13. The Energetics of Gravity Driven Faulting

    NASA Astrophysics Data System (ADS)

    Barrows, L.

    2007-12-01

    Faulting can result from either of two different mechanisms. These involve fundamentally different energetics. In displacement-bounded faulting, locked-in elastic strain energy is transformed into seismic waves plus work done in the fault zone. Elastic rebound is an example of displacement-bounded faulting. In force-driven faulting, the forces that create the stress on the fault supply work or energy to the faulting process. Half of this energy is transformed into seismic waves plus work done in the fault zone and half goes into an increase in locked-in elastic strain. In displacement-bounded faulting the locked-in elastic strain drives slip on the fault. In force-driven faulting it stops slip on the fault. Tectonic stress is reasonably attributed to gravity acting on topography and the Earth's lateral density variations. This includes the thermal convection that ultimately drives plate tectonics. The gravity collapse seismic mechanism assumes the fault fails and slips in direct response to the gravitational tectonic stress. Gravity collapse is an example of force-driven faulting. In the simplest case, energy that is released from the gravitational potential of the topography and internal stress-causing density variations is equally split between the seismic waves plus work done in the fault zone and the increase in locked-in elastic strain. The release of gravitational potential energy requires a change in the Earth's density distribution. Gravitational body forces are solely dependent on density so a change in the density distribution requires a change in the body forces. This implies the existence of volumetric body-force displacements. The volumetric body-force displacements are in addition to displacements generated by slip on the fault. They must exist if gravity participates in the energetics of the faulting process. From the perspective of gravitational tectonics, the gravity collapse mechanism is direct and simple. The related mechanics are a little more

  14. Enantioselective Photocatalytic [3 + 2] Cycloadditions of Aryl Cyclopropyl Ketones.

    PubMed

    Amador, Adrian G; Sherbrook, Evan M; Yoon, Tehshik P

    2016-04-13

    Control of stereochemistry in photocycloaddition reactions remains a substantial challenge; almost all successful catalytic examples to date have involved [2 + 2] photocycloadditions of enones. We report a method for the asymmetric [3 + 2] photocycloaddition of aryl cyclopropyl ketones that enables the enantiocontrolled construction of densely substituted cyclopentane structures not synthetically accessible using other catalytic methods. These results show that the dual-catalyst strategy developed in our laboratory broadens synthetic chemists' access to classes of photochemical cycloadditions that have not previously been feasible in enantioselective form.

  15. Methyl isobutyl ketone as a solvent for wax deoiling

    SciTech Connect

    Larikov, V.I.; Pereverzev, A.N.; Roshchin, Y.N.; Sokolova, S.P.

    1983-09-01

    The solvency of methyl isobutyl ketone (MIBK) for use in deoiling and cold-fractionation of solid paraffin waxes is investigated by a visual polytherm method in the temperature interval 0-36 C. The capability of MIBK for precipitating solid hydrocarbons from solution was found to be greater than acetone/toluene or MEK/toluene, with only MEK better in this respect than MIBK. The quantity of wax remaining in the filtrate is examined. The critical solution temperatures are investigated and it is shown that MIBK surpasses MEK. The results obtained indicate that MIBK is extremely promising for use in processes of deoiling and cold fractionation of waxes.

  16. Effects of trifluoromethyl ketones on the motility of Proteus vulgaris.

    PubMed

    Wolfart, Krisztina; Molnar, Annamaria; Kawase, Masami; Motohashi, Noboru; Molnar, Joseph

    2004-09-01

    In the present study, we showed the inhibition of motility by trifluoromethyl ketone (TF) derivatives (1-8) in Proteus vulgaris (P. vulgaris) cultures. Among them, 1-(2-benzoxazoyl)-3,3,3-trifluoro-2-propanone (1) showed a much stronger inhibitory effect on the motility of P. vulgaris than other TF compounds at 10% MIC. Our results suggest the possibility of an inhibitory action of TF compounds on the proton motive forces by affecting the action of biological motor and proton efflux in the membranes, resulting in a reduction of the ratio of running and the increased number of tumbling and non-motile cells.

  17. Torquoselectivity in the Nazarov reactions of allenyl vinyl ketones.

    PubMed

    Morgan, Timothy D R; LeBlanc, Luc M; Ardagh, Giselle H; Boyd, Russell J; Burnell, D Jean

    2015-01-16

    Nazarov reactions mediated by BF3-etherate of a series of carbon-substituted allenyl vinyl ketones provided intermediates in which substituents on the termini of the allenes had rotated away from the vinyl moieties, and these intermediates were trapped by (4 + 3)-cyclizations. A computational examination of the torquoselectivity of these Nazarov reactions confirmed a kinetic preference for the observed isomers and pointed to steric interactions and the degree of allene deformation as significant factors in determining the torquoselectivity. The study also suggested that the high proportion of one geometrical isomer in the Nazarov products might also be due to some preferential trapping of the major Nazarov intermediate.

  18. Energetic particles in solar flares

    NASA Technical Reports Server (NTRS)

    Ramaty, R.; Paizis, C.; Colgate, S. A.; Dulk, G. A.; Hoyng, P.; Knight, J. W.; Lin, R. P.; Melrose, D. B.; Orrall, F.; Shapiro, P. R.

    1980-01-01

    The various manifestations of energetic particles in solar flares are examined, and possible mechanisms for the acceleration of these particles are considered. Hard X-ray observations and possible mechanisms for the production of the dominant form of solar energetic particles, electrons with energies between 10 and 100 keV, are discussed, with consideration of thin-target models, thick-target models and thick-target models with reverse currents, and first-phase acceleration mechanisms for energetic electrons emitting impulsive microwave and fast-drift Type III radio bursts as well as impulsive hard X rays, which are detected themselves 20 min after the flare at 1 AU are considered. Radio evidence on the number, energy and pitch-angle distributions of energetic particles produced during solar flares is summarized, and observations at 1 AU of proton and electron energy spectra, the proton/electron ratio and energetic particle events rich in He-3 from solar flares are discussed. Finally, consideration is given to gamma-ray evidence of nuclear reactions in flares and white-light flares

  19. Solar flares and energetic particles.

    PubMed

    Vilmer, Nicole

    2012-07-13

    Solar flares are now observed at all wavelengths from γ-rays to decametre radio waves. They are commonly associated with efficient production of energetic particles at all energies. These particles play a major role in the active Sun because they contain a large amount of the energy released during flares. Energetic electrons and ions interact with the solar atmosphere and produce high-energy X-rays and γ-rays. Energetic particles can also escape to the corona and interplanetary medium, produce radio emissions (electrons) and may eventually reach the Earth's orbit. I shall review here the available information on energetic particles provided by X-ray/γ-ray observations, with particular emphasis on the results obtained recently by the mission Reuven Ramaty High-Energy Solar Spectroscopic Imager. I shall also illustrate how radio observations contribute to our understanding of the electron acceleration sites and to our knowledge on the origin and propagation of energetic particles in the interplanetary medium. I shall finally briefly review some recent progress in the theories of particle acceleration in solar flares and comment on the still challenging issue of connecting particle acceleration processes to the topology of the complex magnetic structures present in the corona.

  20. Near-Resonant Thermomechanics of Energetic and Mock Energetic Composite Materials

    DTIC Science & Technology

    2016-11-01

    AFRL-RW-EG-TR-2016-088 Near-Resonant Thermomechanics of Energetic and Mock Energetic Composite Materials Jeffrey F. Rhoads, Steven F...Near-Resonant Thermomechanics of Energetic and Mock Energetic Composite Materials 5a. CONTRACT NUMBER FA8651-16-D-0287 5b. GRANT NUMBER 5c...the near-resonant thermomechanics of energetic and mock energetic particulate composite materials. The effort specifically focuses on: (i

  1. Energetic environment at Titan's orbit

    NASA Astrophysics Data System (ADS)

    Regoli, L.; Roussos, E.; Luhmann, J. G.; Dialynas, K.; Krupp, N.; Jones, G. H.; Coates, A. J.

    2016-12-01

    A statistical study of the energetic plasma environment at Titan's orbit is presented. Using data from the MIMI/LEMMS instrument on board Cassini, ion and electron spectra from more than 10 years are analyzed in order to study the dependence of different factors such as average fluxes or spectral indices with magnetospheric environment derived from thermal plasma and magnetic field data or Saturn Local Time (SLT). The non-negligible field-aligned velocity of the energetic ions and electrons allows them to travel farther from the magnetic equator when compared to lower-energy particles, making it difficult to distinguish among different magnetospheric environments by means of the energetic plasma fluxes. Some asymmetries in terms of SLT are observed, especially on the ion data.

  2. The Principle of Energetic Consistency

    NASA Technical Reports Server (NTRS)

    Cohn, Stephen E.

    2009-01-01

    A basic result in estimation theory is that the minimum variance estimate of the dynamical state, given the observations, is the conditional mean estimate. This result holds independently of the specifics of any dynamical or observation nonlinearity or stochasticity, requiring only that the probability density function of the state, conditioned on the observations, has two moments. For nonlinear dynamics that conserve a total energy, this general result implies the principle of energetic consistency: if the dynamical variables are taken to be the natural energy variables, then the sum of the total energy of the conditional mean and the trace of the conditional covariance matrix (the total variance) is constant between observations. Ensemble Kalman filtering methods are designed to approximate the evolution of the conditional mean and covariance matrix. For them the principle of energetic consistency holds independently of ensemble size, even with covariance localization. However, full Kalman filter experiments with advection dynamics have shown that a small amount of numerical dissipation can cause a large, state-dependent loss of total variance, to the detriment of filter performance. The principle of energetic consistency offers a simple way to test whether this spurious loss of variance limits ensemble filter performance in full-blown applications. The classical second-moment closure (third-moment discard) equations also satisfy the principle of energetic consistency, independently of the rank of the conditional covariance matrix. Low-rank approximation of these equations offers an energetically consistent, computationally viable alternative to ensemble filtering. Current formulations of long-window, weak-constraint, four-dimensional variational methods are designed to approximate the conditional mode rather than the conditional mean. Thus they neglect the nonlinear bias term in the second-moment closure equation for the conditional mean. The principle of

  3. Shock Sensitivity of energetic materials

    NASA Technical Reports Server (NTRS)

    Kim, K.

    1980-01-01

    Viscoplastic deformation is examined as the principal source of hot energy. Some shock sensitivity data on a proposed model is explained. A hollow sphere model is used to approximate complex porous matrix of energetic materials. Two pieces of shock sensitivity data are qualitatively compared with results of the proposed model. The first is the p2 tau law. The second is the desensitization of energetic materials by a ramp wave applied stress. An approach to improve the model based on experimental observations is outlined.

  4. Energetic Oxetane Thermoplastic Elastomer Binders

    DTIC Science & Technology

    1992-12-01

    Naval Air Warfare Center personnel on the project was particularly helpful. We recognize the contributions of Geoff Lindsay, Mostafa Talukder , Mel... Talukder , M.A.H.; Nissan, R.A.; Quintana, R.L; Hasting, M.A.S.; Yee, R.Y.; D-7 Nadler, M.P.; Atwood, A.I.; Reed, R.; Manser, G.E. "Energetic Polyoxetane...G.A.; Talukder , M.A.H.; Nissan, R.A.; Quintana, R.L; Hasting, M.A.S.; Yee, R.Y.; Nadler, M.P.; Atwood, A.I.; Reed, R.; Manser, G.E. "Energetic

  5. Synthesis, conformational parameters and packing considerations of methyl bispyridyl ketones

    NASA Astrophysics Data System (ADS)

    Weck, Christian; Katzsch, Felix; Gruber, Tobias

    2015-10-01

    The crystal structures of two bispyridyl ketones featuring either two methyl residues or one methyl and one bromomethyl residue, respectively, are presented. In order to elucidate the influence of the substituents, a comprehensive comparison with the non-methylated mother compound has been performed. A special focus lies thereby on the relative position of the heteroatoms and their free electron pairs. The two methyl groups at the bispyridyl ketone result in two molecules in the asymmetric unit adopting rather different conformations. Due to the fast crystallization conditions and a melting point differing from the literature, a polymorph close to a local minimum in the energy hypersurface seems possible. After introducing a bromine atom to one of the two methyl groups, the molecular conformation is very similar to the unsubstituted molecule. The packing of both title compounds is dominated by weak contacts of the C-H⋯π and C-H⋯Y type (Y = O, N) and C-H⋯Br- and Br⋯π-contacts for the brominated molecule.

  6. Activation of Acetone and Other Simple Ketones in Anaerobic Bacteria.

    PubMed

    Heider, Johann; Schühle, Karola; Frey, Jasmin; Schink, Bernhard

    2016-01-01

    Acetone and other ketones are activated for subsequent degradation through carboxylation by many nitrate-reducing, phototrophic, and obligately aerobic bacteria. Acetone carboxylation leads to acetoacetate, which is subsequently activated to a thioester and degraded via thiolysis. Two different types of acetone carboxylases have been described, which require either 2 or 4 ATP equivalents as an energy supply for the carboxylation reaction. Both enzymes appear to combine acetone enolphosphate with carbonic phosphate to form acetoacetate. A similar but more complex enzyme is known to carboxylate the aromatic ketone acetophenone, a metabolic intermediate in anaerobic ethylbenzene metabolism in denitrifying bacteria, with simultaneous hydrolysis of 2 ATP to 2 ADP. Obligately anaerobic sulfate-reducing bacteria activate acetone to a four-carbon compound as well, but via a different process than bicarbonate- or CO2-dependent carboxylation. The present evidence indicates that either carbon monoxide or a formyl residue is used as a cosubstrate, and that the overall ATP expenditure of this pathway is substantially lower than in the known acetone carboxylase reactions.

  7. Characterization of synthetic routes to 'Bromo-DragonFLY' and benzodifuranyl isopropylamine homologues utilizing ketone intermediates. Part 1: synthesis of ketone precursors.

    PubMed

    O'Connor, Richard E; Keating, John J

    2014-01-01

    Bromo-DragonFLY (BDF) and many of its analogues are misused as recreational drugs due to their potency as psychoactive substances. To date, none of the published routes to these designer amphetamines have exploited a ketone intermediate. It is well known that benzyl methyl ketone (BMK) can be employed as a precursor in the synthesis of amphetamine. Similarly, it is reasonable to assume that ketone precursors may potentially be utilized in the clandestine synthesis of BDF and its homologues. This paper describes the multifaceted synthesis of novel precursor ketones structurally related to BDF, namely benzodifuranyl propanone 16, its tetrahydrobenzodifuranyl homologue 8, and their brominated analogues 12 and 20. Their characterization by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy ((1) H-NMR), carbon nuclear magnetic resonance spectroscopy ((13) C-NMR), high performance liquid chromatography (HPLC), gas chromatography (GC) and mass spectrometry (MS) is also described. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Turnover and splanchnic metabolism of free fatty acids and ketones in insulin-dependent diabetics at rest and in response to exercise.

    PubMed

    Wahren, J; Sato, Y; Ostman, J; Hagenfeldt, L; Felig, P

    1984-05-01

    Nine insulin-dependent diabetics and six healthy controls were studied at rest, during, and after 60 min of bicycle exercise at a work load corresponding to 45% of their maximal oxygen intake. The catheter technique was employed to determine splanchnic and leg exchange of metabolites. FFA turnover and regional exchange was evaluated using [14C]oleate infusion. Basal glucose (13.8 +/- 1.1 mmol/l), ketone body (1.12 +/- 0.12 mmol/l), and FFA (967 +/- 110 mumol/l) concentrations were elevated in the diabetics in comparison with controls. In the resting state, splanchnic ketone acid production in the diabetics was 6-10-fold greater than in controls. Uptake of oleic acid by the splanchnic bed was increased 2-3-fold, and the proportion of splanchnic FFA uptake converted to ketones (61%) was threefold greater than in controls. In contrast, splanchnic fractional extraction of oleic acid was identical in diabetics and controls. A direct relationship was observed between splanchnic uptake and splanchnic inflow (plasma concentration X hepatic plasma flow) of oleic acid that could be described by the same regression line in the diabetic and control groups. During exercise, splanchnic ketone production rose in both groups. In the control group the increase in ketogenesis was associated with a rise in splanchnic inflow and in uptake of oleic acid, a rise in splanchnic fractional extraction of oleate, and an increase in the proportion of splanchnic FFA uptake converted to ketone acids from 20-40%. In the diabetic group, the increase in ketogenesis occurred in the absence of a rise in splanchnic inflow or uptake of oleic acid, but was associated with an increase in splanchnic fractional extraction of oleic acid and a marked increase in hepatic conversion of FFA to ketones, so that the entire uptake of FFA was accountable as ketone acid output. Splanchnic uptake of oleic acid correlated directly with splanchnic oleic acid inflow in both groups, but the slope of the regression line

  9. [The energetics of obesity].

    PubMed

    Bergouignan, Audrey; Blanc, Stéphane

    2006-01-01

    Although there is little argument about the state of energy imbalance that produces weight gain, there is considerable argument about the respective role of genetics, diet and physical activity in achieving obesity. In the USA, obesity has increased in the last decades despite a concomitant decrease in total energy and fat intake suggesting that there has been a dramatic drop in total energy expenditure. In this review, we investigated the respective role of resting metabolic rate, post-prandial thermogenesis, and activity energy expenditure in this lower energy output, and provided evidence that physical inactivity is the major contributor. Based on Jean Mayer original observation (Mayer et al., 1954), we hypothesize that there is a level of physical activity below which mechanisms of body mass regulation are impaired. The increasing prevalence of obesity may reflect the fact the majority of the population has fallen below such a level of physical activity. However, a causal relation between physical inactivity and obesity is still difficult to prove, probably because of the lack of longitudinal models to investigate the physiological consequences of inactivity and because the deleterious consequences of sedentary behaviors are essentially deduced from the benefits of exercise training. By using long term strict bed rest as a unique model of inactivity, we provide evidence that inactivity per se indeed disrupts fuel homeostasis and partitions post-absorptive and post-prandial fat use towards storage, thus promoting weight gain in the long term. More research is needed to investigate mechanisms and to determine the minimal physical activity our body has been engineered for by evolution.

  10. Ketones prevent oxidative impairment of hippocampal synaptic integrity through KATP channels.

    PubMed

    Kim, Do Young; Abdelwahab, Mohammed G; Lee, Soo Han; O'Neill, Derek; Thompson, Roger J; Duff, Henry J; Sullivan, Patrick G; Rho, Jong M

    2015-01-01

    Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (KATP) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of KATP channel activation. Ketones dose-dependently reversed oxidative impairment of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity, and this action was mirrored by the KATP channel activator diazoxide. Inhibition of KATP channels reversed ketone-evoked hippocampal protection, and genetic ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical component of KATP channels, partially negated the synaptic protection afforded by ketones. This partial protection was completely reversed by co-application of the KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of oxidative injury, ketones induce synaptic protection in part through activation of KATP channels.

  11. Ketones Prevent Oxidative Impairment of Hippocampal Synaptic Integrity through KATP Channels

    PubMed Central

    Kim, Do Young; Abdelwahab, Mohammed G.; Lee, Soo Han; O’Neill, Derek; Thompson, Roger J.; Duff, Henry J.; Sullivan, Patrick G.; Rho, Jong M.

