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Sample records for inborn metabolic defects

  1. Inborn Errors of Metabolism with Acidosis: Organic Acidemias and Defects of Pyruvate and Ketone Body Metabolism.

    Science.gov (United States)

    Schillaci, Lori-Anne P; DeBrosse, Suzanne D; McCandless, Shawn E

    2018-04-01

    When a child presents with high-anion gap metabolic acidosis, the pediatrician can proceed with confidence by recalling some basic principles. Defects of organic acid, pyruvate, and ketone body metabolism that present with acute acidosis are reviewed. Flowcharts for identifying the underlying cause and initiating life-saving therapy are provided. By evaluating electrolytes, blood sugar, lactate, ammonia, and urine ketones, the provider can determine the likelihood of an inborn error of metabolism. Freezing serum, plasma, and urine samples during the acute presentation for definitive diagnostic testing at the provider's convenience aids in the differential diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Inborn errors of metabolism: a clinical overview

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    Ana Maria Martins

    1999-11-01

    Full Text Available CONTEXT: Inborn errors of metabolism cause hereditary metabolic diseases (HMD and classically they result from the lack of activity of one or more specific enzymes or defects in the transportation of proteins. OBJECTIVES: A clinical review of inborn errors of metabolism (IEM to give a practical approach to the physician with figures and tables to help in understanding the more common groups of these disorders. DATA SOURCE: A systematic review of the clinical and biochemical basis of IEM in the literature, especially considering the last ten years and a classic textbook (Scriver CR et al, 1995. SELECTION OF STUDIES: A selection of 108 references about IEM by experts in the subject was made. Clinical cases are presented with the peculiar symptoms of various diseases. DATA SYNTHESIS: IEM are frequently misdiagnosed because the general practitioner, or pediatrician in the neonatal or intensive care units, does not think about this diagnosis until the more common cause have been ruled out. This review includes inheritance patterns and clinical and laboratory findings of the more common IEM diseases within a clinical classification that give a general idea about these disorders. A summary of treatment types for metabolic inherited diseases is given. CONCLUSIONS: IEM are not rare diseases, unlike previous thinking about them, and IEM patients form part of the clientele in emergency rooms at general hospitals and in intensive care units. They are also to be found in neurological, pediatric, obstetrics, surgical and psychiatric clinics seeking diagnoses, prognoses and therapeutic or supportive treatment.

  3. Screening for Inborn Errors of Metabolism

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    F.A. Elshaari

    2013-09-01

    Full Text Available Inborn errors of metabolism (IEM are a heterogeneous group of monogenic diseases that affect the metabolic pathways. The detection of IEM relies on a high index of clinical suspicion and co-ordinated access to specialized laboratory services. Biochemical analysis forms the basis of the final confirmed diagnosis in several of these disorders. The investigations fall into four main categories1.General metabolic screening tests2.Specific metabolite assays3.Enzyme studies4.DNA analysis The first approach to the diagnosis is by a multi-component analysis of body fluids in clinically selected patients, referred to as metabolic screening tests. These include simple chemical tests in the urine, blood glucose, acid-base profile, lactate, ammonia and liver function tests. The results of these tests can help to suggest known groups of metabolic disorders so that specific metabolites such as amino acids, organic acids, etc. can be estimated. However, not all IEM needs the approach of general screening. Lysosomal, peroxisomal, thyroid and adrenal disorders are suspected mainly on clinical grounds and pertinent diagnostic tests can be performed. The final diagnosis relies on the demonstration of the specific enzyme defect, which can be further confirmed by DNA studies.

  4. Clinical pathways for inborn errors of metabolism: warranted and feasible

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    Demirdas Serwet

    2013-02-01

    Full Text Available Abstract Inborn errors of metabolism (IEMs are known for their low prevalence and multidisciplinary care mostly founded on expert opinion. Clinical pathways are multidisciplinary tools to organise care which provide a clear route to the best care and improve communication. In 2010 the Dutch Society for Children and Adults with an Inborn Error of Metabolism (VKS initiated development of clinical pathways for inborn errors of metabolism. In this letter to the editor we describe why it is warranted to develop clinical pathways for IEMs and shortly discuss the process of development for these pathways in the Netherlands.

  5. In vivo enzyme activity in inborn errors of metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. (Clinical Research Centre, Harrow (England))

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  6. In vivo enzyme activity in inborn errors of metabolism

    International Nuclear Information System (INIS)

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D.

    1990-01-01

    Low-dose continuous infusions of [2H5]phenylalanine, [1-13C]propionate, and [1-13C]leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD

  7. Automated Screening for Three Inborn Metabolic Disorders: A Pilot Study

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    Kavitha S

    2006-12-01

    Full Text Available Background: Inborn metabolic disorders (IMDs form a large group of rare, but often serious, metabolic disorders. Aims: Our objective was to construct a decision tree, based on classification algorithm for the data on three metabolic disorders, enabling us to take decisions on the screening and clinical diagnosis of a patient. Settings and Design: A non-incremental concept learning classification algorithm was applied to a set of patient data and the procedure followed to obtain a decision on a patient’s disorder. Materials and Methods: Initially a training set containing 13 cases was investigated for three inborn errors of metabolism. Results: A total of thirty test cases were investigated for the three inborn errors of metabolism. The program identified 10 cases with galactosemia, another 10 cases with fructosemia and the remaining 10 with propionic acidemia. The program successfully identified all the 30 cases. Conclusions: This kind of decision support systems can help the healthcare delivery personnel immensely for early screening of IMDs.

  8. Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment

    NARCIS (Netherlands)

    Bosch, A.M.; Abeling, N.G.G.M.; Ijlst, L.; Knoester, H.; van der Pol, W.L.; Stroomer, A.E.M.; Wanders, R.J.; Visser, G.; Wijburg, F.A.; Duran, M.; Waterham, H.R.

    2011-01-01

    We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation

  9. Pediatric neurological syndromes and inborn errors of purine metabolism.

    Science.gov (United States)

    Camici, Marcella; Micheli, Vanna; Ipata, Piero Luigi; Tozzi, Maria Grazia

    2010-02-01

    This review is devised to gather the presently known inborn errors of purine metabolism that manifest neurological pediatric syndromes. The aim is to draw a comprehensive picture of these rare diseases, characterized by unexpected and often devastating neurological symptoms. Although investigated for many years, most purine metabolism disorders associated to psychomotor dysfunctions still hide the molecular link between the metabolic derangement and the neurological manifestations. This basically indicates that many of the actual functions of nucleosides and nucleotides in the development and function of several organs, in particular central nervous system, are still unknown. Both superactivity and deficiency of phosphoribosylpyrophosphate synthetase cause hereditary disorders characterized, in most cases, by neurological impairments. The deficiency of adenylosuccinate lyase and 5-amino-4-imidazolecarboxamide ribotide transformylase/IMP cyclohydrolase, both belonging to the de novo purine synthesis pathway, is also associated to severe neurological manifestations. Among catabolic enzymes, hyperactivity of ectosolic 5'-nucleotidase, as well as deficiency of purine nucleoside phosphorylase and adenosine deaminase also lead to syndromes affecting the central nervous system. The most severe pathologies are associated to the deficiency of the salvage pathway enzymes hypoxanthine-guanine phosphoribosyltransferase and deoxyguanosine kinase: the former due to an unexplained adverse effect exerted on the development and/or differentiation of dopaminergic neurons, the latter due to a clear impairment of mitochondrial functions. The assessment of hypo- or hyperuricemic conditions is suggestive of purine enzyme dysfunctions, but most disorders of purine metabolism may escape the clinical investigation because they are not associated to these metabolic derangements. This review may represent a starting point stimulating both scientists and physicians involved in the study of

  10. Etiology and outcome of inborn errors of metabolism

    International Nuclear Information System (INIS)

    Choudhry, S.; Khan, M.; Khan, E.A.

    2013-01-01

    Objectives: To study the clinical presentation, diagnostic workup and outcome of children presenting with suspected inborn errors of metabolism. Methods: The cross-sectional study was conducted at the Shifa International Hospital, Islamabad, and included all patients diagnosed with the condition between January 2006 and June 2011. Medical records of the patients were reviewed to collect the relevant data. Results: A total of 10 patients underwent diagnostic work-up. Majority 7 (70%) were males and 6 (60%) presented in the neonatal age group. Seizures and coma were the commonest presentations (n=5; 50% each) followed by breathing difficulty (n=4; 40%) and vomiting (n=2; 20%). The commonest diagnoses were methyl malonic acIdaemia (n=2; 20%), non-ketotic hyperglycinaemia (n=7; 10%), fructose 1,6 diphosphatase deficiency (n=1; 10%), and biotinidase deficiency (n=1; 10%). Mortality was high (n=5; 50%) and half of the survivors had severe neurological impairment. Conclusion: The diagnosis of inborn errors of metabolism requires a high index of suspicion. These disorders have a high mortality and risk of long-term neurological disability. (author)

  11. Inborn Errors of Intermediary Metabolism in Critically Ill Mexican Newborns

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    Ibarra-González Isabel MSc

    2014-04-01

    Full Text Available Inborn errors of intermediary metabolism (IEiM are complex diseases with high clinical heterogeneity, and some patients who have severe enzyme deficiencies or are subjected to stress (catabolism/infections actually decompensate in the neonatal period. In this study, we performed metabolic tests on 2025 newborns in Mexico admitted to 35 neonatal intensive care units or emergency wards (NICUs/EWs over a 6-year period, in whom a metabolic disorder was clinically suspected. Of these 2025 newborns with sickness, 11 had IEiM, revealing a prevalence of 1:184. Clinical characteristics and outcomes of the newborns with confirmed IEiM are shown. Of these 11 patients, 4 had isolated methylmalonic acidemia, 3 had maple syrup urine disease, 2 had urea cycle disorders, 1 had 3-hydroxy-3-methylglutaric acidemia, and 1 had isovaleric acidemia. During the first week of life (average 3 days, all of these newborns presented with impaired alertness, hypotonia, feeding difficulties, and vomiting along with metabolic acidosis and hyperammonemia. Of the 11 newborns with IEiM, 7 died, leading to a mortality rate of 64%. In conclusion, the differential diagnosis of newborns admitted to the NICU/EW must include IEiM, requiring systematic screening of this population.

  12. "Transcriptomics": molecular diagnosis of inborn errors of metabolism via RNA-sequencing.

    Science.gov (United States)

    Kremer, Laura S; Wortmann, Saskia B; Prokisch, Holger

    2018-01-25

    Exome wide sequencing techniques have revolutionized molecular diagnostics in patients with suspected inborn errors of metabolism or neuromuscular disorders. However, the diagnostic yield of 25-60% still leaves a large fraction of individuals without a diagnosis. This indicates a causative role for non-exonic regulatory variants not covered by whole exome sequencing. Here we review how systematic RNA-sequencing analysis (RNA-seq, "transcriptomics") lead to a molecular diagnosis in 10-35% of patients in whom whole exome sequencing failed to do so. Importantly, RNA-sequencing based discoveries cannot only guide molecular diagnosis but might also unravel therapeutic intervention points such as antisense oligonucleotide treatment for splicing defects as recently reported for spinal muscular atrophy.

  13. Metabolic Diet App Suite for inborn errors of amino acid metabolism.

    Science.gov (United States)

    Ho, Gloria; Ueda, Keiko; Houben, Roderick F A; Joa, Jeff; Giezen, Alette; Cheng, Barbara; van Karnebeek, Clara D M

    2016-03-01

    An increasing number of rare inborn errors of metabolism (IEMs) are amenable to targeted metabolic nutrition therapy. Daily adherence is important to attain metabolic control and prevent organ damage. This is challenging however, given the lack of information of disorder specific nutrient content of foods, the limited availability and cost of specialty products as well as difficulties in reliable calculation and tracking of dietary intake and targets. To develop apps for all inborn errors of amino acid metabolism for which the mainstay of treatment is a medical diet, and obtain patient and family feedback throughout the process to incorporate this into subsequent versions. The Metabolic Diet App Suite was created with input from health care professionals as a free, user-friendly, online tool for both mobile devices and desktop computers (http://www.metabolicdietapp.org) for 15 different IEMs. General information is provided for each IEM with links to useful online resources. Nutrient information is based on the MetabolicPro™, a North American food database compiled by the Genetic Metabolic Dietitians International (GMDI) Technology committee. After user registration, a personalized dashboard and management plan including specific nutrient goals are created. Each Diet App has a user-friendly interface and the functions include: nutrient intake counts, adding your own foods and homemade recipes and, managing a daily food diary. Patient and family feedback was overall positive and specific suggestions were used to further improve the App Suite. The Metabolic Diet App Suite aids individuals affected by IEMs to track and plan their meals. Future research should evaluate its impact on patient adherence, metabolic control, quality of life and health-related outcomes. The Suite will be updated and expanded to Apps for other categories of IEMs. Finally, this Suite is a support tool only, and does not replace medical/metabolic nutrition professional advice. Copyright

  14. The Frequencies of Different Inborn Errors of Metabolism in Adult Metabolic Centres: Report from the SSIEM Adult Metabolic Physicians Group

    NARCIS (Netherlands)

    Sirrs, S.; Hollak, C.; Merkel, M.; Sechi, A.; Glamuzina, E.; Janssen, M.C.H.; Lachmann, R.; Langendonk, J.; Scarpelli, M.; Omran, T. Ben; Mochel, F.; Tchan, M.C.

    2016-01-01

    BACKGROUND: There are few centres which specialise in the care of adults with inborn errors of metabolism (IEM). To anticipate facilities and staffing needed at these centres, it is of interest to know the distribution of the different disorders. METHODS: A survey was distributed through the

  15. Inborn Errors of Fructose Metabolism. What Can We Learn from Them?

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    Christel Tran

    2017-04-01

    Full Text Available Fructose is one of the main sweetening agents in the human diet and its ingestion is increasing globally. Dietary sugar has particular effects on those whose capacity to metabolize fructose is limited. If intolerance to carbohydrates is a frequent finding in children, inborn errors of carbohydrate metabolism are rare conditions. Three inborn errors are known in the pathway of fructose metabolism; (1 essential or benign fructosuria due to fructokinase deficiency; (2 hereditary fructose intolerance; and (3 fructose-1,6-bisphosphatase deficiency. In this review the focus is set on the description of the clinical symptoms and biochemical anomalies in the three inborn errors of metabolism. The potential toxic effects of fructose in healthy humans also are discussed. Studies conducted in patients with inborn errors of fructose metabolism helped to understand fructose metabolism and its potential toxicity in healthy human. Influence of fructose on the glycolytic pathway and on purine catabolism is the cause of hypoglycemia, lactic acidosis and hyperuricemia. The discovery that fructose-mediated generation of uric acid may have a causal role in diabetes and obesity provided new understandings into pathogenesis for these frequent diseases.

  16. Redox signalling and mitochondrial stress responses; lessons from inborn errors of metabolism

    DEFF Research Database (Denmark)

    Olsen, Rikke K J; Cornelius, Nanna; Gregersen, Niels

    2015-01-01

    Mitochondria play a key role in overall cell physiology and health by integrating cellular metabolism with cellular defense and repair mechanisms in response to physiological or environmental changes or stresses. In fact, dysregulation of mitochondrial stress responses and its consequences...... in the form of oxidative stress, has been linked to a wide variety of diseases including inborn errors of metabolism. In this review we will summarize how the functional state of mitochondria -- and especially the concentration of reactive oxygen species (ROS), produced in connection with the respiratory...... chain -- regulates cellular stress responses by redox regulation of nuclear gene networks involved in repair systems to maintain cellular homeostasis and health. Based on our own and other's studies we re-introduce the ROS triangle model and discuss how inborn errors of mitochondrial metabolism...

  17. Modeling Inborn Errors of Hepatic Metabolism Using Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Pournasr, Behshad; Duncan, Stephen A

    2017-11-01

    Inborn errors of hepatic metabolism are because of deficiencies commonly within a single enzyme as a consequence of heritable mutations in the genome. Individually such diseases are rare, but collectively they are common. Advances in genome-wide association studies and DNA sequencing have helped researchers identify the underlying genetic basis of such diseases. Unfortunately, cellular and animal models that accurately recapitulate these inborn errors of hepatic metabolism in the laboratory have been lacking. Recently, investigators have exploited molecular techniques to generate induced pluripotent stem cells from patients' somatic cells. Induced pluripotent stem cells can differentiate into a wide variety of cell types, including hepatocytes, thereby offering an innovative approach to unravel the mechanisms underlying inborn errors of hepatic metabolism. Moreover, such cell models could potentially provide a platform for the discovery of therapeutics. In this mini-review, we present a brief overview of the state-of-the-art in using pluripotent stem cells for such studies. © 2017 American Heart Association, Inc.

  18. Inborn errors of metabolism for the diagnostic radiologist

    Energy Technology Data Exchange (ETDEWEB)

    Hendriksz, Chris J. [Birmingham Children' s Hospital NHS Foundation Trust, Department of Clinical Inherited Metabolic Disorders, Birmingham (United Kingdom)

    2009-03-15

    Inherited metabolic disorders are becoming more important with the increasing availability of diagnostic methods and therapies for these conditions. The radiologist has become an important link in making the diagnosis or collaborating with the specialist centre to diagnose these disorders and monitor effects of therapy. The modes of presentation, disease-specific groups, classic radiological features and investigations are explored in this article to try and give the general radiologist some crucial background knowledge. The following presentations are covered: acute intoxication, hypoglycaemia, developmental delay and storage features. Specific groups of disorders covered are the abnormalities of intermediary metabolism, disorders of fatty acid oxidation and ketogenesis, mitochondrial disorders, lysosomal storage disorders, and, briefly, other groups such as peroxisomal disorders, disorders of glycosylation, and creatine synthesis disorders. New advances and the demands for monitoring are also briefly explored. (orig.)

  19. Inborn errors of metabolism for the diagnostic radiologist

    International Nuclear Information System (INIS)

    Hendriksz, Chris J.

    2009-01-01

    Inherited metabolic disorders are becoming more important with the increasing availability of diagnostic methods and therapies for these conditions. The radiologist has become an important link in making the diagnosis or collaborating with the specialist centre to diagnose these disorders and monitor effects of therapy. The modes of presentation, disease-specific groups, classic radiological features and investigations are explored in this article to try and give the general radiologist some crucial background knowledge. The following presentations are covered: acute intoxication, hypoglycaemia, developmental delay and storage features. Specific groups of disorders covered are the abnormalities of intermediary metabolism, disorders of fatty acid oxidation and ketogenesis, mitochondrial disorders, lysosomal storage disorders, and, briefly, other groups such as peroxisomal disorders, disorders of glycosylation, and creatine synthesis disorders. New advances and the demands for monitoring are also briefly explored. (orig.)

  20. Risk factors and birth prevalence of birth defects and inborn errors of ...

    African Journals Online (AJOL)

    Children with any birth defect or metabolic errors of metabolism at birth or in the neonatology section were our sample for study. Control group was randomly selected from the cases with normal live births. Blood tests were performed for children suspected to suffer from genetic blood disorders. The principal BD as per the ...

  1. Clinical Metabolomics: The New Metabolic Window for Inborn Errors of Metabolism Investigations in the Post-Genomic Era

    Science.gov (United States)

    Tebani, Abdellah; Abily-Donval, Lenaig; Afonso, Carlos; Marret, Stéphane; Bekri, Soumeya

    2016-01-01

    Inborn errors of metabolism (IEM) represent a group of about 500 rare genetic diseases with an overall estimated incidence of 1/2500. The diversity of metabolic pathways involved explains the difficulties in establishing their diagnosis. However, early diagnosis is usually mandatory for successful treatment. Given the considerable clinical overlap between some inborn errors, biochemical and molecular tests are crucial in making a diagnosis. Conventional biological diagnosis procedures are based on a time-consuming series of sequential and segmented biochemical tests. The rise of “omic” technologies offers holistic views of the basic molecules that build a biological system at different levels. Metabolomics is the most recent “omic” technology based on biochemical characterization of metabolites and their changes related to genetic and environmental factors. This review addresses the principles underlying metabolomics technologies that allow them to comprehensively assess an individual biochemical profile and their reported applications for IEM investigations in the precision medicine era. PMID:27447622

  2. Inborn errors of metabolism and expanded newborn screening: review and update.

    Science.gov (United States)

    Mak, Chloe Miu; Lee, Han-Chih Hencher; Chan, Albert Yan-Wo; Lam, Ching-Wan

    2013-11-01

    Inborn errors of metabolism (IEM) are a phenotypically and genetically heterogeneous group of disorders caused by a defect in a metabolic pathway, leading to malfunctioning metabolism and/or the accumulation of toxic intermediate metabolites. To date, more than 1000 different IEM have been identified. While individually rare, the cumulative incidence has been shown to be upwards of 1 in 800. Clinical presentations are protean, complicating diagnostic pathways. IEM are present in all ethnic groups and across every age. Some IEM are amenable to treatment, with promising outcomes. However, high clinical suspicion alone is not sufficient to reduce morbidities and mortalities. In the last decade, due to the advent of tandem mass spectrometry, expanded newborn screening (NBS) has become a mandatory public health strategy in most developed and developing countries. The technology allows inexpensive simultaneous detection of more than 30 different metabolic disorders in one single blood spot specimen at a cost of about USD 10 per baby, with commendable analytical accuracy and precision. The sensitivity and specificity of this method can be up to 99% and 99.995%, respectively, for most amino acid disorders, organic acidemias, and fatty acid oxidation defects. Cost-effectiveness studies have confirmed that the savings achieved through the use of expanded NBS programs are significantly greater than the costs of implementation. The adverse effects of false positive results are negligible in view of the economic health benefits generated by expanded NBS and these could be minimized through increased education, better communication, and improved technologies. Local screening agencies should be given the autonomy to develop their screening programs in order to keep pace with international advancements. The development of biochemical genetics is closely linked with expanded NBS. With ongoing advancements in nanotechnology and molecular genomics, the field of biochemical genetics

  3. Cost-benefit analysis: newborn screening for inborn errors of metabolism in Lebanon.

    Science.gov (United States)

    Khneisser, I; Adib, S; Assaad, S; Megarbane, A; Karam, P

    2015-12-01

    Few countries in the Middle East-North Africa region have adopted national newborn screening for inborn errors of metabolism by tandem mass spectrometry (MS/MS). We aimed to evaluate the cost-benefit of newborn screening for such disorders in Lebanon, as a model for other developing countries in the region. Average costs of expected care for inborn errors of metabolism cases as a group, between ages 0 and 18, early and late diagnosed, were calculated from 2007 to 2013. The monetary value of early detection using MS/MS was compared with that of clinical "late detection", including cost of diagnosis and hospitalizations. During this period, 126000 newborns were screened. Incidence of detected cases was 1/1482, which can be explained by high consanguinity rates in Lebanon. A reduction by half of direct cost of care, reaching on average 31,631 USD per detected case was shown. This difference more than covers the expense of starting a newborn screening programme. Although this model does not take into consideration the indirect benefits of the better quality of life of those screened early, it can be argued that direct and indirect costs saved through early detection of these disorders are important enough to justify universal publicly-funded screening, especially in developing countries with high consanguinity rates, as shown through this data from Lebanon. © The Author(s) 2015.

  4. Parenteral nutrition in patients with inborn errors of metabolism - a therapeutic problem.

    Science.gov (United States)

    Kaluzny, L; Szczepanik, M; Siwinska-Mrozek, Z; Borkowska-Klos, M; Cichy, W; Walkowiak, J

    2014-06-01

    Parenteral nutrition is now a standard part of supportive treatment in pediatric departments. We describe four cases in which parenteral nutrition was extremely difficult due to coincidence with inborn errors of metabolism. The first two cases was fatty acid beta-oxidation disorders associated with necrotizing enterocolitis and congenital heart disease. Thus, limitations of intravenous lipid intake made it difficult to maintain a good nutritional status. The third case was phenylketonuria associated with a facial region tumour (rhabdomyosarcoma), in which parenteral nutrition was complicated because of a high phenylalanine content in the amino acid formulas for parenteral nutrition. The fourth patient was a child with late-diagnosed tyrosinemia type 1, complicated with encephalopathy - during intensive care treatment the patient needed nutritional support, including parenteral nutrition - we observed amino acid formula problems similar to those in the phenylketonuria patient. Parenteral nutrition in children with inborn errors of metabolism is a rare, but very important therapeutic problem. Total parenteral nutrition formulas are not prepared for this group of diseases.

  5. The Frequencies of Different Inborn Errors of Metabolism in Adult Metabolic Centres: Report from the SSIEM Adult Metabolic Physicians Group.

    Science.gov (United States)

    Sirrs, S; Hollak, C; Merkel, M; Sechi, A; Glamuzina, E; Janssen, M C; Lachmann, R; Langendonk, J; Scarpelli, M; Ben Omran, T; Mochel, F; Tchan, M C

    2016-01-01

    There are few centres which specialise in the care of adults with inborn errors of metabolism (IEM). To anticipate facilities and staffing needed at these centres, it is of interest to know the distribution of the different disorders. A survey was distributed through the list-serve of the SSIEM Adult Metabolic Physicians group asking clinicians for number of patients with confirmed diagnoses, types of diagnoses and age at diagnosis. Twenty-four adult centres responded to our survey with information on 6,692 patients. Of those 6,692 patients, 510 were excluded for diagnoses not within the IEM spectrum (e.g. bone dysplasias, hemochromatosis) or for age less than 16 years, leaving 6,182 patients for final analysis. The most common diseases followed by the adult centres were phenylketonuria (20.6%), mitochondrial disorders (14%) and lysosomal storage disorders (Fabry disease (8.8%), Gaucher disease (4.2%)). Amongst the disorders that can present with acute metabolic decompensation, the urea cycle disorders, specifically ornithine transcarbamylase deficiency, were most common (2.2%), followed by glycogen storage disease type I (1.5%) and maple syrup urine disease (1.1%). Patients were frequently diagnosed as adults, particularly those with mitochondrial disease and lysosomal storage disorders. A wide spectrum of IEM are followed at adult centres. Specific knowledge of these disorders is needed to provide optimal care including up-to-date knowledge of treatments and ability to manage acute decompensation.

  6. Essential polyunsaturated fatty acids in plasma and erythrocytes of children with inborn errors of amino acid metabolism.

    NARCIS (Netherlands)

    Vlaardingerbroek, H.; Hornstra, G.; Koning, T.J.; Smeitink, J.A.M.; Bakker, H.D.; Klerk, H. de; Rubio-Gozalbo, M.E.

    2006-01-01

    Essential fatty acids (EFAs), and their longer-chain more-unsaturated derivatives (LCPUFAs) in particular, are essential for normal growth and cognitive development during childhood. Children with inborn errors of amino acid metabolism represent a risk population for a reduced LCPUFA status because

  7. N-acetylated metabolites in urine: proton nuclear magnetic resonance spectroscopic study on patients with inborn errors of metabolism.

    NARCIS (Netherlands)

    Engelke, U.F.H.; Liebrand-van Sambeek, M.L.F.; Jong, J.G.N. de; Leroy, J.G.; Morava, E.; Smeitink, J.A.M.; Wevers, R.A.

    2004-01-01

    BACKGROUND: There is no comprehensive analytical technique to analyze N-acetylated metabolites in urine. Many of these compounds are involved in inborn errors of metabolism. In the present study, we examined the potential of proton nuclear magnetic resonance ((1)H-NMR) spectroscopy as a tool to

  8. Identification of Mutations Underlying 20 Inborn Errors of Metabolism in the United Arab Emirates Population

    Science.gov (United States)

    Ben-Rebeh, Imen; Hertecant, Jozef L.; Al-Jasmi, Fatma A.; Aburawi, Hanan E.; Al-Yahyaee, Said A.; Al-Gazali, Lihadh

    2012-01-01

    Inborn errors of metabolism (IEM) are frequently encountered by physicians in the United Arab Emirates (UAE). However, the mutations underlying a large number of these disorders have not yet been determined. Therefore, the objective of this study was to identify the mutations underlying a number of IEM disorders among UAE residents from both national and expatriate families. A case series of patients from 34 families attending the metabolic clinic at Tawam Hospital were clinically evaluated, and molecular testing was carried out to determine their causative mutations. The mutation analysis was carried out at molecular genetics diagnostic laboratories. Thirty-eight mutations have been identified as responsible for twenty IEM disorders, including in the metabolism of amino acids, lipids, steroids, metal transport and mitochondrial energy metabolism, and lysosomal storage disorders. Nine of the identified mutations are novel, including two missense mutations, three premature stop codons and four splice site mutations. Mutation analysis of IEM disorders in the UAE population has an important impact on molecular diagnosis and genetic counseling for families affected by these disorders. PMID:22106832

  9. Tratamento de erros inatos do metabolismo Treatment of inborn errors of metabolism

    Directory of Open Access Journals (Sweden)

    Ida Vanessa Schwartz

    2008-08-01

    metabolism, priority was given to the most important methods for managing intoxication, in view of the importance for pediatricians to treat acute and life-threatening cases. The article also provides a general overview of the treatment for lysosomal and peroxisomal diseases, with emphasis on enzyme replacement therapy, which is a treatment modality that is growing in use and with which pediatricians should make themselves familiar. SUMMARY OF THE FINDINGS: The most important measures used to manage the intoxication present in many inborn errors of intermediate metabolism were presented (restriction of substrate build-up by means of diet or enzymatic inhibition, removal of toxic products, stimulation of residual enzyme activity, replacement of the deficient product. The section on treatment for lysosomal and peroxisomal diseases includes tables providing information on the treatments available. CONCLUSIONS: Treating inborn errors of metabolism is a complex task that should be performed by a multidisciplinary team of which the pediatrician is the key member. This article provides practical information relating to the management of some inborn errors of metabolism and provides pediatricians with a general overview of recent developments in this area of medicine.

  10. Uric acid, an important screening tool to detect inborn errors of metabolism: a case series.

    Science.gov (United States)

    Jasinge, Eresha; Kularatnam, Grace Angeline Malarnangai; Dilanthi, Hewa Warawitage; Vidanapathirana, Dinesha Maduri; Jayasena, Kandana Liyanage Subhashinie Priyadarshika Kapilani Menike; Chandrasiri, Nambage Dona Priyani Dhammika; Indika, Neluwa Liyanage Ruwan; Ratnayake, Pyara Dilani; Gunasekara, Vindya Nandani; Fairbanks, Lynette Dianne; Stiburkova, Blanka

    2017-09-06

    Uric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine. CASE 1: A one-and-half-year-old boy was investigated for haematuria and a calculus in the bladder. Xanthine crystals were seen in microscopic examination of urine sediment. Low uric acid concentrations in serum and low urinary fractional excretion of uric acid associated with high urinary excretion of xanthine and hypoxanthine were compatible with xanthine oxidase deficiency. CASE 2: An 8-month-old boy presented with intractable seizures, feeding difficulties, screaming episodes, microcephaly, facial dysmorphism and severe neuro developmental delay. Low uric acid level in serum, low fractional excretion of uric acid and radiological findings were consistent with possible molybdenum cofactor deficiency. Diagnosis was confirmed by elevated levels of xanthine, hypoxanthine and sulfocysteine levels in urine. CASE 3: A 3-year-10-month-old boy presented with global developmental delay, failure to thrive, dystonia and self-destructive behaviour. High uric acid levels in serum, increased fractional excretion of uric acid and absent hypoxanthine-guanine phosphoribosyltransferase enzyme level confirmed the diagnosis of Lesch-Nyhan syndrome. CASE 4: A 9-year-old boy was investigated for lower abdominal pain, gross haematuria and right renal calculus. Low uric acid level in serum and increased fractional excretion of uric acid pointed towards hereditary renal hypouricaemia which was confirmed by genetic studies. Abnormal uric acid level in blood and urine is a valuable tool in screening for clinical conditions related to derangement of the nucleic acid metabolic pathway.

  11. A targeted metabolomics approach for clinical diagnosis of inborn errors of metabolism.

    Science.gov (United States)

    Jacob, Minnie; Malkawi, Abeer; Albast, Nour; Al Bougha, Salam; Lopata, Andreas; Dasouki, Majed; Abdel Rahman, Anas M

    2018-09-26

    Metabolome, the ultimate functional product of the genome, can be studied through identification and quantification of small molecules. The global metabolome influences the individual phenotype through clinical and environmental interventions. Metabolomics has become an integral part of clinical research and allowed for another dimension of better understanding of disease pathophysiology and mechanism. More than 95% of the clinical biochemistry laboratory routine workload is based on small molecular identification, which can potentially be analyzed through metabolomics. However, multiple challenges in clinical metabolomics impact the entire workflow and data quality, thus the biological interpretation needs to be standardized for a reproducible outcome. Herein, we introduce the establishment of a comprehensive targeted metabolomics method for a panel of 220 clinically relevant metabolites using Liquid chromatography-tandem mass spectrometry (LC-MS/MS) standardized for clinical research. The sensitivity, reproducibility and molecular stability of each targeted metabolite (amino acids, organic acids, acylcarnitines, sugars, bile acids, neurotransmitters, polyamines, and hormones) were assessed under multiple experimental conditions. The metabolic tissue distribution was determined in various rat organs. Furthermore, the method was validated in dry blood spot (DBS) samples collected from patients known to have various inborn errors of metabolism (IEMs). Using this approach, our panel appears to be sensitive and robust as it demonstrated differential and unique metabolic profiles in various rat tissues. Also, as a prospective screening method, this panel of diverse metabolites has the ability to identify patients with a wide range of IEMs who otherwise may need multiple, time-consuming and expensive biochemical assays causing a delay in clinical management. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Expanded Newborn Screening for Inborn Errors of Metabolism and Genetic Characteristics in a Chinese Population

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    Kejian Guo

    2018-04-01

    Full Text Available The incidence of inborn errors of metabolisms (IEMs varies dramatically in different countries and regions. Expanded newborn screening for IEMs by tandem mass spectrometry (MS/MS is an efficient approach for early diagnosis and presymptomatic treatment to prevent severe permanent sequelae and death. To determine the characteristics of IEMs and IEMs-associated mutations in newborns in Jining area, China, 48,297 healthy neonates were recruited for expanded newborn screening by MS/MS. The incidence of IEMs was 1/1178 in Jining, while methylmalonic acidemia, phenylketonuria, and primary carnitine deficiency ranked the top 3 of all detected IEMs. Thirty mutations in nine IEMs-associated genes were identified in 28 confirmed cases. As 19 cases with the mutations in phenylalanine hydroxylase (PAH, solute carrier family 22 member 5 (SLC22A5, and methylmalonic aciduria (cobalamin deficiency cblC type with homocystinuria (MMACHC genes, respectively, it suggested that mutations in the PAH, SLC22A5, and MMACHC genes are the predominant causes of IEMs, leading to the high incidence of phenylketonuria, primary carnitine deficiency, and methylmalonic acidemia, respectively. Our work indicated that the overall incidence of IEMs is high and the mutations in PAH, SLC22A5, and MMACHC genes are the leading causes of IEMs in Jining area. Therefore, it is critical to increase the coverage of expanded newborn screening by MS/MS and prenatal genetic consulting in Jining area.