    2015-01-01

    Dietary and metabolic therapies are increasingly being considered for a variety of neurological disorders, based in part on growing evidence for the neuroprotective properties of the ketogenic diet (KD) and ketones. Earlier, we demonstrated that ketones afford hippocampal synaptic protection against exogenous oxidative stress, but the mechanisms underlying these actions remain unclear. Recent studies have shown that ketones may modulate neuronal firing through interactions with ATP-sensitive potassium (KATP) channels. Here, we used a combination of electrophysiological, pharmacological, and biochemical assays to determine whether hippocampal synaptic protection by ketones is a consequence of KATP channel activation. Ketones dose-dependently reversed oxidative impairment of hippocampal synaptic integrity, neuronal viability, and bioenergetic capacity, and this action was mirrored by the KATP channel activator diazoxide. Inhibition of KATP channels reversed ketone-evoked hippocampal protection, and genetic ablation of the inwardly rectifying K+ channel subunit Kir6.2, a critical component of KATP channels, partially negated the synaptic protection afforded by ketones. This partial protection was completely reversed by co-application of the KATP blocker, 5-hydoxydecanoate (5HD). We conclude that, under conditions of oxidative injury, ketones induce synaptic protection in part through activation of KATP channels. PMID:25848768

  12. [Research on utilization of phage display technology to screen chloramine ketone simulated surface point].

    PubMed

    Xiong, Yonghua; Chen, Xuelan; Liu, Xiaoxing

    2010-09-01

    Utilize phage display technology to screen chloramine ketone simulated surface point, providing the basis for establishing drug-free ELISA test system. Use the anti chloramine ketone monoclonal antibody as the ligand, and screen the Ph.D. -7(TM) phage display peptide library to select the chloramine ketone simulated surface point. After 4 rounds of screening, select the phase, which can combine the chloramines ketone monoclonal antibody with different degrees, and further, determine the positive clone with competitive inhibition of the hydrochloric chloramine ketone by the indirect competitive ELISA method. It is discovered that all the 10 phages can combine the chloramine ketone monoclonal antibody with different degrees. Use the indirect competitive ELISA method to determine, the phenomenon that 5 positive clones, among them, have competitive inhibition with the hydrochloric chloramine ketone exists. The sequencing results of those 5 positive clones show that 4 different amino acid sequenced are obtained. Tentatively judge these 4 phages display the chloramine ketone simulated antigen surface points.

  13. Enantioselective Reduction of Ketones and Imines Catalyzed by (CN-Box)Re(V)-Oxo Complexes

    PubMed Central

    Nolin, Kristine A.; Ahn, Richard W.; Kobayashi, Yusuke; Kennedy-Smith, Joshua J.

    2012-01-01

    The development and application of chiral, non-racemic Re(V)-oxo complexes to the enantioselective reduction of prochiral ketones is described. In addition to the enantioselective reduction of prochiral ketones, we report the application of these complexes to (1) a tandem Meyer-Schuster rearrangement/reduction to access enantioenriched allylic alcohols and (2) the enantioselective reduction of imines. PMID:20623567

  14. Switchable asymmetric bio-epoxidation of α,β-unsaturated ketones.

    PubMed

    Liu, Yu-Chang; Wu, Zhong-Liu

    2016-01-21

    Efficient asymmetric bio-epoxidation of electron-deficient α,β-unsaturated ketones was realized via a tandem reduction-epoxidation-dehydrogenation cascade, which proceeds in a switchable manner to afford either chiral epoxy ketones or allylic epoxy alcohols with up to >99% yield and >99%ee.

  15. Asymmetric Direct 1,2-Addition of Aryl Grignard Reagents to Aryl Alkyl Ketones.

    PubMed

    Osakama, Kazuki; Nakajima, Makoto

    2016-01-15

    The enantioselective addition of Grignard reagents to ketones was promoted by a BINOL derivative bearing alkyl chains at the 3,3'-positions. This is the first asymmetric direct aryl Grignard addition to ketones reported to date. A variety of tertiary diaryl alcohols could be obtained in high yields and enantioselectivities without using any other metal source.

  16. Raspberry Ketone Trifluoroacetate, a new attractant for the Queensland fruit fly (Bactrocera tryoni (Froggatt))

    USDA-ARS?s Scientific Manuscript database

    The Queensland fruit fly (Bactrocera tryoni, Q-fly) is a major agricultural pest in eastern Australia. The deployment of male lures comprises an important component of several control and detection strategies for this pest. A novel fluorinated analog of raspberry ketone, raspberry ketone trifluoroac...

  17. Organocatalytic C3-selective Friedel-Crafts alkylations of indoles with alpha,beta-unsaturated ketones.

    PubMed

    Li, Dong-Ping; Guo, Ying-Cen; Ding, Yu; Xiao, Wen-Jing

    2006-02-21

    The use of an equimolar amount of pyrrolidine and HClO4 (30 mol%) was found to be effective in promoting the conjugate addition of indoles to (E)-alpha,beta-unsaturated ketones, affording the corresponding beta-indolyl ketones in excellent yields.

  18. Further research on the biological activities and the safety of raspberry ketone are needed

    USDA-ARS?s Scientific Manuscript database

    Raspberry ketone supplements have grabbed consumer attention with the possibility they might help burn fat and aid weight loss. While raspberry ketone occurs naturally, and is found in raspberry fruit, most is synthetically produced for use in commercial products as flavorings, fragrances, or dietar...

  19. Beyond ketonization: selective conversion of carboxylic acids to olefins over balanced Lewis acid-base pairs.

    PubMed

    Baylon, Rebecca A L; Sun, Junming; Martin, Kevin J; Venkitasubramanian, Padmesh; Wang, Yong

    2016-04-11

    We report the direct conversion of mixed carboxylic acids to C-C olefins with up to 60 mol% carbon yield through cascade (cross) ketonization, (cross) aldolization and self-deoxygenation reactions. Co-feeding hydrogen provides an additional ketone hydrogenation/dehydration pathway to a wider range of olefins.

  20. Ketones and lactate "fuel" tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism.

    PubMed

    Bonuccelli, Gloria; Tsirigos, Aristotelis; Whitaker-Menezes, Diana; Pavlides, Stephanos; Pestell, Richard G; Chiavarina, Barbara; Frank, Philippe G; Flomenberg, Neal; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2010-09-01

    Previously, we proposed a new model for understanding the "Warburg effect" in tumor metabolism. In this scheme, cancer-associated fibroblasts undergo aerobic glycolysis and the resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter the TCA cycle, resulting in high ATP production via oxidative phosphorylation. We have termed this new paradigm "The Reverse Warburg Effect." Here, we directly evaluate whether the end-products of aerobic glycolysis (3-hydroxy-butyrate and L-lactate) can stimulate tumor growth and metastasis, using MDA-MB-231 breast cancer xenografts as a model system. More specifically, we show that administration of 3-hydroxy-butyrate (a ketone body) increases tumor growth by ∼2.5-fold, without any measurable increases in tumor vascularization/angiogenesis. Both 3-hydroxy-butyrate and L-lactate functioned as chemo-attractants, stimulating the migration of epithelial cancer cells. Although L-lactate did not increase primary tumor growth, it stimulated the formation of lung metastases by ∼10-fold. Thus, we conclude that ketones and lactate fuel tumor growth and metastasis, providing functional evidence to support the "Reverse Warburg Effect". Moreover, we discuss the possibility that it may be unwise to use lactate-containing i.v. solutions (such as Lactated Ringer's or Hartmann's solution) in cancer patients, given the dramatic metastasis-promoting properties of L-lactate. Also, we provide evidence for the up-regulation of oxidative mitochondrial metabolism and the TCA cycle in human breast cancer cells in vivo, via an informatics analysis of the existing raw transcriptional profiles of epithelial breast cancer cells and adjacent stromal cells. Lastly, our findings may explain why diabetic patients have an increased incidence of cancer, due to increased ketone production, and a tendency towards autophagy/mitophagy in their adipose tissue.

  1. [Studies on metabolism of total terpene ketones from Swertia mussotii with human intestinal bacteria].

    PubMed

    Li, Shuang; Tian, Cheng-Wang; Wu, Shuai; Yang, Xiu-Wei; Wang, Li-Li; Zhang, Tie-Jun

    2012-12-01

    To study the metabolism of total terpene ketones from Swertia mussotii with human intestinal bacteria. Total terpene ketones were incubated with human intestinal bacteria under an anaerobic environment and at 37 degrees C. The metabolites were extracted by ethyl acetate processing, detected by HPLC-DAD method. A qualitative analysis was made for its metabolites by HPLC-MS. Eight metabolites were detected from total terpene ketones from S. mussotii with human intestinal bacteria, and two of them were preliminarily identified as gentianine and mangiferin aglycon. Total terpene ketones can be metabolized with human intestinal bacteria, which provides basis for experiments on the metabolism process total terpene ketones from S. mussotii with human intestinal bacteria.

  2. Evaluation of difluoromethyl ketones as agonists of the γ-aminobutyric acid type B (GABAB) receptor.

    PubMed

    Han, Changho; Salyer, Amy E; Kim, Eun Hoo; Jiang, Xinyi; Jarrard, Rachel E; Powers, Matthew S; Kirchhoff, Aaron M; Salvador, Tolani K; Chester, Julia A; Hockerman, Gregory H; Colby, David A

    2013-03-28

    The design, synthesis, biological evaluation, and in vivo studies of difluoromethyl ketones as GABAB agonists that are not structurally analogous to known GABAB agonists, such as baclofen or 3-aminopropyl phosphinic acid, are presented. The difluoromethyl ketones were assembled in three synthetic steps using a trifluoroacetate-release aldol reaction. Following evaluation at clinically relevant GABA receptors, we have identified a difluoromethyl ketone that is a potent GABAB agonist, obtained its X-ray structure, and presented preliminary in vivo data in alcohol-preferring mice. The behavioral studies in mice demonstrated that this compound tended to reduce the acoustic startle response, which is consistent with an anxiolytic profile. Structure-activity investigations determined that replacing the fluorines of the difluoromethyl ketone with hydrogens resulted in an inactive analogue. Resolution of the individual enantiomers of the difluoromethyl ketone provided a compound with full biological activity at concentrations less than an order of magnitude greater than the pharmaceutical, baclofen.

  3. Unusual transannular cyclization products of sarcophytoxide, a 14-membered marine cembranoid: anomalous stereochemistry of epoxide-ketone rearrangement.

    PubMed

    Nii, Keiji; Tagami, Keiko; Matsuoka, Keisuke; Munakata, Tatsuo; Ooi, Takashi; Kusumi, Takenori

    2006-07-06

    [reaction: see text] Treatment of sarcophytoxide with trimethylsilyl trifluoromethanesulfonate afforded an aromatic ketone as an unusual cyclization product. The modified Mosher's method and X-ray analysis performed on the aromatic ketone revealed that it is a 4:1 mixture of 8(R)- and 8(S)-enantiomers. It also suggested that the precursor ketone has 8(R)-configuration, which is contradictory to that expected from the ordinary epoxide-ketone rearrangement.

  4. Jet propagation through energetic materials

    SciTech Connect

    Pincosy, P; Poulsen, P

    2004-01-08

    In applications where jets propagate through energetic materials, they have been observed to become sufficiently perturbed to reduce their ability to effectively penetrate subsequent material. Analytical calculations of the jet Bernoulli flow provides an estimate of the onset and extent of such perturbations. Although two-dimensional calculations show the back-flow interaction pressure pulses, the symmetry dictates that the flow remains axial. In three dimensions the same pressure impulses can be asymmetrical if the jet is asymmetrical. The 3D calculations thus show parts of the jet having a significant component of radial velocity. On the average the downstream effects of this radial flow can be estimated and calculated by a 2D code by applying a symmetrical radial component to the jet at the appropriate position as the jet propagates through the energetic material. We have calculated the 3D propagation of a radio graphed TOW2 jet with measured variations in straightness and diameter. The resultant three-dimensional perturbations on the jet result in radial flow, which eventually tears apart the coherent jet flow. This calculated jet is compared with jet radiographs after passage through the energetic material for various material thickness and plate thicknesses. We noted that confinement due to a bounding metal plate on the energetic material extends the pressure duration and extent of the perturbation.

  5. Heliospheric Observations of Energetic Particles

    NASA Technical Reports Server (NTRS)

    Summerlin, Errol J.

    2011-01-01

    Heliospheric observations of energetic particles have shown that, on long time averages, a consistent v^-5 power-law index arises even in the absence of transient events. This implies an ubiquitous acceleration process present in the solar wind that is required to generate these power-law tails and maintain them against adiabatic losses and coulomb-collisions which will cool and thermalize the plasma respectively. Though the details of this acceleration process are being debated within the community, most agree that the energy required for these tails comes from fluctuations in the magnetic field which are damped as the energy is transferred to particles. Given this source for the tail, is it then reasonable to assume that the turbulent LISM should give rise to such a power-law tail as well? IBEX observations clearly show a power-law tail of index approximately -5 in energetic neutral atoms. The simplest explanation for the origins of these ENAs are that they are energetic ions which have charge-exchanged with a neutral atom. However, this would imply that energetic ions possess a v^-5 power-law distribution at keV energies at the source of these ENAs. If the source is presumed to be the LISM, it provides additional options for explaining the, so called, IBEX ribbon. This presentation will discuss some of these options as well as potential mechanisms for the generation of a power-law spectrum in the LISM.

  6. Degradation characteristics of methyl ethyl ketone by Pseudomonas sp. KT-3 in liquid culture and biofilter.

    PubMed

    Lee, Tae Ho; Kim, Jaisoo; Kim, Min-Joo; Ryu, Hee Wook; Cho, Kyung-Suk

    2006-04-01

    With ketone pollution forming an ever-growing problem, it is important to identify a ketone-degrading microorganism and establish its effect. Here, a methyl ethyl ketone (MEK)-degrading bacterium, Pseudomonas sp. KT-3, was isolated and its MEK degradation characteristics were examined in liquid cultures and a polyurethane-packed biofilter. In liquid cultures, strain KT-3 could degrade other ketone solvents, including diethyl ketone (DK), methyl propyl ketone (MPK), methyl isopropyl ketone (MIPK), methyl isobutyl ketone (MIBK), methyl butyl ketone (MBK) and methyl isoamyl ketone (MIAK). The maximum specific growth rate (mumax) of the isolate was 0.136 h(-1) in MEK medium supplemented with MEK as a sole carbon source, and kinetically, the maximum removal rate (Vm) and saturation constant (Km) for MEK were 12.28 mM g(-1)DCW h(-1) (DCW: dry cell weight) and 1.64 mM, respectively. MEK biodegradation by KT-3 was suppressed by the addition of MIBK or acetone, but not by toluene. In the tested biofilter, KT-3 exhibited a>90% removal efficiency for MEK inlet concentrations of around 500 ppmv at a space velocity (SV) of 150 h(-1). The elimination capacity of MEK was more influenced by SV than by the inlet concentration. Kinetic analysis showed that the maximum MEK removal rate (Vm) was 690 g m(-3) h(-1) and the saturation constant (Km) was 490 ppmv. Collectively, these results indicate the polyurethane sequencing batch biofilter with Pseudomonas sp. KT-3 will provide an excellent performance in the removal of gaseous MEK.

  7. Value of point-of-care ketones in assessing dehydration and acidosis in children with gastroenteritis.

    PubMed

    Levy, Jason A; Waltzman, Mark; Monuteaux, Michael C; Bachur, Richard G

    2013-11-01

    Children with gastroenteritis often develop dehydration with metabolic acidosis. Serum ketones are frequently elevated in this population. The goal was to determine the relationship between initial serum ketone concentration and both the degree of dehydration and the magnitude of acidosis. This was a secondary analysis of a prospective trial of crystalloid administration for rapid rehydration. Children 6 months to 6 years of age with gastroenteritis and dehydration were enrolled. A point-of-care serum ketone (beta-hydroxybutyrate) concentration was obtained at the time of study enrollment. The relationship between initial serum ketone concentration and a prospectively assigned and previously validated clinical dehydration score, and serum bicarbonate concentration, was analyzed. A total of 188 patients were enrolled. The median serum ketone concentration was elevated at 3.1 mmol/L (interquartile range [IQR] = 1.2 to 4.6 mmol/L), and the median dehydration score was consistent with moderate dehydration. A significant positive relationship was found between serum ketone concentration and the clinical dehydration score (Spearman's rho = 0.22, p = 0.003). Patients with moderate dehydration had a higher median serum ketone concentration than those with mild dehydration (3.6 mmol/L vs. 1.4 mmol/L, p = 0.007). Additionally, the serum ketone concentration was inversely correlated with serum bicarbonate concentration (ρ = -0.26, p < 0.001). Children with gastroenteritis and dehydration have elevated serum ketone concentrations that correlate with both degree of dehydration and magnitude of metabolic acidosis. Point-of-care serum ketone measurement may be a useful tool to inform management decisions at the point of triage or in the initial evaluation of children with gastroenteritis and dehydration. © 2013 by the Society for Academic Emergency Medicine.

  8. 40 CFR 63.61 - Deletion of methyl ethyl ketone from the list of hazardous air pollutants.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Deletion of methyl ethyl ketone from... Designations, Source Category List § 63.61 Deletion of methyl ethyl ketone from the list of hazardous air pollutants. The substance methyl ethyl ketone (MEK, 2-Butanone) (CAS Number 78-93-3) is deleted from the list...

  9. 40 CFR 63.61 - Deletion of methyl ethyl ketone from the list of hazardous air pollutants.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 10 2014-07-01 2014-07-01 false Deletion of methyl ethyl ketone from... Designations, Source Category List § 63.61 Deletion of methyl ethyl ketone from the list of hazardous air pollutants. The substance methyl ethyl ketone (MEK, 2-Butanone) (CAS Number 78-93-3) is deleted from the list...

  10. 40 CFR 63.61 - Deletion of methyl ethyl ketone from the list of hazardous air pollutants.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 10 2012-07-01 2012-07-01 false Deletion of methyl ethyl ketone from... Designations, Source Category List § 63.61 Deletion of methyl ethyl ketone from the list of hazardous air pollutants. The substance methyl ethyl ketone (MEK, 2-Butanone) (CAS Number 78-93-3) is deleted from the list...

  11. DMF Dimethyl Acetal as Carbon Source for α-Methylation of Ketones: A Hydrogenation-Hydrogenolysis Strategy of Enaminones.

    PubMed

    Borah, Ashwini; Goswami, Limi; Neog, Kashmiri; Gogoi, Pranjal

    2015-05-01

    A novel heterogeneous catalytic hydrogenation-hydrogenolysis strategy has been developed for the α-methylation of ketones via enaminones using DMF dimethyl acetal as carbon source. This strategy provides a very convenient route to α-methylated ketones using a variety of ketones without any base or oxidant.

  12. 40 CFR 63.61 - Deletion of methyl ethyl ketone from the list of hazardous air pollutants.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 10 2013-07-01 2013-07-01 false Deletion of methyl ethyl ketone from... Designations, Source Category List § 63.61 Deletion of methyl ethyl ketone from the list of hazardous air pollutants. The substance methyl ethyl ketone (MEK, 2-Butanone) (CAS Number 78-93-3) is deleted from the list...

  13. Aryl ketone synthesis via tandem orthoplatinated triarylphosphite-catalyzed addition reactions of arylboronic acids with aldehydes followed by oxidation.

    PubMed

    Liao, Yuan-Xi; Hu, Qiao-Sheng

    2010-10-15

    Tandem orthoplatinated triaryl phosphite-catalyzed addition reactions of arylboronic acids with aldehydes followed by oxidation to yield aryl ketones is described. 3-Pentanone was identified as a suitable oxidant for the tandem aryl ketone formation reaction. By using microwave energy, aryl ketones were obtained in high yields with the catalyst loading as low as 0.01%.

  14. 40 CFR 63.61 - Deletion of methyl ethyl ketone from the list of hazardous air pollutants.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Deletion of methyl ethyl ketone from... Designations, Source Category List § 63.61 Deletion of methyl ethyl ketone from the list of hazardous air pollutants. The substance methyl ethyl ketone (MEK, 2-Butanone) (CAS Number 78-93-3) is deleted from the list...

  15. Aryl Ketone Synthesis via Tandem Orthoplatinated Triarylphosphite-Catalyzed Addition Reactions of Arylboronic Acids with Aldehydes Followed by Oxidation

    PubMed Central

    Liao, Yuan-Xi; Hu, Qiao-Sheng

    2010-01-01

    Tandem orthoplatinated triarylphosphite-catalyzed addition reactions of arylboronic acids with aldehydes followed by oxidation to yield aryl ketones is described. 3-Pentanone was identified as a suitable oxidant for the tandem aryl ketone formation reaction. By using microwave energy, aryl ketones were obtained in high yields with the catalyst loading as low as 0.01%. PMID:20849092

  16. Low temperature (550-700 K) oxidation pathways of cyclic ketones: Dominance of HO2-elimination channels yielding conjugated cyclic coproducts

    DOE PAGES

    Scheer, Adam M.; Welz, Oliver; Vasu, Subith S.; ...

    2015-04-13

    The low-temperature oxidation of three cyclic ketones, cyclopentanone (CPO; C5H8O), cyclohexanone (CHO; C6H10 O), and 2-methyl-cyclopentanone (2-Me-CPO; CH3–C5H7 O), is studied between 550 and 700 K and at 4 or 8 Torr total pressure. Initial fuel radicals R are formedvia fast H-abstraction from the ketones by laser-photolytically generated chlorine atoms. Intermediates and products from the subsequent reactions of these radicals in the presence of excess O2 are probed with time and isomeric resolution using multiplexed photoionization mass spectrometry with tunable synchrotron ionizing radiation. For CPO and CHO the dominant product channel in the R + O2 reactions is chain-terminating HO2-eliminationmore » yielding the conjugated cyclic coproducts 2-cyclopentenone and 2-cyclohexenone, respectively. Results on oxidation of 2-Me-CPO also show a dominant contribution from HO2-elimination. Moreover, the photoionization spectrum of the co-product suggests formation of 2-methyl-2-cyclopentenone and/or 2-cyclohexenone, resulting from a rapid Dowd–Beckwith rearrangement, preceding addition to O2, of the initial (2-oxocyclopentyl)methyl radical to 3-oxocyclohexyl. Cyclic ethers, markers for hydroperoxyalkyl radicals (QOOH), key intermediates in chain-propagating and chain-branching low-temperature combustion pathways, are only minor products. The interpretation of the experimental results is supported by stationary point calculations on the potential energy surfaces of the associated R + O2 reactions at the CBS-QB3 level. Furthermore, the calculations indicate that HO2-elimination channels are energetically favored and product formation via QOOH is disfavored. Lastly, the prominence of chain-terminating pathways linked with HO2 formation in low-temperature oxidation of cyclic ketones suggests little low-temperature reactivity of these species as fuels in internal combustion engines.« less

  17. Low temperature (550-700 K) oxidation pathways of cyclic ketones: dominance of HO2-elimination channels yielding conjugated cyclic coproducts.

    PubMed

    Scheer, Adam M; Welz, Oliver; Vasu, Subith S; Osborn, David L; Taatjes, Craig A

    2015-05-14

    The low-temperature oxidation of three cyclic ketones, cyclopentanone (CPO; C5H8=O), cyclohexanone (CHO; C6H10=O), and 2-methyl-cyclopentanone (2-Me-CPO; CH3-C5H7=O), is studied between 550 and 700 K and at 4 or 8 Torr total pressure. Initial fuel radicals R are formed via fast H-abstraction from the ketones by laser-photolytically generated chlorine atoms. Intermediates and products from the subsequent reactions of these radicals in the presence of excess O2 are probed with time and isomeric resolution using multiplexed photoionization mass spectrometry with tunable synchrotron ionizing radiation. For CPO and CHO the dominant product channel in the R + O2 reactions is chain-terminating HO2-elimination yielding the conjugated cyclic coproducts 2-cyclopentenone and 2-cyclohexenone, respectively. Results on oxidation of 2-Me-CPO also show a dominant contribution from HO2-elimination. The photoionization spectrum of the co-product suggests formation of 2-methyl-2-cyclopentenone and/or 2-cyclohexenone, resulting from a rapid Dowd-Beckwith rearrangement, preceding addition to O2, of the initial (2-oxocyclopentyl)methyl radical to 3-oxocyclohexyl. Cyclic ethers, markers for hydroperoxyalkyl radicals (QOOH), key intermediates in chain-propagating and chain-branching low-temperature combustion pathways, are only minor products. The interpretation of the experimental results is supported by stationary point calculations on the potential energy surfaces of the associated R + O2 reactions at the CBS-QB3 level. The calculations indicate that HO2-elimination channels are energetically favored and product formation via QOOH is disfavored. The prominence of chain-terminating pathways linked with HO2 formation in low-temperature oxidation of cyclic ketones suggests little low-temperature reactivity of these species as fuels in internal combustion engines.

  18. Computational rationalization of the selective C-H and C-F activations of fluoroaromatic imines and ketones by cobalt complexes.

    PubMed

    Li, Jingjing; Zhang, Dongju; Sun, Hongjian; Li, Xiaoyan

    2014-03-28

    While selective C-H and C-F activations of fluoroaromatic imines and ketones with transition metal complexes supported by PMe3 have been successfully achieved in recent publications, insight into the molecular mechanism and energetics of those reactions is still lacking. Focusing on three typical substrates, 2,6-difluorobenzophenone imine (A) and 2,6-difluorobenzophenone (B), and 2,4'-difluorobenzophenone (C), the present work theoretically studied their C-H and C-F cyclometalation reactions promoted by the activator Co(PMe3)4 or CoMe(PMe3)4. It is found that reaction A + Co(PMe3)4 favors the C-F activation, reaction A + CoMe(PMe3)4 prefers the C-H activation, whereas both the C-H and C-F activation pathways may be viable for reactions B + CoMe(PMe3)4 and C + CoMe(PMe3)4. The experimentally observed C-H and C-F cyclometalation products have been rationalized by analyzing the thermodynamic and kinetic properties of two activation pathways. From calculated results combined with the experimental observations, we believe that three factors, i.e. the oxidation state of the metal center in the activators, the anchoring group of substrates, and substituted fluoroatom counts of the aromatic ring in substrates, affect the selectivity of C-H and C-F activations of fluoroaromatic ketones and imines. Calculated results are enlightening about the rational design of activators and substrates of fluoroaromatic imines and ketones to obtain the exclusive C-H or C-F bond activation product.

  19. [Synthesis and immunosuppressive effects of novel phthalazine ketone derivatives].

    PubMed

    Wang, Ya-Li; Wang, Qing-He; Yang, Hong-Guang; Hao, Bo-Jun; Liang, Guo-Dong; Jiang, Chong-Guo; Cheng, Mao-Sheng

    2013-10-01

    A series of phthalazine ketone compounds were synthesized and the structures were confirmed by H NMR and HR-MS spectrum. All target compounds were obtained through 7 steps, including selective reduction, nitration, bromination, ring enlargement, reduction, Knoevenagel and acylated reaction. The compounds were evaluated for their immunosuppressive effects of T-cell proliferation and inhibitory activity of IMPDH type II in vitro, as well as their structure-activity relationship were assessed. Several compounds exhibited strong immunosuppressive properties, especially compounds 7f and 7h, with IC50 values of 0.093 micromol x L(-1) and 0.14 micromol x L(-1) respectively, which were superior to mycophenolic acid. The information obtained from the studies may be useful for further research on the immunosuppressive agents.

  20. The rotational spectrum of Roesky’s ketone

    NASA Astrophysics Data System (ADS)

    Blockhuys, Frank; Tersago, Karla; Shlykov, Sergey A.; Konrad, Alexander; Christen, Dines

    2010-08-01

    The experimental rotational spectrum of 5-oxo-1,3,2,4-dithiadiazole (Roesky's ketone) has been recorded and the experimental rotational constants have been determined. The latter have been used to evaluate the performance of a large number of quantum chemical methods combined with different basis sets, by comparing the calculated with the experimental values. The results of this comparison indicate that, in general, the wave-function-based methods perform better than those from Density Functional Theory. Four of the 42 investigated method/basis set combinations prove to be the most valuable, i.e., MP4(SDQ)/(aug-)cc-pVTZ, B3PW91/cc-pV(T+d)Z and MPW1PW91/aug-cc-pVTZ, as they produce rotational constants with a root-mean-square deviation from the experimental values of only about 5 MHz.

  1. Chain-extended poly(aryl ether ketones)

    SciTech Connect

    Robeson, L.M.; Winslow, P.A.; Matzner, M.; Harris, J.E.; Maresca, L.M.

    1992-06-09

    This patent describes a process for preparing a poly(aryl ether ketone) polymer. It comprises reacting (n) moles of HAr H with (n + 1) moles of YCOAr{sub 1}COY under Friedel-Crafts polymerization conditions; reacting the product obtained with 2XAR{sub 2}H under Friedel-Crafts polymerization conditions; reacting the product obtained with HOAr{sub 3}OH in the presence of a base and an aprotic solvent; wherein Ar and Ar{sub 1} are divalent aromatic groups, Ar{sub 2} is a divalent aromatic group wherein the substituents X and CO are in para or ortho position relative to each other, Ar{sub 3} is a residue of a dihydric phenol, X and Y are halogen, n is an integer of 1 to 50 and X is one or greater.

  2. Synthesis of ketones from biomass-derived feedstock

    NASA Astrophysics Data System (ADS)

    Meng, Qinglei; Hou, Minqiang; Liu, Huizhen; Song, Jinliang; Han, Buxing

    2017-01-01

    Cyclohexanone and its derivatives are very important chemicals, which are currently produced mainly by oxidation of cyclohexane or alkylcyclohexane, hydrogenation of phenols, and alkylation of cyclohexanone. Here we report that bromide salt-modified Pd/C in H2O/CH2Cl2 can efficiently catalyse the transformation of aromatic ethers, which can be derived from biomass, to cyclohexanone and its derivatives via hydrogenation and hydrolysis processes. The yield of cyclohexanone from anisole can reach 96%, and the yields of cyclohexanone derivatives produced from the aromatic ethers, which can be extracted from plants or derived from lignin, are also satisfactory. Detailed study shows that the Pd, bromide salt and H2O/CH2Cl2 work cooperatively to promote the desired reaction and inhibit the side reaction. Thus high yields of desired products can be obtained. This work opens the way for production of ketones from aromatic ethers that can be derived from biomass.

  3. Thionation of some alpha,beta-unsaturated steroidal ketones.

    PubMed

    Krstić, Natalija M; Bjelaković, Mira S; Dabović, Milan M; Pavlović, Vladimir D

    2010-05-12

    The reactions of selected alpha,beta-unsaturated steroidal ketones with Lawesson's reagent (LR) in CH(2)Cl(2) and toluene under the standard reaction conditions and with a combination of phosphorus pentasulfide with hexamethyldisiloxane (P(4)S(10)/HMDO) in 1,2-dichlorobenzene (ODCB) under microwave irradiation were investigated and for this purpose several cholestane, androstane and pregnane carbonyl derivatives were chosen. Depending on the reagent and the solvent, 19 new sulfur containing compounds, including dithiones 4c and 4d, alpha,beta-unsaturated 3-thiones 3a-e, dimer-sulfides 2a-e, 1,2,4-trithiolanes 5a-e and phosphonotrithioates 6b-e were synthesized. All newly prepared compounds were characterized by IR, (1)H- and (13)C-NMR spectroscopy and elemental analysis.

  4. Electron impact ionization of cycloalkanes, aldehydes, and ketones

    SciTech Connect

    Gupta, Dhanoj; Antony, Bobby

    2014-08-07

    The theoretical calculations of electron impact total ionization cross section for cycloalkane, aldehyde, and ketone group molecules are undertaken from ionization threshold to 2 keV. The present calculations are based on the spherical complex optical potential formalism and complex scattering potential ionization contribution method. The results of most of the targets studied compare fairly well with the recent measurements, wherever available and the cross sections for many targets are predicted for the first time. The correlation between the peak of ionization cross sections with number of target electrons and target parameters is also reported. It was found that the cross sections at their maximum depend linearly with the number of target electrons and with other target parameters, confirming the consistency of the values reported here.

  5. Synthesis of ketones from biomass-derived feedstock

    PubMed Central

    Meng, Qinglei; Hou, Minqiang; Liu, Huizhen; Song, Jinliang; Han, Buxing

    2017-01-01

    Cyclohexanone and its derivatives are very important chemicals, which are currently produced mainly by oxidation of cyclohexane or alkylcyclohexane, hydrogenation of phenols, and alkylation of cyclohexanone. Here we report that bromide salt-modified Pd/C in H2O/CH2Cl2 can efficiently catalyse the transformation of aromatic ethers, which can be derived from biomass, to cyclohexanone and its derivatives via hydrogenation and hydrolysis processes. The yield of cyclohexanone from anisole can reach 96%, and the yields of cyclohexanone derivatives produced from the aromatic ethers, which can be extracted from plants or derived from lignin, are also satisfactory. Detailed study shows that the Pd, bromide salt and H2O/CH2Cl2 work cooperatively to promote the desired reaction and inhibit the side reaction. Thus high yields of desired products can be obtained. This work opens the way for production of ketones from aromatic ethers that can be derived from biomass. PMID:28139709

  6. SIMULATION OF ENERGETIC NEUTRAL ATOMS FROM SOLAR ENERGETIC PARTICLES

    SciTech Connect

    Wang, Linghua; Li, Gang; Shih, Albert Y.; Lin, Robert P.; Wimmer-Schweingruber, Robert F.

    2014-10-01

    Energetic neutral atoms (ENAs) provide the only way to observe the acceleration site of coronal-mass-ejection-driven (CME-driven) shock-accelerated solar energetic particles (SEPs). In gradual SEP events, energetic protons can charge exchange with the ambient solar wind or interstellar neutrals to become ENAs. Assuming a CME-driven shock with a constant speed of 1800 km s{sup –1} and compression ratio of 3.5, propagating from 1.5 to 40 R{sub S} , we calculate the accelerated SEPs at 5-5000 keV and the resulting ENAs via various charge-exchange interactions. Taking into account the ENA losses in the interplanetary medium, we obtain the flux-time profiles of these solar ENAs reaching 1 AU. We find that the arriving ENAs at energies above ∼100 keV show a sharply peaked flux-time profile, mainly originating from the shock source below 5 R{sub S} , whereas the ENAs below ∼20 keV have a flat-top time profile, mostly originating from the source beyond 10 R{sub S} . Assuming the accelerated protons are effectively trapped downstream of the shock, we can reproduce the STEREO ENA fluence observations at ∼2-5 MeV/nucleon. We also estimate the flux of ENAs coming from the charge exchange of energetic storm protons, accelerated by the fast CME-driven shock near 1 AU, with interstellar hydrogen and helium. Our results suggest that appropriate instrumentation would be able to detect ENAs from SEPs and to even make ENA images of SEPs at energies above ∼10-20 keV.

  7. Biofiltration of ketone compounds by a composite bead biofilter.

    PubMed

    Chan, Wu-Chung; Peng, Kang-Hong

    2008-05-01

    In this study, the biochemical kinetic behaviors of ketone compounds in a composite bead biofilter were investigated. Both microbial growth rate kg and biochemical reaction rate kd would be inhibited at higher average inlet concentration. For the microbial growth process, the inhibitive effect was the least pronounced for acetone and the order of kg value was MEK>MIPK>acetone in the average inlet concentration range of 100-150 ppm. The degree of inhibitive effect was almost the same for three ketone compounds and the order of kg value was acetone>MEK>MIPK in the average inlet concentration range of 200-300 ppm. The values of half-saturation constant Ks for acetone, MEK and MIPK were 26.80, 21.56 and 22.96 ppm, respectively. The values of maximum reaction rate Vm for acetone, MEK and MIPK were 8.55, 9.06 and 7.55 g-C/h-kg packed material, respectively. The zero-order kinetic with the diffusion rate limitation could be regarded as the most adequate biochemical reaction model. For the biochemical reaction process, the inhibitive effect was the most pronounced for MEK and the order of kd value was MEK>acetone>MIPK in the average inlet concentration range of 100-150 ppm. The degree of inhibitive effect was MIPK>MEK>acetone and the order of kd value was acetone>MEK>MIPK in the average inlet concentration range of 200-300 ppm. The maximum elimination capacity of acetone, MEK and MIPK were 0.157, 0.127 and 0.101 g-C/h-kg packed material.

  8. Homogenization and lipase treatment of milk and resulting methyl ketone generation in blue cheese.

    PubMed

    Cao, Mingkai; Fonseca, Leorges M; Schoenfuss, Tonya C; Rankin, Scott A

    2014-06-25

    A specific range of methyl ketones contribute to the distinctive flavor of traditional blue cheeses. These ketones are metabolites of lipid metabolism by Penicillium mold added to cheese for this purpose. Two processes, namely, the homogenization of milk fat and the addition of exogenous lipase enzymes, are traditionally applied measures to control the formation of methyl ketones in blue cheese. There exists little scientific validation of the actual effects of these treatments on methyl ketone development. The present study evaluated the effects of milk fat homogenization and lipase treatments on methyl ketone and free fatty acid development using sensory methods and the comparison of selected volatile quantities using gas chromatography. Initial work was conducted using a blue cheese system model; subsequent work was conducted with manufactured blue cheese. In general, there were modest effects of homogenization and lipase treatments on free fatty acid (FFA) and methyl ketone concentrations in blue cheese. Blue cheese treatments involving Penicillium roqueforti lipase with homogenized milk yielded higher FFA and methyl ketone levels, for example, a ∼20-fold increase for hexanoic acid and a 3-fold increase in 2-pentanone.

  9. KETONES INHIBIT MITOCHONDRIAL PRODUCTION OF REACTIVE OXYGEN SPECIES PRODUCTION FOLLOWING GLUTAMATE EXCITOTOXICITY BY INCREASING NADH OXIDATION

    PubMed Central

    Maalouf, Marwan; Sullivan, Patrick G.; Davis, Laurie; Kim, Do Young; Rho, Jong M.