  13. Consanguinity, endogamy and inborn errors of metabolism in Oman: a cross-sectional study.

    Science.gov (United States)

    Al-Thihli, Khalid; Al-Murshedi, Fathiya; Al-Hashmi, Nadia; Al-Mamari, Watfa; Islam, M Mazharul; Al-Yahyaee, Said A

    2014-01-01

    The Sultanate of Oman, like many other Arab countries, has relatively high rates of consanguinity. Reports suggest that the incidence of inborn errors of metabolism (IEM) is also high in Oman. This retrospective cross-sectional study was designed to evaluate the number of patients with IEM being followed at the only two tertiary centers in Oman treating such patients, and to calculate the consanguinity rates among these families. The electronic medical records of all patients were reviewed for demographic and clinical characteristics. A total of 285 patients with IEM were being followed at the 2 centers involved; 162 (56.8%) were male and 123 (43.2%) were female. The history of consanguinity was documented or available for 241 patients: 229 patients (95%) were born to consanguineous parents related as second cousins or closer. First-cousin marriages were reported in 191 families (79.3%), while 31 patients (12.9%) were born to second cousins. The parents of 5 patients (2%) were related as double first cousins, and 2 patients (1%) were born to first cousins once removed. The average coefficient of inbreeding (F) in our study was 0.081. Seventeen patients (6%) had associated comorbid conditions other than IEM. Our study highlights the clinical burden of IEM in Oman and emphasizes the high consanguinity rates among the parents of affected patients. © 2014 S. Karger AG, Basel

  14. Neonatal screening for inborn errors of metabolism: cost, yield and outcome.

    Science.gov (United States)

    Pollitt, R J; Green, A; McCabe, C J; Booth, A; Cooper, N J; Leonard, J V; Nicholl, J; Nicholson, P; Tunaley, J R; Virdi, N K

    1997-01-01

    OBJECTIVES. To systematically review the literature on inborn errors of metabolism, neonatal screening technology and screening programmes in order to analyse the costs and benefits of introducing screening based on tandem mass-spectrometry (tandem MS) for a wide range of disorders of amino acid and organic acid metabolism in the UK. To evaluate screening for cystic fibrosis, Duchenne muscular dystrophy and other disorders which are tested on an individual basis. HOW THE RESEARCH WAS CONDUCTED. Systematic searches were carried out of the literature on inborn errors of metabolism, neonatal screening programmes, tandem MS-based neonatal screening technology, economic evaluations of neonatal screening programmes and psychological aspects of neonatal screening. Background material on the biology of inherited metabolic disease, the basic philosophy, and the history and current status of the UK screening programme was also collected. Relevant papers in the grey literature and recent publications were identified by hand-searching. Each paper was graded. For each disease an aggregate grade for the state of knowledge in six key areas was awarded. Additional data were prospectively collected on activity and costs in UK neonatal screening laboratories, and expert clinical opinion on current treatment modalities and outcomes. These data were used to construct a decision-analysis model of neonatal screening technologies, comparing tandem MS with the existing phenylketonuria screening methods. This model determined the cost per additional case identified and, for each disease, the additional treatment costs per case, and the cost per life-year saved. All costs and benefits were discounted at 6% per annum. One-way sensitivity analysis was performed showing the effect of varying the discount rate, the incidence rate of each disorder, the number of neonates screened and the cost of tandem MS, on the cost per life-year gained. RESEARCH FINDINGS. The UK screening programmes for

  15. Identification and Quantitation of Malonic Acid Biomarkers of In-Born Error Metabolism by Targeted Metabolomics

    Science.gov (United States)

    Ambati, Chandra Shekar R.; Yuan, Furong; Abu-Elheiga, Lutfi A.; Zhang, Yiqing; Shetty, Vivekananda

    2017-05-01

    Malonic acid (MA), methylmalonic acid (MMA), and ethylmalonic acid (EMA) metabolites are implicated in various non-cancer disorders that are associated with inborn-error metabolism. In this study, we have slightly modified the published 3-nitrophenylhydrazine (3NPH) derivatization method and applied it to derivatize MA, MMA, and EMA to their hydrazone derivatives, which were amenable for liquid chromatography- mass spectrometry (LC-MS) quantitation. 3NPH was used to derivatize MA, MMA, and EMA, and multiple reaction monitoring (MRM) transitions of the corresponding derivatives were determined by product-ion experiments. Data normalization and absolute quantitation were achieved by using 3NPH derivatized isotopic labeled compounds 13C2-MA, MMA-D3, and EMA-D3. The detection limits were found to be at nanomolar concentrations and a good linearity was achieved from nanomolar to millimolar concentrations. As a proof of concept study, we have investigated the levels of malonic acids in mouse plasma with malonyl-CoA decarboxylase deficiency (MCD-D), and we have successfully applied 3NPH method to identify and quantitate all three malonic acids in wild type (WT) and MCD-D plasma with high accuracy. The results of this method were compared with that of underivatized malonic acid standards experiments that were performed using hydrophilic interaction liquid chromatography (HILIC)-MRM. Compared with HILIC method, 3NPH derivatization strategy was found to be very efficient to identify these molecules as it greatly improved the sensitivity, quantitation accuracy, as well as peak shape and resolution. Furthermore, there was no matrix effect in LC-MS analysis and the derivatized metabolites were found to be very stable for longer time.

  16. Incidence of Inborn Errors of Metabolism by Expanded Newborn Screening in a Mexican Hospital

    Directory of Open Access Journals (Sweden)

    Consuelo Cantú-Reyna MD

    2016-09-01

    Full Text Available Newborn screening for the detection of inborn errors of metabolism (IEM, endocrinopathies, hemoglobinopathies, and other disorders is a public health initiative aimed at identifying specific diseases in a timely manner. Mexico initiated newborn screening in 1973, but the national incidence of this group of diseases is unknown or uncertain due to the lack of large sample sizes of expanded newborn screening (ENS programs and lack of related publications. The incidence of a specific group of IEM, endocrinopathies, hemoglobinopathies, and other disorders in newborns was obtained from a Mexican hospital. These newborns were part of a comprehensive ENS program at Ginequito (a private hospital in Mexico, from January 2012 to August 2014. The retrospective study included the examination of 10 000 newborns’ results obtained from the ENS program (comprising the possible detection of more than 50 screened disorders. The findings were the following: 34 newborns were confirmed with an IEM, endocrinopathies, hemoglobinopathies, or other disorders and 68 were identified as carriers. Consequently, the estimated global incidence for those disorders was 3.4 in 1000 newborns; and the carrier prevalence was 6.8 in 1000. Moreover, a 0.04% false-positive rate was unveiled as soon as diagnostic testing revealed negative results. The most frequent diagnosis was glucose-6-phosphate dehydrogenase deficiency; and in the case of carriers, it was hemoglobinopathies. The benefit of the ENS is clear as it offers prompt treatment on the basis of an early diagnosis including proper genetic counseling. Furthermore, these results provide a good estimation of the frequencies of different forms of newborn IEM, endocrinopathies, hemoglobinopathies, and other disorders at Ginequito.

  17. Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

    Science.gov (United States)

    Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

    2010-07-01

    The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.

  18. Simultaneous analysis of amino acid and organic acid by NMR spectrometry, 2. Diagnostic aids for inborn error of metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Koda, Naoya; Yamaguchi, Shuichi; Mori, Takeshi.

    1987-09-01

    Analysis of urine from patients with inborn error of metabolism were studied by /sup 1/H-nuclear magnetic resonance (NMR) spectrometry. Diseases studied were as follows; phenylketonuria, biotin responsive multiple carboxylase deficiency, non-ketotic hyperglycinemia, 3-ketothiolase deficiency, alkaptonuria, methylmalonic acidemia, isovaleric acidemia, glutaric aciduria, argininosuccinic aciduria and hyperornithinemia. In each disease, specific metabolites in urine were recognized by NMR spectrometry. This method is accomplished within 10 minutes with non-treated small volume of urine and will be successfully available for the screening andor diagnosis of inherited metabolic diseases of amino acid and organic acid.

  19. Assessment of quality of life of the children and parents affected by inborn errors of metabolism with restricted diet: preliminary results of a cross-sectional study.

    Science.gov (United States)

    Fabre, Alexandre; Baumstarck, Karine; Cano, Aline; Loundou, Anderson; Berbis, Julie; Chabrol, Brigitte; Auquier, Pascal

    2013-09-19

    The development in therapeutic strategies has increased survival of children affected by inborn errors of metabolism with restricted diet (IEMRD). These diseases have mild- and long-term consequences on the health. Little is known about the impact on the quality of life (QoL) of children and their families. The aims of this study were: to compare the QoL of the children and parents affected by IEMRD with the QoL of the general population and one pathology associated with long-term consequences. This cross-sectional study was performed at the French Reference Center for inborn metabolic disorders (Marseille, France). Inclusion criteria were: a child with a diagnosis of organic aciduria, urea cycle defect, or maple syrups urine disease (MSUD). Socio-demographics, clinical data, and QoL were recorded. Twenty-one of 32 eligible families were included during a planned routine visit. Ten (47%, 95% CI 27-69%) children were affected by organic aciduria, six (29%, 95% CI 10-48%) by urea cycle defects, and five (24%, 95% CI 6-42%) by MSUD. Among the younger children, the general well-being was significantly lower in the children with IEMRD than in the leukemia children (58 ± 16 versus 76 ± 15, p = 0.012), and among the older children, the leisure activities were significantly lower in the children with IEMRD than in the leukemia children (29 ± 18 versus 62 ± 22, p eating and neurologic disorders, enteral nutrition, and feeding modalities. The children and the parents of children affected presented altered 'physical' and 'social' QoL scores compared with the norms and patients with leukemia and their families. Future studies based on larger cohort studies should determine the different weights of potential predictive factors of QoL.

  20. ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism

    NARCIS (Netherlands)

    Peters, Heidi; Buck, Nicole; Wanders, Ronald; Ruiter, Jos; Waterham, Hans; Koster, Janet; Yaplito-Lee, Joy; Ferdinandusse, Sacha; Pitt, James

    2014-01-01

    Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl)cysteine and several other metabolites that are features of 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency, a rare defect in the valine catabolic pathway associated with Leigh-like disease. However, this

  1. Gene therapy for the circumvention of inborn errors of metabolism (IEM) caused by single-nucleotide-polymorphisms (SNPs).

    Science.gov (United States)

    Wiseman, Alan

    2004-01-01

    Single nucleotide polymorphisms (SNPs) are the result of point mutations in nuclear (and mitochondrial) DNA. Such localised damage to DNA (and its replicative mechanisms) may not be excised fully by the DNA repair mechanism in the genome: and therefore can become inheritable; subsequently to manifest later as an inborn error of metabolism (IEM). Causes of mutagenic damage to the DNA can include background radiation (such as emitted by radon gas), and by reactive oxygen species (ROS): and also by mutagenic chemicals that occur naturally (inter alia in the diet). Other causes of DNA damage are variable environmental hazards such as solar-derived short wave ultraviolet light A. Gene therapy involves the placement of missing genes into particular tissues by the harnessing of suitable vectors (originally these were animal viruses such as SV40). For example, gene therapy in the rat for diabetes has succeeded by liver-production of insulin (using genes obtained from pancreatic Islets of Langerhans cells). Many inborn errors of metabolism could be treated in this way: examples may include 100 haemoglobinopathies (such as sickle cell anaemia), phenylketonuria; and other diseases caused by lack of tissue-production of a particular enzyme (in its catalytically-active conformation).

  2. /sup 1/H-NMR urinalysis. Simultaneous screening of inborn errors of metabolism of amino acid and organic acid disorders

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Hideaki; Yamaguchi, Shuichi

    1988-02-01

    In an effort to examine the usefulness of /sup 1/H-nuclear magnetic resonance (NMR) urinalysis in the diagnosis of congenital metabolic disorders, 70 kinds of urinary metabolites were analysed in relation to the diagnosis of inborn errors of amino acid and organic acid disorders. Homogated decoupling (HMG) method failed to analyze six metabolites within the undetectable range. When non-decoupling method (NON), in which the materials are dissolved in dimethyl sulfoxide, was used, the identification of signals became possible. The combination of HMG and NON methods was, therefore, considered to identify all of the metabolites. When the urine samples, which were obtained from patients with hyperglycerolemia, hyperornithinemia, glutaric acidemia type II, or glycerol kinase deficiency, were analysed by using both HMG and NON methods, abnormally increased urinary metabolites were detected. /sup 1/H-NMR urinalysis, if used in the combination of HMG and NON methods, may allow simultanenous screening of inborn errors of metabolism of amino acid and organic acid disorders. (Namekawa, K.).

  3. Inborn Errors of Metabolism with Hypoglycemia Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis : Glycogen Storage Diseases and Inherited Disorders of Gluconeogenesis

    NARCIS (Netherlands)

    Weinstein, David A.; Steuerwald, Ulrike; De Souza, Carolina F. M.; Derks, Terry G. J.

    Although hyperinsulinism is the predominant inherited cause of hypoglycemia in the newborn period, inborn errors of metabolism are the primary etiologies after 1 month of age. Disorders of carbohydrate metabolism often present with hypoglycemia when fasting occurs. The presentation, diagnosis, and

  4. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities.

    Science.gov (United States)

    Quintana, Anita M; Yu, Hung-Chun; Brebner, Alison; Pupavac, Mihaela; Geiger, Elizabeth A; Watson, Abigail; Castro, Victoria L; Cheung, Warren; Chen, Shu-Huang; Watkins, David; Pastinen, Tomi; Skovby, Flemming; Appel, Bruce; Rosenblatt, David S; Shaikh, Tamim H

    2017-08-01

    CblX (MIM309541) is an X-linked recessive disorder characterized by defects in cobalamin (vitamin B12) metabolism and other developmental defects. Mutations in HCFC1, a transcriptional co-regulator which interacts with multiple transcription factors, have been associated with cblX. HCFC1 regulates cobalamin metabolism via the regulation of MMACHC expression through its interaction with THAP11, a THAP domain-containing transcription factor. The HCFC1/THAP11 complex potentially regulates genes involved in diverse cellular functions including cell cycle, proliferation, and transcription. Thus, it is likely that mutation of THAP11 also results in biochemical and other phenotypes similar to those observed in patients with cblX. We report a patient who presented with clinical and biochemical phenotypic features that overlap cblX, but who does not have any mutations in either MMACHC or HCFC1. We sequenced THAP11 by Sanger sequencing and discovered a potentially pathogenic, homozygous variant, c.240C > G (p.Phe80Leu). Functional analysis in the developing zebrafish embryo demonstrated that both THAP11 and HCFC1 regulate the proliferation and differentiation of neural precursors, suggesting important roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role for HCFC1 in vertebrate craniofacial development. High throughput RNA-sequencing analysis reveals several overlapping gene targets of HCFC1 and THAP11. Thus, both HCFC1 and THAP11 play important roles in the regulation of cobalamin metabolism as well as other pathways involved in early vertebrate development. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Diagnostic potential of stored dried blood spots for inborn errors of metabolism: a metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency.

    Science.gov (United States)

    Kaku, Noriyuki; Ihara, Kenji; Hirata, Yuichiro; Yamada, Kenji; Lee, Sooyoung; Kanemasa, Hikaru; Motomura, Yoshitomo; Baba, Haruhisa; Tanaka, Tamami; Sakai, Yasunari; Maehara, Yoshihiko; Ohga, Shouichi

    2018-05-02

    It is estimated that 1-5% of sudden infant death syndrome (SIDS) cases might be caused by undiagnosed inborn errors of metabolism (IEMs); however, the postmortem identification of IEMs remains difficult. This study aimed to evaluate the usefulness of dried blood spots (DBSs) stored after newborn screening tests as a metabolic autopsy to determine the causes of death in infants and children who died suddenly and unexpectedly. Infants or toddlers who had suddenly died without a definite diagnosis between July 2008 and December 2012 at Kyushu University Hospital in Japan were enrolled in this study. Their Guthrie cards, which had been stored for several years at 4-8°C, were used for an acylcarnitine analysis by tandem mass spectrometry to identify inborn errors of metabolism. Fifteen infants and children who died at less than 2 years of age and for whom the cause of death was unknown were enrolled for the study. After correcting the C0 and C8 values assuming the hydrolysation of acylcarnitine in the stored DBSs, the corrected C8 value of one case just exceeded the cut-off level for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency screening. Genetic and biochemical analyses confirmed this patient to have MCAD deficiency. DBSs stored after newborn screening tests are a promising tool for metabolic autopsy. The appropriate compensation of acylcarnitine data and subsequent genetic and biochemical analyses are essential for the postmortem diagnosis of inborn errors of metabolism. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Alkaptonuria--first inborn error of metabolism known for a century and new treatment option--preliminary report.

    Science.gov (United States)

    Sykut-Cegielska, Jolanta

    2015-01-01

    Alkaptonuria is a rare inborn error of metabolism, identified over a century ago. But its basic pathomechanism (i.e. ochronosis) is still not completely explained. Though clinical onset of osteoarthropathy and complications from other organs (including: heart and blood vessels, skin, eyes, kidneys) occurs at adult age, the symptoms are progressive, cause severe pains and significantly limit everyday life of the patients. Until now no effective therapeutic methods have been known in alkaptonuria. Recently, thanks to an initiative of the international patient organization for alkaptonuria, a hope for a potential treatment availability, appears. So, alkaptonuria is an example of a role of multidysciplinary care, cooperation and ongoing progress in the area of rare diseases.

  7. TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State.

    Science.gov (United States)

    Cardaci, Simone; Ciriolo, Maria Rosa

    2012-01-01

    Inborn defects of the tricarboxylic acid (TCA) cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH), fumarate hydratase (FH), and isocitrate dehydrogenase (IDH), pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

  8. TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State

    Directory of Open Access Journals (Sweden)

    Simone Cardaci

    2012-01-01

    Full Text Available Inborn defects of the tricarboxylic acid (TCA cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH, fumarate hydratase (FH, and isocitrate dehydrogenase (IDH, pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology.

  9. Errores innatos del metabolismo de las purinas y otras enfermedades relacionadas Inborn purine metabolism errors and other related diseases

    Directory of Open Access Journals (Sweden)

    Jiovanna Contreras Roura

    2012-06-01

    Full Text Available Los errores innatos en el metabolismo de las purinas son trastornos hereditarios complejos de gran impacto clínico, que presentan síntomas variables de acuerdo con el tipo de enfermedad. Pueden presentarse problemas renales de origen desconocido, retardo mental con manifestaciones neurológicas, retardo del crecimiento, infecciones recurrentes, automutilación, inmunodeficiencias, anemia hemolítica inexplicable, artritis gotosa, historia familiar, consanguinidad y reacciones adversas a fármacos que son análogos de las purinas. Las investigaciones de estas enfermedades comienzan generalmente con la cuantificación del ácido úrico en suero y en orina, por ser el producto final del metabolismo de las purinas en humanos. La dieta y el consumo de medicamentos, entre otras condiciones patológicas, fisiológicas y clínicas, también pueden modificar los niveles de este compuesto. Esta revisión pretende divulgar información de los errores innatos en el metabolismo de las purinas, y facilitar la interpretación de los niveles del ácido úrico y otros marcadores bioquímicos útiles en el diagnóstico de estas enfermedades. Se incluyen tablas que relacionan estas enfermedades con los niveles de excreción de ácido úrico y otros marcadores bioquímicos, las enzimas alteradas, los síntomas clínicos, el modo de herencia y, en algunos casos, el tratamiento propuesto. Este trabajo nos permite afirmar que las variaciones en los niveles del ácido úrico y la presencia de otros marcadores bioquímicos en orina, constituyen una herramienta importante en la pesquisa de algunos errores innatos en el metabolismo de las purinas, así como de otras condiciones patológicas relacionadas.Inborn purine metabolism errors are complex inherited disorders of great clinical impact that present with variable symptoms according to the type of disease. It might occur renal problems of unknown origin, metal retardation with neurological manifestations, retarded

  10. A patient with an inborn error of vitamin B12 metabolism (cblF) detected by newborn screening.

    Science.gov (United States)

    Armour, Christine M; Brebner, Alison; Watkins, David; Geraghty, Michael T; Chan, Alicia; Rosenblatt, David S

    2013-07-01

    A neonate, who was found to have an elevated C3/C2 ratio and minimally elevated propionylcarnitine on newborn screening, was subsequently identified as having the rare cblF inborn error of vitamin B12 (cobalamin) metabolism. This disorder is characterized by the retention of unmetabolized cobalamin in lysosomes such that it is not readily available for cellular metabolism. Although cultured fibroblasts from the patient did not show the expected functional abnormalities of the cobalamin-dependent enzymes, methylmalonyl-CoA mutase and methionine synthase, they did show reduced synthesis of the active cobalamin cofactors adenosylcobalamin and methylcobalamin. Mutation analysis of LMBRD1 established that the patient had the cblF disorder. Treatment was initiated promptly, and the patient showed a robust response to regular injections of cyanocobalamin, and she was later switched to hydroxocobalamin. Currently, at 3 years of age, the child is clinically well, with appropriate development. Adjusted newborn screening cutoffs in Ontario allowed detection of a deficiency that might not have otherwise been identified, allowing early treatment and perhaps preventing the adverse sequelae seen in some untreated patients.

  11. Clinical characteristics of adult patients with inborn errors of metabolism in Spain: A review of 500 cases from university hospitals

    Directory of Open Access Journals (Sweden)

    J. Pérez-López

    2017-03-01

    Full Text Available Patients with inborn errors of metabolism (IEMs have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification. The most prevalent group of IEMs was amino acid disorders, with 108 (21.6% patients diagnosed with phenylketonuria. Lysosomal storage disorders were the second group, in which 32 (6.4% and 25 (5% patients had Fabry disease and Gaucher disease respectively. The great clinical heterogeneity, the significant delay in diagnosis after symptom onset, the existence of some degree of physical dependence in a great number of patients, the need for a multidisciplinary and coordinated approach, and the lack of specific drug treatment are common features in this group of conditions.

  12. Evidence for Treatable Inborn Errors of Metabolism in a Cohort of 187 Greek Patients with Autism Spectrum Disorder (ASD

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    Martha eSpilioti

    2013-12-01

    Full Text Available We screened for the presence of inborn errors of metabolism (IEM in 187 children (105 males; 82 females, ages 4 -14 years old who presented with confirmed features of ASD. Twelve patients (7% manifested increased 3-hydroxyisovaleric acid (3-OH-IVA excretion in urine, and minor to significant improvement in autistic features was observed in seven patients following supplementation with biotin. Five diagnoses included: Lesch Nyhan syndrome (2, succinic semialdehyde dehydrogenase (SSADH deficiency (2 and phenylketonuria (1 (2.7%. Additional metabolic disturbances suggestive of IEMs included two patients whose increased urine 3-OH-IVA was accompanied by elevated methylcitrate and lactate in sera, and 30 patients that showed abnormal glucose-loading tests. In the latter group, 16/30 patients manifested increased sera beta hydroxybutyrate (b-OH-b production and 18/30 had a paradoxical increase of sera lactate. Six patients with elevated b-OH-b in sera showed improved autistic features following implementation of a ketogenic diet. Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated nonspecific MRI pathology, while 25/187 had abnormal EEG findings. Finally, family history was positive for 22/187 patients (1st or 2nd degree relative with comparable symptomatology and consanguinity was documented for 12/187 patients. Our data provide evidence for a new biomarker (3-OH-IVA and novel treatment approaches in ASD patients.Concise 1 sentence take-home message: Detailed metabolic screening in a Greek cohort of autismspectrum disorder (ASD patients revealed biomarkers (urine 3-hydroxyisovaleric acid and serum b-OH-b in 7% (13/187 of patients for whom biotin supplementation or institution of a ketogenic diet resulted in mild to significant clinical improvement in autistic features.

  13. Child and family experiences with inborn errors of metabolism: a qualitative interview study with representatives of patient groups.

    Science.gov (United States)

    Khangura, Sara D; Tingley, Kylie; Chakraborty, Pranesh; Coyle, Doug; Kronick, Jonathan B; Laberge, Anne-Marie; Little, Julian; Miller, Fiona A; Mitchell, John J; Prasad, Chitra; Siddiq, Shabnaz; Siriwardena, Komudi; Sparkes, Rebecca; Speechley, Kathy N; Stockler, Sylvia; Trakadis, Yannis; Wilson, Brenda J; Wilson, Kumanan; Potter, Beth K

    2016-01-01

    Patient-centered health care for children with inborn errors of metabolism (IEM) and their families is important and requires an understanding of patient experiences, needs, and priorities. IEM-specific patient groups have emerged as important voices within these rare disease communities and are uniquely positioned to contribute to this understanding. We conducted qualitative interviews with IEM patient group representatives to increase understanding of patient and family experiences, needs, and priorities and inform patient-centered research and care. We developed a sampling frame of patient groups representing IEM disease communities from Canada, the United States, and United Kingdom. With consent, we interviewed participants to explore their views on experiences, needs, and outcomes that are most important to children with IEM and their families. We analyzed the data using a qualitative descriptive approach to identify key themes and sub-themes. We interviewed 18 organizational representatives between February 28 and September 17, 2014, representing 16 IEMs and/or disease categories. Twelve participants voluntarily self-identified as parents and/or were themselves patients. Three key themes emerged from the coded data: managing the uncertainty associated with raising and caring for a child with a rare disease; challenges associated with the affected child's life transitions, and; the collective struggle for improved outcomes and interventions that rare disease communities navigate. Health care providers can support children with IEM and their families by acknowledging and reducing uncertainty, supporting families through children's life transitions, and contributing to rare disease communities' progress toward improved interventions, experiences, and outcomes.

  14. Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations

    Directory of Open Access Journals (Sweden)

    Abdellah Tebani

    2016-09-01

    Full Text Available The rise of technologies that simultaneously measure thousands of data points represents the heart of systems biology. These technologies have had a huge impact on the discovery of next-generation diagnostics, biomarkers, and drugs in the precision medicine era. Systems biology aims to achieve systemic exploration of complex interactions in biological systems. Driven by high-throughput omics technologies and the computational surge, it enables multi-scale and insightful overviews of cells, organisms, and populations. Precision medicine capitalizes on these conceptual and technological advancements and stands on two main pillars: data generation and data modeling. High-throughput omics technologies allow the retrieval of comprehensive and holistic biological information, whereas computational capabilities enable high-dimensional data modeling and, therefore, accessible and user-friendly visualization. Furthermore, bioinformatics has enabled comprehensive multi-omics and clinical data integration for insightful interpretation. Despite their promise, the translation of these technologies into clinically actionable tools has been slow. In this review, we present state-of-the-art multi-omics data analysis strategies in a clinical context. The challenges of omics-based biomarker translation are discussed. Perspectives regarding the use of multi-omics approaches for inborn errors of metabolism (IEM are presented by introducing a new paradigm shift in addressing IEM investigations in the post-genomic era.

  15. Omics-Based Strategies in Precision Medicine: Toward a Paradigm Shift in Inborn Errors of Metabolism Investigations.

    Science.gov (United States)

    Tebani, Abdellah; Afonso, Carlos; Marret, Stéphane; Bekri, Soumeya

    2016-09-14

    The rise of technologies that simultaneously measure thousands of data points represents the heart of systems biology. These technologies have had a huge impact on the discovery of next-generation diagnostics, biomarkers, and drugs in the precision medicine era. Systems biology aims to achieve systemic exploration of complex interactions in biological systems. Driven by high-throughput omics technologies and the computational surge, it enables multi-scale and insightful overviews of cells, organisms, and populations. Precision medicine capitalizes on these conceptual and technological advancements and stands on two main pillars: data generation and data modeling. High-throughput omics technologies allow the retrieval of comprehensive and holistic biological information, whereas computational capabilities enable high-dimensional data modeling and, therefore, accessible and user-friendly visualization. Furthermore, bioinformatics has enabled comprehensive multi-omics and clinical data integration for insightful interpretation. Despite their promise, the translation of these technologies into clinically actionable tools has been slow. In this review, we present state-of-the-art multi-omics data analysis strategies in a clinical context. The challenges of omics-based biomarker translation are discussed. Perspectives regarding the use of multi-omics approaches for inborn errors of metabolism (IEM) are presented by introducing a new paradigm shift in addressing IEM investigations in the post-genomic era.

  16. Quality of Life and Associated Factors in Japanese Children With Inborn Errors of Metabolism and Their Families

    Directory of Open Access Journals (Sweden)

    Keiko Yamaguchi RN, PHN

    2018-02-01

    Full Text Available To reveal the associated factors of quality of life (QoL in children with inborn errors of metabolism (IEM, their siblings, and their primary caregivers and partners, we conducted an anonymous questionnaire survey in Japan. Descriptive, correlation, and multiple regression analyses were performed. Fifty-six children with IEM, 35 siblings, 143 primary caregivers, and 86 partners completed our questionnaires. There were significant positive correlations between higher QoL in children with IEM and lower disease influence ( r = 0.46 and higher perceived emotional support ( r = 0.67. We could not find any associated factor of siblings’ QoL. Lower parental distress, higher family empowerment, and higher household income contributed to higher QoL in primary caregivers (adjusted R 2 = 0.636. Higher household income, lower anxiety about childrearing, and higher satisfaction in the relationship with the child and entire family contributed to higher QoL of partners (adjusted R 2 = 0.398. We concluded that developing effective interventions to improve QoL is needed for the entire family in future outpatient settings.

  17. Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis.

    Science.gov (United States)

    Lee, Jessica J Y; Gottlieb, Michael M; Lever, Jake; Jones, Steven J M; Blau, Nenad; van Karnebeek, Clara D M; Wasserman, Wyeth W

    2018-05-01

    Phenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze phenotypes. Such methods have allowed phenotypic data to be widely used in medical applications, from assisting clinical diagnoses to prioritizing genomic diagnoses. To channel the benefits of phenomics into the field of inborn errors of metabolism (IEM), we have recently launched IEMbase, an expert-curated knowledgebase of IEM and their disease-characterizing phenotypes. While our efforts with IEMbase have realized benefits, taking full advantage of phenomics requires a comprehensive curation of IEM phenotypes in core phenomics projects, which is dependent upon contributions from the IEM clinical and research community. Here, we assess the inclusion of IEM biochemical phenotypes in a core phenomics project, the Human Phenotype Ontology. We then demonstrate the utility of biochemical phenotypes using a text-based phenomics method to predict gene-disease relationships, showing that the prediction of IEM genes is significantly better using biochemical rather than clinical profiles. The findings herein provide a motivating goal for the IEM community to expand the computationally accessible descriptions of biochemical phenotypes associated with IEM in phenomics resources.

  18. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

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    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases.Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients.Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death.Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  19. Selective screening of 650 high risk Iranian patients for detection of inborn error of metabolism

    Directory of Open Access Journals (Sweden)

    Narges Pishva

    2015-02-01

    Full Text Available Objective: Although metabolic diseases individually are rare ,but overall have an incidence of 1/2000 and can cause devastating and irreversible effect if not diagnosed early and treated promptly. selective screening is an acceptable method for detection of these multi presentation diseases. Method: using panel neonatal screening for detection of metabolic diseases in 650 high risk Iranian patients in Fars province. The following clinical features were used as inclusion criteria for investigation of the patients. Lethargy, poor feeding ,persistent vomiting, cholestasis, intractable seizure ,decreased level of consciousness ,persistent hypoglycemia, unexplained acid base disturbance and unexplained neonatal death. Result: Organic acidemia with 40 cases (42% was the most frequent disorder diagnosed in our high risk populations, followed by disorder of galactose metabolism(30%, 15 patient had classic galactosemia(GALT

  20. Congenital genetic inborn errors of metabolism presenting as an adult or persisting into adulthood: neuroimaging in the more common or recognizable disorders.

    Science.gov (United States)

    Krishna, Shri H; McKinney, Alexander M; Lucato, Leandro T

    2014-04-01

    Numerous congenital-genetic inborn errors of metabolism (CIEMs) have been identified and characterized in detail within recent decades, with promising therapeutic options. Neuroimaging is becoming increasingly utilized in earlier stages of CIEMs, and even in asymptomatic relatives of patients with a CIEM, so as to monitor disease progress and treatment response. This review attempts to summarize in a concise fashion the neuroimaging findings of various CIEMs that may present in adulthood, as well as those that may persist into adulthood, whether because of beneficial therapy or a delay in diagnosis. Notably, some of these disorders have neuroimaging findings that differ from their classic infantile or early childhood forms, whereas others are identical to their early pediatric forms. The focus of this review is their appearance on routine magnetic resonance imaging sequences, with some basic attention to the findings of such CIEMs on specialized neuroimaging, based on recent or preliminary research. The general classes of disorders covered in this complex review are: peroxisomal disorders (adrenoleukodystrophy), lysosomal storage disorders (including metachromatic leukodystrophy, Krabbe or globoid cell leukodystrophy, Fabry, Niemann-Pick, GM1, GM2, Gaucher, mucopolysaccharidoses, and Salla diseases), mitochondrial disorders (including mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes, myoclonic epilepsy with ragged red fibers, Leigh disease, and Kearns-Sayre syndrome), urea cycle disorders, several organic acidemias (including phenylketonuria, maple syrup urine disease, 3-hydroxy-3-methylglutaryl colyase deficiency, glutaric acidurias, methylmalonic academia, proprionic academia, 3-methylglucatonic aciduria, and 2-hydroxyglutaric acidurias), cytoskeletal or transporter molecule defects (including Alexander or fibrinoid leukodystrophy, proteolipid protein-1 defect or Pelizaeus Merzbacher, Wilson, and Huntington diseases), and several

  1. Application of nuclear magnetic resonance spectroscopy combined with principal component analysis in detecting inborn errors of metabolism using blood spots: a metabonomic approach

    International Nuclear Information System (INIS)

    Constantinou, M.A.; Papakonstantinou, E.; Benaki, D.; Spraul, M.; Shulpis, K.; Koupparis, M.A.; Mikros, E.

    2004-01-01

    NMR spectra of extracted blood spots were used to investigate the possibility for the development of a new method for mass screening concerning the diagnosis of inborn errors of metabolism (IEM). Blood spots were collected on filter papers from normal, phenylketonuric (PKU) and maple syrup urine disease (MSUD) subjects and their Carr-Purcell-Meiboom-Gill (CPMG) 1 H NMR spectra were acquired. The spectra were reduced to a number of spectral descriptors and principal component analysis (PCA) was performed. The scores plot showed that PKU and MSUD samples were well discriminated from the main cluster of points

  2. Insight on the impacts of free amino acids and their metabolites on the immune system from a perspective of inborn errors of amino acid metabolism.

    Science.gov (United States)

    Pakula, Malgorzata M; Maier, Thorsten J; Vorup-Jensen, Thomas

    2017-06-01

    Amino acids (AAs) support a broad range of functions in living organisms, including several that affect the immune system. The functions of the immune system are affected when free AAs are depleted or in excess because of external factors, such as starvation, or because of genetic factors, such as inborn errors of metabolism. Areas covered: In this review, we discuss the current insights into how free AAs affect immune responses. When possible, we make comparisons to known disease states resulting from inborn errors of metabolism, in which changed levels of AAs or AA metabolites provide insight into the impact of AAs on the human immune system in vivo. We also explore the literature describing how changes in AA levels might provide pharmaceutical targets for safe immunomodulatory treatment. Expert opinion: The impact of free AAs on the immune system is a neglected topic in most immunology textbooks. That neglect is undeserved, because free AAs have both direct and indirect effects on the immune system. Consistent choices of pre-clinical models and better strategies for creating formulations are required to gain clinical impact.

  3. Inborn Errors of Metabolism with Hyperammonemia: Urea Cycle Defects and Related Disorders.

    Science.gov (United States)

    Summar, Marshall L; Mew, Nicholas Ah

    2018-04-01

    The urea cycle disorders are a group of inherited biochemical diseases caused by a complete or partial deficiency of any one of the enzymes or transport proteins required to convert toxic ammonia into urea and to produce arginine and citrulline. The clinical manifestations of these disorders are mostly the result of acute or chronic hyperammonemia, which affects the central nervous system. Affected individuals can also develop hepatic dysfunction. These disorders can present at any age from the immediate newborn to later in life. Early diagnosis and treatment are key to improving outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Novel inborn error of folate metabolism: identification by exome capture and sequencing of mutations in the MTHFD1 gene in a single proband.