    2007-01-01

    Dietary protocols that increase serum levels of ketones, such as calorie restriction and the ketogenic diet, offer robust protection against a multitude of acute and chronic neurological diseases. The underlying mechanisms, however, remain unclear. Previous studies have suggested that the ketogenic diet may reduce free radical levels in the brain. Thus, one possibility is that ketones may mediate neuroprotection through antioxidant activity. In the present study, we examined the effects of the ketones β-hydroxybutyrate and acetoacetate on acutely dissociated rat neocortical neurons subjected to glutamate excitotoxicity using cellular electrophysiological and single-cell fluorescence imaging techniques. Further, we explored the effects of ketones on acutely isolated mitochondria exposed to high levels of calcium. A combination of β-hydroxybutyrate and acetoacetate (1 mM each) decreased neuronal death and prevented changes in neuronal membrane properties induced by 10 μM glutamate. Ketones also significantly decreased mitochondrial production of reactive oxygen species and the associated excitotoxic changes by increasing NADH oxidation in the mitochondrial respiratory chain, but did not affect levels of the endogenous antioxidant glutathione. In conclusion, we demonstrate that ketones reduce glutamate-induced free radical formation by increasing the NAD+/NADH ratio and enhancing mitochondrial respiration in neocortical neurons. This mechanism may, in part, contribute to the neuroprotective activity of ketones by restoring normal bioenergetic function in the face of oxidative stress. PMID:17240074

  10. Continuous flow synthesis of α-halo ketones: essential building blocks of antiretroviral agents.

    PubMed

    Pinho, Vagner D; Gutmann, Bernhard; Miranda, Leandro S M; de Souza, Rodrigo O M A; Kappe, C Oliver

    2014-02-21

    The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor. The anhydride is subsequently combined with anhydrous diazomethane in a tube-in-tube reactor. The tube-in-tube reactor consists of an inner tube, made from a gas-permeable, hydrophobic material, enclosed in a thick-walled, impermeable outer tube. Diazomethane is generated in the inner tube in an aqueous medium, and anhydrous diazomethane subsequently diffuses through the permeable membrane into the outer chamber. The α-diazo ketone is produced from the mixed anhydride and diazomethane in the outer chamber, and the resulting diazo ketone is finally converted to the halo ketone with anhydrous ethereal hydrogen halide. This method eliminates the need to store, transport, or handle diazomethane and produces α-halo ketone building blocks in a multistep system without racemization in excellent yields. A fully continuous process allowed the synthesis of 1.84 g of α-chloro ketone from the respective N-protected amino acid within ~4.5 h (87% yield).

  11. Synthesis of trifluoromethyl ketones via tandem Claisen condensation and retro-Claisen C-C bond-cleavage reaction.

    PubMed

    Yang, Dongmei; Zhou, Yuhan; Xue, Na; Qu, Jingping

    2013-04-19

    A highly efficient, operationally simple approach to trifluoromethyl ketones has been developed that builds on the use of a tandem process involving Claisen condensation and retro-Claisen C-C bond cleavage reaction. Enolizable alkyl phenyl ketones were found to react readily with ethyl trifuoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones, which were quite different from the general Claisen condensation products, β-diketones. This procedure uses readily available starting materials and can be extended to the preparation of perfluoroalkyl ketones in excellent yield.

  12. Ru (III) catalyzed oxidation of aliphatic ketones by N-bromosuccinimide in aqueous acetic acid: a kinetic study.

    PubMed

    Giridhar Reddy, P; Ramesh, K; Shylaja, S; Rajanna, K C; Kandlikar, S

    2012-01-01

    Kinetics of Ru (III) catalyzed oxidation of aliphatic ketones such as acetone, ethyl methyl ketone, diethyl ketone, iso-butylmethyl ketone by N-bromosuccinimide in the presence of Hg(II) acetate have been studied in aqueous acid medium. The order of [N-bromosuccinimide] was found to be zero both in catalyzed as well as uncatalyzed reactions. However, the order of [ketone] changed from unity to a fractional one in the presence of Ru (III). On the basis of kinetic features, the probable mechanisms are discussed and individual rate parameters evaluated.

  13. A new alternative to expandable pedicle screws: Expandable poly-ether-ether-ketone shell.

    PubMed

    Demir, Teyfik

    2015-05-01

    Screw pullout is a very common problem in the fixation of sacrum with pedicle screws. The principal cause of this problem is that the cyclic micro motions in the fixation of sacrum are higher than the other regions of the vertebrae that limit the osteo-integration between bone and screw. In addition to that, the bone quality is very poor at sacrum region. This study investigated a possible solution to the pullout problem without the expandable screws' handicaps. Newly designed poly-ether-ether-ketone expandable shell and classical pedicle screws were biomechanically compared. Torsion test, pullout tests, fatigue tests, flexion/extension moment test, axial gripping capacity tests and torsional gripping capacity tests were conducted in accordance with ASTM F543, F1798 and F1717. Standard polyurethane foam and calf vertebrae were used as embedding medium for pullout tests. Classical pedicle screw pullout load on polyurethane foam was 564.8 N compared to the failure load for calf vertebrae's 1264 N. Under the same test conditions, expandable poly-ether-ether-ketone shell system's pullout loads from polyurethane foam and calf vertebrae were 1196.3 and 1890 N, respectively. The pullout values for expandable poly-ether-ether-ketone shell were 33% and 53% higher than classical pedicle screw on polyurethane foam and calf vertebrae, respectively. The expandable poly-ether-ether-ketone shell exhibited endurance on its 90% of yield load. Contrary to poly-ether-ether-ketone shell, classical pedicle screw exhibited endurance on 70% of its yield load. Expandable poly-ether-ether-ketone shell exhibited much higher pullout performance than classical pedicle screw. Fatigue performance of expandable poly-ether-ether-ketone shell is also higher than classical pedicle screw due to damping the micro motion capacity of the poly-ether-ether-ketone. Expandable poly-ether-ether-ketone shell is a safe alternative to all other expandable pedicle screw systems on mechanical perspective.

  14. Energetic costs of cellular computation.

    PubMed

    Mehta, Pankaj; Schwab, David J

    2012-10-30

    Cells often perform computations in order to respond to environmental cues. A simple example is the classic problem, first considered by Berg and Purcell, of determining the concentration of a chemical ligand in the surrounding media. On general theoretical grounds, it is expected that such computations require cells to consume energy. In particular, Landauer's principle states that energy must be consumed in order to erase the memory of past observations. Here, we explicitly calculate the energetic cost of steady-state computation of ligand concentration for a simple two-component cellular network that implements a noisy version of the Berg-Purcell strategy. We show that learning about external concentrations necessitates the breaking of detailed balance and consumption of energy, with greater learning requiring more energy. Our calculations suggest that the energetic costs of cellular computation may be an important constraint on networks designed to function in resource poor environments, such as the spore germination networks of bacteria.

  15. Energetic costs of cellular computation

    PubMed Central

    Mehta, Pankaj; Schwab, David J.

    2012-01-01

    Cells often perform computations in order to respond to environmental cues. A simple example is the classic problem, first considered by Berg and Purcell, of determining the concentration of a chemical ligand in the surrounding media. On general theoretical grounds, it is expected that such computations require cells to consume energy. In particular, Landauer’s principle states that energy must be consumed in order to erase the memory of past observations. Here, we explicitly calculate the energetic cost of steady-state computation of ligand concentration for a simple two-component cellular network that implements a noisy version of the Berg–Purcell strategy. We show that learning about external concentrations necessitates the breaking of detailed balance and consumption of energy, with greater learning requiring more energy. Our calculations suggest that the energetic costs of cellular computation may be an important constraint on networks designed to function in resource poor environments, such as the spore germination networks of bacteria. PMID:23045633

  16. Cardiac energetics: sense and nonsense.

    PubMed

    Gibbs, Colin L

    2003-08-01

    1. The background to current ideas in cardiac energetics is outlined and, in the genomic era, the need is stressed for detailed knowledge of mouse heart mechanics and energetics. 2. The mouse heart is clearly different to the rat in terms of its excitation-contraction (EC) coupling and the common assumption that heart rate difference between mice and humans will account for the eightfold difference in myocardial oxygen consumption is wrong, because the energy per beat of the mouse heart is approximately one-third that of the human heart. 3. In vivo evidence suggests that there may well be an eightfold species difference in the non-beating metabolism of mice and human hearts. It is speculated that the magnitude of basal metabolism in the heart is regulatable and that, in the absence of perfusion, it falls to approximately one-quarter of its in vivo rate and that in clinical conditions, such as hibernation, it probably decreases; its magnitude may be controlled by the endothelium. 4. The active energy balance sheet is briefly discussed and it is suggested that the activation heat accounts for 20-25% of the active energy per beat and cross-bridge turnover accounts for the balance. It is argued that force, not shortening, is the major determinant of cardiac energy usage. 5. The outcome of recent cardiac modelling with variants of the Huxley and Hill/Eisenberg models is described. It has been necessary to invoke 'loose coupling' to replicate the low cardiac energy flux measured at low afterloads (medium to high velocities of shortening). 6. Lastly, some of the unexplained or 'nonsense' energetic data are outlined and eight unsolved problems in cardiac energetics are discussed.

  17. Iridium-Catalyzed Diastereoselective and Enantioselective Allylic Substitutions with Acyclic α-Alkoxy Ketones

    DOE PAGES

    Jiang, Xingyu; Chen, Wenyong; Hartwig, John F.

    2016-04-01

    The asymmetric alkylation of acyclic ketones is a longstanding challenge in organic synthesis. Here, are the diastereoselective and enantioselective allylic substitutions with acyclic α-alkoxy ketones catalyzed by a metallacyclic iridium complex to form products with contiguous stereogenic centers derived from the nucleophile and electrophile. These reactions occur between allyl methyl carbonates and unstabilized copper(I) enolates generated in situ from acyclic α-alkoxy ketones. The resulting products can be readily converted into enantioenriched tertiary alcohols and tetrahydrofuran derivatives without erosion of enantiomeric purity.

  18. Synthesis of α-Halo-α,α-Difluoromethyl Ketones by a Trifluoroacetate Release/Halogenation Protocol

    PubMed Central

    John, Jinu P.; Colby, David A.

    2011-01-01

    Three series of α-halo-α,α-difluoromethyl ketones are prepared from highly α-fluorinated gem-diols by exploiting the facile release of trifluoroacetate, followed by immediate trapping of the liberated α,α-difluoroenolate with an electrophilic chlorine, bromine, or iodine source. The products are typically isolated in good yields, even in the case of sensitive, α-iodo-α,α-difluoromethyl ketones. Also, we demonstrate that an α-iodo-α,α-difluoromethyl ketone will participate in a copper-promoted reaction to forge a new carbon–carbon bond. PMID:21995668

  19. Novel and Efficient Chromium(II)-Mediated Desulfonylation of α-Sulfonyl Ketone.

    PubMed

    Inanaga, Kazato; Fukuyama, Takashi; Kubota, Manabu; Komatsu, Yuki; Chiba, Hiroyuki; Kayano, Akio; Tagami, Katsuya

    2015-06-19

    A novel and efficient method for the Cr(II)-mediated desulfonylation of α-sulfonyl ketone by a Cr-ligand-Mn system has been developed during the course of process research on Halaven (eribulin mesylate). This reaction is dramatically accelerated in the presence of an appropriate bipyridyl-type ligand. This system is applicable to reduction of α-sulfur-substituted ketones. In addition, a Cr-Cp2ZrCl2-Mn catalytic system is also applicable to desulfonylation of α-sulfonyl ketone.

  20. Direct asymmetric amination of α-branched cyclic ketones catalyzed by a chiral phosphoric acid.

    PubMed

    Yang, Xiaoyu; Toste, F Dean

    2015-03-11

    Here we report the direct asymmetric amination of α-substituted cyclic ketones catalyzed by a chiral phosphoric acid, yielding products with a N-containing quaternary stereocenter in high yields and excellent enantioselectivities. Kinetic resolution of the starting ketone was also found to occur on some of the substrates under milder conditions, providing enantioenriched α-branched ketones, another important building block in organic synthesis. The utility of this methodology was demonstrated in the short synthesis of (S)-ketamine, the more active enantiomer of this versatile pharmaceutical.

  1. Direct Asymmetric Amination of α-Branched Cyclic Ketones Catalyzed by a Chiral Phosphoric Acid

    PubMed Central

    Yang, Xiaoyu; Toste, F. Dean

    2015-01-01

    Here we report the direct asymmetric amination of α-substituted cyclic ketones catalyzed by a chiral phosphoric acid, yielding products with a N-containing quaternary stereocenter in high yields and excellent enantioselectivities. Kinetic resolution of the starting ketone was also found to occur on some of the substrates under milder conditions, providing enantio-enriched α-branched ketones, another important building block in organic synthesis. The utility of this methodology was demonstrated in the short synthesis of (S)-ketamine, the more active enantiomer of this versatile pharmaceutical. PMID:25719604

  2. Energetic Charged Particles Above Thunderclouds

    NASA Astrophysics Data System (ADS)

    Füllekrug, Martin; Diver, Declan; Pinçon, Jean-Louis; Phelps, Alan D. R.; Bourdon, Anne; Helling, Christiane; Blanc, Elisabeth; Honary, Farideh; Harrison, R. Giles; Sauvaud, Jean-André; Renard, Jean-Baptiste; Lester, Mark; Rycroft, Michael; Kosch, Mike; Horne, Richard B.; Soula, Serge; Gaffet, Stéphane

    2013-01-01

    The French government has committed to launch the satellite TARANIS to study transient coupling processes between the Earth's atmosphere and near-Earth space. The prime objective of TARANIS is to detect energetic charged particles and hard radiation emanating from thunderclouds. The British Nobel prize winner C.T.R. Wilson predicted lightning discharges from the top of thunderclouds into space almost a century ago. However, new experiments have only recently confirmed energetic discharge processes which transfer energy from the top of thunderclouds into the upper atmosphere and near-Earth space; they are now denoted as transient luminous events, terrestrial gamma-ray flashes and relativistic electron beams. This meeting report builds on the current state of scientific knowledge on the physics of plasmas in the laboratory and naturally occurring plasmas in the Earth's atmosphere to propose areas of future research. The report specifically reflects presentations delivered by the members of a novel Franco-British collaboration during a meeting at the French Embassy in London held in November 2011. The scientific subjects of the report tackle ionization processes leading to electrical discharge processes, observations of transient luminous events, electromagnetic emissions, energetic charged particles and their impact on the Earth's atmosphere. The importance of future research in this area for science and society, and towards spacecraft protection, is emphasized.

  3. Energetic Neutral Atom Precipitation (ENAP)

    NASA Technical Reports Server (NTRS)

    Tinsley, B. A.

    1988-01-01

    The Energetic Neutral Atom Precipitation experiment is scheduled to be flown on the Atmospheric Laboratory for Applications and Science (ATLAS 1) NASA mission. The objective of this experiment is to measure very faint emissions at nighttime arising from fluxes of energetic neutral atoms in the thermosphere. These energetic atoms have energies ranging up to about 50 keV, and arise from ions of hydrogen, helium, and oxygen trapped in the inner magnetosphere. Some of these ions become neutralized in charge exchange reactions with neutral hydrogen in the hydrogen geocorona that extends through the region. The ions are trapped on magnetic field lines which cross the equatorial plane at 2 to 6 earth radii distance, and they mirror at a range of heights on these field lines, extending down to the thermosphere at 500 km altitude. The ATLAS 1 measurements will not be of the neutral atoms themselves but of the optical emission produced by those on trajectories that intersect the thermosphere. The ENAP measurements are to be made using the Imaging Spectrometric Observatory (ISO) which is being flown on the ATLAS mission primarily for daytime spectral observations, and the ENAP measurements will all be nighttime measurements because of the faintness of the emissions and the relatively low level of magnetic activity expected.

  4. Energetic ions in ITER plasmas

    SciTech Connect

    Pinches, S. D.; Chapman, I. T.; Sharapov, S. E.; Lauber, Ph. W.; Oliver, H. J. C.; Shinohara, K.; Tani, K.

    2015-02-15

    This paper discusses the behaviour and consequences of the expected populations of energetic ions in ITER plasmas. It begins with a careful analytic and numerical consideration of the stability of Alfvén Eigenmodes in the ITER 15 MA baseline scenario. The stability threshold is determined by balancing the energetic ion drive against the dominant damping mechanisms and it is found that only in the outer half of the plasma (r/a>0.5) can the fast ions overcome the thermal ion Landau damping. This is in spite of the reduced numbers of alpha-particles and beam ions in this region but means that any Alfvén Eigenmode-induced redistribution is not expected to influence the fusion burn process. The influence of energetic ions upon the main global MHD phenomena expected in ITER's primary operating scenarios, including sawteeth, neoclassical tearing modes and Resistive Wall Modes, is also reviewed. Fast ion losses due to the non-axisymmetric fields arising from the finite number of toroidal field coils, the inclusion of ferromagnetic inserts, the presence of test blanket modules containing ferromagnetic material, and the fields created by the Edge Localised Mode (ELM) control coils in ITER are discussed. The greatest losses and associated heat loads onto the plasma facing components arise due to the use of the ELM control coils and come from neutral beam ions that are ionised in the plasma edge.

  5. Process for preparing energetic materials

    DOEpatents

    Simpson, Randall L [Livermore, CA; Lee, Ronald S [Livermore, CA; Tillotson, Thomas M [Tracy, CA; Hrubesh, Lawrence W [Pleasanton, CA; Swansiger, Rosalind W [Livermore, CA; Fox, Glenn A [Livermore, CA

    2011-12-13

    Sol-gel chemistry is used for the preparation of energetic materials (explosives, propellants and pyrotechnics) with improved homogeneity, and/or which can be cast to near-net shape, and/or made into precision molding powders. The sol-gel method is a synthetic chemical process where reactive monomers are mixed into a solution, polymerization occurs leading to a highly cross-linked three dimensional solid network resulting in a gel. The energetic materials can be incorporated during the formation of the solution or during the gel stage of the process. The composition, pore, and primary particle sizes, gel time, surface areas, and density may be tailored and controlled by the solution chemistry. The gel is then dried using supercritical extraction to produce a highly porous low density aerogel or by controlled slow evaporation to produce a xerogel. Applying stress during the extraction phase can result in high density materials. Thus, the sol-gel method can be used for precision detonator explosive manufacturing as well as producing precision explosives, propellants, and pyrotechnics, along with high power composite energetic materials.

  6. Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes

    DOE PAGES

    Griffith, David A.; Kung, Daniel W.; Esler, William P.; ...

    2014-11-25

    Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. We disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate formore » the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. In conclusion, this demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.« less

  7. Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes

    SciTech Connect

    Griffith, David A.; Kung, Daniel W.; Esler, William P.; Amor, Paul A.; Bagley, Scott W.; Beysen, Carine; Carvajal-Gonzalez, Santos; Doran, Shawn D.; Limberakis, Chris; Mathiowetz, Alan M.; McPherson, Kirk; Price, David A.; Ravussin, Eric; Sonnenberg, Gabriele E.; Southers, James A.; Sweet, Laurel J.; Turner, Scott M.; Vajdos, Felix F.

    2014-11-25

    Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. We disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate for the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. In conclusion, this demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.

  8. Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes

    SciTech Connect

    Griffith, David A.; Kung, Daniel W.; Esler, William P.; Amor, Paul A.; Bagley, Scott W.; Beysen, Carine; Carvajal-Gonzalez, Santos; Doran, Shawn D.; Limberakis, Chris; Mathiowetz, Alan M.; McPherson, Kirk; Price, David A.; Ravussin, Eric; Sonnenberg, Gabriele E.; Southers, James A.; Sweet, Laurel J.; Turner, Scott M.; Vajdos, Felix F.

    2014-12-26

    We found that Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. Here, we disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate for the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. This demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease.

  9. Decreasing the Rate of Metabolic Ketone Reduction in the Discovery of a Clinical Acetyl-CoA Carboxylase Inhibitor for the Treatment of Diabetes

    PubMed Central

    2015-01-01

    Acetyl-CoA carboxylase (ACC) inhibitors offer significant potential for the treatment of type 2 diabetes mellitus (T2DM), hepatic steatosis, and cancer. However, the identification of tool compounds suitable to test the hypothesis in human trials has been challenging. An advanced series of spirocyclic ketone-containing ACC inhibitors recently reported by Pfizer were metabolized in vivo by ketone reduction, which complicated human pharmacology projections. We disclose that this metabolic reduction can be greatly attenuated through introduction of steric hindrance adjacent to the ketone carbonyl. Incorporation of weakly basic functionality improved solubility and led to the identification of 9 as a clinical candidate for the treatment of T2DM. Phase I clinical studies demonstrated dose-proportional increases in exposure, single-dose inhibition of de novo lipogenesis (DNL), and changes in indirect calorimetry consistent with increased whole-body fatty acid oxidation. This demonstration of target engagement validates the use of compound 9 to evaluate the role of DNL in human disease. PMID:25423286

  10. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease.

    PubMed

    Kashiwaya, Yoshihiro; Bergman, Christian; Lee, Jong-Hwan; Wan, Ruiqian; King, M Todd; Mughal, Mohamed R; Okun, Eitan; Clarke, Kieran; Mattson, Mark P; Veech, Richard L

    2013-06-01

    Alzheimer's disease (AD) involves progressive accumulation of amyloid β-peptide (Aβ) and neurofibrillary pathologies, and glucose hypometabolism in brain regions critical for memory. The 3xTgAD mouse model was used to test the hypothesis that a ketone ester-based diet can ameliorate AD pathogenesis. Beginning at a presymptomatic age, 2 groups of male 3xTgAD mice were fed a diet containing a physiological enantiomeric precursor of ketone bodies (KET) or an isocaloric carbohydrate diet. The results of behavioral tests performed at 4 and 7 months after diet initiation revealed that KET-fed mice exhibited significantly less anxiety in 2 different tests. 3xTgAD mice on the KET diet also exhibited significant, albeit relatively subtle, improvements in performance on learning and memory tests. Immunohistochemical analyses revealed that KET-fed mice exhibited decreased Aβ deposition in the subiculum, CA1 and CA3 regions of the hippocampus, and the amygdala. KET-fed mice exhibited reduced levels of hyperphosphorylated tau deposition in the same regions of the hippocampus, amygdala, and cortex. Thus, a novel ketone ester can ameliorate proteopathic and behavioral deficits in a mouse AD model.

  11. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer’s disease

    PubMed Central

    Kashiwaya, Yoshihiro; Bergman, Christian; Lee, Jong-Hwan; Wan, Ruiqian; King, M. Todd; Mughal, Mohamed R.; Okun, Eitan; Clarke, Kieran; Mattson, Mark P.; Veech, Richard L.

    2013-01-01

    Alzheimer’s disease (AD) involves progressive accumulation of amyloid β-peptide (Aβ) and neurofibrillary pathologies, and glucose hypometabolism in brain regions critical for memory. The 3xTgAD mouse model was used to test the hypothesis that a ketone ester–based diet can ameliorate AD pathogenesis. Beginning at a presymptomatic age, 2 groups of male 3xTgAD mice were fed a diet containing a physiological enantiomeric precursor of ketone bodies (KET) or an isocaloric carbohydrate diet. The results of behavioral tests performed at 4 and 7 months after diet initiation revealed that KET-fed mice exhibited significantly less anxiety in 2 different tests. 3xTgAD mice on the KET diet also exhibited significant, albeit relatively subtle, improvements in performance on learning and memory tests. Immunohistochemical analyses revealed that KET-fed mice exhibited decreased Aβ deposition in the subiculum, CA1 and CA3 regions of the hippocampus, and the amygdala. KET-fed mice exhibited reduced levels of hyperphosphorylated tau deposition in the same regions of the hippocampus, amygdala, and cortex. Thus, a novel ketone ester can ameliorate proteopathic and behavioral deficits in a mouse AD model. PMID:23276384

  12. An experimental study of the combined effects of n-hexane and methyl ethyl ketone.

    PubMed Central

    Takeuchi, Y; Ono, Y; Hisanaga, N; Iwata, M; Aoyama, M; Kitoh, J; Sugiura, Y

    1983-01-01

    This study was intended to determine whether or not methyl ethyl ketone (MEK) enhances the neurotoxicity of n-hexane at low concentration and after long term exposure. Separate groups of eight rats were exposed to 100 ppm n-hexane, 200 ppm MEK, 100 ppm n-hexane plus 200 ppm MEK, or fresh air in an exposure chamber for 12 hours a day for 24 weeks. The body weight, motor nerve conduction velocity (MCV), distal motor latency (DL), and mixed nerve conduction velocities (MNCVs) were measured before exposure and after four, eight, 12, 16, 20, and 24 weeks' exposure. One rat of each group was histopathologically examined after 24 weeks' exposure. Exposure of 100 ppm n-hexane did not significantly decrease the functions of the peripheral nerve throughout the experiment. Exposure to 200 ppm MEK significantly increased MCV and MNCVs and decreased DL after four weeks' exposure, but at this later stage no significant changes were found throughout the experiment by comparison with the controls. Mixed exposure to 100 ppm n-hexane plus 200 ppm MEK significantly decreased by comparison with the controls. On histopathological examination of the tail nerve, however, no changes were found in any of the exposed groups or the controls. These results suggest that MEK might enhance the neurotoxicity of n-hexane at a low concentration, and mixed exposures to n-hexane and MEK should be avoided. PMID:6830718

  13. Virtual Energetic Particle Observatory (VEPO)

    NASA Technical Reports Server (NTRS)

    Cooper, John F.; Lal, Nand; McGuire, Robert E.; Szabo, Adam; Narock, Thomas W.; Armstrong, Thomas P.; Manweiler, Jerry W.; Patterson, J. Douglas; Hill, Matthew E.; Vandergriff, Jon D.; McKibben, Robert B.; Lopate, Clifford; Tranquille, Cecil

    2008-01-01

    The Virtual Energetic Particle Observatory (VEPO) focuses on improved discovery, access, and usability of heliospheric energetic particle and ancillary data products from selected spacecraft and sub-orbital instruments of the heliophysics data environment. The energy range of interest extends over the full range of particle acceleration from keV energies of suprathermal seed particles to GeV energies of galactic cosmic ray particles. Present spatial coverage is for operational and legacy spacecraft operating from the inner to the outer heliosphere, e.g. from measurements by the two Helios spacecraft to 0.3 AU to the inner heliosheath region now being traversed by the two Voyager spacecraft. This coverage will eventually be extended inward to ten solar radii by the planned NASA solar probe mission and at the same time beyond the heliopause into the outer heliosheath by continued Voyager operations. The geospace fleet of spacecraft providing near-Earth interplanetary measurements, selected magnetospheric spacecraft providing direct measurements of penetrating interplanetary energetic particles, and interplanetary cruise measurements from planetary spacecraft missions further extend VEPO resources to the domain of geospace and planetary interactions. Ground-based (e.g., neutron monitor) and high-altitude suborbital measurements can expand coverage to the highest energies of galactic cosmic rays affected by heliospheric interaction and of solar energetic particles. Science applications include investigation of solar flare and coronal mass ejection events. acceleration and transport of interplanetary particles within the inner heliosphere, cosmic ray interactions with planetary surfaces and atmospheres, sources of suprathermal and anomalous cosmic ray ions in the outer heliosphere, and solar cycle modulation of galactic cosmic rays. Robotic and human exploration, and eventual habitation, of planetary and space environments beyond the Earth require knowledge of radiation

  14. Virtual Energetic Particle Observatory (VEPO)

    NASA Technical Reports Server (NTRS)

    Cooper, John F.; Lal, Nand; McGuire, Robert E.; Szabo, Adam; Narock, Thomas W.; Armstrong, Thomas P.; Manweiler, Jerry W.; Patterson, J. Douglas; Hill, Matthew E.; Vandergriff, Jon D.; hide

    2008-01-01

    The Virtual Energetic Particle Observatory (VEPO) focuses on improved discovery, access, and usability of heliospheric energetic particle and ancillary data products from selected spacecraft and sub-orbital instruments of the heliophysics data environment. The energy range of interest extends over the full range of particle acceleration from keV energies of suprathermal seed particles to GeV energies of galactic cosmic ray particles. Present spatial coverage is for operational and legacy spacecraft operating from the inner to the outer heliosphere, e.g. from measurements by the two Helios spacecraft to 0.3 AU to the inner heliosheath region now being traversed by the two Voyager spacecraft. This coverage will eventually be extended inward to ten solar radii by the planned NASA solar probe mission and at the same time beyond the heliopause into the outer heliosheath by continued Voyager operations. The geospace fleet of spacecraft providing near-Earth interplanetary measurements, selected magnetospheric spacecraft providing direct measurements of penetrating interplanetary energetic particles, and interplanetary cruise measurements from planetary spacecraft missions further extend VEPO resources to the domain of geospace and planetary interactions. Ground-based (e.g., neutron monitor) and high-altitude suborbital measurements can expand coverage to the highest energies of galactic cosmic rays affected by heliospheric interaction and of solar energetic particles. Science applications include investigation of solar flare and coronal mass ejection events. acceleration and transport of interplanetary particles within the inner heliosphere, cosmic ray interactions with planetary surfaces and atmospheres, sources of suprathermal and anomalous cosmic ray ions in the outer heliosphere, and solar cycle modulation of galactic cosmic rays. Robotic and human exploration, and eventual habitation, of planetary and space environments beyond the Earth require knowledge of radiation

  15. Analysis of performance of prepubertal swimmers assessed from anthropometric and bio-energetic characteristics.

    PubMed

    Duché, P; Falgairette, G; Bedu, M; Lac, G; Robert, A; Coudert, J

    1993-01-01

    The relationship between anthropometric and bio-energetic data and timed performance over 50 to 400 m was studied in 25 young male swimmers [11.3 (SD 1) years]. Anthropometric measurements included height, body mass, body fat mass, body area, thoracic section area (Ats) thoracic circumferences, lengths of upper limb, bi-acromial and bi-iliac diameters. Maximal oxygen consumption (VO2max; direct method), maximal anaerobic power (W(an),max; force-velocity test) and mean power in 30 s sprint (W30 s; Wingate test) were also measured. Each of these bio-energetic variables was expressed in absolute terms, relating to body mass, body area and Ats. The stepwise regression method was used to determine contribution of the variables (anthropometric and/or bio-energetic) of the time achieved over the distance. The W30 s/Ats accounted for 46% of the time over 50 m (negative correlation). The VO2max/Ats and height were negatively correlated with the times of performances over 100 m, 200 m and 400 m, these two variables accounted for 71% to 77% of the performance. These results would indicate that even in young boys, anthropometric and bio-energetic characteristics are both important in swimming performance, particularly the bio-energetic variables expressed per Ats.

  16. Energetics, lifestyle, and reproduction in birds.

    PubMed

    Sibly, Richard M; Witt, Christopher C; Wright, Natalie A; Venditti, Chris; Jetz, Walter; Brown, James H

    2012-07-03

    Theoretical and empirical studies of life history aim to account for resource allocation to the different components of fitness: survival, growth, and reproduction. The pioneering evolutionary ecologist David Lack [(1968) Ecological Adaptations for Breeding in Birds (Methuen and Co., London)] suggested that reproductive output in birds reflects adaptation to environmental factors such as availability of food and risk of predation, but subsequent studies have not always supported Lack's interpretation. Here using a dataset for 980 bird species (Dataset S1), a phylogeny, and an explicit measure of reproductive productivity, we test predictions for how mass-specific productivity varies with body size, phylogeny, and lifestyle traits. We find that productivity varies negatively with body size and energetic demands of parental care and positively with extrinsic mortality. Specifically: (i) altricial species are 50% less productive than precocial species; (ii) species with female-only care of offspring are about 20% less productive than species with other methods of parental care; (iii) nonmigrants are 14% less productive than migrants; (iv) frugivores and nectarivores are about 20% less productive than those eating other foods; and (v) pelagic foragers are 40% less productive than those feeding in other habitats. A strong signal of phylogeny suggests that syndromes of similar life-history traits tend to be conservative within clades but also to have evolved independently in different clades. Our results generally support both Lack's pioneering studies and subsequent research on avian life history.

  17. Carbonyl-bridged energetic materials: biomimetic synthesis, organic catalytic synthesis, and energetic performances.

    PubMed

    Feng, Yong-An; Qiu, Hao; Yang, Sa-Sha; Du, Jiang; Zhang, Tong-Lai

    2016-11-01

    In order to obtain high-performance energetic materials, in this work, carbonyl groups (C[double bond, length as m-dash]O) have been newly introduced as sole bridging groups in the field of energetic materials. To this end, two tailored green methods for the synthesis of carbonyl-bridged energetic compounds have been developed for the first time. One is a biomimetic synthesis, in which the conversion route of heme to biliverdin has been used to obtain metal-containing energetic compounds. The other one is an organocatalysis, in which guanidinium serves as an energetic catalyst to afford other energetic compounds. Experimental studies and theoretical calculations have shown that carbonyl-bridged energetic compounds exhibit excellent energetic properties, which is promising for the carbonyl group as a new important and effective linker in energetic materials.

  18. Methodology for in situ protection of aldehydes and ketones using trimethylsilyl trifluoromethanesulfonate and phosphines: selective alkylation and reduction of ketones, esters, amides, and nitriles.

    PubMed

    Yahata, Kenzo; Minami, Masaki; Yoshikawa, Yuki; Watanabe, Kei; Fujioka, Hiromichi

    2013-01-01

    A methodology for selective transformations of ketones, esters, Weinreb amides, and nitriles in the presence of aldehydes has been developed. The use of a combination of PPh(3)-trimethylsilyl trifluoromethanesulfonate (TMSOTf) promotes selective transformation of aldehydes to their corresponding, temporarily protected, O,P-acetal type phosphonium salts. Because, hydrolytic work-up following ensuing reactions of other carbonyl moieties in the substrates liberates the aldehyde moiety, a sequence involving aldehyde protection, transformation of other carbonyl groups, and deprotection can be accomplished in a one-pot manner. Furthermore, the use of PEt(3) instead of PPh(3) enables ketones to be converted in situ to their corresponding O,P-ketal type phosphonium salts and, consequently, selective transformations of esters, Weinreb amides, and nitriles in the presence of ketones can be performed. This methodology is applicable to various dicarbonyl compounds, including substrates that possess heteroaromatic skeletons and hydroxyl protecting groups.

  19. A mechanistic analysis of the quantitation of α-hydroxy ketones by the bicinchoninic acid assay.

    PubMed

    Weiser, Jennifer R; Ricapito, Nicole G; Yueh, Alice; Weiser, Ellen L; Putnam, David

    2012-11-15

    A new class of compounds amenable to quantification by the bicinchoninic acid (BCA) assay was identified, allowing an expansion of compounds quantifiable within the assay's capacity. In this article, we demonstrate that compounds containing the α-hydroxy ketone structure are easily measured under standard BCA assay conditions. A nonchromophore analyte containing the α-hydroxy ketone structure, 1,3-dihydroxypropan-2-one (commonly known as dihydroxyacetone), and various structural derivatives were explored on an equimolar basis in the BCA assay. Combined with earlier studies exploring α-hydroxy ketones within copper oxidation systems, the data support the mechanism of this class of compound's ability to enolize through an enediol intermediate to generate a strong signal in the BCA assay. This new quantification technique also highlights the potential for α-hydroxy ketones to interfere with other analytes quantified by the BCA assay.

  20. Lewis base catalyzed, enantioselective aldol addition of methyl trichlorosilyl ketene acetal to ketones.

    PubMed

    Denmark, Scott E; Fan, Yu; Eastgate, Martin D

    2005-06-24

    The catalytic enantioselective addition of an acetate enolate equivalent to ketones is described. Methyl trichlorosilyl ketene acetal reacts with a wide range of ketones in the presence of pyridine N-oxide to afford the aldol addition products in excellent yields. Chiral 2,2'-pyridyl bis-N-oxides bearing various substituents at the 3,3'- and 6,6'-positions also provide excellent yields of the aldol products with variable enantioselectivities ranging from 94/6 er for aromatic ketones to nearly racemic for aliphatic ketones. An X-ray crystal structure of the complex between a catalyst and silicon tetrachloride (((P)-(R,R)-19.SiCl(4))) has been obtained. Extensive computational analysis provides a stereochemical rationale for the observed trends in enantioselectivities.

  1. Radical photocyclization route for macrocyclic lactone ring expansion and conversion to macrocyclic lactams and ketones.

    PubMed

    Nishikawa, Keisuke; Yoshimi, Yasuharu; Maeda, Kousuke; Morita, Toshio; Takahashi, Ichiro; Itou, Tatsuya; Inagaki, Sho; Hatanaka, Minoru

    2013-01-18

    A new method for the synthesis of macrocyclic lactones, lactams, and ketones, which utilizes photoinduced intramolecular radical cyclization reactions of substrates containing tethered carboxylic acids and α,β-unsaturated carbonyl moieties, has been uncovered. Photocyclization of the carboxylic acids tethered acrylate ester, which were prepared starting from the macrocyclic lactones, gave the two-carbon elongated macrocyclic lactones via decarboxylation. Similar photoreactions of carboxylic acid tethered acryl amide or α,β-unsaturated ketone moieties, which were also prepared starting from the macrocyclic lactones, produced macrocyclic lactams or ketones, respectively. The simple approach can be readily applied to the preparation of a variety of macrocyclic lactones, lactams, and ketones with tunable ring sizes.

  2. Whole-cell biotransformation with recombinant cytochrome P450 for the selective oxidation of Grundmann's ketone.

    PubMed

    Hernández-Martín, Alba; von Bühler, Clemens J; Tieves, Florian; Fernández, Susana; Ferrero, Miguel; Urlacher, Vlada B

    2014-10-15

    25-Hydroxy-Grundmann's ketone is a key building block in the chemical synthesis of vitamin D3 and its derivatives through convergent routes. Generally, the chemical synthesis of this compound involves tedious procedures and results in a mixture of several products. Recently, the selective hydroxylation of Grundmann's ketone at position C25 by cytochrome P450 (CYP) 154E1 from Thermobifida fusca YX was described. In this study a recombinant whole-cell biocatalyst was developed and applied for hydroxylation of Grundmann's ketone. Biotransformation was performed by Escherichia coli cells expressing CYP154E1 along with two redox partner systems, Pdx/PdR and YkuN/FdR. The system comprising CYP154E1/Pdx/PdR showed the highest production of 25-hydroxy-Grundmann's ketone and resulted in 1.1mM (300mgL(-1)) product concentration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Addition of optically pure H-phosphinate to ketones: selectivity, stereochemistry and mechanism.