    Science.gov (United States)

    Watkins, David; Schwartzentruber, Jeremy A; Ganesh, Jaya; Orange, Jordan S; Kaplan, Bernard S; Nunez, Laura Dempsey; Majewski, Jacek; Rosenblatt, David S

    2011-09-01

    An infant was investigated because of megaloblastic anaemia, atypical hemolytic uraemic syndrome, severe combined immune deficiency, elevated blood levels of homocysteine and methylmalonic acid, and a selective decreased synthesis of methylcobalamin in cultured fibroblasts. Exome sequencing was performed on patient genomic DNA. Two mutations were identified in the MTHFD1 gene, which encodes a protein that catalyses three reactions involved in cellular folate metabolism. This protein is essential for the generation of formyltetrahydrofolate and methylenetetrahydrofolate and important for nucleotide and homocysteine metabolism. One mutation (c.727+1G>A) affects the splice acceptor site of intron 8. The second mutation, c.517C>T (p.R173C), changes a critical arginine residue in the NADP-binding site of the protein. Mutations affecting this arginine have previously been shown to affect enzyme activity. Both parents carry a single mutation and an unaffected sibling carries neither mutation. The combination of two mutations in the MTHFRD1 gene, predicted to have severe consequences, in the patient and their absence in the unaffected sibling, supports causality. This patient represents the first case of an inborn error of folate metabolism affecting the trifunctional MTHFD1 protein. This report reinforces the power of exome capture and sequencing for the discovery of novel genes, even when only a single proband is available for study.

  5. Living with an inborn error of metabolism detected by newborn screening-parents' perspectives on child development and impact on family life.

    Science.gov (United States)

    Gramer, Gwendolyn; Haege, Gisela; Glahn, Esther M; Hoffmann, Georg F; Lindner, Martin; Burgard, Peter

    2014-03-01

    Newborn screening for inborn errors of metabolism is regarded as highly successful by health professionals. Little is known about parents' perspectives on child development and social impact on families. Parents of 187 patients with metabolic disorders detected by newborn screening rated child development, perceived burdens on child and family, and future expectations on a questionnaire with standardized answers. Parental ratings were compared with standardized psychometric test results. Regression analysis was performed to identify factors associated with extent of perceived burden. In 26.2% of patients, parents perceived delays in global development and/or specific developmental domains (physical, social, intellectual, language). Parents expected normal future development in 95.7%, and an independent adult life for their child in 94.6%. Comparison with psychometric test results showed that parents of children with cognitive impairments tended to overrate their child's abilities. Mild/medium burden posed on the family (child) by the metabolic disorder was stated by 56.1% (48.9%) of parents, severe/very severe burden by 19.3% (8.6%). One third of families reported financial burden due to the metabolic disorder. Dietary treatment and diagnoses with risk for metabolic decompensation despite treatment were associated with higher perceived burden for the family. Disorders rated as potentially very burdensome by experts were not rated accordingly by parents, demonstrating different perspectives of professionals and parents. Although newborn screening leads to favourable physical and cognitive outcome, living with a metabolic disorder may cause considerable stress on patients and families, emphasizing the need for comprehensive multidisciplinary care including psychological and social support.

  6. Phenylketonuria as a model for protein misfolding diseases and for the development of next generation orphan drugs for patients with inborn errors of metabolism.

    Science.gov (United States)

    Muntau, Ania C; Gersting, Søren W

    2010-12-01

    The lecture dedicated to Professor Horst Bickel describes the advances, successes, and opportunities concerning the understanding of the biochemical and molecular basis of phenylketonuria and the innovative treatment strategies introduced for these patients during the last 60 years. These concepts were transferred to other inborn errors of metabolism and led to significant reduction in morbidity and to an improvement in quality of life. Important milestones were the successful development of a low-phenylalanine diet for phenylketonuria patients, the recognition of tetrahydrobiopterin as an option to treat these individuals pharmacologically, and finally market approval of this drug. The work related to the discovery of a pharmacological treatment led metabolic researchers and pediatricians to new insights into the molecular processes linked to mutations in the phenylalanine hydroxylase gene at the cellular and structural level. Again, phenylketonuria became a prototype disorder for a previously underestimated but now rapidly expanding group of diseases: protein misfolding disorders with loss of function. Due to potential general biological mechanisms underlying these disorders, the door may soon open to a systematic development of a new class of pharmaceutical products. These pharmacological chaperones are likely to correct misfolding of proteins involved in numerous genetic and nongenetic diseases.

  7. Cystinuria: an inborn cause of urolithiasis

    Directory of Open Access Journals (Sweden)

    Eggermann Thomas

    2012-04-01

    Full Text Available Abstract Cystinuria (OMIM 220100 is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two genes responsible for cystinuria have been identified: SLC3A1 (chromosome 2p21 encodes the heavy subunit rBAT of a renal b0,+ transporter while SLC7A9 (chromosome 19q12 encodes its interacting light subunit b0,+AT. Mutations in SLC3A1 are generally associated with an autosomal-recessive mode of inheritance whereas SLC7A9 variants result in a broad clinical variability even within the same family. The detection rate for mutations in these genes is larger than 85%, but it is influenced by the ethnic origin of a patient and the pathophysiological significance of the mutations. In addition to isolated cystinuria, patients suffering from the hypotonia-cystinuria syndrome have been reported carrying deletions including at least the SLC3A1 and the PREPL genes in 2p21. By extensive molecular screening studies in large cohort of patients a broad spectrum of mutations could be identified, several of these variants were functionally analysed and thereby allowed insights in the pathology of the disease as well as in the renal trafficking of cystine and the dibasic amino acids. In our review we will summarize the current knowledge on the physiological and the genetic basis of cystinuria as an inborn cause of kidney stones, and the application of this knowledge in genetic testing strategies.

  8. Genetic screening: programs, principles, and research--thirty years later. Reviewing the recommendations of the Committee for the Study of Inborn Errors of Metabolism (SIEM).

    Science.gov (United States)

    Simopoulos, A P

    2009-01-01

    Screening programs for genetic diseases and characteristics have multiplied in the last 50 years. 'Genetic Screening: Programs, Principles, and Research' is the report of the Committee for the Study of Inborn Errors of Metabolism (SIEM Committee) commissioned by the Division of Medical Sciences of the National Research Council at the National Academy of Sciences in Washington, DC, published in 1975. The report is considered a classic in the field worldwide, therefore it was thought appropriate 30 years later to present the Committee's modus operandi and bring the Committee's recommendations to the attention of those involved in genetics, including organizational, educational, legal, and research aspects of genetic screening. The Committee's report anticipated many of the legal, ethical, economic, social, medical, and policy aspects of genetic screening. The recommendations are current, and future committees should be familiar with them. In 1975 the Committee stated: 'As new screening tests are devised, they should be carefully reviewed. If the experimental rate of discovery of new genetic characteristics means an accelerating rate of appearance of new screening tests, now is the time to develop the medical and social apparatus to accommodate what later on may otherwise turn out to be unmanageable growth.' What a prophetic statement that was. If the Committee's recommendations had been implemented on time, there would be today a federal agency in existence, responsive and responsible to carry out the programs and support research on various aspects of genetic screening, including implementation of a federal law that protects consumers from discrimination by their employers and the insurance industry on the basis of genetic information. Copyright 2008 S. Karger AG, Basel.

  9. Investigation of metabolic encephalopathy

    African Journals Online (AJOL)

    cycle defects is the X-linked recessive disorder, ornithine ... life, or if the child is fed the compounds that they are unable .... as learning difficulties, drowsiness and avoidance of ... Table 2. Laboratory investigation of suspected metabolic encephalopathy. Laboratory .... Clinical approach to treatable inborn metabolic diseases:.

  10. Quality of life, psychological adjustment, and adaptive functioning of patients with intoxication-type inborn errors of metabolism - a systematic review.

    Science.gov (United States)

    Zeltner, Nina A; Huemer, Martina; Baumgartner, Matthias R; Landolt, Markus A

    2014-10-25

    In recent decades, considerable progress in diagnosis and treatment of patients with intoxication-type inborn errors of metabolism (IT-IEM) such as urea cycle disorders (UCD), organic acidurias (OA), maple syrup urine disease (MSUD), or tyrosinemia type 1 (TYR 1) has resulted in a growing group of long-term survivors. However, IT-IEM still require intense patient and caregiver effort in terms of strict dietetic and pharmacological treatment, and the threat of metabolic crises is always present. Furthermore, crises can affect the central nervous system (CNS), leading to cognitive, behavioural and psychiatric sequelae. Consequently, the well-being of the patients warrants consideration from both a medical and a psychosocial viewpoint by assessing health-related quality of life (HrQoL), psychological adjustment, and adaptive functioning. To date, an overview of findings on these topics for IT-IEM is lacking. We therefore aimed to systematically review the research on HrQoL, psychological adjustment, and adaptive functioning in patients with IT-IEM. Relevant databases were searched with predefined keywords. Study selection was conducted in two steps based on predefined criteria. Two independent reviewers completed the selection and data extraction. Eleven articles met the inclusion criteria. Studies were of varying methodological quality and used different assessment measures. Findings on HrQoL were inconsistent, with some showing lower and others showing higher or equal HrQoL for IT-IEM patients compared to norms. Findings on psychological adjustment and adaptive functioning were more consistent, showing mostly either no difference or worse adjustment of IT-IEM patients compared to norms. Single medical risk factors for HrQoL, psychological adjustment, or adaptive functioning have been addressed, while psychosocial risk factors have not been addressed. Data on HrQoL, psychological adjustment, and adaptive functioning for IT-IEM are sparse. Studies are inconsistent in

  11. Inborn anemias in mice

    International Nuclear Information System (INIS)

    Bernstein, S.E.; Barker, J.E.; Russell, E.S.

    1981-06-01

    hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, five hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an α-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values, (b) determinations of radiosensitivity under a variety of conditions, (c) measurements of iron metabolism and heme synthesis, (d) histological and biochemical study of blood-forming tissue, (e) functional tests of the stem cell component, (f) examination of responses to erythroid stimuli, and (g) transplantation of tissue between individuals of differently affected genotypes

  12. Determination of the spectrum of low molecular mass organic acids in urine by capillary electrophoresis with contactless conductivity and ultraviolet photometric detection-An efficient tool for monitoring of inborn metabolic disorders

    Energy Technology Data Exchange (ETDEWEB)

    Tuma, Petr, E-mail: petr.tuma@lf3.cuni.cz [Institute of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague 10 (Czech Republic); Samcova, Eva [Institute of Biochemistry, Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague 10 (Czech Republic); Stulik, Karel [Department of Analytical Chemistry, Charles University, Albertov 2030, 128 43 Prague 2 (Czech Republic)

    2011-01-24

    A mixture of 29 organic acids (OAs) occurring in urine was analyzed by capillary electrophoresis (CE) with capacitively coupled contactless conductivity detection (C{sup 4}D) and UV photometric detection. The optimized analytical system involved a 100 cm long polyacrylamide-coated capillary (50 {mu}m i.d.) and the background electrolyte of 20 mM 2-morpholinoethanesulfonic acid (MES)/NaOH + 10% (v/v) methanol, pH 6.0 (pH is related to the 20 mM MES/NaOH buffer in water). The LOD values obtained by C{sup 4}D for the OAs which do not absorb UV radiation range from 0.6 {mu}M (oxalic acid) to 6.8 {mu}M (pyruvic acid); those obtained by UV photometry for the remaining OAs range from 2.9 {mu}M (5-hydroxy-3-indoleacetic acid) to 10.2 {mu}M (uric acid). The repeatability of the procedure developed is characterized by the coefficients of variation, which vary between 0.3% (tartaric acid) and 0.6% (5-hydroxy-3-indoleacetic acid) for the migration time and between 1.3% (tartaric acid) and 3.5% (lactic acid) for the peak area. The procedure permitted quantitation of 20 OAs in a real urine sample and was applied to monitoring of the occurrence of the inborn metabolic fault of methylmalonic aciduria.

  13. Metabolic encephalopathy and lipid storage myopathy associated with a presumptive mitochondrial fatty acid oxidation defect in a dog

    Directory of Open Access Journals (Sweden)

    Vanessa R Biegen

    2015-11-01

    Full Text Available A 1-year-old spayed female Shih Tzu presented for episodic abnormalities of posture and mentation. Neurologic examination was consistent with a bilaterally symmetric multifocal encephalopathy. The dog had a waxing-and-waning hyperlactemia and hypoglycemia. Magnetic resonance imaging revealed bilaterally symmetric cavitated lesions of the caudate nuclei with less severe abnormalities in the cerebellar nuclei. Empirical therapy was unsuccessful and the patient was euthanized. Post-mortem histopathology revealed bilaterally symmetric necrotic lesions of the caudate and cerebellar nuclei and multi-organ lipid accumulation, including a lipid storage myopathy. Malonic aciduria and ketonuria were found on urinary organic acid screen. Plasma acylcarnitine analysis suggested a fatty acid oxidation defect. Fatty acid oxidation disorders are inborn errors of metabolism documented in humans, but poorly described in dogs. Although neurologic signs have been described in humans with this group of diseases, descriptions of advanced imaging and histopathology are severely lacking. This report suggests that abnormalities of fatty acid metabolism may cause severe, bilateral gray matter necrosis and lipid accumulation in multiple organs including the skeletal muscles, liver, and kidneys. Veterinarians should be aware that fatty acid oxidation disorders, although potentially fatal, may be treatable. A timely definitive diagnosis is essential in guiding therapy.

  14. Clinical neurogenetics: neurologic presentations of metabolic disorders.

    Science.gov (United States)

    Kwon, Jennifer M; D'Aco, Kristin E

    2013-11-01

    This article reviews aspects of the neurologic presentations of selected treatable inborn errors of metabolism within the category of small molecule disorders caused by defects in pathways of intermediary metabolism. Disorders that are particularly likely to be seen by neurologists include those associated with defects in amino acid metabolism (organic acidemias, aminoacidopathies, urea cycle defects). Other disorders of small molecule metabolism are discussed as additional examples in which early treatments have the potential for better outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Genetic analysis of metabolic defects in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Musilová, Alena; Šimáková, Miroslava; Kostka, Vlastimil; Mlejnek, Petr; Křen, Vladimír; Křenová, D.; Bílá, V.; Míková, B.; Jáchymová, M.; Horký, K.; Kazdová, L.; St.Lezin, E.; Kurtz, W. T.

    2002-01-01

    Roč. 13, č. 5 (2002), s. 253-258 ISSN 0938-8990 R&D Projects: GA MŠk LN00A079; GA ČR GV204/98/K015; GA ČR GA305/00/1646; GA MŠk NB5299 Grant - others:NIH(US) RO1 HL56028; NIH(US) PO1 HL35018; HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : metabolic defects * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.233, year: 2002

  16. Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina

    2015-09-03

    Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntington’s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

  17. Early metabolic defects in dexamethasone-exposed and undernourished intrauterine growth restricted rats.

    Directory of Open Access Journals (Sweden)

    Emmanuel Somm

    Full Text Available Poor fetal growth, also known as intrauterine growth restriction (IUGR, is a worldwide health concern. IUGR is commonly associated with both an increased risk in perinatal mortality and a higher prevalence of developing chronic metabolic diseases later in life. Obesity, type 2 diabetes or metabolic syndrome could result from noxious "metabolic programming." In order to better understand early alterations involved in metabolic programming, we modeled IUGR rat pups through either prenatal exposure to synthetic glucocorticoid (dams infused with dexamethasone 100 µg/kg/day, DEX or prenatal undernutrition (dams feeding restricted to 30% of ad libitum intake, UN. Physiological (glucose and insulin tolerance, morphometric (automated tissue image analysis and transcriptomic (quantitative PCR approaches were combined during early life of these IUGR pups with a special focus on their endocrine pancreas and adipose tissue development. In the absence of catch-up growth before weaning, DEX and UN IUGR pups both presented basal hyperglycaemia, decreased glucose tolerance, and pancreatic islet atrophy. Other early metabolic defects were model-specific: DEX pups presented decreased insulin sensitivity whereas UN pups exhibited lowered glucose-induced insulin secretion and more marked alterations in gene expression of pancreatic islet and adipose tissue development regulators. In conclusion, these results show that before any catch-up growth, IUGR rats present early physiologic, morphologic and transcriptomic defects, which can be considered as initial mechanistic basis of metabolic programming.

  18. Human myotubes from myoblast cultures undergoing senescence exhibit defects in glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Nehlin, Jan O; Just, Marlene; Rustan, Arild C

    2011-01-01

    Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways. As the prolif......Adult stem cells are known to have a finite replication potential. Muscle biopsy-derived human satellite cells (SCs) were grown at different passages and differentiated to human myotubes in culture to analyze the functional state of various carbohydrate and lipid metabolic pathways...... number and could be explained by reduced incorporation into diacyl- and triacylglycerols. The levels of long-chain acyl-CoA esters decreased with increased passage number. Late-passage, non-proliferating, myoblast cultures showed strong senescence-associated β-galactosidase activity indicating...... that the observed metabolic defects accompany the induction of a senescent state. The main function of SCs is regeneration and skeletal muscle-build up. Thus, the metabolic defects observed during aging of SC-derived myotubes could have a role in sarcopenia, the gradual age-related loss of muscle mass and strength....

  19. Selective screening in neonates suspected to have inborn errors of ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2015-02-16

    Feb 16, 2015 ... Objective: The aim of this work was to detect the prevalence of IEM among neonates ... defect, mitochondrial disease, and galactosemia were diagnosed in one patient each (7.7%). ... relation of symptoms to feeding, similar cases in the family, ... The extended metabolic screening test showed high leucine,.

  20. Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders.

    Science.gov (United States)

    Henriques, Bárbara J; Lucas, Tânia G; Gomes, Cláudio M

    2016-01-01

    Riboflavin, or vitamin B2, plays an important role in the cell as biological precursor of FAD and FMN, two important flavin cofactors which are essential for the structure and function of flavoproteins. Riboflavin has been used in therapeutic approaches of various inborn errors of metabolism, notably in metabolic disorders resulting either from defects in proteins involved in riboflavin metabolism and transport or from defects in flavoenzymes. The scope of this review is to provide an updated perspective of clinical cases in which riboflavin was used as a potential therapeutic agent in disorders affecting mitochondrial energy metabolism. In particular, we discuss available mechanistic insights on the role of riboflavin as a pharmacological chaperone for the recovery of misfolded metabolic flavoenzymes.

  1. Age-Related Defects in Erythrocyte 2,3-Diphosphoglycerate Metabolism in Dementia

    OpenAIRE

    Kaminsky, Yury G.; Reddy, V. Prakash; Ashraf, Ghulam Md; Ahmad, Ausaf; Benberin, Valery V.; Kosenko, Elena A.; Aliev, Gjumrakch

    2013-01-01

    Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive “reporter cells” that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) an...

  2. Supplementary Material for: Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina

    2015-01-01

    Abstract Background Protein aggregation and its pathological effects are the major cause of several neurodegenerative diseases. In Huntingtonâ s disease an elongated stretch of polyglutamines within the protein Huntingtin leads to increased aggregation propensity. This induces cellular defects, culminating in neuronal loss, but the connection between aggregation and toxicity remains to be established. Results To uncover cellular pathways relevant for intoxication we used genome-wide analyses in a yeast model system and identify fourteen genes that, if deleted, result in higher polyglutamine toxicity. Several of these genes, like UGO1, ATP15 and NFU1 encode mitochondrial proteins, implying that a challenged mitochondrial system may become dysfunctional during polyglutamine intoxication. We further employed microarrays to decipher the transcriptional response upon polyglutamine intoxication, which exposes an upregulation of genes involved in sulfur and iron metabolism and mitochondrial Fe-S cluster formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth is impossible after intoxication with the polyglutamine protein. NMR-based metabolic analyses reveal that mitochondrial metabolism is reduced, leading to accumulation of metabolic intermediates in polyglutamine-intoxicated cells. Conclusion These data show that damages to the mitochondrial system occur in polyglutamine intoxicated yeast cells and suggest an intricate connection between polyglutamine-induced toxicity, mitochondrial functionality and iron homeostasis in this model system.

  3. Age-related defects in erythrocyte 2,3-diphosphoglycerate metabolism in dementia.

    Science.gov (United States)

    Kaminsky, Yury G; Reddy, V Prakash; Ashraf, Ghulam Md; Ahmad, Ausaf; Benberin, Valery V; Kosenko, Elena A; Aliev, Gjumrakch

    2013-01-01

    Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive "reporter cells" that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA.

  4. Stem Cell Transplant for Inborn Errors of Metabolism

    Science.gov (United States)

    2017-12-03

    Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Gaucher's Disease; Fucosidosis; Wolman Disease; Niemann-Pick Disease; Batten Disease; GM1 Gangliosidosis; Tay Sachs Disease; Sandhoff Disease

  5. Gene-Gene Interactions in the Folate Metabolic Pathway and the Risk of Conotruncal Heart Defects

    Directory of Open Access Journals (Sweden)

    Philip J. Lupo

    2010-01-01

    Full Text Available Conotruncal and related heart defects (CTRD are common, complex malformations. Although there are few established risk factors, there is evidence that genetic variation in the folate metabolic pathway influences CTRD risk. This study was undertaken to assess the association between inherited (i.e., case and maternal gene-gene interactions in this pathway and the risk of CTRD. Case-parent triads (n=727, ascertained from the Children's Hospital of Philadelphia, were genotyped for ten functional variants of nine folate metabolic genes. Analyses of inherited genotypes were consistent with the previously reported association between MTHFR A1298C and CTRD (adjusted P=.02, but provided no evidence that CTRD was associated with inherited gene-gene interactions. Analyses of the maternal genotypes provided evidence of a MTHFR C677T/CBS 844ins68 interaction and CTRD risk (unadjusted P=.02. This association is consistent with the effects of this genotype combination on folate-homocysteine biochemistry but remains to be confirmed in independent study populations.

  6. Nutrition, One-Carbon Metabolism and Neural Tube Defects: A Review

    Directory of Open Access Journals (Sweden)

    Kelei Li

    2016-11-01

    Full Text Available Neural tube defects (NTDs are a group of severe congenital malformations, induced by the combined effects of genes and the environment. The most valuable finding so far has been the protective effect of folic acid supplementation against NTDs. However, many women do not take folic acid supplements until they are pregnant, which is too late to prevent NTDs effectively. Long-term intake of folic acid–fortified food is a good choice to solve this problem, and mandatory folic acid fortification should be further promoted, especially in Europe, Asia and Africa. Vitamin B2, vitamin B-6, vitamin B-12, choline, betaine and n-3 polyunsaturated fatty acids (PUFAs can also reduce the NTD risk by interacting with the one-carbon metabolism pathway. This suggest that multivitamin B combined with choline, betaine and n-3 PUFAs supplementation may have a better protective effect against NTDs than folic acid alone. Genetic polymorphisms involved in one-carbon metabolism are associated with NTD risk, and gene screening for women of childbearing age prior to pregnancy may help prevent NTDs induced by the risk allele. In addition, the consumption of alcohol, tea and coffee, and low intakes of fruit and vegetable are also associated with the increased risk of NTDs, and should be avoided by women of childbearing age.

  7. Intracellular trafficking of the free cholesterol derived from LDL cholesteryl ester is defective in vivo in Niemann-Pick C disease: insights on normal metabolism of HDL and LDL gained from the NP-C mutation.

    Science.gov (United States)

    Shamburek, R D; Pentchev, P G; Zech, L A; Blanchette-Mackie, J; Carstea, E D; VandenBroek, J M; Cooper, P S; Neufeld, E B; Phair, R D; Brewer, H B; Brady, R O; Schwartz, C C

    1997-12-01

    Niemann-Pick C disease (NP-C) is a rare inborn error of metabolism with hepatic involvement and neurological sequelae that usually manifest in childhood. Although in vitro studies have shown that the lysosomal distribution of LDL-derived cholesterol is defective in cultured cells of NP-C subjects, no unusual characteristics mark the plasma lipoprotein profiles. We set out to determine whether anomalies exist in vivo in the cellular distribution of newly synthesized, HDL-derived or LDL-derived cholesterol under physiologic conditions in NP-C subjects. Three affected and three normal male subjects were administered [14C]mevalonate as a tracer of newly synthesized cholesterol and [3H]cholesteryl linoleate in either HDL or LDL to trace the distribution of lipoprotein-derived free cholesterol. The rate of appearance of free [14C]- and free [3H]cholesterol in the plasma membrane was detected indirectly by monitoring their appearance in plasma and bile. The plasma disappearance of [3H]cholesteryl linoleate was slightly faster in NP-C subjects regardless of its lipoprotein origin. Appearance of free [14C] cholesterol ill the plasma (and in bile) was essentially identical in normal and affected individuals as was the initial appearance of free [3H]cholesterol derived from HDL, observed before extensive exchange occurred of the [3H]cholesteryl linoleate among lipoproteins. In contrast, the rate of appearance of LDL-derived free [3H]cholesterol in the plasma membrane of NP-C subjects, as detected in plasma and bile, was retarded to a similar extent that LDL cholesterol metabolism was defective in cultured fibroblasts of these affected subjects. These findings show that intracellular distribution of both newly synthesized and HDL-derived cholesterol are essentially unperturbed by the NP-C mutation, and therefore occur by lysosomal-independent paths. In contrast, in NP-C there is defective trafficking of LDL-derived cholesterol to the plasma membrane in vivo as well as in vitro

  8. Dental care of patients after surgical therapy of inborn oro-facial clefts 3D technologies in diagnostics and therapy of cleft patients

    OpenAIRE

    Kašparová, Magdaléna

    2015-01-01

    Patients with orofacial defects, inborn or acquired, isolated or in combination with other handicaps in syndroms, suffer from various problems including psychological problems. Morphological changes within these handicaps burden not only the patients themselves, but also their families. Among the main problems are difficulties with feeding, speech or breathing. Anomalies in number or position of deciduous and permanent teeth, development of jaws and dental arches are often present. Multidisci...

  9. Inherited metabolic disorders in Thailand.

    Science.gov (United States)

    Wasant, Pornswan; Svasti, Jisnuson; Srisomsap, Chantragan; Liammongkolkul, Somporn

    2002-08-01

    The study of inborn errors of metabolism (IEM) in Thailand is in its infancy. The majority are clinically diagnosed since there are only a handful of clinicians and scientists with expertise in inherited metabolic disorders, shortage of well-equipped laboratory facilities and lack of governmental financial support. Genetic metabolic disorders are usually not considered a priority due to prevalence of infectious diseases and congenital infections. From a retrospective study at the Medical Genetics Unit, Department of Pediatrics, Siriraj Hospital; estimated pediatrics patients with suspected IEM were approximately 2-3 per cent of the total pediatric admissions of over 5,000 annually. After more than 10 years of research and accumulated clinical experiences, a genetic metabolic center is being established in collaboration with expert laboratories both in Bangkok (Chulabhorn Research Institute) and abroad (Japan and the United States). Numerous inherited metabolic disorders were identified--carbohydrate, amino acids, organic acids, mitochondrial fatty acid oxidation, peroxisomal, mucopolysaccharidoses etc. This report includes the establishment of genetic metabolic center in Thailand, research and pilot studies in newborn screening in Thailand and a multicenter study from 5 institutions (Children's National Center, King Chulalongkorn Memorial Hospital, Pramongkutklao Hospital, Ramathibodi and Siriraj Hospitals). Inherited metabolic disorders reported are fructose-1,6-bisphosphatase deficiency, phenylketonuria, homocystinuria, nonketotic hyperglycinemia, urea cycle defect (arginino succinate lyase deficiency, argininosuccinate synthetase deficiency), Menkes disease, propionic acidemia and mucopolysaccharidoses (Hurler, Hurler-Scheie).

  10. Mendelian susceptibility to mycobacterial disease: genetic, immunological, and clinical features of inborn errors of IFN-γ immunity

    Science.gov (United States)

    Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Abel, Laurent; Casanova, Jean-Laurent

    2014-01-01

    Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by predisposition to clinical disease caused by weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria, in otherwise healthy individuals with no overt abnormalities in routine hematological and immunological tests. MSMD designation does not recapitulate all the clinical features, as patients are also prone to salmonellosis, candidiasis and tuberculosis, and more rarely to infections with other intramacrophagic bacteria, fungi, or parasites, and even, perhaps, a few viruses. Since 1996, nine MSMD-causing genes, including seven autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1, ISG15, and IRF8) and two X-linked (NEMO, CYBB) genes have been discovered. The high level of allelic heterogeneity has already led to the definition of 18 different disorders. The nine gene products are physiologically related, as all are involved in IFN-γ-dependent immunity. These disorders impair the production of (IL12B, IL12RB1, IRF8, ISG15, NEMO) or the response to (IFNGR1, IFNGR2, STAT1, IRF8, CYBB) IFN-γ. These defects account for only about half the known MSMD cases. Patients with MSMD-causing genetic defects may display other infectious diseases, or even remain asymptomatic. Most of these inborn errors do not show complete clinical penetrance for the case-definition phenotype of MSMD. We review here the genetic, immunological, and clinical features of patients with inborn errors of IFN-γ-dependent immunity. PMID:25453225

  11. Fat and Sugar Metabolism During Exercise in Patients With Metabolic Myopathy

    Science.gov (United States)

    2017-08-31

    Metabolism, Inborn Errors; Lipid Metabolism, Inborn Errors; Carbohydrate Metabolism, Inborn Errors; Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency; Glycogenin-1 Deficiency (Glycogen Storage Disease Type XV); Carnitine Palmitoyl Transferase 2 Deficiency; VLCAD Deficiency; Medium-chain Acyl-CoA Dehydrogenase Deficiency; Multiple Acyl-CoA Dehydrogenase Deficiency; Carnitine Transporter Deficiency; Neutral Lipid Storage Disease; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Muscle Phosphofructokinase Deficiency; Phosphoglucomutase 1 Deficiency; Phosphoglycerate Mutase Deficiency; Phosphoglycerate Kinase Deficiency; Phosphorylase Kinase Deficiency; Beta Enolase Deficiency; Lactate Dehydrogenase Deficiency; Glycogen Synthase Deficiency

  12. Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes

    Science.gov (United States)

    Boisson-Dupuis, Stephanie; Kong, Xiao-Fei; Okada, Satoshi; Cypowyj, Sophie; Puel, Anne; Abel, Laurent; Casanova, Jean-Laurent

    2012-01-01

    The genetic dissection of various human infectious diseases has led to the definition of inborn errors of human STAT1 immunity of four types, including (i) autosomal recessive (AR) complete STAT1 deficiency, (ii) AR partial STAT1 deficiency, (iii) autosomal dominant (AD) STAT1 deficiency, and (iv) AD gain of STAT1 activity. The two types of AR STAT1 defect give rise to a broad infectious phenotype with susceptibility to intramacrophagic bacteria (mostly mycobacteria) and viruses (herpes viruses at least), due principally to the impairment of IFN-γ-mediated and IFN-α/β-mediated immunity, respectively. Clinical outcome depends on the extent to which the STAT1 defect decreases responsiveness to these cytokines. AD STAT1 deficiency selectively predisposes individuals to mycobacterial disease, owing to the impairment of IFN-γ-mediated immunity, as IFN-α/β-mediated immunity is maintained. Finally, AD gain of STAT1 activity is associated with autoimmunity, probably owing to an enhancement of IFN-α/β-mediated immunity. More surprisingly, it is also associated with chronic mucocutaneous candidiasis, through as yet undetermined mechanisms involving an inhibition of the development of IL-17-producing T cells. Thus, germline mutations in human STAT1 define four distinct clinical disorders. Various combinations of viral, mycobacterial and fungal infections are therefore allelic at the human STAT1 locus. These experiments of Nature neatly highlight the clinical and immunological impact of the human genetic dissection of infectious phenotypes. PMID:22651901

  13. Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

    Science.gov (United States)

    Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

    Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Defects in mitophagy promote redox-driven metabolic syndrome in the absence of TP53INP1.

    Science.gov (United States)

    Seillier, Marion; Pouyet, Laurent; N'Guessan, Prudence; Nollet, Marie; Capo, Florence; Guillaumond, Fabienne; Peyta, Laure; Dumas, Jean-François; Varrault, Annie; Bertrand, Gyslaine; Bonnafous, Stéphanie; Tran, Albert; Meur, Gargi; Marchetti, Piero; Ravier, Magalie A; Dalle, Stéphane; Gual, Philippe; Muller, Dany; Rutter, Guy A; Servais, Stéphane; Iovanna, Juan L; Carrier, Alice

    2015-06-01

    The metabolic syndrome covers metabolic abnormalities including obesity and type 2 diabetes (T2D). T2D is characterized by insulin resistance resulting from both environmental and genetic factors. A genome-wide association study (GWAS) published in 2010 identified TP53INP1 as a new T2D susceptibility locus, but a pathological mechanism was not identified. In this work, we show that mice lacking TP53INP1 are prone to redox-driven obesity and insulin resistance. Furthermore, we demonstrate that the reactive oxygen species increase in TP53INP1-deficient cells results from accumulation of defective mitochondria associated with impaired PINK/PARKIN mitophagy. This chronic oxidative stress also favors accumulation of lipid droplets. Taken together, our data provide evidence that the GWAS-identified TP53INP1 gene prevents metabolic syndrome, through a mechanism involving prevention of oxidative stress by mitochondrial homeostasis regulation. In conclusion, this study highlights TP53INP1 as a molecular regulator of redox-driven metabolic syndrome and provides a new preclinical mouse model for metabolic syndrome clinical research. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  15. [PULMONARY COMPLICATIONS IN CHILDREN, OPERATED ON FOR INBORN HEART FAILURES IN THE ARTIFICIAL BLOOD CIRCULATION ENVIRONMENT].

    Science.gov (United States)

    Moshkivska, L V; Nastenko, E A; Golovenko, O S; Lazoryshynets, V V

    2015-11-01

    The risk factors of pulmonary complications occurrence were analyzed in children, operated on for inborn heart failures in atrificial blood circulation environment. Pulmonary complications rate and the risk factors of their occurrence were analyzed.

  16. Novel Models to Study Effect of High-Altitude Hypoxic Exposure and Placental Insufficiency on Fetal Oxygen Metabolism and Congenital Heart Defects

    Science.gov (United States)

    2017-10-01

    Metabolism and Congenital Heart Defects PRINCIPAL INVESTIGATOR: Steven Fisher, MD RECIPIENT: University of Maryland, Baltimore REPORT DATE...examined in fetal heart vs other tissues. Pregnant ODD-Luc dams age 3-6 months will inhale O2 concentrations ranging from 8-21% O2 x 4 h...Congenital Heart Defects in at-risk pregnancies. The first objective was to use a novel reporter of O2 concentrations, the ODDLuc mouse, to determine the

  17. Framing the inborn aging process and longevity science.

    Science.gov (United States)

    Farrelly, Colin

    2010-06-01

    The medical sciences are currently dominated by the "disease-model" approach to health extension, an approach that prioritizes the study of pathological mechanisms with the goal of discovering treatment modalities for specific diseases. This approach has marginalized research on the aging process itself, research that could lead to an intervention that retards aging, thus conferring health dividends that would far exceed what could be expected by eliminating any specific disease of aging. This paper offers a diagnosis of how this sub-optimal approach to health extension arose and some general prescriptions concerning how progress could be made in terms of adopting a more rational approach to health extension. Drawing on empirical findings from psychology and economics, "prospect theory" is applied to the challenges of "framing" the inborn aging process given the cognitive capacities of real (rather than rational) decision-makers under conditions of risk and uncertainty. Prospect theory reveals that preferences are in fact dependent on whether particular outcomes of a choice are regarded as "a loss" or "a gain", relative to a reference point (or "aspiration level for survival"). And this has significant consequences for the way biogerontologists ought to characterise the central aspirations of the field (i.e. to prevent disease versus extend lifespan). Furthermore, it reveals the importance of shifting the existing reference point of the medical sciences to one that is shaped by the findings of evolutionary biology and biodemography.