    PubMed

    Sun, Yong-Ming; Xin, Nana; Xu, Zhong-Yuan; Liu, Li-Juan; Meng, Fan-Jie; Zhang, He; Fu, Bao-Ci; Liang, Qiu-Ju; Zheng, Hong-Xing; Sun, Li-Jun; Zhao, Chang-Qiu; Han, Li-Biao

    2014-12-14

    Aromatic methyl ketones and cyclic asymmetric ketones underwent hydrophosphorylation with P-stereogenic H-P species in the presence of potassium carbonate to produce P,C-stereogenic tertiary α-hydroxyl phosphinates in excellent yields with up to 99 : 1 dr. The diastereoselectivity was induced by a reversible conversion of less stable stereomer of product to that of a more stable one via an equilibrium, which was confirmed by aldehyde/ketone exchanging reaction. Toward the exchange, aliphatic or aldehyde carbonyl were more active than aromatic or ketone carbonyls, respectively. The stability difference between the two diastereomers was controlled by the sizes of substituents linking to phosphorus or α-carbon.

  4. Comparative inhibition of tetrameric carbonyl reductase activity in pig heart cytosol by alkyl 4-pyridyl ketones.

    PubMed

    Shimada, Hideaki; Tanigawa, Takahiro; Matayoshi, Kazunori; Katakura, Kazufumi; Babazono, Ken; Takayama, Hiroyuki; Murahashi, Tsuyoshi; Akita, Hiroyuki; Higuchi, Toshiyuki; Eto, Masashi; Imamura, Yorishige

    2014-06-01

    The present study is to elucidate the comparative inhibition of tetrameric carbonyl reductase (TCBR) activity by alkyl 4-pyridyl ketones, and to characterize its substrate-binding domain. The inhibitory effects of alkyl 4-pyridyl ketones on the stereoselective reduction of 4-benzoylpyridine (4-BP) catalyzed by TCBR were examined in the cytosolic fraction of pig heart. Of alkyl 4-pyridyl ketones, 4-hexanoylpyridine, which has a straight-chain alkyl group of five carbon atoms, inhibited most potently TCBR activity and was a competitive inhibitor. Furthermore, cyclohexyl pentyl ketone, which is substituted by cyclohexyl group instead of phenyl group of hexanophenone, had much lower ability to be reduced than hexanophenone. These results suggest that in addition to a hydrophobic cleft corresponding to a straight-chain alkyl group of five carbon atoms, a hydrophobic pocket with affinity for an aromatic group is located in the substrate-binding domain of TCBR.

  5. Direct reductive amination of aldehydes and ketones using phenylsilane: catalysis by dibutyltin dichloride.

    PubMed

    Apodaca, R; Xiao, W

    2001-05-31

    A procedure for direct reductive amination of aldehydes and ketones was developed which uses phenylsilane as a stoichiometric reductant and dibutyltin dichloride as a catalyst. Suitable amines included anilines and dialkylamines but not monoalkylamines.

  6. Acetylleucine chloromethyl ketone, an inhibitor of acylpeptide hydrolase, induces apoptosis of U937 cells.

    PubMed

    Yamaguchi, M; Kambayashi, D; Toda, J; Sano, T; Toyoshima, S; Hojo, H

    1999-09-16

    Acetylleucine chloromethyl ketone (ALCK), an inhibitor of acylpeptide hydrolase (ACPH), inhibited the growth of human monoblastic U937 cells in a dose- and time-dependent manner. Morphology of the ALCK-exposed cells showed typical apoptosis, judging from the nuclear condensation and segmentation. Chromosomal DNA of U937 cells treated with ALCK showed an internucleosomal ladder-like pattern on electrophoresis, being characteristic of apoptosis. Of the other leucine chloromethyl ketone analogues, butyloylleucine chloromethyl ketone (BLCK) induced a weak ladder-like formation but caploylleucine chloromethyl ketone (CLCK)barely did. On the other hand, intracellular ACPH activity of U937 cells was strongly inhibited by culturing with ALCK, moderately with BLCK, and not with CLCK. These findings indicate that the inhibition of ACPH activity leads to apoptosis and suggest that ACPH may play a vital role in eukaryotic cells. Copyright 1999 Academic Press.

  7. Ultrasound mediation for efficient synthesis of monoarylidene derivatives of homo- and heterocyclic ketones.

    PubMed

    Mojtahedi, Mohammad M; Abaee, M Saeed; Samianifard, Mehdieh; Shamloo, Akram; Padyab, Masoomeh; Mesbah, A Wahid; Harms, Klaus

    2013-05-01

    Ultrasonic irradiation was efficiently used for high yield synthesis of monoarylidene derivatives of cyclic systems directly from the reaction of ketone with various aldehydes under solvent-free conditions. Reactions took place rapidly in the presence of catalytic amounts of pyrrolidine, while no significant formation of the undesired bis by-products was observed. Moreover, the procedure was applicable to both homo- and heterocyclic ketones. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Preparation of unsymmetrical ketones from tosylhydrazones and aromatic aldehydes via formyl C-H bond insertion.

    PubMed

    Allwood, Daniel M; Blakemore, David C; Ley, Steven V

    2014-06-06

    Preparation of ketones by insertion of diazo compounds into the formyl C-H bond of an aldehyde is an attractive procedure, but use of structurally diverse diazo compounds is hampered by preparation and safety issues. A convenient procedure for the synthesis of unsymmetrical ketones from bench-stable tosylhydrazones and aryl aldehydes is reported. The procedure can be performed in one pot from the parent carbonyl compound and needs only a base, with no additional promoters being required.

  9. Direct conversion of alcohols to α-chloro aldehydes and α-chloro ketones.

    PubMed

    Jing, Yuanyuan; Daniliuc, Constantin G; Studer, Armido

    2014-09-19

    Direct conversion of primary and secondary alcohols into the corresponding α-chloro aldehydes and α-chloro ketones using trichloroisocyanuric acid, serving both as stoichiometric oxidant and α-halogenating reagent, is reported. For primary alcohols, TEMPO has to be added as an oxidation catalyst, and for the transformation of secondary alcohols (TEMPO-free protocol), MeOH as an additive is essential to promote chlorination of the intermediary ketones.

  10. Sources and concentrations of aldehydes and ketones in indoor environments in the UK

    SciTech Connect

    Crump, D.R.; Gardiner, D. )

    1989-01-01

    Individual aldehydes and ketones can be separated, identified and quantitatively estimated by trapping the 2,4-dinitrophenylhydrazine (DNPH) derivatives and analysis by HPLC. Appropriate methods and detection limits are reported. Many sources of formaldehyde have been identified by this means and some are found to emit other aldehydes and ketones. The application of this method to determine the concentration of these compounds in the atmospheres of buildings is described and the results compared with those obtained using chromotropic acid or MBTH.

  11. Enantioselective Synthesis of β-(3-Hydroxypyrazol-1-yl)ketones Using An Organocatalyzed Michael Addition Reaction

    PubMed Central

    Gogoi, Sanjib; Zhao, Cong-Gui; Ding, Derong

    2009-01-01

    β-(3-Hydroxypyrazol-1-yl)ketones have been prepared in high yields and excellent enantioselectivities (94–98% ee) via a Michael addition reaction between 2-pyrazolin-5-ones and aliphatic acyclic α,β-unsaturated ketones using 9-epi-9-amino-9-deoxyquinine as the catalyst. These results account for the first example of an aza-Michael addition of the ambident 2-pyrazolin-5-one anion to a Michael acceptor. PMID:19415906

  12. Extent of charge transfer in the photoreduction of phenyl ketones by alkylbenzenes

    SciTech Connect

    Wagner, P.J.; Truman, R.J.; Puchalski, A.E.; Wake, R.

    1986-11-26

    Rate constants for triplet-state reaction of various ring-substituted benzophenones (BPs), acetophenones (APs), and ..cap alpha..,..cap alpha..,..cap alpha..-trifluoroacetophenones (TFAs) with toluene and p-xylene have been determined by a combination of flash kinetics, steady-state quenching, and quantum yield measurements. The relative amounts of primary and tertiary radicals formed by reaction of the same ketones with p-cymene have also been measured. For all three types of ketones, rate constants correlate well with triplet ketone reduction potentials. The magnitude of the kinetic isotope effects observed with toluene-d/sub 8/ and p-xylene-d/sub 10/ diminishes as the ketones become easier to reduce. All of the ketone triplets react with alkylbenzenes primarily by a charge-transfer mechanism, with the rate-determining step changing from complexation to hydrogen transfer as the ketones become harder to reduce. The least reactive AP triplets probably react significantly via simple hydrogen atom abstraction as well. Those ketones with n,..pi..* lowest triplets (all BPs and some APs) react with p-cymene to give primary/tertiary radical ratios that vary no more than a factor of 2 from the 0.40 value displayed by tert-butoxy radicals; those with ..pi..,..pi..* lowest triplets (TFAs and some APs) give ratios that favor primary radicals and that vary by an order of magnitude with the triplet ketone reduction potential. The variation in cymene product ratios reflects different orientations for attack on cymene by n,..pi..* and ..pi..,..pi..* triplets and differing degrees of partial electron transfer within the exciplexes, which are not tight radical ion pairs.

  13. Synthesis and evaluation of phenylalanine-derived trifluoromethyl ketones for peptide-based oxidation catalysis.

    PubMed

    Featherston, Aaron L; Miller, Scott J

    2016-10-15

    We report the synthesis of phenylalanine-derived trifluoromethyl ketones for the in situ generation of dioxiranes for the purpose of oxidation catalysis. The key features of this synthesis include the use of a masked ketone strategy and a Negishi cross-coupling to access the parent amino acid. The derivatives can be readily incorporated into a peptide for use in oxidation chemistry and exhibit good stability and reactivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Tyrosine-derived 4-hydroxyphenylpyruvate reacts with ketone test fields of 3 commercially available urine dipsticks.

    PubMed

    Cartwright, James; Green, Richard M

    2010-09-01

    The enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD) is key in tyrosine catabolism. Inhibition of HPPD results in tyrosinemia and increased urinary excretion of 3 phenylketones: 4-hydroxyphenylpyruvate (HPPA), 4-hydroxyphenyllactate (HPLA), and 4-hydroxyphenylacetate (HPAA). A previous study involving administration of a novel HPPD inhibitor to dogs resulted in detection of ketonuria in treated animals using urine dipsticks read by reflectance photometry. Dipstick-positive results were suspected to be false because high concentrations of urinary phenylketones have been reported to react with ketone test fields of urine dipsticks, but visual confirmation was not performed. The purpose of this study was to determine which of the 4- hydroxyphenolic acids produced by HPPD inhibition react with ketone test fields of 3 commercially available urine dipsticks. Canine urine samples were prepared with HPPA, HPLA, HPAA, and lithium acetoacetate (positive control) at 6 concentrations. Unmodified urine samples were used as negative controls. All samples were tested for ketones using Combur 10 Test M dipsticks read by a Miditron dipstick analyzer. Urinalysis was also performed by visually inspecting ketone test fields on the Combur 10 Test M, Multistix 10 SG, and Aution 10 EA dipsticks. Urine samples containing HPPA were positive for ketones with Combur 10 Test M dipsticks read by the Miditron analyzer and produced a red–brown color change in ketone test fields of all 3 dipsticks. Urine samples containing HPLA and HPAA were negative by all methods. The phenylketone HPPA reacts with ketone test fields of 3 commercially available urine dipsticks, producing a red–brown color change that may be misinterpreted as positive for ketones by reflectance photometry.

  15. Photoredox Activation for the Direct β-Arylation of Ketones and Aldehydes

    PubMed Central

    Pirnot, Michael T.; Rankic, Danica A.; Martin, David B. C.; MacMillan, David W. C.

    2013-01-01

    The direct β-activation of saturated aldehydes and ketones has long been an elusive transformation. We found that photoredox catalysis in combination with organocatalysis can lead to the transient generation of 5π-electron β-enaminyl radicals from ketones and aldehydes that rapidly couple with cyano-substituted aryl rings at the carbonyl β-position. This mode of activation is suitable for a broad range of carbonyl β-functionalization reactions and is amenable to enantioselective catalysis. PMID:23539600

  16. Domino hydroformylation/aldol condensation/hydrogenation catalysis: highly selective synthesis of ketones from olefins.

    PubMed

    Fang, Xianjie; Jackstell, Ralf; Börner, Armin; Beller, Matthias

    2014-11-24

    A general and highly chemo- and regioselective synthesis of ketones from olefins by domino hydroformylation/aldol condensation/hydrogenation reaction has been developed. A variety of olefins are efficiently converted into various ketones in good to excellent yields and regioselectivities in the presence of a specific rhodium phosphine/base-acid catalyst system. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Unexpected metal-free transformation of gem-Dibromomethylenes to ketones under acetylation conditions.

    PubMed

    Kimura, Rino; Sawayama, Yusuke; Nakazaki, Atsuo; Miyamoto, Kazunori; Uchiyama, Masanobu; Nishikawa, Toshio

    2015-04-01

    Novel conditions for the transformation of gem-dibromomethylenes to ketones are described. gem-Dibromo compounds were treated with acetic anhydride and triethylamine in dichloromethane/water at room temperature under an air atmosphere to give the corresponding ketones in moderate yields. A radical mechanism is proposed based on experimental results. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Reductive cyclizations of hydroxysulfinyl ketones: enantioselective access to tetrahydropyran and tetrahydrofuran derivatives.

    PubMed

    Carreño, M Carmen; Des Mazery, Renaud; Urbano, Antonio; Colobert, Françoise; Solladié, Guy

    2003-10-03

    The stereocontrolled formation of cis-2,5-disubstituted tetrahydrofurans and cis-2,6-disubstituted tetrahydropyrans is achieved from enantiopure ketosulfinyl esters by reduction, Weinreb's amide, and ketone formation, followed by the reductive cyclization (Et3SiH/TMSOTf) of the resulting hydroxysulfinyl ketones. The sulfoxide-bearing heterocycles were transformed into two natural products, (-)-centrolobine (1) and both enantiomers of cis-(6-methyltetrahydropyran-2-yl)acetic acid (2).

  19. Catalytic transformation of esters of 1,2-azido alcohols into α-amido ketones.

    PubMed

    Kim, Yongjin; Pak, Han Kyu; Rhee, Young Ho; Park, Jaiwook

    2016-05-05

    The esters of 1,2-azido alcohols were transformed into α-amido ketones without external oxidants through the Ru-catalyzed formation of N-H imines with the liberation of N2 followed by intramolecular migration of the acyl moiety. A wide range of α-amido ketones were obtained, and one-pot transformation into the corresponding oxazoles (or a thiazole) was demonstrated.

  20. Efficient Domino Hydroformylation/Benzoin Condensation: Highly Selective Synthesis of α-Hydroxy Ketones.

    PubMed

    Dong, Kaiwu; Sang, Rui; Soule, Jean-Francois; Bruneau, Christian; Franke, Robert; Jackstell, Ralf; Beller, Matthias

    2015-12-07

    An improved domino hydroformylation/benzoin condensation to give α-hydroxy ketones has been developed. Easily available olefins are smoothly converted into the corresponding α-hydroxy ketones in high yields with excellent regioselectivities. Key to success is the use of a specific catalytic system consisting of a rhodium/phosphine complex and the CO2 adduct of an N-heterocyclic carbene. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Mass spectral determination of aldehydes, ketones, and carboxylic acids using 1,1-dimethylhydrazine.

    PubMed

    McDaniel, C A; Howard, R W

    1985-03-01

    Analyses of nanogram to milligram quantities of aliphatic aldehydes, fatty acids, and unhindered aliphatic ketones such as those typically found in pheromonal blends have been effected by treating these mixtures with 1,1-dimethylhydrazine. The aldehydes and ketones formN,N-dimethylhydrazones, while the fatty acids form methyl esters. Structural elucidation of the reaction products was achieved using EI and CI gas chromatography-mass spectrometry.

  2. Ketone-imide versus ketone-oxime reductive cross-coupling promoted by samarium diiodide: new mechanistic insight gained from a failed aminocyclopentitol synthesis.

    PubMed

    Chiara, Jose Luis; García, Angela; Cristóbal-Lumbroso, Gabriella

    2005-05-13

    [reaction: see text] The intramolecular 1,6-ketone/imide reductive coupling promoted by samarium diiodide competes favorably with an alternative 1,5-ketone/oxime ether coupling in a keto-oxime substrate derived from D-glucosamine N-protected with a phthalimido group. This pinacol coupling reaction affords new homochiral alpha-hydroxylactam scaffolds that could be useful in diversity-oriented synthesis. A mechanistic proposal for this reaction that explains the experimental results is supported by DFT quantum-mechanical calculations on model compounds.

  3. Energetic Particles in Saturn's Magnetotail

    NASA Astrophysics Data System (ADS)

    Mitchell, D. G.; Carbary, J. F.; Krupp, N.; Krimigis, S. M.; Hamilton, D. C.; Kane, M.

    2007-12-01

    Energetic particle measurements in Saturn's magnetotail reveal a magnetotail dominated by Saturn's rotational dynamics as far back in the tail as 60 Rs, rarely but sometimes spectacularly disrupted by tail reconnection events. Although Cassini spent little time in the tail, and even less at the location of the tail current sheet, the time spent there revealed a pattern of very regular encounters with the energetic particles that fill the current sheet, usually once every Saturn rotation. Carbary et al. 2007a, b show that energetic electrons reappear every rotation when the spacecraft is sufficiently close to the current sheet location, and further that they lie along a spiral in longitude when mapped into the SKR coordinate system (Kurth et al., 2007). Energetic ions are also observed in the same locations, with a mix of hydrogen and oxygen not very different from that observed in the magnetosphere between 10 and 20 Rs. These ions generally display velocities approximately in the corotation direction, but with magnitudes well below rigid corotation (Kane et al., 2007, manuscript in preparation). Two other classes of energetic particle events are also seen in the magnetotail. The first consists of energetic ion and electron beams, likely accelerated in the auroral zone over downward current regions. The second are those generated in tail reconnection events (e.g., Jackman et al., 2007; Hill et al. 2007). We will give examples of all of these phenomena, including both in situ measurements and ENA images/movies. Carbary, J.~F., Mitchell, D.~G., Krimigis, S.~M., Hamilton, D.~C., Krupp, N., Charged particle periodicities in Saturn's outer magnetosphere, Journal of Geophysical Research (Space Physics) 112, 6246 {2007JGRA..11206246C} 2007a Carbary, J. F., D. G. Mitchell, S. M. Krimigis, and N. Krupp (2007), Evidence for spiral pattern in Saturn's magnetosphere using the new SKR longitudes, Geophys. Res. Lett., 34, L13105, doi:10.1029/2007GL030167 2007b Kurth, W. S., A

  4. Amination of energetic anions: high-performing energetic materials.

    PubMed

    Klapötke, Thomas M; Piercey, Davin G; Stierstorfer, Jörg

    2012-08-21

    The new energetic materials 2-amino-5-nitrotetrazole (ANT, 1), 1-amino-3,4-dinitro-1,2,4-triazole (ADNT, 2), and both 1,1'-diamino-5,5'-bistetrazole and 1,2'-diamino-5,5'-bistetrazole (11DABT, 3 and 12DABT, 4) have been prepared by the amination of the parent anion with O-tosylhydroxylamine. The 5-H-tetrazolate anion has also been aminated using hydroxylamine O-sulfonic acid to both 1-aminotetrazole and 2-aminotetrazole (1AT, 5 and 2AT, 6). The prepared materials have been characterized chemically (XRD (1-4, 6·AtNO(2), 8), multinuclear NMR, IR, Raman) and as explosives (mechanical and electrostatic sensitivity) and their explosive performances calculated using the EXPLO5 computer code. The prepared N-amino energetic materials, which can also be used as new ligands for high energy-capacity transition metal complexes, exhibit high explosive performances (in the range of hexogen and octogen) and a range of sensitivities from low to extremely high.

  5. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives.

    PubMed

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a-b) as well as chalcone derivatives (3a-c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans.

  6. Studies on the interaction between ethanol and two industrial solvents (methyl isobutyl ketone) in mice

    SciTech Connect

    Granvil, C.P.; Sharkawi, M.; Plaa, G.L. )

    1991-03-11

    Methyl n-butyl ketone (MnBK) and methyl isobutyl ketone (MiBK) prolong the duration of ethanol-induced loss of righting reflex (EILRR) in mice. MnBK was almost twice as potent in this regard. To explain this difference, the metabolism of both ketones was studied in male CD-1 mice using GC. MiBK was converted to 4-methyl-2-pentanol (4MPOL) and 4-hydroxy methyl isobutyl ketone (HMP). MnBK metabolites were 2-hexanol (2HOL) and 2,5-hexanedione (2,5HD). The effects of both ketones and metabolites on EILRR and ethanol (E) elimination were studied in mice. The ketones and their metabolites were dissolved in corn oil and injected intraperitoneally 30 min before E 4g/kg for EILRR and 2g/kg for E elimination. In the following doses: MnBK, 5; MiBK, 5; 2HOL, 2.5; 4MPOL, 2.5; and HMP 2.5, significantly prolonged EILRR. Concentrations of E in blood and brain upon return of the righting reflex were similar in solvent-treated and control animals. The mean elimination rate of E was slower in groups given MnBK or 2HOL than in control animals. No change in E elimination was observed with MiBK, HMP, 4MPOL, or 2, 5HD.

  7. Study of the antibacterial and antifungal activities of synthetic benzyl bromides, ketones, and corresponding chalcone derivatives

    PubMed Central

    Shakhatreh, Muhamad Ali K; Al-Smadi, Mousa L; Khabour, Omar F; Shuaibu, Fatima A; Hussein, Emad I; Alzoubi, Karem H

    2016-01-01

    Several applications of chalcones and their derivatives encouraged researchers to increase their synthesis as an alternative for the treatment of pathogenic bacterial and fungal infections. In the present study, chalcone derivatives were synthesized through cross aldol condensation reaction between 4-(N,N-dimethylamino)benzaldehyde and multiarm aromatic ketones. The multiarm aromatic ketones were synthesized through nucleophilic substitution reaction between 4-hydroxy acetophenone and benzyl bromides. The benzyl bromides, multiarm aromatic ketones, and corresponding chalcone derivatives were evaluated for their activities against eleven clinical pathogenic Gram-positive, Gram-negative bacteria, and three pathogenic fungi by the disk diffusion method. The minimum inhibitory concentration was determined by the microbroth dilution technique. The results of the present study demonstrated that benzyl bromide derivatives have strong antibacterial and antifungal properties as compared to synthetic chalcone derivatives and ketones. Benzyl bromides (1a and 1c) showed high ester activity against Gram-positive bacteria and fungi but moderate activity against Gram-negative bacteria. Therefore, these compounds may be considered as good antibacterial and antifungal drug discovery. However, substituted ketones (2a–b) as well as chalcone derivatives (3a–c) showed no activity against all the tested strains except for ketone (2c), which showed moderate activity against Candida albicans. PMID:27877017

  8. Mesoscale Modeling of Energetic Materials

    DTIC Science & Technology

    2014-10-23

    This briefing represents interim progress towards these goals. 15. SUBJECT TERMS Heterogeneous explosives , Mesoscale dynamics, Level set method...High  Explosives  Research and Development Branch (RWME) – Damage Mechanisms Branch (RWMW) • Goal: Predict survivability of energetic payload of high...the mechanical  behavior of simple  explosive – Pristine – Damaged • Performed simulations on mechanical RVE’s – From XCMT – Idealized • Developed and

  9. Method for calculating alloy energetics

    NASA Technical Reports Server (NTRS)

    Bozzolo, Guillermo; Ferrante, John; Smith, John R.

    1992-01-01

    A semiempirical method for the computation of alloy energies is introduced. It is based on the equivalent-crystal theory of defect-formation energies in elemental solids. The method is both simple and accurate. Heats of formation as a function of composition are computed for some binary alloys of Cu, Ni, Al, Ag, Pd, Pt, and Au using the heats of solution in the dilute limit as experimental input. The separation of heats into strain and chemical components helps in understanding the energetics. In addition, lattice-parameter contractions seen in solid solutions of Ag and Au are accurately predicted. Good agreement with experiment is obtained in all cases.

  10. Method for calculating alloy energetics

    NASA Technical Reports Server (NTRS)

    Bozzolo, Guillermo; Ferrante, John; Smith, John R.

    1992-01-01

    A semiempirical method for the computation of alloy energies is introduced. It is based on the equivalent-crystal theory of defect-formation energies in elemental solids. The method is both simple and accurate. Heats of formation as a function of composition are computed for some binary alloys of Cu, Ni, Al, Ag, Pd, Pt, and Au using the heats of solution in the dilute limit as experimental input. The separation of heats into strain and chemical components helps in understanding the energetics. In addition, lattice-parameter contractions seen in solid solutions of Ag and Au are accurately predicted. Good agreement with experiment is obtained in all cases.

  11. Determination of acetone and methyl ethyl ketone in water

    USGS Publications Warehouse

    Tai, D.Y.

    1978-01-01

    Analytical procedures for the determination of acetone and methyl ethyl ketone in water samples were developed. Concentrations in the milligram-per-liter range were determined by injecting an aqueous sample into the analysis system through an injection port, trapping the organics on Tenax-GC at room temperature, and thermally desorbing the organics into a gas chromatograph with a flame ionization detector for analysis. Concentrations in the microgram-per-liter range were determined by sweeping the headspace vapors over a water sample at 50C, trapping on Tenax-GC, and thermally desorbing the organics into the gas chromatograph. The precision for two operators of the milligram-per-liter concentration procedure, expressed as the coefficient of variation, was generally less than 2 percent for concentrations ranging from 16 to 160 milligrams per liter. The precision from two operators of the microgram-per-liter concentration procedure was between 2 and 4 percent for concentrations of 20 and 60 micrograms per liter. (Woodard-USGS)

  12. Catalytic copolymerization of co/olefin with ketone additive

    SciTech Connect

    Drent, E.

    1989-03-07

    The process of producing a linear alternating polymer of carbon dioxide and at least one ethylenically unsaturated hydrocarbon of 2 to 20 carbon atoms inclusive is described. It consists of contacting carbon monoxide and the hydrocarbon under polymerization conditions in the presence of a catalyst composition prepared from a palladium compound, a non-transition metal salt of a non-hydrohalogenic acid having a pKa less than about 6, a bidentate phosphorus ligand of the formula R/sup 1/R/sup 2/--P--R--P--R/sup 3/R/sup 4/ in which R/sup 1/,R/sup 2/,R/sup 3/ and R/sup 4/ independently are organic radicals of from 1 to 14 carbon atoms inclusive and R is a divalent bridging group of up to 20 carbon atoms and up to 3 carbon atoms in the bridge, and a ketone of from 3 to 20 carbon atoms inclusive and recovering from the resulting product mixture the linear alternating polymer of carbon monoxide and the hydrocarbon.

  13. Detection of Active Matriptase Using a Biotinylated Chloromethyl Ketone Peptide

    PubMed Central

    Godiksen, Sine; Soendergaard, Christoffer; Friis, Stine; Jensen, Jan K.; Bornholdt, Jette; Sales, Katiuchia Uzzun; Huang, Mingdong; Bugge, Thomas H.; Vogel, Lotte K.

    2013-01-01

    Matriptase is a member of the family of type II transmembrane serine proteases that is essential for development and maintenance of several epithelial tissues. Matriptase is synthesized as a single-chain zymogen precursor that is processed into a two-chain disulfide-linked form dependent on its own catalytic activity leading to the hypothesis that matriptase functions at the pinnacle of several protease induced signal cascades. Matriptase is usually found in either its zymogen form or in a complex with its cognate inhibitor hepatocyte growth factor activator inhibitor 1 (HAI-1), whereas the active non-inhibited form has been difficult to detect. In this study, we have developed an assay to detect enzymatically active non-inhibitor-complexed matriptase by using a biotinylated peptide substrate-based chloromethyl ketone (CMK) inhibitor. Covalently CMK peptide-bound matriptase is detected by streptavidin pull-down and subsequent analysis by Western blotting. This study presents a novel assay for detection of enzymatically active matriptase in living human and murine cells. The assay can be applied to a variety of cell systems and species. PMID:24204759

  14. Organocatalytic asymmetric conjugate addition to allenic esters and ketones.

    PubMed

    Elsner, Petteri; Bernardi, Luca; Dela Salla, Giorgio; Overgaard, Jacob; Jørgensen, Karl Anker

    2008-04-09

    The first example of an organocatalytic enantioselective conjugate addition of cyclic beta-ketoesters and glycine imine derivatives to electron-deficient allenes is described. We disclose that the corresponding chiral beta,gamma-unsaturated carbonyl compounds are formed exclusively under phase-transfer conditions using either cinchona-alkaloid-derived or biphenyl-based chiral quaternary ammonium salts as catalysts. The scope of the reaction for beta-ketoesters is outlined for allenes having a ketone or ester motif as electron-withdrawing group as well as different substituents in the 3-position, giving the optically active products in high yields and excellent diastereo- and enantioselectivities (90-96% ee). The conjugate addition also proceeds for a number of cyclic beta-ketoesters having different ring sizes, ring systems, and substituents in high yields and enantioselectivities. Glycine imine derivatives also undergo the asymmetric conjugate addition to electron-deficient allenes in high yields and with enantioselectivities in the range of 60-88% ee, thus providing a rapid entry to optically active alpha-vinyl-substituted alpha-amino acid derivatives. It is shown that the enantioselectivity is strongly dependent on the size of the ester moiety of the nucleophile in combination with the catalytic system used. The high synthetic value of the chiral products arising from these new catalytic processes is demonstrated by two straightforward transformations leading in one case to optically active hexahydrobenzopyranones and in the other to substituted pyroglutamates (gamma-lactames).

  15. Measurements Alcohols, Ketones, and Aldehydes During Trace-P

    NASA Astrophysics Data System (ADS)

    Apel, E. C.; Riemer, D. D.; Hills, A.; Lueb, R.; Fried, A.; Sachse, G.; Crawford, J.; Singh, H.; Blake, D.

    2002-12-01

    A sensitive and selective instrument (fast gas chromatographic mass spectrometer - FGCMS) was developed for the continuous measurement of oxygenated volatile organic compounds (OVOCs: alcohols, ketones and aldehydes (except for formaldehyde)) containing fewer than 6 carbon atoms and subsequently deployed during the NASA's TRACE-P (Transport and Chemical Evolution over the Pacific) experiment. This paper will briefly describe the instrument and present results obtained from 15 mission flights. Dramatic differences were observed in the mixing ratios and vertical profiles of the longer-lived species, acetone and methanol, compared to the shorter-lived species. For example, between 6 and 7 km, the median mixing ratios for the two longest lived species measured, acetone and methanol, are 765 pptv and 1061 pptv, respectively whereas the combined mixing ratio for all other species measured was less than 500 pptv. A large variety of air masses were encountered during this experiment and this is reflected in the behavior of the measured OVOCs. Relationships between the OVOCs and other trace species will be explored. Implications of these measurements for our current understanding of global tropospheric chemistry will be discussed.

  16. Energetics, Biomechanics, and Performance in Masters' Swimmers: A Systematic Review.

    PubMed

    Ferreira, Maria I; Barbosa, Tiago M; Costa, Mário J; Neiva, Henrique P; Marinho, Daniel A

    2016-07-01

    Ferreira, MI, Barbosa, TM, Costa, MJ, Neiva, HP, and Marinho, DA. Energetics, biomechanics, and performance in masters' swimmers: a systematic review. J Strength Cond Res 30(7): 2069-2081, 2016-This study aimed to summarize evidence on masters' swimmers energetics, biomechanics, and performance gathered in selected studies. An expanded search was conducted on 6 databases, conference proceedings, and department files. Fifteen studies were selected for further analysis. A qualitative evaluation of the studies based on the Quality Index (QI) was performed by 2 independent reviewers. The studies were thereafter classified into 3 domains according to the reported data: performance (10 studies), energetics (4 studies), and biomechanics (6 studies). The selected 15 articles included in this review presented low QI scores (mean score, 10.47 points). The biomechanics domain obtained higher QI (11.5 points), followed by energetics and performance (10.6 and 9.9 points, respectively). Stroke frequency (SF) and stroke length (SL) were both influenced by aging, although SF is more affected than SL. Propelling efficiency (ηp) decreased with age. Swimming performance declined with age. The performance declines with age having male swimmers deliver better performances than female counterparts, although this difference tends to be narrow in long-distance events. One single longitudinal study is found in the literature reporting the changes in performance over time. The remaining studies are cross-sectional designs focusing on the energetics and biomechanics. Overall, biomechanics parameters, such as SF, SL, and ηp, tend to decrease with age. This review shows the lack of a solid body of knowledge (reflected in the amount and quality of the articles published) on the changes in biomechanics, energetics, and performance of master swimmers over time. The training programs for this age-group should aim to preserve the energetics as much as possible and, concurrently, improve the

  17. Energetic aspects of skeletal muscle contraction: implications of fiber types.

    PubMed

    Rall, J A

    1985-01-01

    . Unlike economy, maximum efficiency of work production varies little across the animal kingdom. There are difficulties associated with the measurement of maximum efficiency of contraction, and it has yet to be determined unequivocally if the maximum efficiency of contraction varies in different fiber types. The intrinsic properties of force per cross-sectional area, economy, and Vmax determine the basic energetic properties of skeletal muscles. Nonetheless, the mechanics and energetics of skeletal muscles in the body are profoundly influenced by muscle architecture, attachment of muscles to the skeleton, and motor unit organization.(ABSTRACT TRUNCATED AT 400 WORDS)

  18. Onshore energetics in penguins: theory, estimation and ecological implications.

    PubMed

    Halsey, Lewis G; White, Craig R; Fahlman, Andreas; Handrich, Yves; Butler, Patrick J

    2007-08-01

    Penguins are known to have high pedestrian locomotory costs in comparison to other cursorial birds, but the ecological consequences of this difference have received limited attention. Here we present a method for the accurate estimation of onshore energetics based on measurements of body mass, simple morphometrics and distance moved. The method is shown to be similarly accurate to other field-based estimates of energy expenditure, but has the advantage of logistical simplicity. King penguins spend 30-50% of their time ashore and may walk distances of several kilometres to and from their breeding colonies. However, in such cases the total energetic cost of pedestrian locomotion is estimated to be only 1.0% of the energy expended whilst ashore. Thus, despite a high instantaneous cost, pedestrian locomotion is a small and possibly negligible component of total energy turnover in king penguins.

  19. Simulated Shockwaves in Nanoparticles Embedded Energetics

    NASA Astrophysics Data System (ADS)

    Mattson, William; Johnson, Donald; Mullin, Jonathan

    2015-06-01

    Practical energetic materials often consist of mixtures of distinct materials formulated to optimize specific properties. Nanoparticles of traditional as well as novel additives, with their large surface to volume ratio, have been of particular recent interest to the energetics community. Using density functional theory, we have simulated high-velocity shocks of an energetic material containing nanoparticles. We will report on simulations of shocks in crystalline PETN embedded with nanodiamonds of different sizes, and at various shock speeds.

  20. Dynamic Deformation Properties of Energetic Composite Materials

    DTIC Science & Technology

    2002-12-01

    the dynamic mechanical properties and detonation of energetic materials. It also included some preliminary data on the effect of particle size on the...study of the dynamic mechanical properties and detonation of energetic materials. It also included some preliminary data on the effect of particle size...qualitative only. 33 5. DEFLAGRATION-TO- DETONATION (DDT) STUDIES As part of an on-going programme to investigate the properties of ultrafine energetic

  1. The effect of ketone bodies and fatty acid on intestinal glucose metabolism during development.

    PubMed

    Kimura, R E; Thulin, G; Warshaw, J B

    1984-07-01

    Glucose oxidation by developing rat intestine changed dramatically during the period of suckling and weaning. After weaning, glucose oxidation to CO2 by intestinal slices increased over 3-fold This was associated with an increase in lactate production from glucose and an increase in the rate of pyruvate decarboxylation. Active pyruvate dehydrogenase in intestine of developing rats also increases in activity at the time of weaning, suggesting that the suppression of glucose oxidation during the suckling period is controlled by pyruvate dehydrogenase. Glucose oxidation to CO2 and pyruvate decarboxylation to CO2 by intestinal slices of postweaned animals was inhibited by exogenous 3-hydroxybutyrate. But exogenous 3-hydroxybutyrate did not inhibit glucose and pyruvate oxidation in intestine of suckling animals which have higher levels of endogenous 3-hydroxybutyrate than intestine of postweaned rats. Palmitate, in contrast, inhibited glucose and pyruvate oxidation by both pre- and postweaned intestine.

  2. Hosting anions. The energetic perspective.

    PubMed

    Schmidtchen, Franz P

    2010-10-01

    Hosting anions addresses the widely spread molecular recognition event of negatively charged species by dedicated organic compounds in condensed phases at equilibrium. The experimentally accessible energetic features comprise the entire system including the solvent, any buffers, background electrolytes or other components introduced for e.g. analysis. The deconvolution of all these interaction types and their dependence on subtle structural variation is required to arrive at a structure-energy correlation that may serve as a guide in receptor construction. The focus on direct host-guest interactions (lock-and-key complementarity) that have dominated the binding concepts of artificial receptors in the past must be widened in order to account for entropic contributions which constitute very significant fractions of the total free energy of interaction. Including entropy necessarily addresses the ambiguity and fuzziness of the host-guest structural ensemble and requires the appreciation of the fact that most liquid phases possess distinct structures of their own. Apparently, it is the perturbation of the intrinsic solvent structure occurring upon association that rules ion binding in polar media where ions are soluble and abundant. Rather than specifying peculiar structural elements useful in anion binding this critical review attempts an illumination of the concepts and individual energetic contributions resulting in the final observation of specific anion recognition (95 references).