  18. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism.

    Science.gov (United States)

    Lerin, Carles; Goldfine, Allison B; Boes, Tanner; Liu, Manway; Kasif, Simon; Dreyfuss, Jonathan M; De Sousa-Coelho, Ana Luisa; Daher, Grace; Manoli, Irini; Sysol, Justin R; Isganaitis, Elvira; Jessen, Niels; Goodyear, Laurie J; Beebe, Kirk; Gall, Walt; Venditti, Charles P; Patti, Mary-Elizabeth

    2016-10-01

    Plasma levels of branched-chain amino acids (BCAA) are consistently elevated in obesity and type 2 diabetes (T2D) and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28). We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut) and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D.

  19. Pitfall in metabolic screening in a patient with fatal peroxisomal beta-oxidation defect

    NARCIS (Netherlands)

    Rosewich, H.; Waterham, H. R.; Wanders, R. J. A.; Ferdinandusse, S.; Henneke, M.; Hunneman, D.; Gärtner, J.

    2006-01-01

    We present a rare case of peroxisomal acyl-CoA oxidase deficiency that was not detected by the common metabolic screening program for peroxisomal disorders. The patient presented with a typical MRI pattern showing pachygyria, perisylvian polymicrogyria, cerebral and cerebellar white matter

  20. Defects in muscle branched-chain amino acid oxidation contribute to impaired lipid metabolism

    Directory of Open Access Journals (Sweden)

    Carles Lerin

    2016-10-01

    Full Text Available Objective: Plasma levels of branched-chain amino acids (BCAA are consistently elevated in obesity and type 2 diabetes (T2D and can also prospectively predict T2D. However, the role of BCAA in the pathogenesis of insulin resistance and T2D remains unclear. Methods: To identify pathways related to insulin resistance, we performed comprehensive gene expression and metabolomics analyses in skeletal muscle from 41 humans with normal glucose tolerance and 11 with T2D across a range of insulin sensitivity (SI, 0.49 to 14.28. We studied both cultured cells and mice heterozygous for the BCAA enzyme methylmalonyl-CoA mutase (Mut and assessed the effects of altered BCAA flux on lipid and glucose homeostasis. Results: Our data demonstrate perturbed BCAA metabolism and fatty acid oxidation in muscle from insulin resistant humans. Experimental alterations in BCAA flux in cultured cells similarly modulate fatty acid oxidation. Mut heterozygosity in mice alters muscle lipid metabolism in vivo, resulting in increased muscle triglyceride accumulation, increased plasma glucose, hyperinsulinemia, and increased body weight after high-fat feeding. Conclusions: Our data indicate that impaired muscle BCAA catabolism may contribute to the development of insulin resistance by perturbing both amino acid and fatty acid metabolism and suggest that targeting BCAA metabolism may hold promise for prevention or treatment of T2D. Keywords: Insulin sensitivity, BCAA, Fatty acid oxidation, TCA cycle

  1. Production of xylitol by a Coniochaeta ligniaria strain tolerant of inhibitors and defective in xylose metabolism

    Science.gov (United States)

    In conversion of biomass to fuels or chemicals, inhibitory compounds arising from physical-chemical pretreatment of the feedstock can interfere with fermentation of the sugars to product. Fungal strain Coniochaeta ligniaria NRRL30616, metabolizes the furan aldehydes furfural and 5-hydroxymethylfurfu...

  2. Pathophysiology of Adipocyte Defects and Dyslipidemia in HIV Lipodystrophy: New Evidence from Metabolic and Molecular Studies

    OpenAIRE

    Ashok Balasubramanyam; Rajagopal V. Sekhar; Farook Jahoor; Henry J. Pownall; Dorothy Lewis

    2006-01-01

    Despite a burgeoning mass of descriptive information regarding the epidemiology, clinical features, body composition changes, hormonal alterations and dyslipidemic patterns in patients with HIV lipodystrophy syndrome (HLS), the specific biochemical pathways that are dysregulated in the condition and the molecular mechanisms that lead to their dysfunction, remain relatively unexplored. In this paper, we review studies that detail the metabolic basis of the dyslipidemia - specifically, the hype...

  3. Selective screening in neonates suspected to have inborn errors of ...

    African Journals Online (AJOL)

    Results: 13 patients (32.5%) were diagnosed as having IEM, 7 of them (53.8%) had urea cycle defect, 2 (15.4%) had maple syrup urine disease, while methylmalonic acidemia, fatty acid oxidation defect, mitochondrial disease, and galactosemia were diagnosed in one patient each (7.7%). Out of these patients, 12 patients ...

  4. Enzyme replacement prevents enamel defects in hypophosphatasia mice

    Science.gov (United States)

    Yadav, Manisha C.; de Oliveira, Rodrigo Cardoso; Foster, Brian L.; Fong, Hanson; Cory, Esther; Narisawa, Sonoko; Sah, Robert L.; Somerman, Martha; Whyte, Michael P.; Millán, José Luis

    2012-01-01

    Hypophosphatasia (HPP) is the inborn error of metabolism characterized by deficiency of alkaline phosphatase activity leading to rickets or osteomalacia and to dental defects. HPP occurs from loss-of-function mutations within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNAP). TNAP knockout (Alpl−/−, a.k.a. Akp2−/−) mice closely phenocopy infantile HPP, including the rickets, vitamin B6-responsive seizures, improper dentin mineralization, and lack of acellular cementum. Here, we report that lack of TNAP in Alpl−/− mice also causes severe enamel defects, which are preventable by enzyme replacement with mineral-targeted TNAP (ENB-0040). Immunohistochemistry was used to map the spatiotemporal expression of TNAP in the tissues of the developing enamel organ of healthy mouse molars and incisors. We found strong, stage-specific expression of TNAP in ameloblasts. In the Alpl−/− mice, histological, μCT, and scanning electron microscopy analysis showed reduced mineralization and disrupted organization of the rods and inter-rod structures in enamel of both the molars and incisors. All of these abnormalities were prevented in mice receiving from birth daily subcutaneous injections of mineral-targeting, human TNAP (sALP-FcD10, a.k.a. ENB-0040) at 8.2 mg/kg/day for up to 44 days. These data reveal an important role for TNAP in enamel mineralization, and demonstrate the efficacy of mineral-targeted TNAP to prevent enamel defects in HPP. PMID:22461224

  5. Risk factors and birth prevalence of birth defects and inborn errors of ...

    African Journals Online (AJOL)

    raoul

    2011-02-23

    Feb 23, 2011 ... methylmalonic aciduria, and maple syrup urine disease (MSUD) had their diagnoses confirmed by enzyme assay. The diagnosis of all ... Personal information like date of birth, sex, area of residence, mother's age at birth, father's age, order of birth, birth weight, gestational age on birth, medical history and ...

  6. Inborn defects in the antioxidant systems of human red blood cells

    NARCIS (Netherlands)

    van Zwieten, Rob; Verhoeven, Arthur J.; Roos, Dirk

    2014-01-01

    Red blood cells (RBCs) contain large amounts of iron and operate in highly oxygenated tissues. As a result, these cells encounter a continuous oxidative stress. Protective mechanisms against oxidation include prevention of formation of reactive oxygen species (ROS), scavenging of various forms of

  7. A Yeast Mutant Deleted of GPH1 Bears Defects in Lipid Metabolism.

    Directory of Open Access Journals (Sweden)

    Martina Gsell

    Full Text Available In a previous study we demonstrated up-regulation of the yeast GPH1 gene under conditions of phosphatidylethanolamine (PE depletion caused by deletion of the mitochondrial (M phosphatidylserine decarboxylase 1 (PSD1 (Gsell et al., 2013, PLoS One. 8(10:e77380. doi: 10.1371/journal.pone.0077380. Gph1p has originally been identified as a glycogen phosphorylase catalyzing degradation of glycogen to glucose in the stationary growth phase of the yeast. Here we show that deletion of this gene also causes decreased levels of phosphatidylcholine (PC, triacylglycerols and steryl esters. Depletion of the two non-polar lipids in a Δgph1 strain leads to lack of lipid droplets, and decrease of the PC level results in instability of the plasma membrane. In vivo labeling experiments revealed that formation of PC via both pathways of biosynthesis, the cytidine diphosphate (CDP-choline and the methylation route, is negatively affected by a Δgph1 mutation, although expression of genes involved is not down regulated. Altogether, Gph1p besides its function as a glycogen mobilizing enzyme appears to play a regulatory role in yeast lipid metabolism.

  8. UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

    Science.gov (United States)

    2018-03-15

    Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

  9. Association of main folate metabolic pathway gene polymorphisms with neural tube defects in Han population of Northern China.

    Science.gov (United States)

    Fang, Yulian; Zhang, Ruiping; Zhi, Xiufang; Zhao, Linsheng; Cao, Lirong; Wang, Yizheng; Cai, Chunquan

    2018-04-01

    Neural tube defects (NTDs) are one of the most prevalent and the most severe congenital malformations worldwide. Studies have confirmed that folic acid supplementation could effectively reduce NTDs risk, but the genetic mechanism remains unclear. In this study, we explored association of single nucleotide polymorphisms (SNP) within folate metabolic pathway genes with NTDs in Han population of Northern China. We performed a case-control study to compare genotype and allele distributions of SNPs in 152 patients with NTDs and 169 controls. A total of 16 SNPs within five genes were genotyped by the Sequenom MassARRAY assay. Our results indicated that three SNPs associated significantly with NTDs (P<0.05). For rs2236225 within MTHFD1, children with allele A or genotype AA had a high NTDs risk (OR=1.500, 95%CI=1.061~2.120; OR=2.862, 95%CI=1.022~8.015, respectively). For rs1801133 within MTHFR, NTDs risk markedly increased in patients with allele T or genotype TT (OR=1.552, 95%CI=1.130~2.131; OR=2.344, 95%CI=1.233~4.457, respectively). For rs1801394 within MTRR, children carrying allele G and genotype GG had a higher NTDs risk (OR=1.533, 95%CI=1.102~2.188; OR=2.355, 95%CI=1.044~5.312, respectively). Our results suggest that rs2236225 of MTHFD1 gene, rs1801133 of MTHFR gene and rs1801394 of MTRR gene were associated with NTDs in Han population of Northern China.

  10. Endocrine manifestations related to inherited metabolic diseases in adults

    Directory of Open Access Journals (Sweden)

    Vantyghem Marie-Christine

    2012-01-01

    Full Text Available Abstract Most inborn errors of metabolism (IEM are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.. IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects, and metal (hemochromatosis and storage disorders (cystinosis. Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes, whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure, congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last. This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses.

  11. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study.

    Science.gov (United States)

    Cadenas-Benitez, N M; Yanes-Sosa, F; Gonzalez-Meneses, A; Cerrillos, L; Acosta, D; Praena-Fernandez, J M; Neth, O; Gomez de Terreros, I; Ybot-González, P

    2014-03-26

    Abnormalities in maternal folate and carbohydrate metabolism have both been shown to induce neural tube defects (NTD) in humans and animal models. However, the relationship between these two factors in the development of NTDs remains unclear. Data from mothers of children with spina bifida seen at the Unidad de Espina Bífida del Hospital Infantil Virgen del Rocío (case group) were compared to mothers of healthy children with no NTD (control group) who were randomly selected from patients seen at the outpatient ward in the same hospital. There were 25 individuals in the case group and 41 in the control group. Analysis of genotypes for the methylenetetrahydrofolate reductase (MTHFR) 677CT polymorphism in women with or without risk factors for abnormal carbohydrate metabolism revealed that mothers who were homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism were more likely to have offspring with spina bifida and high levels of homocysteine, compared to the control group. The increased incidence of NTDs in mothers homozygous for the MTHFR 677TT polymorphism and at risk of abnormal carbohydrate metabolism stresses the need for careful metabolic screening in pregnant women, and, if necessary, determination of the MTHFR 677CT genotype in those mothers at risk of developing abnormal carbohydrate metabolism.

  12. Metabolically induced heteroplasmy shifting and L-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS

    Science.gov (United States)

    Desquiret-Dumas, Valerie; Gueguen, Naig; Barth, Magalie; Chevrollier, Arnaud; Hancock, Saege; Wallace, Douglas C; Amati-Bonneau, Patrizia; Henrion, Daniel; Bonneau, Dominique; Reynier, Pascal; Procaccio, Vincent

    2012-01-01

    The m.3243A>G variant in the mitochondrial tRNALeu (UUR) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of L-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of L-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and L-arginine therapy may constitute promising therapeutic strategies against MELAS. PMID:22306605

  13. γ-Aminobutyric acid transaminase deficiency impairs central carbon metabolism and leads to cell wall defects during salt stress in Arabidopsis roots.

    Science.gov (United States)

    Renault, Hugues; El Amrani, Abdelhak; Berger, Adeline; Mouille, Grégory; Soubigou-Taconnat, Ludivine; Bouchereau, Alain; Deleu, Carole

    2013-05-01

    Environmental constraints challenge cell homeostasis and thus require a tight regulation of metabolic activity. We have previously reported that the γ-aminobutyric acid (GABA) metabolism is crucial for Arabidopsis salt tolerance as revealed by the NaCl hypersensitivity of the GABA transaminase (GABA-T, At3g22200) gaba-t/pop2-1 mutant. In this study, we demonstrate that GABA-T deficiency during salt stress causes root and hypocotyl developmental defects and alterations of cell wall composition. A comparative genome-wide transcriptional analysis revealed that expression levels of genes involved in carbon metabolism, particularly sucrose and starch catabolism, were found to increase upon the loss of GABA-T function under salt stress conditions. Consistent with the altered mutant cell wall composition, a number of cell wall-related genes were also found differentially expressed. A targeted quantitative analysis of primary metabolites revealed that glutamate (GABA precursor) accumulated while succinate (the final product of GABA metabolism) significantly decreased in mutant roots after 1 d of NaCl treatment. Furthermore, sugar concentration was twofold reduced in gaba-t/pop2-1 mutant roots compared with wild type. Together, our results provide strong evidence that GABA metabolism is a major route for succinate production in roots and identify GABA as a major player of central carbon adjustment during salt stress. © 2012 Blackwell Publishing Ltd.

  14. Critical Newborn Screens in Double Heterozygotes of Inborn Errors of Metabolism—A Clinical Report and Recommendations

    Directory of Open Access Journals (Sweden)

    Katherine G. Langley

    2016-11-01

    Full Text Available The practice of newborn screening has been in place in the USA since the 1960s, with individual states initially screening for different numbers of disorders. In the early 2000s many efforts were made to standardize the various disorders being screened. Currently, there are at least 34 disorders that each state is mandated to include on their screening panel. Of those 34 disorders, the majority are inborn errors of metabolism (IEM which include urea cycle disorders (UCD, citrullinemia (CIT and argininosuccinic aciduria (ASA, as well as a number of fatty acid oxidation disorders. We present here four cases of infants who had critical newborn screens (NBS in the Commonwealth of Virginia and underwent genetic testing because their clinical presentation and follow-up laboratory studies were not consistent with the disorder that was flagged by NBS. These newborns were found to be carriers for two different IEMs (in three cases or compound heterozygotes (in one case. Currently no guidelines exist with respect to the appropriate way to manage these children who may or may not be symptomatic in the newborn period. We propose some general recommendations for management based on our experience with these four probands, and discuss the necessity for further conversation and collaboration between physicians encountering these not-so-infrequent presentations.

  15. OPPORTUNITIES OF TRANSVAGINAL ECHOCARDIOGRAPHY FOR EARLY PRENATAL DIAGNOSIS OF INBORN HEART DISEASES IN FETUS

    Directory of Open Access Journals (Sweden)

    E.A. Shevchenko

    2008-01-01

    Full Text Available According to the literature data, transvaginal echocardiography (Echocg is the method, used for the doppler diagnostics in early terms of pregnancy (if principles of safety are observed. This method allows detecting about 70–97% of all prognostic cally significant inborn heart diseases in fetus, beginning at 12 week of pregnancy. a scheme of research includes estimation of four chamber cut of fetus heart, and study of state of its main arteries. This is an expert investigation, because it needs special grounding of specialist, high resolution ultrasonic equipment, and considerable expense of time. Wile parameters are estimated, it is necessary to use normative rates of sizes of ventricles and main arteries of fetus, developed by Russian experts, taking into account individual variations.Key words: transvaginal echocardiography, diagnosis, inborn heart disease.

  16. A Neurological Enigma: The Inborn Numerical Competence of Humans and Animals

    Science.gov (United States)

    Gross, Hans J.

    2012-03-01

    "Subitizing" means our ability to recognize and memorize object numbers precisely under conditions where counting is impossible. This is an inborn archaic process which was named after the Latin "subito" = suddenly, immediately, indicating that the objects in question are presented to test persons only for the fraction of a second in order to prevent counting. Sequential counting, however, is an outstanding cultural achievement of mankind and means to count "1, 2, 3, 4, 5, 6, 7, 8 ..." without a limit. In contrast to inborn "subitizing", counting has to be trained, beginning in our early childhood with the help of our fingers. For humans we know since 140 years that we can "subitize" only up to 4 objects correctly and that mistakes occur from 5 objects on. Similar results have been obtained for a number of non-human vertebrates from salamanders to pigeons and dolphins. To our surprise, we have detected this inborn numerical competence for the first time in case of an invertebrate, the honeybee which recognizes and memorizes 3 to 4 objects under rigorous test conditions. This common ability of humans and honeybees to "subitize" up to 4 objects correctly and the miraculous but rare ability of persons with Savant syndrome to "subitize" more than hundred objects precisely raises a number of intriguing questions concerning the evolution and the significance of this biological enigma.

  17. Metabolism

    Science.gov (United States)

    ... Are More Common in People With Type 1 Diabetes Metabolic Syndrome Your Child's Weight Healthy Eating Endocrine System Blood Test: Basic Metabolic Panel (BMP) Activity: Endocrine System Growth Disorders Diabetes Center Thyroid Disorders Your Endocrine System Movie: Endocrine ...

  18. Mutations in THAP11 cause an inborn error of cobalamin metabolism and developmental abnormalities

    DEFF Research Database (Denmark)

    Quintana, Anita M; Yu, Hung-Chun; Brebner, Alison

    2017-01-01

    roles in normal brain development. The loss of THAP11 in zebrafish embryos results in craniofacial abnormalities including the complete loss of Meckel's cartilage, the ceratohyal, and all of the ceratobranchial cartilages. These data are consistent with our previous work that demonstrated a role...

  19. The impact of consanguinity on the frequency of inborn errors of metabolism

    DEFF Research Database (Denmark)

    Afzal, Raja Majid; Lund, Allan Meldgaard; Skovby, Flemming

    2018-01-01

    for selected IEM with autosomal recessive mode of inheritance, a national screening program of newborns covering the period from 2002 until April 2017. Among the 838,675 newborns from Denmark, the Faroe Islands and Greenland, a total of 196 newborns had an IEM of whom 155 from Denmark were included...... children. The data indicate a strong association between consanguinity and IEM. These figures could be useful to health professionals providing antenatal, pediatric, and clinical genetic services....

  20. Selective screening in neonates suspected to have inborn errors of metabolism

    Directory of Open Access Journals (Sweden)

    Rabah M. Shawky

    2015-04-01

    Conclusion: IEM represent a high percent (32.5% of neonates who had sepsis like symptoms, and when diagnosed, patients showed marked improvement after therapy. IEM should be considered in differential diagnosis of the sick neonates, and investigations, and management should be started rapidly to decrease morbidity, and mortality till nationwide screen for IEM is applied in Egypt.

  1. Fifteen years experience: Egyptian metabolic lab

    Directory of Open Access Journals (Sweden)

    Ekram M. Fateen

    2014-10-01

    Conclusion: This study illustrates the experience of the reference metabolic lab in Egypt over 15 years. The lab began metabolic disorder screening by using simple diagnostic techniques like thin layer chromatography and colored tests in urine which by time updated and upgraded the methods to diagnose a wide range of disorders. This study shows the most common diagnosed inherited inborn errors of metabolism among the Egyptian population.

  2. Outline of metabolic diseases in adult neurology.

    Science.gov (United States)

    Mochel, F

    2015-01-01

    Inborn errors of metabolism (IEM) are traditionally defined by enzymatic deficiencies or defects in proteins involved in cellular metabolism. Historically discovered and characterized in children, a growing number of IEM are described in adults, and especially in the field of neurology. In daily practice, it is important to recognize emergency situations as well as neurodegenerative diseases for which a metabolic disease is likely, especially when therapeutic interventions are available. Here, the goal is to provide simple clinical, imaging and biochemical tools that can first orientate towards and then confirm the diagnosis of IEM. General guidelines are presented to treat the most common IEM during metabolic crises - acute encephalopathies with increased plasma ammonia, lactate or homocystein, as well as rhabdomyolysis. Examples of therapeutic strategies currently applied to chronic neurometabolic diseases are also provided - GLUT1 deficiency, adrenoleukodystrophy, cerebrotendinous xanthomatosis, Niemann-Pick type C and Wilson disease. Genetic counseling is mandatory in some X-linked diseases - ornithine transcarbamylase deficiency and adrenoleukodystrophy - and recommended in maternally inherited mitochondrial diseases - mutations of mitochondrial DNA. Besides these practical considerations, the contribution of metabolism to the field of adult neurology and neurosciences is much greater: first, with the identification of blood biomarkers that are progressively changing our diagnostic strategies thanks to lipidomic approaches, as illustrated in the field of spastic paraplegia and atypical psychiatric presentations; and second, through the understanding of pathophysiological mechanisms involved in common neurological diseases thanks to the study of these rare diseases. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Rewiring AMPK and Mitochondrial Retrograde Signaling for Metabolic Control of Aging and Histone Acetylation in Respiratory-Defective Cells

    Directory of Open Access Journals (Sweden)

    R. Magnus N. Friis

    2014-04-01

    Full Text Available Abnormal respiratory metabolism plays a role in numerous human disorders. We find that regulation of overall histone acetylation is perturbed in respiratory-incompetent (ρ0 yeast. Because histone acetylation is highly sensitive to acetyl-coenzyme A (acetyl-CoA availability, we sought interventions that suppress this ρ0 phenotype through reprogramming metabolism. Nutritional intervention studies led to the discovery that genetic coactivation of the mitochondrion-to-nucleus retrograde (RTG response and the AMPK (Snf1 pathway prevents abnormal histone deacetylation in ρ0 cells. Metabolic profiling of signaling mutants uncovered links between chromatin-dependent phenotypes of ρ0 cells and metabolism of ATP, acetyl-CoA, glutathione, branched-chain amino acids, and the storage carbohydrate trehalose. Importantly, RTG/AMPK activation reprograms energy metabolism to increase the supply of acetyl-CoA to lysine acetyltransferases and extend the chronological lifespan of ρ0 cells. Our results strengthen the framework for rational design of nutrient supplementation schemes and drug-discovery initiatives aimed at mimicking the therapeutic benefits of dietary interventions.

  4. Metabolism

    Science.gov (United States)

    ... lin), which signals cells to increase their anabolic activities. Metabolism is a complicated chemical process, so it's not ... how those enzymes or hormones work. When the metabolism of body chemicals is ... Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism ...

  5. Mechanisms underlying metabolic and neural defects in zebrafish and human multiple acyl-CoA dehydrogenase deficiency (MADD.

    Directory of Open Access Journals (Sweden)

    Yuanquan Song

    2009-12-01

    Full Text Available In humans, mutations in electron transfer flavoprotein (ETF or electron transfer flavoprotein dehydrogenase (ETFDH lead to MADD/glutaric aciduria type II, an autosomal recessively inherited disorder characterized by a broad spectrum of devastating neurological, systemic and metabolic symptoms. We show that a zebrafish mutant in ETFDH, xavier, and fibroblast cells from MADD patients demonstrate similar mitochondrial and metabolic abnormalities, including reduced oxidative phosphorylation, increased aerobic glycolysis, and upregulation of the PPARG-ERK pathway. This metabolic dysfunction is associated with aberrant neural proliferation in xav, in addition to other neural phenotypes and paralysis. Strikingly, a PPARG antagonist attenuates aberrant neural proliferation and alleviates paralysis in xav, while PPARG agonists increase neural proliferation in wild type embryos. These results show that mitochondrial dysfunction, leading to an increase in aerobic glycolysis, affects neurogenesis through the PPARG-ERK pathway, a potential target for therapeutic intervention.

  6. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats.

    Science.gov (United States)

    Reygner, Julie; Lichtenberger, Lydia; Elmhiri, Ghada; Dou, Samir; Bahi-Jaber, Narges; Rhazi, Larbi; Depeint, Flore; Bach, Veronique; Khorsi-Cauet, Hafida; Abdennebi-Najar, Latifa

    2016-01-01

    Increasing evidence indicates that chlorpyrifos (CPF), an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1) or 3.5 mg/kg/day (CPF3.5) with free access to inulin (10g/L in drinking water). Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR) expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs) in the colon, were analyzed at postnatal day 60 in the offspring (PND 60). CPF3.5 increased offspring's birth body weight (BW) but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA) production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

  7. Inulin Supplementation Lowered the Metabolic Defects of Prolonged Exposure to Chlorpyrifos from Gestation to Young Adult Stage in Offspring Rats.

    Directory of Open Access Journals (Sweden)

    Julie Reygner

    Full Text Available Increasing evidence indicates that chlorpyrifos (CPF, an organophosphorus insecticide, is involved in metabolic disorders. We assess the hypothesis whether supplementation with prebiotics from gestation to adulthood, through a modulation of microbiota composition and fermentative activity, alleviates CPF induced metabolic disorders of 60 days old offspring. 5 groups of Wistar rats, from gestation until weaning, received two doses of CPF pesticide: 1 mg/kg/day (CPF1 or 3.5 mg/kg/day (CPF3.5 with free access to inulin (10g/L in drinking water. Then male pups received the same treatment as dams. Metabolic profile, leptin sensitivity, insulin receptor (IR expression in liver, gut microbiota composition and short chain fatty acid composition (SCFAs in the colon, were analyzed at postnatal day 60 in the offspring (PND 60. CPF3.5 increased offspring's birth body weight (BW but decreased BW at PND60. Inulin supplementation restored the BW at PND 60 to control levels. Hyperinsulinemia and decrease in insulin receptor β in liver were seen in CPF1 exposed rats. In contrast, hyperglycemia and decrease in insulin level were found in CPF3.5 rats. Inulin restored the levels of some metabolic parameters in CPF groups to ranges comparable with the controls. The total bacterial population, short chain fatty acid (SCFA production and butyrate levels were enhanced in CPF groups receiving inulin. Our data indicate that developmental exposure to CPF interferes with metabolism with dose related effects evident at adulthood. By modulating microbiota population and fermentative activity, inulin corrected adult metabolic disorders of rats exposed to CPF during development. Prebiotics supply may be thus considered as a novel nutritional strategy to counteract insulin resistance and diabetes induced by a continuous pesticide exposure.

  8. Genetic Disruption of Protein Kinase STK25 Ameliorates Metabolic Defects in a Diet-Induced Type 2 Diabetes Model

    DEFF Research Database (Denmark)

    Amrutkar, Manoj; Cansby, Emmelie; Chursa, Urszula

    2015-01-01

    Understanding the molecular networks controlling ectopic lipid deposition, glucose tolerance, and insulin sensitivity is essential to identifying new pharmacological approaches to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a negative regulator...... to the metabolic phenotype of Stk25 transgenic mice, reinforcing the validity of the results. The findings suggest that STK25 deficiency protects against the metabolic consequences of chronic exposure to dietary lipids and highlight the potential of STK25 antagonists for the treatment of type 2 diabetes....

  9. Pantothenate kinase-associated neurodegeneration: altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model.

    Science.gov (United States)

    Brunetti, Dario; Dusi, Sabrina; Morbin, Michela; Uggetti, Andrea; Moda, Fabio; D'Amato, Ilaria; Giordano, Carla; d'Amati, Giulia; Cozzi, Anna; Levi, Sonia; Hayflick, Susan; Tiranti, Valeria

    2012-12-15

    Neurodegeneration with brain iron accumulation (NBIA) comprises a group of neurodegenerative disorders characterized by high brain content of iron and presence of axonal spheroids. Mutations in the PANK2 gene, which encodes pantothenate kinase 2, underlie an autosomal recessive inborn error of coenzyme A metabolism, called pantothenate kinase-associated neurodegeneration (PKAN). PKAN is characterized by dystonia, dysarthria, rigidity and pigmentary retinal degeneration. The pathogenesis of this disorder is poorly understood and, although PANK2 is a mitochondrial protein, perturbations in mitochondrial bioenergetics have not been reported. A knock-out (KO) mouse model of PKAN exhibits retinal degeneration and azoospermia, but lacks any neurological phenotype. The absence of a clinical phenotype has partially been explained by the different cellular localization of the human and murine PANK2 proteins. Here we demonstrate that the mouse Pank2 protein localizes to mitochondria, similar to its human orthologue. Moreover, we show that Pank2-defective neurons derived from KO mice have an altered mitochondrial membrane potential, a defect further corroborated by the observations of swollen mitochondria at the ultra-structural level and by the presence of defective respiration.

  10. Severe infectious diseases of childhood as monogenic inborn errors of immunity

    Science.gov (United States)

    Casanova, Jean-Laurent

    2015-01-01

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications. PMID:26621750

  11. Severe infectious diseases of childhood as monogenic inborn errors of immunity.

    Science.gov (United States)

    Casanova, Jean-Laurent

    2015-12-22

    This paper reviews the developments that have occurred in the field of human genetics of infectious diseases from the second half of the 20th century onward. In particular, it stresses and explains the importance of the recently described monogenic inborn errors of immunity underlying resistance or susceptibility to specific infections. The monogenic component of the genetic theory provides a plausible explanation for the occurrence of severe infectious diseases during primary infection. Over the last 20 y, increasing numbers of life-threatening infectious diseases striking otherwise healthy children, adolescents, and even young adults have been attributed to single-gene inborn errors of immunity. These studies were inspired by seminal but neglected findings in plant and animal infections. Infectious diseases typically manifest as sporadic traits because human genotypes often display incomplete penetrance (most genetically predisposed individuals remain healthy) and variable expressivity (different infections can be allelic at the same locus). Infectious diseases of childhood, once thought to be archetypal environmental diseases, actually may be among the most genetically determined conditions of mankind. This nascent and testable notion has interesting medical and biological implications.

  12. Use of cultured cells with defects of citrulline metabolism in diagnosis and in the study of intercellular communication

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J S

    1985-01-01

    Citrullinemia and argininosuccinic aciduria are two disorders resulting from defects in two consecutive enzymes of the urea cycle, argininosuccinate synthetase and argininosuccinate lyase. Fibroblast cell lines were derived from patients with these disorders and the diagnoses, which had been made on the basis of amino acid levels in plasma and urine, were confirmed by demonstrating that the cell lines were unable to incorporate /sup 14/C-citrulline into protein. DNA from the argininosuccinate synthetase-deficient (ASS-) cells was analysed by restriction enzyme digestion and hybridisation to a cDNA probe which had been cloned from human argininosuccinate synthetase mRNA. No defect in the patient's DNA could be demonstrated, indicating that no major deletions in the argininosuccinate synthetase genes were present in this patient. Co-cultures of the ASS- and argininosuccinate lyase-deficient (ASL-) fibroblasts were able to incorporate /sup 14/C-citrulline into protein. Co-cultures of ASS- and ASL-cells were used as an assay system for measuring intercellular junctional communication. This allowed quantitation of the effects of pH and extra-cellular divalent cations on junctional communication. Tumor promoters such as phorbol esters and organochlorine pesticides have been reported to inhibit intercellular junctional communication in other systems, and this inhibitory activity may be related to the mechanism of tumor promotion. Retinoic acid and other retinoids also inhibited junctional communication, and the inhibitory effects of retinoic acid and TPA were additive. It is concluded that co-cultures of ASS- and ASL-cells constitute a useful system for providing quantitative measurements of intercellular junctional communication under a wide range of experimental conditions.

  13. The use of cultured cells with defects of citrulline metabolism in diagnosis and in the study of intercellular communication

    International Nuclear Information System (INIS)

    Davidson, J.S.

    1985-02-01

    Citrullinemia and argininosuccinic aciduria are two disorders resulting from defects in two consecutive enzymes of the urea cycle, argininosuccinate synthetase and argininosuccinate lyase. Fibroblast cell lines were derived from patients with these disorders and the diagnoses, which had been made on the basis of amino acid levels in plasma and urine, were confirmed by demonstrating that the cell lines were unable to incorporate 14 C-citrulline into protein. DNA from the argininosuccinate synthetase-deficient (ASS-) cells was analysed by restriction enzyme digestion and hybridisation to a cDNA probe which had been cloned from human argininosuccinate synthetase mRNA. No defect in the patient's DNA could be demonstrated, indicating that no major deletions in the argininosuccinate synthetase genes were present in this patient. Co-cultures of the ASS- and argininosuccinate lyase-deficient (ASL-) fibroblasts were able to incorporate 14 C-citrulline into protein. Co-cultures of ASS- and ASL-cells were used as an assay system for measuring intercellular junctional communication. This allowed quantitation of the effects of pH and extra-cellular divalent cations on junctional communication. Tumor promoters such as phorbol esters and organochlorine pesticides have been reported to inhibit intercellular junctional communication in other systems, and this inhibitory activity may be related to the mechanism of tumor promotion. Retinoic acid and other retinoids also inhibited junctional communication, and the inhibitory effects of retinoic acid and TPA were additive. It is concluded that co-cultures of ASS- and ASL-cells constitute a useful system for providing quantitative measurements of intercellular junctional communication under a wide range of experimental conditions

  14. Attempt to Determine the Prevalence of Two Inborn Errors of Primary Bile Acid Synthesis : Results of a European Survey

    NARCIS (Netherlands)

    Jahnel, Jörg; Zöhrer, Evelyn; Fischler, Björn; D'Antiga, Lorenzo; Debray, Dominique; Dezsofi, Antal; Haas, Dorothea; Hadzic, Nedim; Jacquemin, Emmanuel; Lamireau, Thierry; Maggiore, Giuseppe; McKiernan, Pat J; Calvo, Pier Luigi; Verkade, Henkjan J; Hierro, Loreto; McLin, Valerie; Baumann, Ulrich; Gonzales, Emmanuel

    2017-01-01

    Objective: Inborn errors of primary bile acid (BA) synthesis are genetic cholestatic disorders leading to accumulation of atypical BA with deficiency of normal BA. Unless treated with primary BA, chronic liver disease usually progresses to cirrhosis and liver failure before adulthood. We sought to

  15. Effect of inborn versus outborn delivery on clinical outcomes in ventilated preterm neonates: secondary results from the NEOPAIN trial.

    Science.gov (United States)

    Palmer, Kristine G; Kronsberg, Shari S; Barton, Bruce A; Hobbs, Charlotte A; Hall, Richard W; Anand, K J S

    2005-04-01

    The objective of this study was to evaluate the effect of birth center (inborn versus outborn) on morbidity and mortality for preterm neonates (23 to 32 weeks) using data collected prospectively within a uniform protocol. Secondary analyses of data from the NEurologic Outcomes and Pre-emptive Analgesia In Neonates (NEOPAIN) trial (n=898) were performed to evaluate the effect of inborn versus outborn delivery on neonatal outcomes, including the occurrence of severe intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), chronic lung disease (CLD), and mortality. Outborn babies were more likely to have severe IVH (p=0.0005); this increased risk persisted after controlling for severity of illness. When adjustments for antenatal steroids were added, the effect of birth center was no longer significant. Neither the occurrences of PVL or CLD nor mortality were significantly different between the inborn and outborn infants. Outborn babies are more likely to have severe IVH than inborn babies, perhaps because their mothers are less likely to receive antenatal steroids. Improvements in antenatal steroid administration to high-risk women may substantially reduce neonatal morbidity.

  16. Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: phylogenetic timing and the role of hypercarnivory.

    Directory of Open Access Journals (Sweden)

    Binu Shrestha

    2011-03-01

    Full Text Available The domestic cat (Felis catus shows remarkable sensitivity to the adverse effects of phenolic drugs, including acetaminophen and aspirin, as well as structurally-related toxicants found in the diet and environment. This idiosyncrasy results from pseudogenization of the gene encoding UDP-glucuronosyltransferase (UGT 1A6, the major species-conserved phenol detoxification enzyme. Here, we established the phylogenetic timing of disruptive UGT1A6 mutations and explored the hypothesis that gene inactivation in cats was enabled by minimal exposure to plant-derived toxicants. Fixation of the UGT1A6 pseudogene was estimated to have occurred between 35 and 11 million years ago with all extant Felidae having dysfunctional UGT1A6. Out of 22 additional taxa sampled, representative of most Carnivora families, only brown hyena (Parahyaena brunnea and northern elephant seal (Mirounga angustirostris showed inactivating UGT1A6 mutations. A comprehensive literature review of the natural diet of the sampled taxa indicated that all species with defective UGT1A6 were hypercarnivores (>70% dietary animal matter. Furthermore those species with UGT1A6 defects showed evidence for reduced amino acid constraint (increased dN/dS ratios approaching the neutral selection value of 1.0 as compared with species with intact UGT1A6. In contrast, there was no evidence for reduced amino acid constraint for these same species within UGT1A1, the gene encoding the enzyme responsible for detoxification of endogenously generated bilirubin. Our results provide the first evidence suggesting that diet may have played a permissive role in the devolution of a mammalian drug metabolizing enzyme. Further work is needed to establish whether these preliminary findings can be generalized to all Carnivora.

  17. Genomic analysis of an attenuated Chlamydia abortus live vaccine strain reveals defects in central metabolism and surface proteins.

    Science.gov (United States)

    Burall, L S; Rodolakis, A; Rekiki, A; Myers, G S A; Bavoil, P M

    2009-09-01

    Comparative genomic analysis of a wild-type strain of the ovine pathogen Chlamydia abortus and its nitrosoguanidine-induced, temperature-sensitive, virulence-attenuated live vaccine derivative identified 22 single nucleotide polymorphisms unique to the mutant, including nine nonsynonymous mutations, one leading to a truncation of pmpG, which encodes a polymorphic membrane protein, and two intergenic mutations potentially affecting promoter sequences. Other nonsynonymous mutations mapped to a pmpG pseudogene and to predicted coding sequences encoding a putative lipoprotein, a sigma-54-dependent response regulator, a PhoH-like protein, a putative export protein, two tRNA synthetases, and a putative serine hydroxymethyltransferase. One of the intergenic mutations putatively affects transcription of two divergent genes encoding pyruvate kinase and a putative SOS response nuclease, respectively. These observations suggest that the temperature-sensitive phenotype and associated virulence attenuation of the vaccine strain result from disrupted metabolic activity due to altered pyruvate kinase expression and/or alteration in the function of one or more membrane proteins, most notably PmpG and a putative lipoprotein.

  18. Glucotoxicity promotes aberrant activation and mislocalization of Ras-related C3 botulinum toxin substrate 1 [Rac1] and metabolic dysfunction in pancreatic islet β-cells: reversal of such metabolic defects by metformin.

    Science.gov (United States)

    Baidwan, Sartaj; Chekuri, Anil; Hynds, DiAnna L; Kowluru, Anjaneyulu

    2017-11-01

    Emerging evidence suggests that long-term exposure of insulin-secreting pancreatic β-cells to hyperglycemic (HG; glucotoxic) conditions promotes oxidative stress, which, in turn, leads to stress kinase activation, mitochondrial dysfunction, loss of nuclear structure and integrity and cell apoptosis. Original observations from our laboratory have proposed that Rac1 plays a key regulatory role in the generation of oxidative stress and downstream signaling events culminating in the onset of dysfunction of pancreatic β-cells under the duress of metabolic stress. However, precise molecular and cellular mechanisms underlying the metabolic roles of hyperactive Rac1 remain less understood. Using pharmacological and molecular biological approaches, we now report mistargetting of biologically-active Rac1 [GTP-bound conformation] to the nuclear compartment in clonal INS-1 cells, normal rat islets and human islets under HG conditions. Our findings also suggest that such a signaling step is independent of post-translational prenylation of Rac1. Evidence is also presented to highlight novel roles for sustained activation of Rac1 in HG-induced expression of Cluster of Differentiation 36 [CD36], a fatty acid transporter protein, which is implicated in cell apoptosis. Finally, our findings suggest that metformin, a biguanide anti-diabetic drug, at a clinically relevant concentration, prevents β-cell defects [Rac1 activation, nuclear association, CD36 expression, stress kinase and caspase-3 activation, and loss in metabolic viability] under the duress of glucotoxicity. Potential implications of these findings in the context of novel and direct regulation of islet β-cell function by metformin are discussed.

  19. Clinical approach to inherited metabolic disorders in neonates

    NARCIS (Netherlands)

    Saudubray, J. M.; Narcy, C.; Lyonnet, L.; Bonnefont, J. P.; Poll The, B. T.; Munnich, A.

    1990-01-01

    Most inborn errors of intermediary metabolism presenting in the neonatal period fall schematically into three clinical categories: (1) those which lead to a neurological distress 'intoxication type' with a symptom-free interval, vomiting, comas, hypertonia, abnormal movements and frequent humoral

  20. Fatal ammonia toxicity in an adult due to an undiagnosed urea cycle defect: under-recognition of ornithine transcarbamylase deficiency.

    Science.gov (United States)

    Thurlow, Vanessa R; Asafu-Adjaye, Michelle; Agalou, Stamatina; Rahman, Yusof

    2010-05-01

    There is a lack of awareness of acutely presenting inborn errors of metabolism in adults, of which the X-linked urea cycle defect ornithine transcarbamylase (OTC) deficiency is an example, many comparatively mild mutations having been identified. In male hemizygotes clinical manifestations and age at presentation vary and depend on the mutation. In female heterozygotes the clinical spectrum depends on the extent to which the abnormal gene is expressed. Milder versions of the defect may not cause clear clinical symptoms and may remain unrecognized until the person is subjected to an unusually high nitrogen load when they develop severe hyperammonaemia. During acute episodes liver enzymes may be normal or only slightly elevated and occasionally accompanied by coagulopathy, but the key finding is hyperammonaemia. Boys with these milder forms may exhibit abnormal behaviour and be diagnosed with attention deficit hyperactivity disorder. This case illustrates how late presentation of OTC deficiency in a non-specialist centre can be difficult to differentiate from drug abuse, psychiatric illness or encephalopathy. Failure to measure blood ammonia in adults with unexplained key symptoms - particularly prolonged vomiting without diarrhoea and altered mental state/hallucinations, or to recognize the significance of elevated blood ammonia without evidence of liver decompensation can lead to delayed or missed diagnosis.

  1. Birth Defects

    Science.gov (United States)

    A birth defect is a problem that happens while a baby is developing in the mother's body. Most birth defects happen during the first 3 months of ... in the United States is born with a birth defect. A birth defect may affect how the ...

  2. Modeling congenital disease and inborn errors of development in Drosophila melanogaster

    Science.gov (United States)

    Moulton, Matthew J.; Letsou, Anthea

    2016-01-01

    ABSTRACT Fly models that faithfully recapitulate various aspects of human disease and human health-related biology are being used for research into disease diagnosis and prevention. Established and new genetic strategies in Drosophila have yielded numerous substantial successes in modeling congenital disorders or inborn errors of human development, as well as neurodegenerative disease and cancer. Moreover, although our ability to generate sequence datasets continues to outpace our ability to analyze these datasets, the development of high-throughput analysis platforms in Drosophila has provided access through the bottleneck in the identification of disease gene candidates. In this Review, we describe both the traditional and newer methods that are facilitating the incorporation of Drosophila into the human disease discovery process, with a focus on the models that have enhanced our understanding of human developmental disorders and congenital disease. Enviable features of the Drosophila experimental system, which make it particularly useful in facilitating the much anticipated move from genotype to phenotype (understanding and predicting phenotypes directly from the primary DNA sequence), include its genetic tractability, the low cost for high-throughput discovery, and a genome and underlying biology that are highly evolutionarily conserved. In embracing the fly in the human disease-gene discovery process, we can expect to speed up and reduce the cost of this process, allowing experimental scales that are not feasible and/or would be too costly in higher eukaryotes. PMID:26935104

  3. In-Born Radio Frequency Identification Devices for Safeguards Use at Gas-Centrifuge Enrichment Plants

    International Nuclear Information System (INIS)

    Ward, R.; Rosenthal, M.

    2009-01-01

    Global expansion of nuclear power has made the need for improved safeguards measures at Gas Centrifuge Enrichment Plants (GCEPs) imperative. One technology under consideration for safeguards applications is Radio Frequency Identification Devices (RFIDs). RFIDs have the potential to increase IAEA inspector's efficiency and effectiveness either by reducing the number of inspection visits necessary or by reducing inspection effort at those visits. This study assesses the use of RFIDs as an integral component of the 'Option 4' safeguards approach developed by Bruce Moran, U.S. Nuclear Regulatory Commission (NRC), for a model GCEP [1]. A previous analysis of RFIDs was conducted by Jae Jo, Brookhaven National Laboratory (BNL), which evaluated the effectiveness of an RFID tag applied by the facility operator [2]. This paper presents a similar evaluation carried out in the framework of Jo's paper, but it is predicated on the assumption that the RFID tag is applied by the manufacturer at the birth of the cylinder, rather than by the operator. Relevant diversion scenarios are examined to determine if RFIDs increase the effectiveness and/ or efficiency of safeguards in these scenarios. Conclusions on the benefits offered to inspectors by using in-born RFID tagging are presented.

  4. Life-threatening infectious diseases of childhood: single-gene inborn errors of immunity?

    Science.gov (United States)

    Alcaïs, Alexandre; Quintana-Murci, Lluis; Thaler, David S; Schurr, Erwin; Abel, Laurent; Casanova, Jean-Laurent

    2010-12-01

    The hypothesis that inborn errors of immunity underlie infectious diseases is gaining experimental support. However, the apparent modes of inheritance of predisposition or resistance differ considerably among diseases and among studies. A coherent genetic architecture of infectious diseases is lacking. We suggest here that life-threatening infectious diseases in childhood, occurring in the course of primary infection, result mostly from individually rare but collectively diverse single-gene variations of variable clinical penetrance, whereas the genetic component of predisposition to secondary or reactivation infections in adults is more complex. This model is consistent with (i) the high incidence of most infectious diseases in early childhood, followed by a steady decline; (ii) theoretical modeling of the impact of monogenic or polygenic predisposition on the incidence distribution of infectious diseases before reproductive age; (iii) available molecular evidence from both monogenic and complex genetics of infectious diseases in children and adults; (iv) current knowledge of immunity to primary and secondary or latent infections; (v) the state of the art in the clinical genetics of noninfectious pediatric and adult diseases; and (vi) evolutionary data for the genes underlying single-gene and complex disease risk. With the recent advent of new-generation deep resequencing, this model of single-gene variations underlying severe pediatric infectious diseases is experimentally testable. © 2010 New York Academy of Sciences.

  5. Assessment of a pioneer metabolic information service in Brazil.

    Science.gov (United States)

    Brustolin, Silvia; Souza, Carolina; Puga, Ana Cristina; Refosco, Lilia; Pires, Ricardo; Peres, Rossana; Giugliani, Roberto

    2006-01-01

    The Information Service on Inborn Errors of Metabolism (SIEM), a pioneer toll-free service in both Brazil and South America, is based in Porto Alegre, Southern Brazil. SIEM has been operating since October 2001 providing support to health care professionals involved in the diagnosis and management of suspected metabolic diseases. We analyzed the demographic and clinical characteristics of the 376 consults received and followed in the first two and half years of SIEM. Our results show that the suspicion of a metabolic disease was most often associated with neurological symptoms. Among the consults, 24.4% were eventually confirmed as inborn errors of metabolism (IEM), with organic acidurias and amino acid disorders being the two most frequent diagnostic groups. Our conclusion shows this kind of service to provide helpful support to the diagnosis and acute management of IEM, especially to health professionals working in developing countries who are often far from reference centers.

  6. Defect modelling

    International Nuclear Information System (INIS)

    Norgett, M.J.

    1980-01-01

    Calculations, drawing principally on developments at AERE Harwell, of the relaxation about lattice defects are reviewed with emphasis on the techniques required for such calculations. The principles of defect modelling are outlined and various programs developed for defect simulations are discussed. Particular calculations for metals, ionic crystals and oxides, are considered. (UK)

  7. Primary biochemical defect in copper metabolism in mice with a recessive X-linked mutation analogous to Menkes' disease in man

    International Nuclear Information System (INIS)

    Prins, H.W.; Hamer, C.J.A. van den.

    1979-01-01

    The defect in Menkes' disease in man is identical to that in Brindled mice. The defect manifests itself in a accumulation of copper in some tissues, such as renal, intestinal (mucosa and muscle), pancreatic, osseous, muscular, and dermal. Hence a fatal copper deficiency results in other tissues (e.g., hepatic). The copper transport through the intestine is impaired and copper, which circumvents the block in the copper resorption, is irreversibly trapped in the above-mentioned, copper accumulating tissues where it is bound to a cytoplasmatic protein with molecular weight 10,000 daltons, probably the primary cytoplasmatic copper transporting protein. This protein shows a Cu-S absorption band at 250 nm, and the copper:protein ratio is increased. Such copper rich protein was found neither in the kidneys of the unaffected mica nor in the liver of the mice that do have the defect. Three models of the primary defect in Menkes' disease are proposed

  8. Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis

    NARCIS (Netherlands)

    Lee, Jessica J. Y.; Gottlieb, Michael M.; Lever, Jake; Jones, Steven J. M.; Blau, Nenad; van Karnebeek, Clara D. M.; Wasserman, Wyeth W.

    2018-01-01

    Phenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze

  9. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review.

    Science.gov (United States)

    Ray, J G; Laskin, C A

    1999-09-01

    Placental infarction or abruption, recurrent pregnancy loss and pre-eclampsia are thought to arise due to defects within the placental vascular bed. Deficiencies of vitamin B12 and folate, or other abnormalities within the methionine-homocyst(e)ine pathway have been implicated in the development of such placental diseases. We conducted a systematic literature review to quantify the risk of placental disease in the presence of these metabolic defects. Studies were identified through OVID Medline between 1966 and February 1999. Terms relating to the measurement of vitamin B12, folic acid, methylenetetrahydrofolate reductase or homocyst(e)ine were combined with those of pre-eclampsia, placental abruption/infarction or spontaneous and habitual abortion. Human studies comprising both cases and controls and published in the English language were accepted. Their references were explored for other publications. Data were abstracted on the matching of cases with controls, the mean levels of folate, B12 or homocyst(e)ine in each group or the frequency of the homozygous state for the thermolabile variant of methylenetetrahydrofolate reductase. The definition of 'abnormal' for each exposure was noted and the presence or absence of the exposure of interest for each outcome was calculated as an absolute rate with a 95 per cent confidence interval. The crude odds ratios were calculated for each study and then pooled using a random effects model. Eighteen studies were finally included. Eight studies examined the risk of placental abruption/infarction in the presence of vitamin B12 or folate deficiency, or hyperhomocyst(e)inaemia. Folate deficiency was a prominent risk factor for placental abruption/infarction among four studies, though not statistically significant (pooled odds ratio 25.9, 95 per cent CI 0.9-736.3). Hyperhomocyst(e)inaemia was also associated with placental abruption/infarction both without (pooled odds ratio 5.3, 95 per cent CI 1.8-15.9) and with methionine

  10. To bee or not to bee, this is the question…: The inborn numerical competence of humans and honeybees.

    Science.gov (United States)

    Gross, Hans J

    2011-09-01

    Human inborn numerical competence means our ability to recognize object numbers precisely under circumstances which do not allow sequential counting. This archaic process has been called "subitizing," from the Latin "subito" = suddenly, immediately, indicating that the objects in question are presented to test persons only for a fraction of a second in order to prevent counting. In contrast, however, sequential counting, an outstanding cultural achievement of mankind, means to count "1, 2, 3, 4, 5, 6, 7, 8…" without a limit. The following essay will explain how the limit of numerical competence, i.e., the recognition of object numbers without counting, has been determined for humans and how this has been achieved for the first time in case of an invertebrate, the honeybee. Finally, a hypothesis explaining the influence of our limited, inborn numerical competence on counting in our times, e.g., in the Russian language, will be presented. Subitizing versus counting by young Down syndrome infants and autistics and the Savant syndrome will be discussed.

  11. Metabolic Myopathies.

    Science.gov (United States)

    Tarnopolsky, Mark A

    2016-12-01

    Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies. The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing. Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.

  12. Non-decussating retinal-fugal fibre syndrome. An inborn achiasmatic malformation associated with visuotopic misrouting, visual evoked potential ipsilateral asymmetry and nystagmus

    NARCIS (Netherlands)

    Apkarian, P.; Bour, L. J.; Barth, P. G.; Wenniger-Prick, L.; Verbeeten, B.

    1995-01-01

    We report a newly identified syndrome in which nasal retinal fibres fail to decussate due to the inborn absence of an optic chiasm. Visual evoked potential (VEP) assessment and neuro-opththalmic evaluation in two unrelated, non-albino children revealed the unusual visual pathway anomaly in the form

  13. Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia.

    NARCIS (Netherlands)

    Mudd, S.H.; Cerone, R.; Schiaffino, M.C.; Fantasia, A.R.; Minniti, G.; Caruso, U.; Lorini, R.; Watkins, D.; Matiaszuk, N.; Rosenblatt, D.S.; Schwahn, B.; Rozen, R.; Gros, L. Le; Kotb, M.; Capdevila, A.; Luka, Z.; Finkelstein, J.; Tangerman, A.; Stabler, S.P.; Allen, R.; Wagner, C.

    2001-01-01

    This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or

  14. Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.

    Science.gov (United States)

    Scaglia, Fernando; Carter, Susan; O'Brien, William E; Lee, Brendan

    2004-04-01

    Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea. These disorders often result in life-threatening hyperammonemia and hyperglutaminemia. A combination of sodium phenylbutyrate and sodium phenylacetate/benzoate is used in the clinical management of children with urea cycle defects as a glutamine trap, diverting nitrogen from urea synthesis to alternatives routes of excretion. We have observed that patients treated with these compounds have selective branched chain amino acid (BCAA) deficiency despite adequate dietary protein intake. However, the direct effect of alternative therapy on the steady state levels of plasma branched chain amino acids has not been well characterized. We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. Steady-state leucine levels were noted to be significantly lower in treated urea cycle disorder patients when compared to either untreated ornithine transcarbamylase deficiency females or control subjects (Purea cycle disorder patients. These findings suggest that better titration of protein restriction could be achieved with branched chain amino acid supplementation in patients with UCDs who are on alternative route therapy.

  15. Defects and defect processes in nonmetallic solids

    CERN Document Server

    Hayes, W

    2004-01-01

    This extensive survey covers defects in nonmetals, emphasizing point defects and point-defect processes. It encompasses electronic, vibrational, and optical properties of defective solids, plus dislocations and grain boundaries. 1985 edition.

  16. Inborn anemias in mice. Progress report, 1 August 1979-15 July 1980

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, S.E.; Russell, E.S.

    1980-08-01

    Four macrocytic anemias, four hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia are under investigation in mice. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus the wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: (a) characterization of peripheral blood values; (b) determinations of radiosensitivity under a variety of conditions; (c) measurements of iron metabolism and heme synthesis; (d) histological and biochemical study of blood-forming tissue; (e) functional tests of the stem cell component; (f) examination of responses to erythroid stimuli; and (g) transplantation of tissue between individuals of differently affected genotypes.

  17. [Mutants of bacterium Azospirillum brasilense Sp245 with Omegon insertion in mmsB or fabG genes of lipid metabolism are defective in motility and flagellation].

    Science.gov (United States)

    Kovtunov, E A; Shelud'ko, A V; Chernyshova, M P; Petrova, L P; Katsy, E I

    2013-11-01

    Bacteria Azospirillum brasilense have mixed flagellation: in addition to the polar flagellum, numerous lateral flagella are formed in their cells on medium with increased density. Flagella determine the active swimming and swarming capacities of azospirilla. Using A. brasilense Sp245 as an example, we showed that the Omegon-Km artificial transposon insertion into the chromosomal gene for 3-hydroxyisobutyrate dehydrogenase (mmsB) was concurrent with the appearance of significant defects in the formation of polar flagella and with the paralysis of lateral flagella. The Sp245 mutant with the Omegon insertion into the plasmid AZOBR_p1-borne gene for 3-oxoacyl-[acyl-carrier protein]-reductase (fabG) showed the complete loss of flagella and the swarming capacity, as well as significant defects in polar flagellar assembly (though some cells are still motile in liquid medium). The viability of the A. brasilense Sp245 mutants with the Omegon insertion into the mmsB or fabG gene was not reduced. No considerable differences in the fatty acid composition of whole cell lipid extracts were found for the A. brasilense Sp245 strain and its mmsB and fabG mutants.

  18. Defective glucose and lipid metabolism in human immunodeficiency virus-infected patients with lipodystrophy involve liver, muscle tissue and pancreatic beta-cells

    DEFF Research Database (Denmark)

    Haugaard, Steen B; Andersen, Ove; Dela, Flemming

    2005-01-01

    .01. Disposition index (i.e. first-phase insulin response to intravenous glucose multiplied by incremental glucose disposal) was reduced by 46% (P = 0.05) in LIPO compared with the combined groups of NONLIPO and NAIVE, indicating an impaired adaptation of beta-cell function to insulin resistance in LIPO...... of glucose metabolism, lipid metabolism and beta-cell function in lipodystrophic HIV-infected patients. METHODS: [3-3H]glucose was applied during euglycaemic hyperinsulinaemic clamps in association with indirect calorimetry in 43 normoglycaemic HIV-infected patients (18 lipodystrophic patients on HAART (LIPO......), 18 patients without lipodystrophy on HAART (NONLIPO) and seven patients who were naive to antiretroviral therapy (NAIVE) respectively). beta-cell function was evaluated by an intravenous glucose tolerance test. RESULTS: Compared with NONLIPO and NAIVE separately, LIPO displayed markedly reduced ratio...

  19. Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

    Science.gov (United States)

    Xu, Minjun; Kitaura, Yasuyuki; Ishikawa, Takuya; Kadota, Yoshihiro; Terai, Chihaya; Shindo, Daichi; Morioka, Takashi; Ota, Miki; Morishita, Yukako; Ishihara, Kengo; Shimomura, Yoshiharu

    2017-01-01

    It is known that the catabolism of branched-chain amino acids (BCAAs) in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA) dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK). In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice) to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

  20. Endurance performance and energy metabolism during exercise in mice with a muscle-specific defect in the control of branched-chain amino acid catabolism.

    Directory of Open Access Journals (Sweden)

    Minjun Xu

    Full Text Available It is known that the catabolism of branched-chain amino acids (BCAAs in skeletal muscle is suppressed under normal and sedentary conditions but is promoted by exercise. BCAA catabolism in muscle tissues is regulated by the branched-chain α-keto acid (BCKA dehydrogenase complex, which is inactivated by phosphorylation by BCKA dehydrogenase kinase (BDK. In the present study, we used muscle-specific BDK deficient mice (BDK-mKO mice to examine the effect of uncontrolled BCAA catabolism on endurance exercise performance and skeletal muscle energy metabolism. Untrained control and BDK-mKO mice showed the same performance; however, the endurance performance enhanced by 2 weeks of running training was somewhat, but significantly less in BDK-mKO mice than in control mice. Skeletal muscle of BDK-mKO mice had low levels of glycogen. Metabolome analysis showed that BCAA catabolism was greatly enhanced in the muscle of BDK-mKO mice and produced branched-chain acyl-carnitine, which induced perturbation of energy metabolism in the muscle. These results suggest that the tight regulation of BCAA catabolism in muscles is important for homeostasis of muscle energy metabolism and, at least in part, for adaptation to exercise training.

  1. Inborn anemias in mice. Progress report, 1 May 1977--31 July 1978

    Energy Technology Data Exchange (ETDEWEB)

    Bernstein, S.E.; Russell, E.S.

    1978-08-01

    Hereditary anemias of mice have been the chief objects of investigation. At present under study are four macrocytic anemias, four hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, and the autoimmune hemolytic anemia of NZB. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse. Each anemia is studied through: characterization of peripheral blood values, determinations of radiosensitivity under a variety of conditions, measurements of iron metabolism and heme synthesis, histological and biochemical study of blood-forming tissue, functional tests of the stem cell component, examination of responses to erythroid stimuli, and transplantation of tissue between individuals of differently affected genotypes. Considerable effort is devoted to perfection of hematologic, cell culture, and transplant methods to make these techniques useful in dealing with special problems associated with abnormal function.

  2. Embedded defects

    International Nuclear Information System (INIS)

    Barriola, M.; Vachaspati, T.; Bucher, M.

    1994-01-01

    We give a prescription for embedding classical solutions and, in particular, topological defects in field theories which are invariant under symmetry groups that are not necessarily simple. After providing examples of embedded defects in field theories based on simple groups, we consider the electroweak model and show that it contains the Z string and a one-parameter family of strings called the W(α) string. It is argued that although the members of this family are gauge equivalent when considered in isolation, each member becomes physically distinct when multistring configurations are considered. We then turn to the issue of stability of embedded defects and demonstrate the instability of a large class of such solutions in the absence of bound states or condensates. The Z string is shown to be unstable for all values of the Higgs boson mass when θ W =π/4. W strings are also shown to be unstable for a large range of parameters. Embedded monopoles suffer from the Brandt-Neri-Coleman instability. Finally, we connect the electroweak string solutions to the sphaleron

  3. Toxigenic and metabolic causes of ketosis and ketoacidotic syndromes.

    Science.gov (United States)

    Cartwright, Martina M; Hajja, Waddah; Al-Khatib, Sofian; Hazeghazam, Maryam; Sreedhar, Dharmashree; Li, Rebecca Na; Wong-McKinstry, Edna; Carlson, Richard W

    2012-10-01

    Ketoacidotic syndromes are frequently encountered in acute care medicine. This article focuses on ketosis and ketoacidotic syndromes associated with intoxications, alcohol abuse, starvation, and certain dietary supplements as well as inborn errors of metabolism. Although all of these various processes are characterized by the accumulation of ketone bodies and metabolic acidosis, there are differences in the mechanisms, clinical presentations, and principles of therapy for these heterogeneous disorders. Pathophysiologic mechanisms that account for these disorders are presented, as well as guidance regarding identification and management. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Serine biosynthesis and transport defects.

    Science.gov (United States)

    El-Hattab, Ayman W

    2016-07-01

    l-serine is a non-essential amino acid that is biosynthesized via the enzymes phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). Besides its role in protein synthesis, l-serine is a potent neurotrophic factor and a precursor of a number of essential compounds including phosphatidylserine, sphingomyelin, glycine, and d-serine. Serine biosynthesis defects result from impairments of PGDH, PSAT, or PSP leading to systemic serine deficiency. Serine biosynthesis defects present in a broad phenotypic spectrum that includes, at the severe end, Neu-Laxova syndrome, a lethal multiple congenital anomaly disease, intermediately, infantile serine biosynthesis defects with severe neurological manifestations and growth deficiency, and at the mild end, the childhood disease with intellectual disability. A serine transport defect resulting from deficiency of the ASCT1, the main transporter for serine in the central nervous system, has been recently described in children with neurological manifestations that overlap with those observed in serine biosynthesis defects. l-serine therapy may be beneficial in preventing or ameliorating symptoms in serine biosynthesis and transport defects, if started before neurological damage occurs. Herein, we review serine metabolism and transport, the clinical, biochemical, and molecular aspects of serine biosynthesis and transport defects, the mechanisms of these diseases, and the potential role of serine therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study.

    Science.gov (United States)

    Lindheim, Lisa; Bashir, Mina; Münzker, Julia; Trummer, Christian; Zachhuber, Verena; Leber, Bettina; Horvath, Angela; Pieber, Thomas R; Gorkiewicz, Gregor; Stadlbauer, Vanessa; Obermayer-Pietsch, Barbara

    2017-01-01

    Polycystic ovary syndrome (PCOS) is a common female endocrinopathy of unclear origin characterized by hyperandrogenism, oligo-/anovulation, and ovarian cysts. Women with PCOS frequently display overweight, insulin resistance, and systemic low-grade inflammation. We hypothesized that endotoxemia resulting from a leaky gut is associated with inflammation, insulin resistance, fat accumulation, and hyperandrogenemia in PCOS. In this pilot study, we compared the stool microbiome, gut permeability, and inflammatory status of women with PCOS and healthy controls. 16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls. Data processing and microbiome analysis were conducted in mothur and QIIME using different relative abundance cut-offs. Gut barrier integrity, endotoxemia, and inflammatory status were evaluated using serum and stool markers and associations with reproductive, metabolic, and anthropometric parameters were investigated. The stool microbiome of PCOS patients showed a lower diversity and an altered phylogenetic composition compared to controls. We did not observe significant differences in any taxa with a relative abundance>1%. When looking at rare taxa, the relative abundance of bacteria from the phylum Tenericutes, the order ML615J-28 (phylum Tenericutes) and the family S24-7 (phylum Bacteroidetes) was significantly lower and associated with reproductive parameters in PCOS patients. Patients showed alterations in some, but not all markers of gut barrier function and endotoxemia. Patients with PCOS have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters. Gut barrier dysfunction and endotoxemia were not driving factors in this patient cohort, but may contribute to the clinical phenotype in certain PCOS patients.

  6. Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Lisa Lindheim

    Full Text Available Polycystic ovary syndrome (PCOS is a common female endocrinopathy of unclear origin characterized by hyperandrogenism, oligo-/anovulation, and ovarian cysts. Women with PCOS frequently display overweight, insulin resistance, and systemic low-grade inflammation. We hypothesized that endotoxemia resulting from a leaky gut is associated with inflammation, insulin resistance, fat accumulation, and hyperandrogenemia in PCOS. In this pilot study, we compared the stool microbiome, gut permeability, and inflammatory status of women with PCOS and healthy controls.16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls. Data processing and microbiome analysis were conducted in mothur and QIIME using different relative abundance cut-offs. Gut barrier integrity, endotoxemia, and inflammatory status were evaluated using serum and stool markers and associations with reproductive, metabolic, and anthropometric parameters were investigated.The stool microbiome of PCOS patients showed a lower diversity and an altered phylogenetic composition compared to controls. We did not observe significant differences in any taxa with a relative abundance>1%. When looking at rare taxa, the relative abundance of bacteria from the phylum Tenericutes, the order ML615J-28 (phylum Tenericutes and the family S24-7 (phylum Bacteroidetes was significantly lower and associated with reproductive parameters in PCOS patients. Patients showed alterations in some, but not all markers of gut barrier function and endotoxemia.Patients with PCOS have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters. Gut barrier dysfunction and endotoxemia were not driving factors in this patient cohort, but may contribute to the clinical phenotype in certain PCOS patients.

  7. Cerebral ketone body metabolism.

    Science.gov (United States)

    Morris, A A M

    2005-01-01

    Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids. The rate of cerebral KB metabolism depends primarily on the concentration in blood; high concentrations occur during fasting and on a high-fat diet. Cerebral KB metabolism is also regulated by the permeability of the blood-brain barrier (BBB), which depends on the abundance of monocarboxylic acid transporters (MCT1). The BBB's permeability to KBs increases with fasting in humans. In rats, permeability increases during the suckling period, but human neonates have not been studied. Monocarboxylic acid transporters are also present in the plasma membranes of neurons and glia but their role in regulating KB metabolism is uncertain. Finally, the rate of cerebral KB metabolism depends on the activities of the relevant enzymes in brain. The activities vary with age in rats, but reliable results are not available for humans. Cerebral KB metabolism in humans differs from that in the rat in several respects. During fasting, for example, KBs supply more of the brain's energy in humans than in the rat. Conversely, KBs are probably used more extensively in the brain of suckling rats than in human neonates. These differences complicate the interpretation of rodent studies. Most patients with inborn errors of ketogenesis develop normally, suggesting that the only essential role for KBs is as an alternative fuel during illness or prolonged fasting. On the other hand, in HMG-CoA lyase deficiency, imaging generally shows asymptomatic white-matter abnormalities. The ability of KBs to act as an alternative fuel explains the effectiveness of the ketogenic diet in GLUT1 deficiency, but its effectiveness in epilepsy remains unexplained.

  8. Fifteen years experience: Egyptian metabolic lab

    African Journals Online (AJOL)

    Ekram M. Fateen

    2014-08-20

    Aug 20, 2014 ... defective enzymes or transport proteins which results in a block of the metabolic pathway and accumulation ... The detection of metabolic disorder is done ..... [42] Wood TC, Harvey K, Beck M, Burin MG, Chien YH, Church HJ,.

  9. Facts about Birth Defects

    Science.gov (United States)

    ... label> Information For… Media Policy Makers Facts about Birth Defects Language: English (US) Español (Spanish) Recommend on ... having a baby born without a birth defect. Birth Defects Are Common Every 4 ½ minutes, a ...

  10. Neural Tube Defects

    Science.gov (United States)

    Neural tube defects are birth defects of the brain, spine, or spinal cord. They happen in the ... that she is pregnant. The two most common neural tube defects are spina bifida and anencephaly. In ...

  11. Defective carbohydrate metabolism in multiple sclerosis

    OpenAIRE

    Mathur, Deepali

    2015-01-01

    La esclerosis múltiple (EM) es una enfermedad crónica del sistema nervioso central (SNC) en el que episodios repetidos de inflamación (bortes), dan lugar a inflamación que conduce a la interrupción de la vaina de mielina por daños producidos en la misma. Junto a este fenómeno de inflación focal, existe una inflamación difusa en el SNC, que unida a la anterior, dará lugar a que aparezca un proceso de neurodegeneración, que será el responsable último de la afectación axonal y neuronal difusa qu...

  12. Insulin resistance and postreceptor changes of liver metabolism in fat-fed mice

    DEFF Research Database (Denmark)

    Hedeskov, Carl Jørgen; Capito, Kirsten; Hansen, Svend Erik

    1992-01-01

    Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet......Medicinsk biokemi, animal diabetes, insulin resistance, postreceptor defects, liver metabolism, high-fat diet...

  13. Craniotomy Frontal Bone Defect

    African Journals Online (AJOL)

    2018-03-01

    Mar 1, 2018 ... Defect reconstruction and fixation of the graft: The defect of ... where all loose fragments of fractured frontal bone was removed via the ... Mandible. • Ilium. • Allograft ... pediatric patients owing to skull growth. Thus, autologous ...

  14. Congenital platelet function defects

    Science.gov (United States)

    ... pool disorder; Glanzmann's thrombasthenia; Bernard-Soulier syndrome; Platelet function defects - congenital ... Congenital platelet function defects are bleeding disorders that cause reduced platelet function. Most of the time, people with these disorders have ...

  15. Defect of the Eyelids.

    Science.gov (United States)

    Lu, Guanning Nina; Pelton, Ron W; Humphrey, Clinton D; Kriet, John David

    2017-08-01

    Eyelid defects disrupt the complex natural form and function of the eyelids and present a surgical challenge. Detailed knowledge of eyelid anatomy is essential in evaluating a defect and composing a reconstructive plan. Numerous reconstructive techniques have been described, including primary closure, grafting, and a variety of local flaps. This article describes an updated reconstructive ladder for eyelid defects that can be used in various permutations to solve most eyelid defects. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Point defects in solids

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    The principal properties of point defects are studied: thermodynamics, electronic structure, interactions with etended defects, production by irradiation. Some measuring methods are presented: atomic diffusion, spectroscopic methods, diffuse scattering of neutron and X rays, positron annihilation, molecular dynamics. Then points defects in various materials are investigated: ionic crystals, oxides, semiconductor materials, metals, intermetallic compounds, carbides, nitrides [fr

  17. Fibrous metaphyseal defects

    International Nuclear Information System (INIS)

    Ritschl, P.; Hajek, P.C.; Pechmann, U.

    1989-01-01

    Sixteen patients with fibrous metaphyseal defects were examined with both plain radiography and magnetic resonance (MR) imaging. Depending on the age of the fibrous metaphyseal defects, characteristic radiomorphologic changes were found which correlated well with MR images. Following intravenous Gadolinium-DTPA injection, fibrous metaphyseal defects invariably exhibited a hyperintense border and signal enhancement. (orig./GDG)

  18. Birth Defects (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Birth Defects KidsHealth / For Parents / Birth Defects What's in ... Prevented? Print en español Anomalías congénitas What Are Birth Defects? While still in the womb, some babies ...

  19. Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.

    Science.gov (United States)

    Watson, Emma; MacNeil, Lesley T; Arda, H Efsun; Zhu, Lihua Julie; Walhout, Albertha J M

    2013-03-28

    Expression profiles are tailored according to dietary input. However, the networks that control dietary responses remain largely uncharacterized. Here, we combine forward and reverse genetic screens to delineate a network of 184 genes that affect the C. elegans dietary response to Comamonas DA1877 bacteria. We find that perturbation of a mitochondrial network composed of enzymes involved in amino acid metabolism and the TCA cycle affects the dietary response. In humans, mutations in the corresponding genes cause inborn diseases of amino acid metabolism, most of which are treated by dietary intervention. We identify several transcription factors (TFs) that mediate the changes in gene expression upon metabolic network perturbations. Altogether, our findings unveil a transcriptional response system that is poised to sense dietary cues and metabolic imbalances, illustrating extensive communication between metabolic networks in the mitochondria and gene regulatory networks in the nucleus. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Human diseases associated with defective DNA repair

    International Nuclear Information System (INIS)

    Friedberg, E.C.; Ehmann, U.K.; Williams, J.I.

    1979-01-01

    The observations on xeroderma pigmentosum (XP) cells in culture were the first indications of defective DNA repair in association with human disease. Since then, a wealth of information on DNA repair in XP, and to a lesser extent in other diseases, has accumulated in the literature. Rather than clarifying the understanding of DNA repair mechanisms in normal cells and of defective DNA repair in human disease, the literature suggests an extraordinary complexity of both of the phenomena. In this review a number of discrete human diseases are considered separately. An attempt was made to systematically describe the pertinent clinical features and cellular and biochemical defects in these diseases, with an emphasis on defects in DNA metabolism, particularly DNA repair. Wherever possible observations have been correlated and unifying hypotheses presented concerning the nature of the basic defect(s) in these diseases. Discussions of the following diseases are presented: XP, ataxia telangiectasia; Fanconi's anemia; Hutchinson-Gilford progeria syndrome; Bloom's syndrome, Cockayne's syndrome; Down's syndrome; retinoblastoma; chronic lymphocytic leukemia; and other miscellaneous human diseases with possble DNA repair defects

  1. What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?

    Science.gov (United States)

    Liss, D B; Paden, M S; Schwarz, E S; Mullins, M E

    2013-11-01

    Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR "acetaminophen"). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients

  2. Dirichlet topological defects

    International Nuclear Information System (INIS)

    Carroll, S.M.; Trodden, M.

    1998-01-01

    We propose a class of field theories featuring solitonic solutions in which topological defects can end when they intersect other defects of equal or higher dimensionality. Such configurations may be termed open-quotes Dirichlet topological defects,close quotes in analogy with the D-branes of string theory. Our discussion focuses on defects in scalar field theories with either gauge or global symmetries, in 3+1 dimensions; the types of defects considered include walls ending on walls, strings on walls, and strings on strings. copyright 1998 The American Physical Society

  3. Synthetic Defects for Vibrothermography

    Science.gov (United States)

    Renshaw, Jeremy; Holland, Stephen D.; Thompson, R. Bruce; Eisenmann, David J.

    2010-02-01

    Synthetic defects are an important tool used for characterizing the performance of nondestructive evaluation techniques. Viscous material-filled synthetic defects were developed for use in vibrothermography (also known as sonic IR) as a tool to improve inspection accuracy and reliability. This paper describes how the heat-generation response of these VMF synthetic defects is similar to the response of real defects. It also shows how VMF defects can be applied to improve inspection accuracy for complex industrial parts and presents a study of their application in an aircraft engine stator vane.

  4. Defect production in ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J. [Oak Ridge National Lab., TN (United States); Kinoshita, C. [Kyushu Univ. (Japan)

    1997-08-01

    A review is given of several important defect production and accumulation parameters for irradiated ceramics. Materials covered in this review include alumina, magnesia, spinel silicon carbide, silicon nitride, aluminum nitride and diamond. Whereas threshold displacement energies for many ceramics are known within a reasonable level of uncertainty (with notable exceptions being AIN and Si{sub 3}N{sub 4}), relatively little information exists on the equally important parameters of surviving defect fraction (defect production efficiency) and point defect migration energies for most ceramics. Very little fundamental displacement damage information is available for nitride ceramics. The role of subthreshold irradiation on defect migration and microstructural evolution is also briefly discussed.

  5. On holographic defect entropy

    International Nuclear Information System (INIS)

    Estes, John; Jensen, Kristan; O’Bannon, Andy; Tsatis, Efstratios; Wrase, Timm

    2014-01-01

    We study a number of (3+1)- and (2+1)-dimensional defect and boundary conformal field theories holographically dual to supergravity theories. In all cases the defects or boundaries are planar, and the defects are codimension-one. Using holography, we compute the entanglement entropy of a (hemi-)spherical region centered on the defect (boundary). We define defect and boundary entropies from the entanglement entropy by an appropriate background subtraction. For some (3+1)-dimensional theories we find evidence that the defect/boundary entropy changes monotonically under certain renormalization group flows triggered by operators localized at the defect or boundary. This provides evidence that the g-theorem of (1+1)-dimensional field theories generalizes to higher dimensions

  6. Inborn anemias in mice. Progress report to accompany twenty-first renewal proposal, 1 May 1975--30 April 1976

    Energy Technology Data Exchange (ETDEWEB)

    Russell, E.S.; Bernstein, S.E.

    1976-05-15

    Progress is reported on studies on hereditary anemias of mice. At present under study are four macrocytic anemias, four hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, and the autoimmune hemolytic anemia of NZB. Each of these blood dyscrasias is caused by the action of a unique mutant gene, each of which determines the structure of different intracellular molecules, and thus controls a different metabolic process. Thus our wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse.

  7. Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism

    NARCIS (Netherlands)

    Andresen, B. S.; Christensen, E.; Corydon, T. J.; Bross, P.; Pilgaard, B.; Wanders, R. J.; Ruiter, J. P.; Simonsen, H.; Winter, V.; Knudsen, I.; Schroeder, L. D.; Gregersen, N.; Skovby, F.

    2000-01-01

    Acyl-CoA dehydrogenase (ACAD) defects in isoleucine and valine catabolism have been proposed in clinically diverse patients with an abnormal pattern of metabolites in their urine, but they have not been proved enzymatically or genetically, and it is unknown whether one or two ACADs are involved. We

  8. Genital and Urinary Tract Defects

    Science.gov (United States)

    ... conditions > Genital and urinary tract defects Genital and urinary tract defects E-mail to a friend Please fill ... and extra fluids. What problems can genital and urinary tract defects cause? Genital and urinary tract defects affect ...

  9. Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach

    Directory of Open Access Journals (Sweden)

    Swati Chaturvedi

    2016-01-01

    Full Text Available One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches.

  10. Defects in semiconductors

    CERN Document Server

    Romano, Lucia; Jagadish, Chennupati

    2015-01-01

    This volume, number 91 in the Semiconductor and Semimetals series, focuses on defects in semiconductors. Defects in semiconductors help to explain several phenomena, from diffusion to getter, and to draw theories on materials' behavior in response to electrical or mechanical fields. The volume includes chapters focusing specifically on electron and proton irradiation of silicon, point defects in zinc oxide and gallium nitride, ion implantation defects and shallow junctions in silicon and germanium, and much more. It will help support students and scientists in their experimental and theoret

  11. Cardiac protein expression patterns are associated with distinct inborn exercise capacity in non-selectively bred rats

    Directory of Open Access Journals (Sweden)

    L.P. Ribeiro

    2018-01-01

    Full Text Available In the present study, we successfully demonstrated for the first time the existence of cardiac proteomic differences between non-selectively bred rats with distinct intrinsic exercise capacities. A proteomic approach based on two-dimensional gel electrophoresis coupled to mass spectrometry was used to study the left ventricle (LV tissue proteome of rats with distinct intrinsic exercise capacity. Low running performance (LRP and high running performance (HRP rats were categorized by a treadmill exercise test, according to distance run to exhaustion. The running capacity of HRPs was 3.5-fold greater than LRPs. Protein profiling revealed 29 differences between HRP and LRP rats (15 proteins were identified. We detected alterations in components involved in metabolism, antioxidant and stress response, microfibrillar and cytoskeletal proteins. Contractile proteins were upregulated in the LVs of HRP rats (α-myosin heavy chain-6, myosin light chain-1 and creatine kinase, whereas the LVs of LRP rats exhibited upregulation in proteins associated with stress response (aldehyde dehydrogenase 2, α-crystallin B chain and HSPβ-2. In addition, the cytoskeletal proteins desmin and α-actin were upregulated in LRPs. Taken together, our results suggest that the increased contractile protein levels in HRP rats partly accounted for their improved exercise capacity, and that proteins considered risk factors to the development of cardiovascular disease were expressed in higher amounts in LRP animals.

  12. Metallography of defects

    International Nuclear Information System (INIS)

    Borisova, E.A.; Bochvar, G.A.; Brun, M.Ya.

    1980-01-01

    Different types of defects of metallurgical, technological and exploitation origin in intermediate and final products of titanium alloys, are considered. The examples of metallic and nonmetallic inclusions, chemical homogeneity, different grains, bands, cracks, places of searing, porosity are given; methods of detecting the above defects are described. The methods of metallography, X-ray spectral analysis, measuring microhardness are used

  13. Beating Birth Defects

    Centers for Disease Control (CDC) Podcasts

    Each year in the U.S., one in 33 babies is affected by a major birth defect. Women can greatly improve their chances of giving birth to a healthy baby by avoiding some of the risk factors for birth defects before and during pregnancy. In this podcast, Dr. Stuart Shapira discusses ways to improve the chances of giving birth to a healthy baby.

  14. Prolonged platelet preservation by transient metabolic suppression

    NARCIS (Netherlands)

    Badlou, Bahram Alamdary

    2006-01-01

    Introduction: Different clinical studies have shown that transfusion of stored platelets results in better haemostasis in patients with thrombocytopenia with and without a platelet function defect. Objectives: Current preservation procedures aim to optimally preserve the metabolic status of

  15. Defects at oxide surfaces

    CERN Document Server

    Thornton, Geoff

    2015-01-01

    This book presents the basics and characterization of defects at oxide surfaces. It provides a state-of-the-art review of the field, containing information to the various types of surface defects, describes analytical methods to study defects, their chemical activity and the catalytic reactivity of oxides. Numerical simulations of defective structures complete the picture developed. Defects on planar surfaces form the focus of much of the book, although the investigation of powder samples also form an important part. The experimental study of planar surfaces opens the possibility of applying the large armoury of techniques that have been developed over the last half-century to study surfaces in ultra-high vacuum. This enables the acquisition of atomic level data under well-controlled conditions, providing a stringent test of theoretical methods. The latter can then be more reliably applied to systems such as nanoparticles for which accurate methods of characterization of structure and electronic properties ha...

  16. Defects in dilute nitrides

    International Nuclear Information System (INIS)

    Chen, W.M.; Buyanova, I.A.; Tu, C.W.; Yonezu, H.

    2005-01-01

    We provide a brief review our recent results from optically detected magnetic resonance studies of grown-in non-radiative defects in dilute nitrides, i.e. Ga(In)NAs and Ga(Al,In)NP. Defect complexes involving intrinsic defects such as As Ga antisites and Ga i self interstitials were positively identified.Effects of growth conditions, chemical compositions and post-growth treatments on formation of the defects are closely examined. These grown-in defects are shown to play an important role in non-radiative carrier recombination and thus in degrading optical quality of the alloys, harmful to performance of potential optoelectronic and photonic devices based on these dilute nitrides. (author)

  17. Formation of topological defects

    International Nuclear Information System (INIS)

    Vachaspati, T.

    1991-01-01

    We consider the formation of point and line topological defects (monopoles and strings) from a general point of view by allowing the probability of formation of a defect to vary. To investigate the statistical properties of the defects at formation we give qualitative arguments that are independent of any particular model in which such defects occur. These arguments are substantiated by numerical results in the case of strings and for monopoles in two dimensions. We find that the network of strings at formation undergoes a transition at a certain critical density below which there are no infinite strings and the closed-string (loop) distribution is exponentially suppressed at large lengths. The results are contrasted with the results of statistical arguments applied to a box of strings in dynamical equilibrium. We argue that if point defects were to form with smaller probability, the distance between monopoles and antimonopoles would decrease while the monopole-to-monopole distance would increase. We find that monopoles are always paired with antimonopoles but the pairing becomes clean only when the number density of defects is small. A similar reasoning would also apply to other defects

  18. L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.

    Science.gov (United States)

    Choe, Chi-un; Nabuurs, Christine; Stockebrand, Malte C; Neu, Axel; Nunes, Patricia; Morellini, Fabio; Sauter, Kathrin; Schillemeit, Stefan; Hermans-Borgmeyer, Irm; Marescau, Bart; Heerschap, Arend; Isbrandt, Dirk

    2013-01-01

    Phosphorylated creatine (Cr) serves as an energy buffer for ATP replenishment in organs with highly fluctuating energy demand. The central role of Cr in the brain and muscle is emphasized by severe neurometabolic disorders caused by Cr deficiency. Common symptoms of inborn errors of creatine synthesis or distribution include mental retardation and muscular weakness. Human mutations in l-arginine:glycine amidinotransferase (AGAT), the first enzyme of Cr synthesis, lead to severely reduced Cr and guanidinoacetate (GuA) levels. Here, we report the generation and metabolic characterization of AGAT-deficient mice that are devoid of Cr and its precursor GuA. AGAT-deficient mice exhibited decreased fat deposition, attenuated gluconeogenesis, reduced cholesterol levels and enhanced glucose tolerance. Furthermore, Cr deficiency completely protected from the development of metabolic syndrome caused by diet-induced obesity. Biochemical analyses revealed the chronic Cr-dependent activation of AMP-activated protein kinase (AMPK), which stimulates catabolic pathways in metabolically relevant tissues such as the brain, skeletal muscle, adipose tissue and liver, suggesting a mechanism underlying the metabolic phenotype. In summary, our results show marked metabolic effects of Cr deficiency via the chronic activation of AMPK in a first animal model of AGAT deficiency. In addition to insights into metabolic changes in Cr deficiency syndromes, our genetic model reveals a novel mechanism as a potential treatment option for obesity and type 2 diabetes mellitus.

  19. Ventricular Septal Defect (VSD)

    Science.gov (United States)

    ... Call your doctor if your baby or child: Tires easily when eating or playing Is not gaining ... heart procedures. Risk factors Ventricular septal defects may run in families and sometimes may occur with other ...

  20. Birth Defects: Cerebral Palsy

    Science.gov (United States)

    ... Loss > Birth defects & other health conditions > Cerebral palsy Cerebral palsy E-mail to a friend Please fill in ... this page It's been added to your dashboard . Cerebral palsy (also called CP) is a group of conditions ...

  1. Endocardial cushion defect

    Science.gov (United States)

    ... Philadelphia, PA: Elsevier; 2016:chap 426. Kouchoukos NT, Blackstone EH, Hanley FL, Kirklin JK. Atrioventricular septal defect. In: Kouchoukos NT, Blackstone EH, Hanley FL, Kirklin JK, eds. Kirklin/Barratt- ...

  2. Repairing Nanoparticle Surface Defects

    NARCIS (Netherlands)

    Marino, Emanuele; Kodger, Thomas E.; Crisp, R.W.; Timmerman, Dolf; MacArthur, Katherine E.; Heggen, Marc; Schall, Peter

    2017-01-01

    Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We

  3. Point defects in platinum

    International Nuclear Information System (INIS)

    Piercy, G.R.

    1960-01-01

    An investigation was made of the mobility and types of point defect introduced in platinum by deformation in liquid nitrogen, quenching into water from 1600 o C, or reactor irradiation at 50 o C. In all cases the activation energy for motion of the defect was determined from measurements of electrical resistivity. Measurements of density, hardness, and x-ray line broadening were also made there applicable. These experiments indicated that the principal defects remaining in platinum after irradiation were single vacant lattice sites and after quenching were pairs of vacant lattice sites. Those present after deformation In liquid nitrogen were single vacant lattice sites and another type of defect, perhaps interstitial atoms. (author)

  4. In vivo neuro MR spectroscopy: a non-invasive insight into cerebral metabolism

    International Nuclear Information System (INIS)

    Rose, S.; De Zubicaray, G.; Wang, D.; Galloway, G.; Doddrell, D.; Chalk, J.; University of Queensland, Brisbane, QLD; Eagle, S.; Semple, J.

    1999-01-01

    In addition to conventional magnetic resonance imaging (MRI) for examining anatomical structure, in vivo proton magnetic resonance spectroscopy (MRS) is currently being used as a non-invasive clinical tool for monitoring altered brain metabolism. Conditions such as head injury, dementia, multiple sclerosis, tumour, stroke, epilepsy and inborn errors of metabolism are all presently being investigated with MRS. At the Centre for Magnetic Resonance, we are currently undertaking a longitudinal study of dementia progression in Alzheimer's disease (AD) utilising both MRS and volumetric MRI techniques. The aim is to identify metabolic differences between this patient group and normal older adults and to correlate these measures with cognitive function. Cerebral artrophy, or loss of brain matter, together with ventricular enlargement , or enlargement of normally occuring cavities, is clearly present on MRI exams in patients with moderate and severe AD

  5. Defective lysosomal proteolysis and axonal transport are early pathogenic events that worsen with age leading to increased APP metabolism and synaptic Abeta in transgenic APP/PS1 hippocampus.

    Science.gov (United States)

    Torres, Manuel; Jimenez, Sebastian; Sanchez-Varo, Raquel; Navarro, Victoria; Trujillo-Estrada, Laura; Sanchez-Mejias, Elisabeth; Carmona, Irene; Davila, Jose Carlos; Vizuete, Marisa; Gutierrez, Antonia; Vitorica, Javier

    2012-11-22

    Axonal pathology might constitute one of the earliest manifestations of Alzheimer disease. Axonal dystrophies were observed in Alzheimer's patients and transgenic models at early ages. These axonal dystrophies could reflect the disruption of axonal transport and the accumulation of multiple vesicles at local points. It has been also proposed that dystrophies might interfere with normal intracellular proteolysis. In this work, we have investigated the progression of the hippocampal pathology and the possible implication in Abeta production in young (6 months) and aged (18 months) PS1(M146L)/APP(751sl) transgenic mice. Our data demonstrated the existence of a progressive, age-dependent, formation of axonal dystrophies, mainly located in contact with congophilic Abeta deposition, which exhibited tau and neurofilament hyperphosphorylation. This progressive pathology was paralleled with decreased expression of the motor proteins kinesin and dynein. Furthermore, we also observed an early decrease in the activity of cathepsins B and D, progressing to a deep inhibition of these lysosomal proteases at late ages. This lysosomal impairment could be responsible for the accumulation of LC3-II and ubiquitinated proteins within axonal dystrophies. We have also investigated the repercussion of these deficiencies on the APP metabolism. Our data demonstrated the existence of an increase in the amyloidogenic pathway, which was reflected by the accumulation of hAPPfl, C99 fragment, intracellular Abeta in parallel with an increase in BACE and gamma-secretase activities. In vitro experiments, using APPswe transfected N2a cells, demonstrated that any imbalance on the proteolytic systems reproduced the in vivo alterations in APP metabolism. Finally, our data also demonstrated that Abeta peptides were preferentially accumulated in isolated synaptosomes. A progressive age-dependent cytoskeletal pathology along with a reduction of lysosomal and, in minor extent, proteasomal activity could be

  6. Newborn screening of inherited metabolic disorders by tandem mass spectrometry: past, present and future

    Directory of Open Access Journals (Sweden)

    G. Scaturro

    2013-04-01

    Full Text Available Inborn errors of metabolism are inherited biochemical disorders caused by lack of a functional enzyme, transmembrane transporter, or similar protein, which then results in blockage of the corresponding metabolic pathway. Taken individually, inborn errors of metabolism are rare. However, as a group these diseases are relatively frequent and they may account for most of neonatal mortality and need of health resources. The detection of genetic metabolic disorders should occur in a pre-symptomatic phase. Recently, the introduction of the tandem mass spectrometric methods for metabolite analysis has changed our ability to detect intermediates of metabolism in smaller samples and provides the means to detect a large number of metabolic disorders in a single analytical run. Screening panels now include a large number of disorders that may not meet all the criteria that have been used as a reference for years. The rationale behind inclusion or exclusion of a respective disorder is difficult to understand in most cases and it may impose an ethical dilemma. The current organization is an important tool of secondary preventive medicine, essential for children’s healthcare, but the strong inhomogeneity of the regional models of screening applied today create in the Italian neonatal population macroscopic differences with regards to healthcare, which is in effect mainly diversified by the newborn’s place of birth, in possible violation of the universal criterion of the equality of all citizens. Carefully weighed arguments are urgently needed since patient organizations, opinion leaders and politicians are pressing to proceed with expansion of neonatal population screening.

  7. Secondary psychosis induced by metabolic disorders

    Directory of Open Access Journals (Sweden)

    Olivier eBonnot

    2015-05-01

    Full Text Available Metabolic disorders are not well recognized by psychiatrists as a possible source of secondary psychoses. Inborn errors of metabolism (IEMs are not frequent. Although, their prompt diagnosis may lead to suitable treatments. IEMs are well known to paediatricians, in particular for their most serious forms, having an early expression most of the time. Recent years discoveries have unveiled later expression forms, and sometimes, very discreet first physical signs. There is a growing body of evidence that supports the hypothesis that IEMs can manifest as atypical psychiatric symptoms, even in the absence of clear neurological symptoms. In the present review, we propose a detailed overview at schizophrenia-like and autism-like symptoms that can lead practitioners to bear in mind an IEM. Other psychiatric manifestations are also found, as behavioral., cognitive, learning and mood disorders. However, they are less frequent. Ensuring an accurate IEM diagnosis, in front of these psychiatric symptoms should be a priority, in order to grant suitable and valuable treatment for these pathologies.

  8. Norwegian Pitched Roof Defects

    Directory of Open Access Journals (Sweden)

    Lars Gullbrekken

    2016-06-01

    Full Text Available The building constructions investigated in this work are pitched wooden roofs with exterior vertical drainpipes and wooden load-bearing system. The aim of this research is to further investigate the building defects of pitched wooden roofs and obtain an overview of typical roof defects. The work involves an analysis of the building defect archive from the research institute SINTEF Building and Infrastructure. The findings from the SINTEF archive show that moisture is a dominant exposure factor, especially in roof constructions. In pitched wooden roofs, more than half of the defects are caused by deficiencies in design, materials, or workmanship, where these deficiencies allow moisture from precipitation or indoor moisture into the structure. Hence, it is important to increase the focus on robust and durable solutions to avoid defects both from exterior and interior moisture sources in pitched wooden roofs. Proper design of interior ventilation and vapour retarders seem to be the main ways to control entry from interior moisture sources into attic and roof spaces.

  9. Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.

    Science.gov (United States)

    Amaral, Ana I

    2013-07-01

    Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

  10. Repairing Nanoparticle Surface Defects.

    Science.gov (United States)

    Marino, Emanuele; Kodger, Thomas E; Crisp, Ryan W; Timmerman, Dolf; MacArthur, Katherine E; Heggen, Marc; Schall, Peter

    2017-10-23

    Solar devices based on semiconductor nanoparticles require the use of conductive ligands; however, replacing the native, insulating ligands with conductive metal chalcogenide complexes introduces structural defects within the crystalline nanostructure that act as traps for charge carriers. We utilized atomically thin semiconductor nanoplatelets as a convenient platform for studying, both microscopically and spectroscopically, the development of defects during ligand exchange with the conductive ligands Na 4 SnS 4 and (NH 4 ) 4 Sn 2 S 6 . These defects can be repaired via mild chemical or thermal routes, through the addition of L-type ligands or wet annealing, respectively. This results in a higher-quality, conductive, colloidally stable nanomaterial that may be used as the active film in optoelectronic devices. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  11. Defect identification using positrons

    International Nuclear Information System (INIS)

    Beling, C.D.; Fung, S.

    2001-01-01

    The current use of the lifetime and Doppler broadening techniques in defect identification is demonstrated with two studies, the first being the identification of carbon vacancy in n-6H SiC through lifetime spectroscopy, and the second the production of de-hydrogenated voids in α-Si:H through light soaking. Some less conventional ideas are presented for more specific defect identification, namely (i) the amalgamation of lifetime and Doppler techniques with conventional deep level transient spectroscopy in what may be called ''positron-deep level transient spectroscopy'', and (ii) the extraction of more spatial information on vacancy defects by means of what may be called ''Fourier transform Doppler broadening of annihilation radiation spectroscopy'' (orig.)

  12. Quantum computing with defects

    Science.gov (United States)

    Varley, Joel

    2011-03-01

    The development of a quantum computer is contingent upon the identification and design of systems for use as qubits, the basic units of quantum information. One of the most promising candidates consists of a defect in diamond known as the nitrogen-vacancy (NV-1) center, since it is an individually-addressable quantum system that can be initialized, manipulated, and measured with high fidelity at room temperature. While the success of the NV-1 stems from its nature as a localized ``deep-center'' point defect, no systematic effort has been made to identify other defects that might behave in a similar way. We provide guidelines for identifying other defect centers with similar properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate systems. To elucidate these points, we compare electronic structure calculations of the NV-1 center in diamond with those of several deep centers in 4H silicon carbide (SiC). Using hybrid functionals, we report formation energies, configuration-coordinate diagrams, and defect-level diagrams to compare and contrast the properties of these defects. We find that the NC VSi - 1 center in SiC, a structural analog of the NV-1 center in diamond, may be a suitable center with very different optical transition energies. We also discuss how the proposed criteria can be translated into guidelines to discover NV analogs in other tetrahedrally coordinated materials. This work was performed in collaboration with J. R. Weber, W. F. Koehl, B. B. Buckley, A. Janotti, C. G. Van de Walle, and D. D. Awschalom. This work was supported by ARO, AFOSR, and NSF.

  13. Defects in semiconductors

    International Nuclear Information System (INIS)

    Pimentel, C.A.F.

    1983-01-01

    Some problems openned in the study of defects in semiconductors are presented. In particular, a review is made of the more important problems in Si monocrystals of basic and technological interest: microdefects and the presence of oxigen and carbon. The techniques usually utilized in the semiconductor material characterization are emphatized according its potentialities. Some applications of x-ray techniques in the epitaxial shell characterization in heterostructures, importants in electronic optics, are shown. The increase in the efficiency of these defect analysis methods in semiconductor materials with the use of synchrotron x-ray sources is shown. (L.C.) [pt

  14. Neural Tube Defects, Folic Acid and Methylation

    Science.gov (United States)

    Imbard, Apolline; Benoist, Jean-François; Blom, Henk J.

    2013-01-01

    Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects. PMID:24048206

  15. Defect detection module

    International Nuclear Information System (INIS)

    Ernwein, R.; Westermann, G.

    1986-01-01

    The ''defect detector'' module is aimed at exceptional event or state recording. Foreseen for voltage presence monitoring on high supply voltage module of drift chambers, its characteristics can also show up the vanishing of supply voltage and take in account transitory fast signals [fr

  16. Quantum computing with defects.

    Science.gov (United States)

    Weber, J R; Koehl, W F; Varley, J B; Janotti, A; Buckley, B B; Van de Walle, C G; Awschalom, D D

    2010-05-11

    Identifying and designing physical systems for use as qubits, the basic units of quantum information, are critical steps in the development of a quantum computer. Among the possibilities in the solid state, a defect in diamond known as the nitrogen-vacancy (NV(-1)) center stands out for its robustness--its quantum state can be initialized, manipulated, and measured with high fidelity at room temperature. Here we describe how to systematically identify other deep center defects with similar quantum-mechanical properties. We present a list of physical criteria that these centers and their hosts should meet and explain how these requirements can be used in conjunction with electronic structure theory to intelligently sort through candidate defect systems. To illustrate these points in detail, we compare electronic structure calculations of the NV(-1) center in diamond with those of several deep centers in 4H silicon carbide (SiC). We then discuss the proposed criteria for similar defects in other tetrahedrally coordinated semiconductors.

  17. Prevalence of congenital heart defects among 54 Egyptian children ...

    African Journals Online (AJOL)

    Alyaa A. Kotby

    2017-10-19

    Oct 19, 2017 ... metabolic defect results in accumulation of branched-chain amino acids (BCAAs) (leucine, isoleucine and valine) and their keto acids [1]. Amino acids are key nutrient molecules essential for cell growth, survival, and normal function. In addition to providing building blocks for protein synthesis, many amino ...

  18. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation

    Energy Technology Data Exchange (ETDEWEB)

    Jan, Wajanat; Wang, Zhiyue J. [Department of Radiology, University of Pennsylvania School of Medicine, Children' s Hospital of Philadelphia, Pennsylvania (United States); Zimmerman, Robert A. [Department of Radiology, University of Pennsylvania School of Medicine, Children' s Hospital of Philadelphia, Pennsylvania (United States); Department of Radiology, Children' s Hospital of Philadelphia, 34th Street and Civic Center Boulevard, PA 19104, Philadelphia (United States); Berry, Gerard T.; Kaplan, Paige B.; Kaye, Edward M. [Department of Pediatrics, University of Pennsylvania School of Medicine, The Children' s Hospital of Philadelphia, Philadelphia, Pennsylvania (United States)

    2003-06-01

    Maple syrup urine disease (MSUD) is an inborn error of amino acid metabolism, which affects the brain tissue resulting in impairment or death if untreated. Imaging studies have shown reversible brain edema during acute metabolic decompensation. The purpose of this paper is to describe the diffusion-weighted imaging (DWI) and spectroscopy findings during metabolic decompensation and to assess the value of these findings in the prediction of patient outcome. Six patients with the diagnosis of MSUD underwent conventional MR imaging with DWI during acute presentation with metabolic decompensation. Spectroscopy with long TE was performed in four of the six patients. Follow-up examinations were performed after clinical and metabolic recovery. DWI demonstrated marked restriction of proton diffusion compatible with cytotoxic or intramyelinic sheath edema in the brainstem, basal ganglia, thalami, cerebellar and periventricular white matter and the cerebral cortex. This was accompanied by the presence of an abnormal branched-chain amino acids (BCAA) and branched-chain alpha-keto acids (BCKA) peak at 0.9 ppm as well as elevated lactate on proton spectroscopy in all four patients. The changes in all six patients were reversed with treatment without evidence of volume loss or persistent tissue damage. The presence of cytotoxic or intramyelinic edema as evidenced by restricted water diffusion on DWI, with the presence of lactate on spectroscopy, could imply imminent cell death. However, in the context of metabolic decompensation in MSUD, it appears that changes in cell osmolarity and metabolism can reverse completely after metabolic correction. (orig.)

  19. MR diffusion imaging and MR spectroscopy of maple syrup urine disease during acute metabolic decompensation

    International Nuclear Information System (INIS)

    Jan, Wajanat; Wang, Zhiyue J.; Zimmerman, Robert A.; Berry, Gerard T.; Kaplan, Paige B.; Kaye, Edward M.

    2003-01-01

    Maple syrup urine disease (MSUD) is an inborn error of amino acid metabolism, which affects the brain tissue resulting in impairment or death if untreated. Imaging studies have shown reversible brain edema during acute metabolic decompensation. The purpose of this paper is to describe the diffusion-weighted imaging (DWI) and spectroscopy findings during metabolic decompensation and to assess the value of these findings in the prediction of patient outcome. Six patients with the diagnosis of MSUD underwent conventional MR imaging with DWI during acute presentation with metabolic decompensation. Spectroscopy with long TE was performed in four of the six patients. Follow-up examinations were performed after clinical and metabolic recovery. DWI demonstrated marked restriction of proton diffusion compatible with cytotoxic or intramyelinic sheath edema in the brainstem, basal ganglia, thalami, cerebellar and periventricular white matter and the cerebral cortex. This was accompanied by the presence of an abnormal branched-chain amino acids (BCAA) and branched-chain alpha-keto acids (BCKA) peak at 0.9 ppm as well as elevated lactate on proton spectroscopy in all four patients. The changes in all six patients were reversed with treatment without evidence of volume loss or persistent tissue damage. The presence of cytotoxic or intramyelinic edema as evidenced by restricted water diffusion on DWI, with the presence of lactate on spectroscopy, could imply imminent cell death. However, in the context of metabolic decompensation in MSUD, it appears that changes in cell osmolarity and metabolism can reverse completely after metabolic correction. (orig.)

  20. Metabolic Syndrome

    Science.gov (United States)

    Metabolic syndrome is a group of conditions that put you at risk for heart disease and diabetes. These conditions ... agree on the definition or cause of metabolic syndrome. The cause might be insulin resistance. Insulin is ...

  1. Disruption of the folate pathway in zebrafish causes developmental defects

    Directory of Open Access Journals (Sweden)

    Lee Marina S

    2012-04-01

    Full Text Available Abstract Background Folic acid supplementation reduces the risk of neural tube defects and congenital heart defects. The biological mechanisms through which folate prevents birth defects are not well understood. We explore the use of zebrafish as a model system to investigate the role of folate metabolism during development. Results We first identified zebrafish orthologs of 12 human folate metabolic genes. RT-PCR and in situ analysis indicated maternal transcripts supply the embryo with mRNA so that the embryo has an intact folate pathway. To perturb folate metabolism we exposed zebrafish embryos to methotrexate (MTX, a potent inhibitor of dihydrofolate reductase (Dhfr an essential enzyme in the folate metabolic pathway. Embryos exposed to high doses of MTX exhibited developmental arrest prior to early segmentation. Lower doses of MTX resulted in embryos with a shortened anterior-posterior axis and cardiac defects: linear heart tubes or incomplete cardiac looping. Inhibition of dhfr mRNA with antisense morpholino oligonucleotides resulted in embryonic lethality. One function of the folate pathway is to provide essential one-carbon units for dTMP synthesis, a rate-limiting step of DNA synthesis. After 24 hours of exposure to high levels of MTX, mutant embryos continue to incorporate the thymidine analog BrdU. However, additional experiments indicate that these embryos have fewer mitotic cells, as assayed with phospho-histone H3 antibodies, and that treated embryos have perturbed cell cycles. Conclusions Our studies demonstrate that human and zebrafish utilize similar one-carbon pathways. Our data indicate that folate metabolism is essential for early zebrafish development. Zebrafish studies of the folate pathway and its deficiencies could provide insight into the underlying etiology of human birth defects and the natural role of folate in development.

  2. Congenital Heart Defects (For Parents)

    Science.gov (United States)

    ... to be associated with genetic disorders, such as Down syndrome . But the cause of most congenital heart defects isn't known. While they can't be prevented, many treatments are available for the defects and related health ...

  3. Antigravity from a spacetime defect

    OpenAIRE

    Klinkhamer, F. R.; Queiruga, J. M.

    2018-01-01

    We argue that there may exist spacetime defects embedded in Minkowski spacetime, which have negative active gravitational mass. One such spacetime defect then repels a test particle, corresponding to what may be called "antigravity."

  4. Adherence issues in inherited metabolic disorders treated by low natural protein diets

    DEFF Research Database (Denmark)

    MaCdonald, A; van Rijn, M; Feillet, F

    2012-01-01

    Common inborn errors of metabolism treated by low natural protein diets [amino acid (AA) disorders, organic acidemias and urea cycle disorders] are responsible for a collection of diverse clinical symptoms, each condition presenting at different ages with variable severity. Precursor......-free or essential L-AAs are important in all these conditions. Optimal long-term outcome depends on early diagnosis and good metabolic control, but because of the rarity and severity of conditions, randomized controlled trials are scarce. In all of these disorders, it is commonly described that dietary adherence...... on their neuropsychological profile. There are little data about their ability to self-manage their own diet or the success of any formal educational programs that may have been implemented. Trials conducted in non-phenylketonuria (PKU) patients are rare, and the development of specialist L-AAs for non-PKU AA disorders has...

  5. Studies of defects and defect agglomerates by positron annihilation spectroscopy

    DEFF Research Database (Denmark)

    Eldrup, Morten Mostgaard; Singh, B.N.

    1997-01-01

    A brief introduction to positron annihilation spectroscopy (PAS), and in particular lo its use for defect studies in metals is given. Positrons injected into a metal may become trapped in defects such as vacancies, vacancy clusters, voids, bubbles and dislocations and subsequently annihilate from...... the trapped state iri the defect. The annihilation characteristics (e.g., the lifetime of the positron) can be measured and provide information about the nature of the defect (e.g., size, density, morphology). The technique is sensitive to both defect size (in the range from monovacancies up to cavities...

  6. Congenital Heart Defects and CCHD

    Science.gov (United States)

    ... and more. Stony Point, NY 10980 Close X Home > Complications & Loss > Birth defects & other health conditions > Congenital heart defects and ... in congenital heart defects. You have a family history of congenital heart ... syndrome or VCF. After birth Your baby may be tested for CCHD as ...

  7. [Health and socio-educational needs of the families and children with rare metabolic diseases: Qualitative study in a tertiary hospital].

    Science.gov (United States)

    Tejada-Ortigosa, Eva María; Flores-Rojas, Katherine; Moreno-Quintana, Laura; Muñoz-Villanueva, María Carmen; Pérez-Navero, Juan Luis; Gil-Campos, Mercedes

    2018-05-28

    Rare diseases are a challenge for public health due to the lack of information on their magnitude. These include inborn errors of metabolism. The objective of this study was to assess the quality of life and social, health, economic, and educational needs of a group of paediatric patients with inborn errors of metabolism attended to in a hospital. A questionnaire was developed based on the needs and expectations, based mainly on the Andalusian Plan for Rare Diseases. An analysis was performed on the variables of health, socioeconomic, and educational needs of 65 paediatric patients with inborn errors of metabolism. The respondents showed few possibilities to cope with medication (61%), special diet (86%), and other health benefits (79%). Just under half of them (43%) believed that the quality of family life had been greatly reduced since the onset of the disease. The main caregiver was the mother in 61.5% of cases, compared to 1.5% of cases in which it was the father. The primary caregivers had to reduce their working hours or give up their job in 77% of cases. The multidisciplinary treatment is affected by the inability of families to cope with a high cost, as well as with difficult access to these resources. In addition, there is great impact on the quality of life of patients, and their caregivers. Therefore, there is a need to evaluate the results of government health and socio-economic support plans for patients with rare diseases, and make a real response to their needs. Copyright © 2018. Publicado por Elsevier España, S.L.U.

  8. Immobile defects in ferroelastic walls: Wall nucleation at defect sites

    Science.gov (United States)

    He, X.; Salje, E. K. H.; Ding, X.; Sun, J.

    2018-02-01

    Randomly distributed, static defects are enriched in ferroelastic domain walls. The relative concentration of defects in walls, Nd, follows a power law distribution as a function of the total defect concentration C: N d ˜ C α with α = 0.4 . The enrichment Nd/C ranges from ˜50 times when C = 10 ppm to ˜3 times when C = 1000 ppm. The resulting enrichment is due to nucleation at defect sites as observed in large scale MD simulations. The dynamics of domain nucleation and switching is dependent on the defect concentration. Their energy distribution follows the power law with exponents during yield between ɛ ˜ 1.82 and 2.0 when the defect concentration increases. The power law exponent is ɛ ≈ 2.7 in the plastic regime, independent of the defect concentration.

  9. Benign gastric filling defect

    International Nuclear Information System (INIS)

    Oh, K. K.; Lee, Y. H.; Cho, O. K.; Park, C. Y.

    1979-01-01

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  10. Benign gastric filling defect

    Energy Technology Data Exchange (ETDEWEB)

    Oh, K. K.; Lee, Y. H.; Cho, O. K.; Park, C. Y. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  11. Benign gastric filling defect

    Energy Technology Data Exchange (ETDEWEB)

    Oh, K K; Lee, Y H; Cho, O K; Park, C Y [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1979-06-15

    The gastric lesion is a common source of complaints to Orientals, however, evaluation of gastric symptoms and laboratory examination offer little specific aid in the diagnosis of gastric diseases. Thus roentgenography of gastrointestinal tract is one of the most reliable method for detail diagnosis. On double contract study of stomach, gastric filling defect is mostly caused by malignant gastric cancer, however, other benign lesions can cause similar pictures which can be successfully treated by surgery. 66 cases of benign causes of gastric filling defect were analyzed at this point of view, which was verified pathologically by endoscope or surgery during recent 7 years in Yensei University College of Medicine, Severance Hospital. The characteristic radiological picture of each disease was discussed for precise radiologic diagnosis. 1. Of total 66 cases, there were 52 cases of benign gastric tumor 10 cases of gastric varices, 5 cases of gastric bezoar, 5 cases of corrosive gastritis, 3 cases of granulomatous disease and one case of gastric hematoma. 2. The most frequent causes of benign tumors were adenomatous polyp (35/42) and the next was leiomyoma (4/42). Others were one of case of carcinoid, neurofibroma and cyst. 3. Characteristic of benign adenomatous polyp were relatively small in size, smooth surface and were observed that large size, benign polyp was frequently type IV lesion with a stalk. 4. Submucosal tumors such as leiomyoma needed differential diagnosis with polypoid malignant cancer. However, the characteristic points of differentiation was well circumscribed smooth margined filling defect without definite mucosal destruction on surface. 5. Gastric varices showed multiple lobulated filling defected especially on gastric fundus that changed its size and shape by respiration and posture of patients. Same varices lesions on esophagus and history of liver disease were helpful for easier diagnosis. 6. Gastric bezoar showed well defined movable mass

  12. Surface defects and chiral algebras

    Energy Technology Data Exchange (ETDEWEB)

    Córdova, Clay [School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, NJ 08540 (United States); Gaiotto, Davide [Perimeter Institute for Theoretical Physics,31 Caroline St N, Waterloo, ON N2L 2Y5 (Canada); Shao, Shu-Heng [School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr, Princeton, NJ 08540 (United States)

    2017-05-26

    We investigate superconformal surface defects in four-dimensional N=2 superconformal theories. Each such defect gives rise to a module of the associated chiral algebra and the surface defect Schur index is the character of this module. Various natural chiral algebra operations such as Drinfeld-Sokolov reduction and spectral flow can be interpreted as constructions involving four-dimensional surface defects. We compute the index of these defects in the free hypermultiplet theory and Argyres-Douglas theories, using both infrared techniques involving BPS states, as well as renormalization group flows onto Higgs branches. In each case we find perfect agreement with the predicted characters.

  13. Point defects in nickel

    International Nuclear Information System (INIS)

    Peretto, P.

    1969-01-01

    The defects in electron irradiated nickel (20 deg. K) or neutron irradiated nickel (28 deg. K) are studied by simultaneous analysis using the magnetic after-effect, electron microscopy and electrical resistivity recovery. We use zone refined nickel (99.999 per cent) which, for some experiments, is alloyed with a small amount of iron (for example 0.1 per cent Fe). The temperature dependant electrical recovery may be divided in four stages. The sub-stages I B (31 deg. K), I C (42 deg. K), I D (from to 57 deg. K) and I E (62 deg. K) of stage I are due to the disappearance of single interstitials into vacancies. The interstitial defect has a split configuration with a migration energy of about 0.15 eV. In the close pair which disappears in stage I B the interstitial is found to be in a 3. neighbour position whilst in stage I D it is near the direction from the vacancy. In stage I E there is no longer any interaction between the interstitial and the vacancy. The stage II is due to more complicated interstitial defects: di-interstitials for stage II B (84 deg. K) and larger and larger interstitial loops for the following sub-stages. The loops may be seen by electron microscopy. Impurities can play the role of nucleation centers for the loops. Stages III A (370 deg. K) and III B (376 deg. K) are due to two types of di-vacancies. During stage IV (410 deg. K) the single vacancies migrate. Vacancy type loops and interstitial type loops grow concurrently and disappear at about 800 deg. K as observed by electron microscopy. (author) [fr

  14. Quantitative proteomics suggests metabolic reprogramming during ETHE1 deficiency

    DEFF Research Database (Denmark)

    Sahebekhtiari, Navid; Thomsen, Michelle M.; Sloth, Jens Jørgen

    2016-01-01

    Deficiency of mitochondrial sulfur dioxygenase (ETHE1) causes the severe metabolic disorder ethylmalonic encephalopathy, which is characterized by early-onset encephalopathy and defective cytochrome C oxidase because of hydrogen sulfide accumulation. Although the severe systemic consequences of t...

  15. PORPHYRIN METABOLISM AND LIVER FUNCTION IN THE BANTU

    African Journals Online (AJOL)

    method for the detection of urinary coproporphyrin, Mentz5 calculated that ... defect in porphyrin metabolism which is commonly found in the Bantu could be ..... wood,61 traces of uroporphyrin may be excreted in normal urine. As much as 5 ...

  16. Single ventricle cardiac defect

    International Nuclear Information System (INIS)

    Eren, B.; Turkmen, N.; Fedakar, R.; Cetin, V.

    2010-01-01

    Single ventricle heart is defined as a rare cardiac abnormality with a single ventricle chamber involving diverse functional and physiological defects. Our case is of a ten month-old baby boy who died shortly after admission to the hospital due to vomiting and diarrhoea. Autopsy findings revealed cyanosis of finger nails and ears. Internal examination revealed; large heart, weighing 60 grams, single ventricle, without a septum and upper membranous part. Single ventricle is a rare pathology, hence, this paper aims to discuss this case from a medico-legal point of view. (author)

  17. Cerebellar involvement in metabolic disorders: a pattern-recognition approach

    International Nuclear Information System (INIS)

    Steinlin, M.; Boltshauser, E.; Blaser, S.

    1998-01-01

    Inborn errors of metabolism can affect the cerebellum during development, maturation and later during life. We have established criteria for pattern recognition of cerebellar abnormalities in metabolic disorders. The abnormalities can be divided into four major groups: cerebellar hypoplasia (CH), hyperplasia, cerebellar atrophy (CA), cerebellar white matter abnormalities (WMA) or swelling, and involvement of the dentate nuclei (DN) or cerebellar cortex. CH can be an isolated typical finding, as in adenylsuccinase deficiency, but is also occasionally seen in many other disorders. Differentiation from CH and CA is often difficult, as in carbohydrate deficient glycoprotein syndrome or 2-l-hydroxyglutaric acidaemia. In cases of atrophy the relationship of cerebellar to cerebral atrophy is important. WMA may be diffuse or patchy, frequently predominantly around the DN. Severe swelling of white matter is present during metabolic crisis in maple syrup urine disease. The DN can be affected by metabolite deposition, necrosis, calcification or demyelination. Involvement of cerebellar cortex is seen in infantile neuroaxonal dystrophy. Changes in DN and cerebellar cortex are rather typical and therefore most helpful; additional features should be sought as they are useful in narrowing down the differential diagnosis. (orig.)

  18. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs

    Directory of Open Access Journals (Sweden)

    Wen-I Lee

    2011-12-01

    Full Text Available Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG or nontuberculous mycobacteria (NTM, and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM (CD40L mutation, CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations, chronic granulomatous disease (CGD and hyper IgE recurrent infection syndromes (HIES. The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8 for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one, presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ, which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively

  19. Metabolic flexibility is conserved in diabetic myotubes

    DEFF Research Database (Denmark)

    Gaster, Michael

    2007-01-01

    The purpose of this study was to test the hypothesis that metabolic inflexibility is an intrinsic defect. Glucose and lipid oxidation were studied in human myotubes established from healthy lean and obese subjects and patients with type 2 diabetes (T2D). In lean myotubes, glucose oxidation...... inflexibility described in obese and diabetic patients is not an intrinsic defect; rather, it is based on an extramuscular mechanism (i.e., the inability to vary extracellular fatty acid concentrations during insulin stimulation). Thus, skeletal muscles are metabolic-flexible per se....

  20. Birth defects and genetic disorders among Arab Americans--Michigan, 1992-2003.

    Science.gov (United States)

    Yanni, Emad A; Copeland, Glenn; Olney, Richard S

    2010-06-01

    Birth defects and genetic disorders are leading causes of infant morbidity and mortality in many countries. Population-based data on birth defects among Arab-American children have not been documented previously. Michigan has the second largest Arab-American community in the United States after California. Using data from the Michigan Birth Defects Registry (MBDR), which includes information on parents' country of birth and ancestry, birth prevalences were estimated in offspring of Michigan women of Arab ancestry for 21 major categories of birth defects and 12 congenital endocrine, metabolic, and hereditary disorders. Compared with other non-Hispanic white children in Michigan, Arab-American children had similar or lower birth prevalences of the selected types of structural birth defects, with higher rates of certain hereditary blood disorders and three categories of metabolic disorders. These estimates are important for planning preconception and antenatal health care, genetic counseling, and clinical care for Arab Americans.

  1. Defect detection using transient thermography

    International Nuclear Information System (INIS)

    Mohd Zaki Umar; Ibrahim Ahmad; Ab Razak Hamzah; Wan Saffiey Wan Abdullah

    2008-08-01

    An experimental research had been carried out to study the potential of transient thermography in detecting sub-surface defect of non-metal material. In this research, eight pieces of bakelite material were used as samples. Each samples had a sub-surface defect in the circular shape with different diameters and depths. Experiment was conducted using one-sided Pulsed Thermal technique. Heating of samples were done using 30 kWatt adjustable quartz lamp while infra red (IR) images of samples were recorded using THV 550 IR camera. These IR images were then analysed with ThermofitTMPro software to obtain the Maximum Absolute Differential Temperature Signal value, ΔΤ m ax and the time of its appearance, τ m ax (ΔΤ). Result showed that all defects were able to be detected even for the smallest and deepest defect (diameter = 5 mm and depth = 4 mm). However the highest value of Differential Temperature Signal (ΔΤ m ax), were obtained at defect with the largest diameter, 20 mm and at the shallowest depth, 1 mm. As a conclusion, the sensitivity of the pulsed thermography technique to detect sub-surface defects of bakelite material is proportionately related with the size of defect diameter if the defects are at the same depth. On the contrary, the sensitivity of the pulsed thermography technique inversely related with the depth of defect if the defects have similar diameter size. (Author)

  2. Dipole defects in beryl

    International Nuclear Information System (INIS)

    Holanda, B A; Cordeiro, R C; Blak, A R

    2010-01-01

    Dipole defects in gamma irradiated and thermally treated beryl (Be 3 Al 2 Si 6 O 18 ) samples have been studied using the Thermally Stimulated Depolarization Currents (TSDC) technique. TSDC experiments were performed in pink (morganite), green (emerald), blue (aquamarine) and colourless (goshenite) natural beryl. TSDC spectra present dipole peaks at 190K, 220K, 280K and 310K that change after gamma irradiation and thermal treatments. In morganite samples, for thermal treatments between 700K and 1100K, the 280K peak increase in intensity and the band at 220K disappears. An increase of the 280K peak and a decrease of the 190K peak were observed in the TSDC spectra of morganite after a gamma irradiation of 25kGy performed after the thermal treatments. In the case of emerald samples, thermal treatments enhanced the 280K peak and gamma irradiation partially destroyed this band. The goshenite TSDC spectra present only one band at 280K that is not affected either by thermal treatments or by gamma irradiation. All the observed peaks are of dipolar origin because the intensity of the bands is linearly dependent on the polarization field, behaviour of dipole defects. The systematic study, by means of TSDC measurements, of ionizing irradiation effects and thermal treatments in these crystals makes possible a better understanding of the role played by the impurities in beryl crystals.

  3. Mitochondrial Metabolism in Aging Heart

    Science.gov (United States)

    Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

    2016-01-01

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  4. Computer simulation of defect cluster

    Energy Technology Data Exchange (ETDEWEB)

    Kuramoto, Eiichi [Kyushu Univ., Kasuga, Fukuoka (Japan). Research Inst. for Applied Mechanics

    1996-04-01

    In order to elucidate individual element process of various defects and defect clusters of used materials under irradiation environments, interatomic potential with reliability was investigated. And for comparison with experimental results, it is often required to adopt the temperature effect and to investigate in details mechanism of one dimensional motion of micro conversion loop and so forth using the molecular dynamic (MD) method. Furthermore, temperature effect is also supposed for stable structure of defects and defect clusters, and many problems relating to alloy element are also remained. And, simulation on photon life at the defects and defect clusters thought to be important under comparison with equipment can also be supposed an improvement of effectiveness due to relation to theses products. In this paper, some topics in such flow was extracted to explain them. In particular, future important problems will be potential preparation of alloy, structure, dynamic behavior and limited temperature of intralattice atomic cluster. (G.K.)

  5. Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders

    Directory of Open Access Journals (Sweden)

    Rinki Murphy

    2013-01-01

    Full Text Available Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1 severe, non-syndromic obesity, (2 pancreatic beta cell forms of early-onset diabetes, and (3 severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.

  6. What is Metabolic Syndrome?

    Science.gov (United States)

    ... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

  7. Topological defects in extended inflation

    International Nuclear Information System (INIS)

    Copeland, E.J.; Kolb, E.W.; Chicago Univ., IL; Liddle, A.R.

    1990-04-01

    We consider the production of topological defects, especially cosmic strings, in extended inflation models. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of bubbles when they collide. This mechanism allows a natural combination of inflation and large-scale structure via cosmic strings. 18 refs

  8. Defects in new protective aprons

    International Nuclear Information System (INIS)

    Glaze, S.; LeBlanc, A.D.; Bushong, S.C.

    1984-01-01

    Upon careful examination, several defects have been detected in new protective aprons. The nature of the defects is identified and described. Although the occurrence of such defects has not exceeded 5%, they are significant enough to warrant return of the lead apron to the supplier. It is recommended that the integrity of all new protective aprons be verified upon receipt as well as at yearly intervals

  9. Topological defects in extended inflation

    International Nuclear Information System (INIS)

    Copeland, E.J.; Kolb, E.W.; Liddle, A.R.

    1990-01-01

    We consider the production of topological defects, especially cosmic strings, in extended-inflation models. In extended inflation, the Universe passes through a first-order phase transition via bubble percolation, which naturally allows defects to form at the end of inflation. The correlation length, which determines the number density of the defects, is related to the mean size of the bubbles when they collide. This mechanism allows a natural combination of inflation and large-scale structure via cosmic strings

  10. Evidence that the tri-cellular metabolism of N-acetylaspartate functions as the brain's "operating system": how NAA metabolism supports meaningful intercellular frequency-encoded communications.

    Science.gov (United States)

    Baslow, Morris H

    2010-11-01

    N-acetylaspartate (NAA), an acetylated derivative of L-aspartate (Asp), and N-acetylaspartylglutamate (NAAG), a derivative of NAA and L-glutamate (Glu), are synthesized by neurons in brain. However, neurons cannot catabolize either of these substances, and so their metabolism requires the participation of two other cell types. Neurons release both NAA and NAAG to extra-cellular fluid (ECF) upon stimulation, where astrocytes, the target cells for NAAG, hydrolyze it releasing NAA back into ECF, and oligodendrocytes, the target cells for NAA, hydrolyze it releasing Asp to ECF for recycling to neurons. This sequence is unique as it is the only known amino acid metabolic cycle in brain that requires three cell types for its completion. The results of this cycling are two-fold. First, neuronal metabolic water is transported to ECF for its removal from brain. Second, the rate of neuronal activity is coupled with focal hyperemia, providing stimulated neurons with the energy required for transmission of meaningful frequency-encoded messages. In this paper, it is proposed that the tri-cellular metabolism of NAA functions as the "operating system" of the brain, and is essential for normal cognitive and motor activities. Evidence in support of this hypothesis is provided by the outcomes of two human inborn errors in NAA metabolism.

  11. Metabolic disorders with typical alterations in MRI

    International Nuclear Information System (INIS)

    Warmuth-Metz, M.

    2010-01-01

    The classification of metabolic disorders according to the etiology is not practical for neuroradiological purposes because the underlying defect does not uniformly transform into morphological characteristics. Therefore typical MR and clinical features of some easily identifiable metabolic disorders are presented. Canavan disease, Pelizaeus-Merzbacher disease, Alexander disease, X-chromosomal adrenoleukodystrophy and adrenomyeloneuropathy, mitochondrial disorders, such as MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) and Leigh syndrome as well as L-2-hydroxyglutaric aciduria are presented. (orig.) [de

  12. Polyglutamine toxicity in yeast induces metabolic alterations and mitochondrial defects

    KAUST Repository

    Papsdorf, Katharina; Kaiser, Christoph J. O.; Drazic, Adrian; Grö tzinger, Stefan W.; Haeß ner, Carmen; Eisenreich, Wolfgang; Richter, Klaus

    2015-01-01

    formation. Indeed, we find that in vivo iron concentrations are misbalanced and observe a reduction in the activity of the prominent Fe-S cluster containing protein aconitase. Like in other yeast strains with impaired mitochondria, non-fermentative growth

  13. Gaucher Disease: The Metabolic Defect, Pathophysiology, Phenotypes And Natural History

    Science.gov (United States)

    Baris, Hagit N.; Cohen, Ian J.; Mistry, Pramod K.

    2015-01-01

    Gaucher disease (GD), a prototype lysosomal storage disorder, results from inherited deficiency of lysosomal glucocerebrosidase due to biallelic mutations in GBA. The result is widespread accumulation of macrophages engorged with predominantly lysosomal glucocerebroside. A complex multisystem phenotype arises involving the liver, spleen, bone marrow and occasionally the lungs in type 1 Gaucher disease; in neuronopathic fulminant type 2 and chronic type 3 disease there is in addition progressive neurodegenerative disease. Manifestations of Gaucher disease type 1 (GD1) include hepatosplenomegaly, cytopenia, a complex pattern of bone involvement with avascular osteonecrosis (AVN), osteoporosis, fractures and lytic lesions. Enzyme replacement therapy became the standard of care in 1991, and this has transformed the natural history of GD1. This article reviews the clinical phenotypes of GD, diagnosis, pathophysiology and its natural history. A subsequent chapter discusses the treatment options. PMID:25345088

  14. Computational Modeling of Human Metabolism and Its Application to Systems Biomedicine.

    Science.gov (United States)

    Aurich, Maike K; Thiele, Ines

    2016-01-01

    Modern high-throughput techniques offer immense opportunities to investigate whole-systems behavior, such as those underlying human diseases. However, the complexity of the data presents challenges in interpretation, and new avenues are needed to address the complexity of both diseases and data. Constraint-based modeling is one formalism applied in systems biology. It relies on a genome-scale reconstruction that captures extensive biochemical knowledge regarding an organism. The human genome-scale metabolic reconstruction is increasingly used to understand normal cellular and disease states because metabolism is an important factor in many human diseases. The application of human genome-scale reconstruction ranges from mere querying of the model as a knowledge base to studies that take advantage of the model's topology and, most notably, to functional predictions based on cell- and condition-specific metabolic models built based on omics data.An increasing number and diversity of biomedical questions are being addressed using constraint-based modeling and metabolic models. One of the most successful biomedical applications to date is cancer metabolism, but constraint-based modeling also holds great potential for inborn errors of metabolism or obesity. In addition, it offers great prospects for individualized approaches to diagnostics and the design of disease prevention and intervention strategies. Metabolic models support this endeavor by providing easy access to complex high-throughput datasets. Personalized metabolic models have been introduced. Finally, constraint-based modeling can be used to model whole-body metabolism, which will enable the elucidation of metabolic interactions between organs and disturbances of these interactions as either causes or consequence of metabolic diseases. This chapter introduces constraint-based modeling and describes some of its contributions to systems biomedicine.

  15. Metastable gravity on classical defects

    International Nuclear Information System (INIS)

    Ringeval, Christophe; Rombouts, Jan-Willem

    2005-01-01

    We discuss the realization of metastable gravity on classical defects in infinite-volume extra dimensions. In dilatonic Einstein gravity, it is found that the existence of metastable gravity on the defect core requires violation of the dominant energy condition for codimension N c =2 defects. This is illustrated with a detailed analysis of a six-dimensional hyperstring minimally coupled to dilaton gravity. We present the general conditions under which a codimension N c >2 defect admits metastable modes, and find that they differ from lower codimensional models in that, under certain conditions, they do not require violation of energy conditions to support quasilocalized gravity

  16. Defect Characterization of Pyroelectric Materials

    National Research Council Canada - National Science Library

    Keeble, David

    2002-01-01

    Two methods for identify point defects applicable to the study of technologically relevant pyroelectric oxide materials have been investigated, namely Positron Annihilation Lifetime Spectroscopy (PALS...

  17. Who named the quantum defect?

    International Nuclear Information System (INIS)

    Rau, A.R.P.; Inokuti, M.

    1997-01-01

    The notion of the quantum defect is important in atomic and molecular spectroscopy and also in unifying spectroscopy with collision theory. In the latter context, the quantum defect may be viewed as an ancestor of the phase shift. However, the origin of the term quantum defect does not seem to be explained in standard textbooks. It occurred in a 1921 paper by Schroedinger, preceding quantum mechanics, yet giving the correct meaning as an index of the short-range interactions with the core of an atom. The authors present the early history of the quantum-defect idea, and sketch its recent developments

  18. Fibrous metaphyseal defects

    International Nuclear Information System (INIS)

    Hajek, P.C.; Ritschi, P.; Kramer, J.; Imhof, H.; Karnel, F.

    1988-01-01

    Eighty-two patients (107 fibrous metaphyseal defects [FMDs]) were investigated with standard radiography and MR imaging (N = 15). Twenty-two of these were followed up sequentially up to 10 years (mean, 7.3 years). Histologic studies proved that FMDs originate at the site of insertion of a tendon in the perichondrium of the epiphyseal cartilage. After normal bone growth is regained, all FMDs were found to move diaphysically, following a straight line parallel to the long axis of the FMDs. This line pointed to the insertion of the tendon originally involved, a fact that was proved with MR imaging. Four characteristic stages were found to define a typical radiomorphologic course of an FMD

  19. [Metabolic acidosis].

    Science.gov (United States)

    Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

    2016-01-01

    Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

  20. Substrate kinetics in patients with disorders of skeletal muscle metabolism.

    Science.gov (United States)

    Ørngreen, Mette Cathrine

    2016-07-01

    The main purpose of the following studies was to investigate pathophysiological mechanisms in fat and carbohydrate metabolism and effect of nutritional interventions in patients with metabolic myopathies and in patients with severe muscle wasting. Yet there is no cure for patients with skeletal muscle disorders. The group of patients is heterozygous and this thesis is focused on patients with metabolic myopathies and low muscle mass due to severe muscle wasting. Disorders of fatty acid oxidation (FAO) are, along with myophosphorylase deficiency (McArdle disease), the most common inborn errors of metabolism leading to recurrent episodes of rhabdomyolysis in adults. Prolonged exercise, fasting, and fever are the main triggering factors for rhabdomyolysis in these conditions, and can be complicated by acute renal failure. Patients with low muscle mass are in risk of loosing their functional skills and depend on a wheel chair and respiratory support. We used nutritional interventions and metabolic studies with stable isotope technique and indirect calorimetry in patients with metabolic myopathies and patients with low muscle mass to get information of the metabolism of the investigated diseases, and to gain knowledge of the biochemical pathways of intermediary metabolism in human skeletal muscle. We have shown that patients with fat metabolism disorders in skeletal muscle affecting the transporting enzyme of fat into the mitochondria (carnitine palmitoyltransferase II deficiency) and affecting the enzyme responsible for breakdown of the long-chain fatty acids (very long chain acyl-CoA dehydrogenase deficiency) have a normal fatty acid oxidation at rest, but enzyme activity is too low to increase fatty acid oxidation during exercise. Furthermore, these patients benefit from a carbohydrate rich diet. Oppositely is exercise capacity worsened by a fat-rich diet in these patients. The patients also benefit from IV glucose, however, when glucose is given orally just before

  1. Lumber defect detection by ultrasonics

    Science.gov (United States)

    K. A. McDonald

    1978-01-01

    Ultrasonics, the technology of high-frequency sound, has been developed as a viable means for locating most defects In lumber for use in digital form in decision-making computers. Ultrasonics has the potential for locating surface and internal defects in lumber of all species, green or dry, and rough sawn or surfaced.

  2. Neutron diffraction and lattice defects

    International Nuclear Information System (INIS)

    Hamaguchi, Yoshikazu

    1974-01-01

    Study on lattice defects by neutron diffraction technique is described. Wave length of neutron wave is longer than that of X-ray, and absorption cross-section is small. Number of defects observed by ESR is up to several defects, and the number studied with electron microscopes is more than 100. Information obtained by neutron diffraction concerns the number of defects between these two ranges. For practical analysis, several probable models are selected from the data of ESR or electron microscopes, and most probable one is determined by calculation. Then, defect concentration is obtained from scattering cross section. It is possible to measure elastic scattering exclusively by neutron diffraction. Minimum detectable concentration estimated is about 0.5% and 10 20 - 10 21 defects per unit volume. A chopper and a time of flight system are used as a measuring system. Cold neutrons are obtained from the neutron sources inserted into reactors. Examples of measurements by using similar equipments to PTNS-I system of Japan Atomic Energy Research Institute are presented. Interstitial concentration in the graphite irradiated by fast neutrons is shown. Defects in irradiated MgO were also investigated by measuring scattering cross section. Study of defects in Ge was made by measuring total cross section, and model analysis was performed in comparison with various models. (Kato, T.)

  3. Lectures on cosmic topological defects

    Energy Technology Data Exchange (ETDEWEB)

    Vachaspati, T [Department of Astronomy and Astrophysics, Colaba, Mumbai (India) and Physics Department, Case Western Reserve University, Cleveland (United States)

    2001-11-15

    These lectures review certain topological defects and aspects of their cosmology. Unconventional material includes brief descriptions of electroweak defects, the structure of domain walls in non-Abelian theories, and the spectrum of magnetic monopoles in SU(5) Grand Unified theory. (author)

  4. Toward Intelligent Software Defect Detection

    Science.gov (United States)

    Benson, Markland J.

    2011-01-01

    Source code level software defect detection has gone from state of the art to a software engineering best practice. Automated code analysis tools streamline many of the aspects of formal code inspections but have the drawback of being difficult to construct and either prone to false positives or severely limited in the set of defects that can be detected. Machine learning technology provides the promise of learning software defects by example, easing construction of detectors and broadening the range of defects that can be found. Pinpointing software defects with the same level of granularity as prominent source code analysis tools distinguishes this research from past efforts, which focused on analyzing software engineering metrics data with granularity limited to that of a particular function rather than a line of code.

  5. Holographic Chern-Simons defects

    International Nuclear Information System (INIS)

    Fujita, Mitsutoshi; Melby-Thompson, Charles M.; Meyer, René; Sugimoto, Shigeki

    2016-01-01

    We study SU(N) Yang-Mills-Chern-Simons theory in the presence of defects that shift the Chern-Simons level from a holographic point of view by embedding the system in string theory. The model is a D3-D7 system in Type IIB string theory, whose gravity dual is given by the AdS soliton background with probe D7 branes attaching to the AdS boundary along the defects. We holographically renormalize the free energy of the defect system with sources, from which we obtain the correlation functions for certain operators naturally associated to these defects. We find interesting phase transitions when the separation of the defects as well as the temperature are varied. We also discuss some implications for the Fractional Quantum Hall Effect and for 2-dimensional QCD.

  6. Defect forces, defect couples and path integrals in fracture mechanics

    International Nuclear Information System (INIS)

    Roche, R.L.

    1979-07-01

    In this work, it is shown that the path integrals can be introduced without any reference to the material behavior. The method is based on the definition in a continuous medium of a set of vectors and couples having the dimension of a force or a moment. More precisely, definitions are given of volume defect forces, surface defect forces, volume defect couples, and surface defect couples. This is done with the help of the stress working variation of a particule moving through the solid. The most important result is: the resultant of all the defect forces included in a volume V is the J integral on the surface surrounding V and the moment resultant is the L integral. So these integrals are defined without any assumption on the material constitutive equation. Another result is the material form of the virtual work principle - defect forces are acting like conventional forces in the conventional principles of virtual work. This lead to the introduction of the energy momentum tensor and of the associated couple stress. Application of this method is made to fracture mechanics in studying the defect forces distribution around a crack [fr

  7. Drug Metabolism

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 19; Issue 3. Drug Metabolism: A Fascinating Link Between Chemistry and Biology. Nikhil Taxak Prasad V Bharatam. General Article Volume 19 Issue 3 March 2014 pp 259-282 ...

  8. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    behind metabolic reactions, importance, and consequences with several ... required for drug action. ... lism, which is catalyzed by enzymes present in the above-men- ... catalyze the transfer of one atom of oxygen to a substrate produc-.

  9. Defect assessment benchmark studies

    International Nuclear Information System (INIS)

    Hooton, D.G.; Sharples, J.K.

    1995-01-01

    Assessments of the resistance to fast fracture of the beltline region of a PWR vessel subjected to a pressurized thermal shock (PTS) transient have been carried out using the procedures of French (RCC-M) and German (KTA) design codes, and comparisons made with results obtained using the R6 procedure as applied for Sizewell B. The example chosen for these comparisons is of a generic nature, and is taken as the PTS identified by the Hirsch addendum to the Second Marshall report (1987) as the most severe transient with regard to vessel integrity. All assessment methods show the beltline region of the vessel to be safe from the risk of fast fracture, but by varying factors of safety. These factors are discussed in terms of margins between limiting and reference defect sizes, fracture toughness and stress intensity factor, and material temperature and temperature at the onset of upper-shelf materials behaviour. Based on these studies, consideration is given to issues involved in the harmonization of those sections of the design codes which are concerned with methods for the demonstration of the avoidance of the risk of failure by fast fracture. (author)

  10. Animal metabolism

    International Nuclear Information System (INIS)

    Walburg, H.E.

    1977-01-01

    Studies on placental transport included the following: clearance of tritiated water as a baseline measurement for transport of materials across perfused placentas; transport of organic and inorganic mercury across the perfused placenta of the guinea pig in late gestation; and transport of cadmium across the perfused placenta of the guinea pig in late gestation. Studies on cadmium absorption and metabolism included the following: intestinal absorption and retention of cadmium in neonatal rats; uptake and distribution of an oral dose of cadmium in postweanling male and female, iron-deficient and normal rats; postnatal viability and growth in rat pups after oral cadmium administration during gestation; and the effect of calcium and phosphorus on the absorption and toxicity of cadmium. Studies on gastrointestinal absorption and mineral metabolism included: uptake and distribution of orally administered plutonium complex compounds in male mice; gastrointestinal absorption of 144 Ce in the newborn mouse, rat, and pig; and gastrointestinal absorption of 95 Nb by rats of different ages. Studies on iodine metabolism included the following: influence of thyroid status and thiocyanate on iodine metabolism in the bovine; effects of simulated fallout radiation on iodine metabolism in dairy cattle; and effects of feeding iodine binding agents on iodine metabolism in the calf

  11. Neonatal seizures: the overlap between diagnosis of metabolic disorders and structural abnormalities. Case report

    Directory of Open Access Journals (Sweden)

    Freitas Alessandra

    2003-01-01

    Full Text Available Inborn metabolic errors (IME and cortical developmental malformations are uncommon etiologies of neonatal seizures, however they may represent treatable causes of refractory epilepsy and for this reason must be considered as possible etiological factors. This case report aims to demonstrate the importance of neuroimaging studies in one patient with neonatal seizures, even when there are clues pointing to a metabolic disorder. CASE REPORT: A previously healthy 14 day-old child started presenting reiterated focal motor seizures (FMS which evolved to status epilepticus. Exams showed high serum levels of ammonia and no other abnormalities. A metabolic investigation was conducted with normal results. During follow-up, the patient presented developmental delay and left side hemiparesia. Seizures remained controlled with anti-epileptic drugs for four months, followed by relapse with repetitive FMS on the left side. Temporary improvement was obtained with anti-epileptic drug adjustment. At the age of 6 months, during a new episode of status epilepticus, high ammonia levels were detected. Other metabolic exams remained normal. The child was referred to a video-electroencephalographic monitoring and continuous epileptiform discharges were recorded over the right parasagittal and midline regions, with predominance over the posterior quadrant. A new neuroimaging study was performed and displayed a malformation of cortical development. Our case illustrates that because newborns are prone to present metabolic disarrangement, an unbalance such as hyperammonemia may be a consequence of acute events and conduct to a misdiagnosis of IME.

  12. Spectrum of metabolic myopathies.

    Science.gov (United States)

    Angelini, Corrado

    2015-04-01

    Metabolic myopathies are disorders of utilization of carbohydrates or fat in muscles. The acute nature of energy failure is manifested either by a metabolic crisis with weakness, sometimes associated with respiratory failure, or by myoglobinuria. A typical disorder where permanent weakness occurs is glycogenosis type II (GSDII or Pompe disease) both in infantile and late-onset forms, where respiratory insufficiency is manifested by a large number of cases. In GSDII the pathogenetic mechanism is still poorly understood, and has to be attributed more to structural muscle alterations, possibly in correlation to macro-autophagy, rather than to energetic failure. This review is focused on recent advances about GSDII and its treatment, and the most recent notions about the management and treatment of other metabolic myopathies will be briefly reviewed, including glycogenosis type V (McArdle disease), glycogenosis type III (debrancher enzyme deficiency or Cori disease), CPT-II deficiency, and ETF-dehydrogenase deficiency (also known as riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency or RR-MADD). The discovery of the genetic defect in ETF dehydrogenase confirms the etiology of this syndrome. Other metabolic myopathies with massive lipid storage and weakness are carnitine deficiency, neutral lipid storage-myopathy (NLSD-M), besides RR-MADD. Enzyme replacement therapy is presented with critical consideration and for each of the lipid storage disorders, representative cases and their response to therapy is included. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

  13. Urea cycle disorders: a life-threatening yet treatable cause of metabolic encephalopathy in adults.

    Science.gov (United States)

    Blair, Nicholas F; Cremer, Philip D; Tchan, Michel C

    2015-02-01

    Urea cycle disorders are inborn errors of metabolism that, in rare cases, can present for the first time in adulthood. We report a perplexing presentation in a woman 4 days postpartum of bizarre and out-of-character behaviour interspersed with periods of complete normality. Without any focal neurological signs or abnormality on initial investigations, the diagnosis became clear with the finding of a significantly elevated plasma ammonia level, just as she began to deteriorate rapidly. She improved following intravenous dextrose and lipid emulsion, together with sodium benzoate, arginine and a protein-restricted diet. She remains well 12 months later with no permanent sequelae. Whilst this is a rare presentation of an uncommon disease, it is a treatable disorder and its early diagnosis can prevent a fatal outcome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. A diagnostic algorithm for metabolic myopathies.

    Science.gov (United States)

    Berardo, Andres; DiMauro, Salvatore; Hirano, Michio

    2010-03-01

    Metabolic myopathies comprise a clinically and etiologically diverse group of disorders caused by defects in cellular energy metabolism, including the breakdown of carbohydrates and fatty acids to generate adenosine triphosphate, predominantly through mitochondrial oxidative phosphorylation. Accordingly, the three main categories of metabolic myopathies are glycogen storage diseases, fatty acid oxidation defects, and mitochondrial disorders due to respiratory chain impairment. The wide clinical spectrum of metabolic myopathies ranges from severe infantile-onset multisystemic diseases to adult-onset isolated myopathies with exertional cramps. Diagnosing these diverse disorders often is challenging because clinical features such as recurrent myoglobinuria and exercise intolerance are common to all three types of metabolic myopathy. Nevertheless, distinct clinical manifestations are important to recognize as they can guide diagnostic testing and lead to the correct diagnosis. This article briefly reviews general clinical aspects of metabolic myopathies and highlights approaches to diagnosing the relatively more frequent subtypes (Fig. 1). Fig. 1 Clinical algorithm for patients with exercise intolerance in whom a metabolic myopathy is suspected. CK-creatine kinase; COX-cytochrome c oxidase; CPT-carnitine palmitoyl transferase; cyt b-cytochrome b; mtDNA-mitochondrial DNA; nDNA-nuclear DNA; PFK-phosphofructokinase; PGAM-phosphoglycerate mutase; PGK-phosphoglycerate kinase; PPL-myophosphorylase; RRF-ragged red fibers; TFP-trifunctional protein deficiency; VLCAD-very long-chain acyl-coenzyme A dehydrogenase.

  15. Defect detection based on extreme edge of defective region histogram

    Directory of Open Access Journals (Sweden)

    Zouhir Wakaf

    2018-01-01

    Full Text Available Automatic thresholding has been used by many applications in image processing and pattern recognition systems. Specific attention was given during inspection for quality control purposes in various industries like steel processing and textile manufacturing. Automatic thresholding problem has been addressed well by the commonly used Otsu method, which provides suitable results for thresholding images based on a histogram of bimodal distribution. However, the Otsu method fails when the histogram is unimodal or close to unimodal. Defects have different shapes and sizes, ranging from very small to large. The gray-level distributions of the image histogram can vary between unimodal and multimodal. Furthermore, Otsu-revised methods, like the valley-emphasis method and the background histogram mode extents, which overcome the drawbacks of the Otsu method, require preprocessing steps and fail to use the general threshold for multimodal defects. This study proposes a new automatic thresholding algorithm based on the acquisition of the defective region histogram and the selection of its extreme edge as the threshold value to segment all defective objects in the foreground from the image background. To evaluate the proposed defect-detection method, common standard images for experimentation were used. Experimental results of the proposed method show that the proposed method outperforms the current methods in terms of defect detection.

  16. [Folic acid: Primary prevention of neural tube defects. Literature Review].

    Science.gov (United States)

    Llamas Centeno, M J; Miguélez Lago, C

    2016-03-01

    Neural tube defects (NTD) are the most common congenital malformations of the nervous system, they have a multifactorial etiology, are caused by exposure to chemical, physical or biological toxic agents, factors deficiency, diabetes, obesity, hyperthermia, genetic alterations and unknown causes. Some of these factors are associated with malnutrition by interfering with the folic acid metabolic pathway, the vitamin responsible for neural tube closure. Its deficit produce anomalies that can cause abortions, stillbirths or newborn serious injuries that cause disability, impaired quality of life and require expensive treatments to try to alleviate in some way the alterations produced in the embryo. Folic acid deficiency is considered the ultimate cause of the production of neural tube defects, it is clear the reduction in the incidence of Espina Bifida after administration of folic acid before conception, this leads us to want to further study the action of folic acid and its application in the primary prevention of neural tube defects. More than 40 countries have made the fortification of flour with folate, achieving encouraging data of decrease in the prevalence of neural tube defects. This paper attempts to make a literature review, which clarify the current situation and future of the prevention of neural tube defects.

  17. [Metabolic myopathies].

    Science.gov (United States)

    Papazian, Óscar; Rivas-Chacón, Rafael

    2013-09-06

    To review the metabolic myopathies manifested only by crisis of myalgias, cramps and rigidity of the muscles with decreased voluntary contractions and normal inter crisis neurologic examination in children and adolescents. These metabolic myopathies are autosomic recessive inherited enzymatic deficiencies of the carbohydrates and lipids metabolisms. The end result is a reduction of intra muscle adenosine triphosphate, mainly through mitochondrial oxidative phosphorylation, with decrease of available energy for muscle contraction. The one secondary to carbohydrates intra muscle metabolism disorders are triggered by high intensity brief (fatty acids metabolism disorders are triggered by low intensity prolonged (> 10 min) exercises. The conditions in the first group in order of decreasing frequency are the deficiencies of myophosforilase (GSD V), muscle phosphofructokinase (GSD VII), phosphoglycerate mutase 1 (GSD X) and beta enolase (GSD XIII). The conditions in the second group in order of decreasing frequency are the deficiencies of carnitine palmitoyl transferase II and very long chain acyl CoA dehydrogenase. The differential characteristics of patients in each group and within each group will allow to make the initial presumptive clinical diagnosis in the majority and then to order only the necessary tests to achieve the final diagnosis. Treatment during the crisis includes hydration, glucose and alkalinization of urine if myoglobin in blood and urine are elevated. Prevention includes avoiding exercise which may induce the crisis and fasting. The prognosis is good with the exception of rare cases of acute renal failure due to hipermyoglobinemia because of severe rabdomyolisis.

  18. Protein Homeostasis Defects of Alanine-Glyoxylate Aminotransferase: New Therapeutic Strategies in Primary Hyperoxaluria Type I

    Directory of Open Access Journals (Sweden)

    Angel L. Pey

    2013-01-01

    Full Text Available Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis.

  19. Facts about Congenital Heart Defects

    Science.gov (United States)

    ... types of CHDs. The types marked with a star (*) are considered critical CHDs. Atrial Septal Defect Atrioventricular ... for Disease Control and Prevention Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

  20. Birth Defects Data and Statistics

    Science.gov (United States)

    ... Submit" /> Information For… Media Policy Makers Data & Statistics Recommend on Facebook Tweet Share Compartir On This ... and critical. Read below for the latest national statistics on the occurrence of birth defects in the ...

  1. Defects in semiconductors

    International Nuclear Information System (INIS)

    Tilly, L.

    1993-04-01

    In this thesis, experimental results of the transition metals Ti, V, Nb, Mo, and W as impurity centres in silicon are presented. Transition metal doping was accomplished by ion implantation. Emphasis is put on energy level position, electrical and optical properties of the encountered defect levels. Junction space charge methods (JSCM) such as DLTS, photocapacitance and photocurrent techniques are employed. Three energy levels are found for the 3d-transition metals Ti(E c -0.06eV, E c -0.30eV, E v +0.26) and V(E c -0.21eV, E c -0,48e, E v +0.36eV), and for the 4d-element Nb(E c -0.29eV, E c -0.58eV, E v +0.163eV) in Silicon, whereas only one transition metal induced level is found for Mo(E v +0.30eV) and W(E v +0.38eV) respectively. Electrical and optical characteristics of Si 1-x Ge x ,0.7 7 cm -2 . The solvent Bi, used in the LPE-process, is found to be the dominant impurity element. Furthermore, liquid phase epitaxy of high purity In 0.53 Ga 0.57 As on InP, together with the properties of the Cu-induced acceptor in this material are examined. Free electron concentrations of n=5x10 14 cm -3 and electron Hall-mobilities of μ 77K = 44000 cm 2 /Vs are achieved. The energy level position of the Cu-acceptor is found to be E v +0.025eV. Photoluminescence and Hall-effect measurements, together with JSCM are the main characterization methods used. The band linups of In 0.53 Ga 0.47 As with GaAs and with InP are determined according to the Cu-acceptor energy level position in these materials. Additionally, the hydrostatic pressure dependence of the Cu-acceptor energy level position in In 0.53 Ga 0.47 As is examined. (103 refs.)

  2. Topological defects from the multiverse

    Science.gov (United States)

    Zhang, Jun; Blanco-Pillado, Jose J.; Garriga, Jaume; Vilenkin, Alexander

    2015-05-01

    Many theories of the early universe predict the existence of a multiverse where bubbles continuously nucleate giving rise to observers in their interior. In this paper, we point out that topological defects of several dimensionalities will also be produced in de Sitter like regions of the multiverse. In particular, defects could be spontaneously nucleated in our parent vacuum. We study the evolution of these defects as they collide with and propagate inside of our bubble. We estimate the present distribution of defects in the observable part of the universe. The expected number of such nearby defects turns out to be quite small, even for the highest nucleation rate. We also study collisions of strings and domain walls with our bubble in our past light cone. We obtain simulated full-sky maps of the loci of such collisions, and find their angular size distribution. Similarly to what happens in the case of bubble collisions, the prospect of detecting any collisions of our bubble with ambient defects is greatly enhanced in the case where the cosmological constant of our parent vacuum is much higher than the vacuum energy density during inflation in our bubble.

  3. Topological defects from the multiverse

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jun [Institute of Cosmology, Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States); Blanco-Pillado, Jose J. [Department of Theoretical Physics, University of the Basque Country UPV/EHU, 48080 Bilbao (Spain); IKERBASQUE, Basque Foundation for Science, 48013, Bilbao (Spain); Garriga, Jaume [Departament de Fisica Fonamental i Institut de Ciencies del Cosmos, Universitat de Barcelona, Marti i Franques, 1, 08028, Barcelona (Spain); Vilenkin, Alexander [Institute of Cosmology, Department of Physics and Astronomy, Tufts University, Medford, MA 02155 (United States)

    2015-05-28

    Many theories of the early universe predict the existence of a multiverse where bubbles continuously nucleate giving rise to observers in their interior. In this paper, we point out that topological defects of several dimensionalities will also be produced in de Sitter like regions of the multiverse. In particular, defects could be spontaneously nucleated in our parent vacuum. We study the evolution of these defects as they collide with and propagate inside of our bubble. We estimate the present distribution of defects in the observable part of the universe. The expected number of such nearby defects turns out to be quite small, even for the highest nucleation rate. We also study collisions of strings and domain walls with our bubble in our past light cone. We obtain simulated full-sky maps of the loci of such collisions, and find their angular size distribution. Similarly to what happens in the case of bubble collisions, the prospect of detecting any collisions of our bubble with ambient defects is greatly enhanced in the case where the cosmological constant of our parent vacuum is much higher than the vacuum energy density during inflation in our bubble.

  4. Topological defects from the multiverse

    International Nuclear Information System (INIS)

    Zhang, Jun; Vilenkin, Alexander; Blanco-Pillado, Jose J.; Garriga, Jaume

    2015-01-01

    Many theories of the early universe predict the existence of a multiverse where bubbles continuously nucleate giving rise to observers in their interior. In this paper, we point out that topological defects of several dimensionalities will also be produced in de Sitter like regions of the multiverse. In particular, defects could be spontaneously nucleated in our parent vacuum. We study the evolution of these defects as they collide with and propagate inside of our bubble. We estimate the present distribution of defects in the observable part of the universe. The expected number of such nearby defects turns out to be quite small, even for the highest nucleation rate. We also study collisions of strings and domain walls with our bubble in our past light cone. We obtain simulated full-sky maps of the loci of such collisions, and find their angular size distribution. Similarly to what happens in the case of bubble collisions, the prospect of detecting any collisions of our bubble with ambient defects is greatly enhanced in the case where the cosmological constant of our parent vacuum is much higher than the vacuum energy density during inflation in our bubble

  5. Electrical fingerprint of pipeline defects

    International Nuclear Information System (INIS)

    Mica, Isabella; Polignano, Maria Luisa; Marco, Cinzia De

    2004-01-01

    Pipeline defects are dislocations that connect the source region of the transistor with the drain region. They were widely reported to occur in CMOS, BiCMOS devices and recently in SOI technologies. They can reduce device yield either by affecting the devices functionality or by increasing the current consumption under stand-by conditions. In this work the electrical fingerprint of these dislocations is studied, its purpose is to enable us to identify these defects as the ones responsible for device failure. It is shown that the pipeline defects are responsible for a leakage current from source to drain in the transistors. This leakage has a resistive characteristic and it is lightly modulated by the body bias. It is not sensitive to temperature; vice versa the off-current of a good transistor exhibits the well-known exponential dependence on 1/T. The emission spectrum of these defects was studied and compared with the spectrum of a good transistor. The paper aims to show that the spectrum of a defective transistor is quite peculiar; it shows well defined peaks, whereas the spectrum of a good transistor under saturation conditions is characterized by a broad spectral light emission distribution. Finally the deep-level transient spectroscopy (DLTS) is tried on defective diodes

  6. Energy Metabolism Impairment in Migraine.

    Science.gov (United States)

    Cevoli, Sabina; Favoni, Valentina; Cortelli, Pietro

    2018-06-22

    Migraine is a common disabling neurological disorder which is characterised by recurring headache associated with a variety of sensory and autonomic symptoms. The pathophysiology of migraine remains not entirely understood, although many mechanisms involving the central and peripheral nervous system are now becoming clear. In particular, it is widely accepted that migraine is associated with energy metabolic impairment of the brain. The purpose of this review is to present an update overview of the energy metabolism involvement in the migraine pathophysiology. Several biochemical, morphological and magnetic resonance spectroscopy studies have confirmed the presence of energy production deficiency together with an increment of energy consumption in migraine patients. An increment of energy demand over a certain threshold create metabolic and biochemical preconditions for the onset of the migraine attack. The defect of oxidative energy metabolism in migraine is generalized. It remains to be determined if the mitochondrial deficit in migraine is primary or secondary. Riboflavin and Co-Enzyme Q10, both physiologically implicated in mitochondrial respiratory chain functioning, are effective in migraine prophylaxis, supporting the hypothesis that improving brain energy metabolism may reduce the susceptibility to migraine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Clinical variability in 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency

    NARCIS (Netherlands)

    Ensenauer, Regina; Niederhoff, Helmut; Ruiter, Jos P. N.; Wanders, Ronald J. A.; Schwab, K. Otfried; Brandis, Matthias; Lehnert, Willy

    2002-01-01

    We report the identification of two new 7-year-old patients with 3-hydroxy-2-methylbutyryl-CoA dehydrogenase deficiency, a recently described inborn error of isoleucine metabolism. The defect is localized one step above 3-ketothiolase, resulting in a urinary metabolite pattern similar to that seen

  8. GALACTOSEMIA IN NEWBORN CHILDREN

    Directory of Open Access Journals (Sweden)

    G.V. Yatsyk

    2007-01-01

    Full Text Available Galactosemia is a hereditary disease, the pathogenetic treatment of which is based on dietotherapy. Early diagnosing and the adequate choice of the diet improve the development forecasts for the ill child. The article describes a classical galactosemia case in a newborn. It is shown that despite diagnosing the disease on the second month of life, the adequate selection of etiopathogenetic dietotherapy and etiotropic therapy of the concurrent diseases helped compensate the inborn galactose metabolism defect and optimize the long-term forecast for the child.Key words: inborn metabolism dysfunctions, alactosemia, dietotherapy, newborn children.

  9. Nucleotide Metabolism

    DEFF Research Database (Denmark)

    Martinussen, Jan; Willemoës, M.; Kilstrup, Mogens

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolis...

  10. Investigating host-pathogen behavior and their interaction using genome-scale metabolic network models.

    Science.gov (United States)

    Sadhukhan, Priyanka P; Raghunathan, Anu

    2014-01-01

    Genome Scale Metabolic Modeling methods represent one way to compute whole cell function starting from the genome sequence of an organism and contribute towards understanding and predicting the genotype-phenotype relationship. About 80 models spanning all the kingdoms of life from archaea to eukaryotes have been built till date and used to interrogate cell phenotype under varying conditions. These models have been used to not only understand the flux distribution in evolutionary conserved pathways like glycolysis and the Krebs cycle but also in applications ranging from value added product formation in Escherichia coli to predicting inborn errors of Homo sapiens metabolism. This chapter describes a protocol that delineates the process of genome scale metabolic modeling for analysing host-pathogen behavior and interaction using flux balance analysis (FBA). The steps discussed in the process include (1) reconstruction of a metabolic network from the genome sequence, (2) its representation in a precise mathematical framework, (3) its translation to a model, and (4) the analysis using linear algebra and optimization. The methods for biological interpretations of computed cell phenotypes in the context of individual host and pathogen models and their integration are also discussed.

  11. A Metabolic Signature of Mitochondrial Dysfunction Revealed through a Monogenic Form of Leigh Syndrome

    Directory of Open Access Journals (Sweden)

    Julie Thompson Legault

    2015-11-01

    Full Text Available A decline in mitochondrial respiration represents the root cause of a large number of inborn errors of metabolism. It is also associated with common age-associated diseases and the aging process. To gain insight into the systemic, biochemical consequences of respiratory chain dysfunction, we performed a case-control, prospective metabolic profiling study in a genetically homogenous cohort of patients with Leigh syndrome French Canadian variant, a mitochondrial respiratory chain disease due to loss-of-function mutations in LRPPRC. We discovered 45 plasma and urinary analytes discriminating patients from controls, including classic markers of mitochondrial metabolic dysfunction (lactate and acylcarnitines, as well as unexpected markers of cardiometabolic risk (insulin and adiponectin, amino acid catabolism linked to NADH status (α-hydroxybutyrate, and NAD+ biosynthesis (kynurenine and 3-hydroxyanthranilic acid. Our study identifies systemic, metabolic pathway derangements that can lie downstream of primary mitochondrial lesions, with implications for understanding how the organelle contributes to rare and common diseases.

  12. Computational modeling to predict nitrogen balance during acute metabolic decompensation in patients with urea cycle disorders.

    Science.gov (United States)

    MacLeod, Erin L; Hall, Kevin D; McGuire, Peter J

    2016-01-01

    Nutritional management of acute metabolic decompensation in amino acid inborn errors of metabolism (AA IEM) aims to restore nitrogen balance. While nutritional recommendations have been published, they have never been rigorously evaluated. Furthermore, despite these recommendations, there is a wide variation in the nutritional strategies employed amongst providers, particularly regarding the inclusion of parenteral lipids for protein-free caloric support. Since randomized clinical trials during acute metabolic decompensation are difficult and potentially dangerous, mathematical modeling of metabolism can serve as a surrogate for the preclinical evaluation of nutritional interventions aimed at restoring nitrogen balance during acute decompensation in AA IEM. A validated computational model of human macronutrient metabolism was adapted to predict nitrogen balance in response to various nutritional interventions in a simulated patient with a urea cycle disorder (UCD) during acute metabolic decompensation due to dietary non-adherence or infection. The nutritional interventions were constructed from published recommendations as well as clinical anecdotes. Overall, dextrose alone (DEX) was predicted to be better at restoring nitrogen balance and limiting nitrogen excretion during dietary non-adherence and infection scenarios, suggesting that the published recommended nutritional strategy involving dextrose and parenteral lipids (ISO) may be suboptimal. The implications for patients with AA IEM are that the medical course during acute metabolic decompensation may be influenced by the choice of protein-free caloric support. These results are also applicable to intensive care patients undergoing catabolism (postoperative phase or sepsis), where parenteral nutritional support aimed at restoring nitrogen balance may be more tailored regarding metabolic fuel selection.

  13. Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum

    Science.gov (United States)

    Wanders, Ronald J. A.; Waterham, Hans R.; Ferdinandusse, Sacha

    2016-01-01

    Peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways which include: (1.) etherphospholipid biosynthesis; (2.) fatty acid beta-oxidation; (3.) bile acid synthesis; (4.) docosahexaenoic acid (DHA) synthesis; (5.) fatty acid alpha-oxidation; (6.) glyoxylate metabolism; (7.) amino acid degradation, and (8.) ROS/RNS metabolism. The importance of peroxisomes for human health and development is exemplified by the existence of a large number of inborn errors of peroxisome metabolism in which there is an impairment in one or more of the metabolic functions of peroxisomes. Although the clinical signs and symptoms of affected patients differ depending upon the enzyme which is deficient and the extent of the deficiency, the disorders involved are usually (very) severe diseases with neurological dysfunction and early death in many of them. With respect to the role of peroxisomes in metabolism it is clear that peroxisomes are dependent on the functional interplay with other subcellular organelles to sustain their role in metabolism. Indeed, whereas mitochondria can oxidize fatty acids all the way to CO2 and H2O, peroxisomes are only able to chain-shorten fatty acids and the end products of peroxisomal beta-oxidation need to be shuttled to mitochondria for full oxidation to CO2 and H2O. Furthermore, NADH is generated during beta-oxidation in peroxisomes and beta-oxidation can only continue if peroxisomes are equipped with a mechanism to reoxidize NADH back to NAD+, which is now known to be mediated by specific NAD(H)-redox shuttles. In this paper we describe the current state of knowledge about the functional interplay between peroxisomes and other subcellular compartments notably the mitochondria and endoplasmic reticulum for each of the metabolic pathways in which peroxisomes are involved. PMID:26858947

  14. Dual approaches for defects condensation

    Energy Technology Data Exchange (ETDEWEB)

    Rougemont, Romulo; Grigorio, Leonardo de Souza; Wotzasek, Clovis [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Guimaraes, Marcelo Santos [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil)

    2009-07-01

    Full text. Due to the fact that the QCD running coupling constant becomes larger as we go into the low energy (or large distance) limit of the theory, a perturbative treatment of its infrared (IR) region is impossible. In particular, a formal mathematical demonstration of color confinement and a complete physical understanding of the exact mechanism that confines quarks and gluons are two missing points in our current knowledge of the IR-QCD. It was known that due to the Meissner effect of expulsion of magnetic fields in a electric condensate that usual superconductors should confine magnetic monopoles. That point led to the conjecture that the QCD vacuum could be a condensate of chromomagnetic monopoles, a dual superconductor (DSC). Such a chromomagnetic condensate should be responsible for the dual Meissner effect which is expected to lead to the confinement of color charges immersed in this medium. In dual superconductor models of color confinement, magnetic monopoles appear as topological defects in points of the space where the abelian projection becomes singular. Also, condensation of other kinds of defects such as vortices in superfluids and line-like defects in solids are responsible for a great variety of phase transitions, which once more proves the relevance of the subject. In the present work we review two methods that allow us to approach the condensation of defects: the Kleinert Mechanism (KM) and the Julia-Toulouse Mechanism (JTM). We show that in the limit where the vortex gauge field goes to zero, which we identify as the signature of the condensation of defects in the dual picture, these are two equivalent dual prescriptions for obtaining an effective theory for a phase where defects are condensed, starting from the fundamental theory defined in the normal phase where defects are diluted. (author)

  15. Determination of defect content and defect profile in semiconductor heterostructures

    International Nuclear Information System (INIS)

    Zubiaga, A; Garcia, J A; Plazaola, F; Zuniga-Perez, J; Munoz-Sanjose, V

    2011-01-01

    In this article we present an overview of the technique to obtain the defects depth profile and width of a deposited layer and multilayer based on positron annihilation spectroscopy. In particular we apply the method to ZnO and ZnO/ZnCdO layers deposited on sapphire substrates. After introducing some terminology we first calculate the trend that the W/S parameters of the Doppler broadening measurements must follow, both in a qualitative and quantitative way. From this point we extend the results to calculate the width and defect profiles in deposited layer samples.

  16. Determination of defect content and defect profile in semiconductor heterostructures

    Energy Technology Data Exchange (ETDEWEB)

    Zubiaga, A [Laboratory of Physics, HUT, PO Box 1100, 02015 TKK, Espoo (Finland); Garcia, J A; Plazaola, F [Zientzia eta Teknologia Fakultatea, Euskal Herriko Unbertsitatea, P. K. 644, 48080, Bilbao (Spain); Zuniga-Perez, J; Munoz-Sanjose, V, E-mail: fernando.plazaola@ehu.es [Universitat de Valencia, Departamento de Fisica Aplicada i Electromagnetisme, Dr. Moliner 50, 46100 Burjassot, Valencia (Spain)

    2011-01-10

    In this article we present an overview of the technique to obtain the defects depth profile and width of a deposited layer and multilayer based on positron annihilation spectroscopy. In particular we apply the method to ZnO and ZnO/ZnCdO layers deposited on sapphire substrates. After introducing some terminology we first calculate the trend that the W/S parameters of the Doppler broadening measurements must follow, both in a qualitative and quantitative way. From this point we extend the results to calculate the width and defect profiles in deposited layer samples.

  17. Defects in conformal field theory

    International Nuclear Information System (INIS)

    Billò, Marco; Gonçalves, Vasco; Lauria, Edoardo; Meineri, Marco

    2016-01-01

    We discuss consequences of the breaking of conformal symmetry by a flat or spherical extended operator. We adapt the embedding formalism to the study of correlation functions of symmetric traceless tensors in the presence of the defect. Two-point functions of a bulk and a defect primary are fixed by conformal invariance up to a set of OPE coefficients, and we identify the allowed tensor structures. A correlator of two bulk primaries depends on two cross-ratios, and we study its conformal block decomposition in the case of external scalars. The Casimir equation in the defect channel reduces to a hypergeometric equation, while the bulk channel blocks are recursively determined in the light-cone limit. In the special case of a defect of codimension two, we map the Casimir equation in the bulk channel to the one of a four-point function without defect. Finally, we analyze the contact terms of the stress-tensor with the extended operator, and we deduce constraints on the CFT data. In two dimensions, we relate the displacement operator, which appears among the contact terms, to the reflection coefficient of a conformal interface, and we find unitarity bounds for the latter.

  18. Defects in conformal field theory

    Energy Technology Data Exchange (ETDEWEB)

    Billò, Marco [Dipartimento di Fisica, Università di Torino, and Istituto Nazionale di Fisica Nucleare - sezione di Torino,Via P. Giuria 1 I-10125 Torino (Italy); Gonçalves, Vasco [Centro de Física do Porto,Departamento de Física e Astronomia Faculdade de Ciências da Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto (Portugal); ICTP South American Institute for Fundamental Research Instituto de Física Teórica,UNESP - University Estadual Paulista,Rua Dr. Bento T. Ferraz 271, 01140-070, São Paulo, SP (Brazil); Lauria, Edoardo [Institute for Theoretical Physics, KU Leuven, Celestijnenlaan 200D, B-3001 Leuven (Belgium); Meineri, Marco [Perimeter Institute for Theoretical Physics,Waterloo, Ontario, N2L 2Y5 (Canada); Scuola Normale Superiore, and Istituto Nazionale di Fisica Nucleare - sezione di Pisa,Piazza dei Cavalieri 7 I-56126 Pisa (Italy)

    2016-04-15

    We discuss consequences of the breaking of conformal symmetry by a flat or spherical extended operator. We adapt the embedding formalism to the study of correlation functions of symmetric traceless tensors in the presence of the defect. Two-point functions of a bulk and a defect primary are fixed by conformal invariance up to a set of OPE coefficients, and we identify the allowed tensor structures. A correlator of two bulk primaries depends on two cross-ratios, and we study its conformal block decomposition in the case of external scalars. The Casimir equation in the defect channel reduces to a hypergeometric equation, while the bulk channel blocks are recursively determined in the light-cone limit. In the special case of a defect of codimension two, we map the Casimir equation in the bulk channel to the one of a four-point function without defect. Finally, we analyze the contact terms of the stress-tensor with the extended operator, and we deduce constraints on the CFT data. In two dimensions, we relate the displacement operator, which appears among the contact terms, to the reflection coefficient of a conformal interface, and we find unitarity bounds for the latter.

  19. Metabolic Surgery

    DEFF Research Database (Denmark)

    Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

    2018-01-01

    The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity....... Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further...

  20. Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Sevil Ikinci

    2010-10-01

    Full Text Available Metabolic Syndrome is a combination of risk factors including common etiopathogenesis. These risk factors play different roles in occurence of atherosclerotic diseases, type 2 diabetes, and cancers. Although a compromise can not be achieved on differential diagnosis for MS, the existence of any three criterias enable to diagnose MS. These are abdominal obesity, dislipidemia (hypertrigliceridemia, hypercholesterolemia, and reduced high density lipoprotein hypertension, and elevated fasting blood glucose. According to the results of Metabolic Syndrome Research (METSAR, the overall prevalence of MS in Turkey is 34%; in females 40%, and in males it is 28%. As a result of “Western” diet, and increased frequency of obesity, MS is observed in children and in adolescents both in the world and in Turkey. Resulting in chronic diseases, it is thought that the syndrome can be prevented by healthy lifestyle behaviours. [TAF Prev Med Bull 2010; 9(5.000: 535-540

  1. Cellular metabolism

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Walters, R.A.

    1977-01-01

    Progress is reported on the following research projects: chromatin structure; the use of circular synthetic polydeoxynucleotides as substrates for the study of DNA repair enzymes; human cellular kinetic response following exposure to DNA-interactive compounds; histone phosphorylation and chromatin structure in cell proliferation; photoaddition products induced in chromatin by uv light; pollutants and genetic information transfer; altered RNA metabolism as a function of cadmium accumulation and intracellular distribution in cultured cells; and thymidylate chromophore destruction by water free radicals

  2. Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.

    Science.gov (United States)

    Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

    2015-04-07

    Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.

  3. Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis

    Science.gov (United States)

    Zhang, Yumin; Liu, Gang; Yan, Jingqi; Zhang, Yalin; Li, Bo; Cai, Dongsheng

    2015-01-01

    Metabolic homeostasis is regulated by the brain, whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipids levels. Importantly, this function of metabolic learning requires not only the mushroom body but the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis. PMID:25848677

  4. Detection of paint polishing defects

    Science.gov (United States)