  3. Solar Energetic Particle Spectrometer (SEPS)

    NASA Technical Reports Server (NTRS)

    Christl, Mark J.

    2009-01-01

    An outstanding problem of solar and heliospheric physics is the transport of solar energetic particles. The more energetic particles arriving early in the event can be used to probe the transport processes. The arrival direction distribution of these particles carries information about scattering during their propagation to Earth that can be used to test models of interplanetary transport. Also, of considerable importance to crewed space missions is the level of ionizing radiation in the interplanetary medium, and the dose that the crew experiences during an intense solar particle event, as well as the risk to space systems. A recent study concludes that 90% of the absorbed dose results from particles in the energy range 20-550 MeV. We will describe a new compact instrument concept, SEPS, that can cover the energy range from 50-600 MeV with a single compact detector. This energy range has been difficult to cover. There are only limited data, generally available only in broad energy bins, from a few past and present instruments outside Earth s magnetosphere. The SEPS concept can provide improved measurements for this energy range and its simple light-weight design could be easily accommodated on future missions.

  4. Solar Energetic Particle Spectrometer (SEPS)

    NASA Technical Reports Server (NTRS)

    Christl, Mark J.

    2009-01-01

    An outstanding problem of solar and heliospheric physics is the transport of solar energetic particles. The more energetic particles arriving early in the event can be used to probe the transport processes. The arrival direction distribution of these particles carries information about scattering during their propagation to Earth that can be used to test models of interplanetary transport. Also, of considerable importance to crewed space missions is the level of ionizing radiation in the interplanetary medium, and the dose that the crew experiences during an intense solar particle event, as well as the risk to space systems. A recent study concludes that 90% of the absorbed dose results from particles in the energy range 20-550 MeV. We will describe a new compact instrument concept, SEPS, that can cover the energy range from 50-600 MeV with a single compact detector. This energy range has been difficult to cover. There are only limited data, generally available only in broad energy bins, from a few past and present instruments outside Earth s magnetosphere. The SEPS concept can provide improved measurements for this energy range and its simple light-weight design could be easily accommodated on future missions.

  5. National Ignition Campaign Hohlraum Energetics

    SciTech Connect

    Meezan, N B; Atherton, L J; Callahan, D A; Dewald, E L; Dixit, S N; Dzenitis, E G; Edwards, M J; Haynam, C A; Hinkel, D E; Jones, O S; Landen, O; London, R A; Michel, P A; Moody, J D; Milovich, J L; Schneider, M B; Thomas, C A; Town, R J; Warrick, A L; Weber, S V; Widmann, K; Glenzer, S H; Suter, L J; MacGowan, B J; Kline, J L; Kyrala, G A; Nikroo, A

    2009-11-16

    The first series of experiments on the National Ignition Facility (NIF) [E. I. Moses, R. N. Boyd, B. A. Remington, C. J. Keane, and R. Al-Ayat, 'The National Ignition Facility: ushering in a new age for high energy density science,' Phys. Plasmas 16, 041006 (2009)] tested ignition hohlraum 'energetics,' a term described by four broad goals: (1) Measurement of laser absorption by the hohlraum; (2) Measurement of the x-ray radiation flux (T{sub RAD}{sup 4}) on the surrogate ignition capsule; (3) Quantitative understanding of the laser absorption and resultant x-ray flux; and (4) Determining whether initial hohlraum performance is consistent with requirements for ignition. This paper summarizes the status of NIF hohlraum energetics experiments. The hohlraum targets and experimental design are described, as well as the results of the initial experiments. The data demonstrate low backscattered energy (< 10%) for hohlraums filled with helium gas. A discussion of our current understanding of NIF hohlraum x-ray drive follows, including an overview of the computational tools, i.e., radiation-hydrodynamics codes, that have been used to design the hohlraums. The performance of the codes is compared to x-ray drive and capsule implosion data from the first NIF experiments. These results bode well for future NIF ignition hohlraum experiments.

  6. Energetic Extremes in Aquatic Locomotion by Coral Reef Fishes

    PubMed Central

    Fulton, Christopher J.; Johansen, Jacob L.; Steffensen, John F.

    2013-01-01

    Underwater locomotion is challenging due to the high friction and resistance imposed on a body moving through water and energy lost in the wake during undulatory propulsion. While aquatic organisms have evolved streamlined shapes to overcome such resistance, underwater locomotion has long been considered a costly exercise. Recent evidence for a range of swimming vertebrates, however, has suggested that flapping paired appendages around a rigid body may be an extremely efficient means of aquatic locomotion. Using intermittent flow-through respirometry, we found exceptional energetic performance in the Bluelined wrasse Stethojulis bandanensis, which maintains tuna-like optimum cruising speeds (up to 1 metre s−1) while using 40% less energy than expected for their body size. Displaying an exceptional aerobic scope (22-fold above resting), streamlined rigid-body posture, and wing-like fins that generate lift-based thrust, S. bandanensis literally flies underwater to efficiently maintain high optimum swimming speeds. Extreme energetic performance may be key to the colonization of highly variable environments, such as the wave-swept habitats where S. bandanensis and other wing-finned species tend to occur. Challenging preconceived notions of how best to power aquatic locomotion, biomimicry of such lift-based fin movements could yield dramatic reductions in the power needed to propel underwater vehicles at high speed. PMID:23326566

  7. Energetic extremes in aquatic locomotion by coral reef fishes.

    PubMed

    Fulton, Christopher J; Johansen, Jacob L; Steffensen, John F

    2013-01-01

    Underwater locomotion is challenging due to the high friction and resistance imposed on a body moving through water and energy lost in the wake during undulatory propulsion. While aquatic organisms have evolved streamlined shapes to overcome such resistance, underwater locomotion has long been considered a costly exercise. Recent evidence for a range of swimming vertebrates, however, has suggested that flapping paired appendages around a rigid body may be an extremely efficient means of aquatic locomotion. Using intermittent flow-through respirometry, we found exceptional energetic performance in the Bluelined wrasse Stethojulis bandanensis, which maintains tuna-like optimum cruising speeds (up to 1 metre s(-1)) while using 40% less energy than expected for their body size. Displaying an exceptional aerobic scope (22-fold above resting), streamlined rigid-body posture, and wing-like fins that generate lift-based thrust, S. bandanensis literally flies underwater to efficiently maintain high optimum swimming speeds. Extreme energetic performance may be key to the colonization of highly variable environments, such as the wave-swept habitats where S. bandanensis and other wing-finned species tend to occur. Challenging preconceived notions of how best to power aquatic locomotion, biomimicry of such lift-based fin movements could yield dramatic reductions in the power needed to propel underwater vehicles at high speed.

  8. Tagging the Untaggable: A Difluoroalkyl-Sulfinate Ketone-Based Reagent for Direct C-H Functionalization of Bioactive Heteroarenes.

    PubMed

    Gnaim, Samer; Scomparin, Anna; Li, Xiuling; Baran, Phil S; Rader, Christoph; Satchi-Fainaro, Ronit; Shabat, Doron

    2016-09-21

    We have developed a new difluoroalkyl ketal sulfinate salt reagent suitable for direct derivatization of heteroarene C-H bonds. The reagent is capable of introducing a ketone functional group on heteroarene bioactive compounds via a one-pot reaction. Remarkably, in three examples the ketone analog and its parent drug had almost identical cytotoxicity. In a representative example, the ketone analog was bioconjugated with a delivery vehicle via an acid-labile semicarbazone linkage and with a photolabile protecting group to produce the corresponding prodrug. Controlled release of the drug-ketone analog was demonstrated in vitro for both systems. This study provides a general approach to obtain taggable ketone analogs directly from bioactive heteroarene compounds with limited options for conjugation. We anticipate that this sodium ketal-sulfinate reagent will be useful for derivatization of other heteroarene-based drugs to obtain ketone-taggable analogs with retained efficacy.

  9. Energetic materials and methods of tailoring electrostatic discharge sensitivity of energetic materials

    DOEpatents

    Daniels, Michael A.; Heaps, Ronald J.; Wallace, Ronald S.; Pantoya, Michelle L.; Collins, Eric S.

    2016-11-01

    An energetic material comprising an elemental fuel, an oxidizer or other element, and a carbon nanofiller or carbon fiber rods, where the carbon nanofiller or carbon fiber rods are substantially homogeneously dispersed in the energetic material. Methods of tailoring the electrostatic discharge sensitivity of an energetic material are also disclosed.

  10. Energetics of swimming: a historical perspective.

    PubMed

    Zamparo, P; Capelli, C; Pendergast, D

    2011-03-01

    The energy cost to swim a unit distance (C(sw)) is given by the ratio E/v where E is the net metabolic power and v is the swimming speed. The contribution of the aerobic and anaerobic energy sources to E in swimming competitions is independent of swimming style, gender or skill and depends essentially upon the duration of the exercise. C(sw) is essentially determined by the hydrodynamic resistance (W(d)): the higher W(d) the higher C(sw); and by the propelling efficiency (η(P)): the higher η(P) the lower C(sw). Hence, all factors influencing W(d) and/or η(P) result in proportional changes in C(sw). Maximal metabolic power E max and C(sw) are the main determinants of swimming performance; an improvement in a subject's best performance time can more easily be obtained by a reduction of C sw) rather than by an (equal) increase in E max (in either of its components, aerobic or anaerobic). These sentences, which constitute a significant contribution to today's knowledge about swimming energetics, are based on the studies that Professor Pietro Enrico di Prampero and his co-workers carried out since the 1970s. This paper is devoted to examine how this body of work helped to improve our understanding of this fascinating mode of locomotion.

  11. Raspberry ketone fails to reduce adiposity beyond decreasing food intake in C57BL/6 mice fed a high-fat diet.

    PubMed

    Cotten, Bradley M; Diamond, Stephanie A; Banh, Taylor; Hsiao, Yung-Hsuan; Cole, Rachel M; Li, Jinhui; Simons, Christopher T; Bruno, Richard S; Belury, Martha A; Vodovotz, Yael

    2017-04-05

    As the incidence of obesity continues to increase, identifying novel nutritional therapies to enhance weight loss are needed. Raspberry ketone (RK; 4-(4-hydroxyphenyl) butan-2-one) is a bioactive phytochemical that is marketed as a weight loss supplement in the United States, yet there is scant scientific evidence demonstrating that RK promotes weight loss. The aim of the current study was to investigate the effect of RK on accumulation of adipose mass, hepatic lipid storage, and levels of plasma adiponectin in mice fed a high-fat (HF) diet. Mice were individually housed and fed a HF control diet (45% kcal from fat) for two weeks to induce weight gain, then assigned to HF control, high-dose (1.74% wt/wt) raspberry ketone (HRK), low-dose (0.25% wt/wt) raspberry ketone (LRK), or a pair-fed group (PF) fed similar food intake to LRK mice. Following five weeks of feeding, mice fed LRK and HRK diets showed reduced food intake and body weight compared to mice maintained on control diet. When normalized to body weight, mice fed HRK diet exhibited decreased inguinal fat mass and increased liver mass compared to the control group. Hepatic steatosis was lowest in mice fed HRK diet, whereas LRK diet did not have an effect when compared to the PF group. Plasma adiponectin concentration was unaffected by RK and pair-feeding. Our findings demonstrate that RK supplementation has limited benefit to adipose loss beyond reducing energy intake in mice fed a high-fat diet. The present study supports the need for appropriate study design when validating weight-loss supplements.

  12. Tautomer-selective derivatives of enolate, ketone and enaminone by addition reaction of picolyl-type anions with nitriles

    NASA Astrophysics Data System (ADS)

    Bai, Jianliang; Wang, Peng; Cao, Wei; Chen, Xia

    2017-01-01

    We describe an efficient for the synthesis of compounds of tautomeric β-pyridyl/quinolyl-enol, -ketone, -enaminone, which were finally characterized by standard methods like NMR, IR or SCXRD. The addition reaction of lithiated intermediates of picoline, 2-ethylpyridine and 2-methylquinoline, respectively, with nitriles followed by acid hydrolysis afforded the corresponding tautomeric compounds of enol, ketone and emaminone. Interestingly, treatment of 2-methylpyridine or 2-ethylpyridine with nitriles, respectively, yielded mostly β-pyridyl ketone and enol tautomers without enaminones, while 2-methylquinoline with nitriles gave β-quinolyl ketone and enaminone tautomers without enols. The reaction of 2-benzylpyridine with nitriles was not available under the same conditions.

  13. Nuclear gamma rays from energetic particle interactions

    NASA Technical Reports Server (NTRS)

    Ramaty, R.; Kozlovsky, B.; Lingenfelter, R. E.

    1978-01-01

    Gamma ray line emission from nuclear deexcitation following energetic particle reactions is evaluated. The compiled nuclear data and the calculated gamma ray spectra and intensities can be used for the study of astrophysical sites which contain large fluxes of energetic protons and nuclei. A detailed evaluation of gamma ray line production in the interstellar medium is made.

  14. Anisotropic Decomposition of Energetic Materials

    SciTech Connect

    Pravica, Michael; Quine, Zachary; Romano, Edward; Bajar, Sean; Yulga, Brian; Yang, Wenge; Hooks, Daniel

    2008-01-17

    Using a white x-ray synchrotron beam, we have dynamically studied radiation-induced decomposition in single crystalline PETN and TATB. By monitoring the integrated intensity of selected diffraction spots via a CCD x-ray camera as a function of time, we have found that the decomposition rate varies dramatically depending upon the orientation of the crystalline axes relative to polarized x-ray beam and for differing diffracting conditions (spots) within the same crystalline orientation. We suggest that this effect is due to Compton scattering of the polarized x-rays with electron clouds that is dependent upon their relative orientation. This novel effect may yield valuable insight regarding anisotropic detonation sensitivity in energetic materials such as PETN.

  15. Anisotropic decomposition of energetic materials

    SciTech Connect

    Pravica, Michael; Quine, Zachary; Romano, Edward; Bajar, Sean; Yulga, Brian; Yang Wenge; Hooks, Daniel

    2007-12-12

    Using a white x-ray synchrotron beam, we have dynamically studied radiation-induced decomposition in single crystalline PETN and TATB. By monitoring the integrated intensity of selected diffraction spots via a CCD x-ray camera as a function of time, we have found that the decomposition rate varies dramatically depending upon the orientation of the crystalline axes relative to polarized x-ray beam and for differing diffracting conditions (spots) within the same crystalline orientation. We suggest that this effect is due to Compton scattering of the polarized x-rays with electron clouds that is dependent upon their relative orientation. This novel effect may yield valuable insight regarding anisotropic detonation sensitivity in energetic materials such as PETN.

  16. Extreme solar energetic particle events

    NASA Astrophysics Data System (ADS)

    Vainio, Rami; Afanasiev, Alexandr; Battarbee, Markus

    2016-04-01

    Properties of extreme solar energetic particle (SEP) events, here defined as those leading to ground level enhancements (GLEs) of cosmic rays, are reviewed. We review recent efforts on modeling SEP acceleration to relativistic energies and present simulation results on particle acceleration at shocks driven by fast coronal mass ejections (CMEs) in different types of coronal magnetic structures and turbulent downstream compression regions. Based on these modeling results, we discuss the possible role of solar and CME parameters in the lack of GLEs during the present sunspot cycle. This work has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 637324 (HESPERIA). The Academy of Finland is thanked for financial support.

  17. Comparative primate energetics and hominid evolution.

    PubMed

    Leonard, W R; Robertson, M L

    1997-02-01

    There is currently great interest in developing ecological models for investigating human evolution. Yet little attention has been given to energetics, one of the cornerstones of modern ecosystem ecology. This paper examines the ecological correlates of variation in metabolic requirements among extant primate species, and uses this information to draw inferences about the changes in energy demands over the course of human evolution. Data on body size, resting metabolism, and activity budgets for selected anthropoid species and human hunter-gatherers are used to estimate total energy expenditure (TEE). Analyses indicate that relative energy expenditure levels and day ranges are positively correlated with diet quality; that is, more active species tend to consume more energy-rich diets. Human foragers fall at the positive extremes for modern primates in having high expenditure levels, large ranges, and very high quality diets. During hominid evolution, it appears that TEE increased substantially with the emergence of Homo erectus. This increase is partly attributable to larger body size as well as likely increases in day range and activity level. Assuming similar activity budgets for all early hominid species, estimated TEE for H. erectus is 40-45% greater than for the australopithecines. If, however, it is assumed that the evolution of early Homo was also associated with a shift to a more "human-like" foraging strategy, estimated expenditure levels for H. erectus are 80-85% greater than in the australopithecines. Changing patterns of resource distribution associated with the expansion of African savannas between 2.5 and 1.5 mya may been the impetus for a shift in foraging behavior among early members of the genus Homo. Such ecological changes likely would have made animal foods a more attractive resource. Moreover, greater use of animal foods and the resulting higher quality diet would have been important for supporting the larger day ranges and greater energy

  18. Energetics and the immune system

    PubMed Central

    Reiches, Meredith W.; Prentice, Andrew M.; Moore, Sophie E.; Ellison, Peter T.

    2017-01-01

    Abstract Background and objectives: The human immune system is an ever-changing composition of innumerable cells and proteins, continually ready to respond to pathogens or insults. The cost of maintaining this state of immunological readiness is rarely considered. In this paper we aim to discern a cost to non-acute immune function by investigating how low levels of C-reactive protein (CRP) relate to other energetic demands and resources in adolescent Gambian girls. Methodology: Data from a longitudinal study of 66 adolescent girls was used to test hypotheses around investment in immune function. Non-acute (under 2 mg/L) CRP was used as an index of immune function. Predictor variables include linear height velocity, adiposity, leptin, and measures of energy balance. Results: Non-acute log CRP was positively associated with adiposity (β = 0.16, P < 0.001, R2 = 0.17) and levels of the adipokine leptin (β = 1.17, P = 0.006, R2 = 0.09). CRP was also negatively associated with increased investment in growth, as measured by height velocity (β = −0.58, P < 0.001, R2 = 0.13) and lean mass deposition β = −0.42, P = 0.005, R2 = 0.08). Relationships between adiposity and growth explained some, but not all, of this association. We do not find that CRP was related to energy balance. Conclusions and implications: These data support a hypothesis that investment in non-acute immune function is facultative, and sensitive to energetic resources and demands. We also find support for an adaptive association between the immune system and adipose tissue. PMID:28003312

  19. ON THE THERMODYNAMICS OF SOLID INTRUSION SOLUTIONS WITH BODY-CENTERED CUBIC LATTICE

    DTIC Science & Technology

    THE PROPERTIES OF AN ELASTICALLY DEFORMED SOLID INTRUSION SOLUTION WITH BODY - CENTERED CUBIC LATTICE, UNBALANCED WITH RESPECT TO ENERGETICALLY DIFFERENT POSITIONS OF THE ATOMS OF THE DISSOLVED SUBSTANCE.

  20. Energetic Particle Influence on the Earth's Atmosphere

    NASA Astrophysics Data System (ADS)

    Mironova, Irina A.; Aplin, Karen L.; Arnold, Frank; Bazilevskaya, Galina A.; Harrison, R. Giles; Krivolutsky, Alexei A.; Nicoll, Keri A.; Rozanov, Eugene V.; Turunen, Esa; Usoskin, Ilya G.

    2015-11-01

    This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth's atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere.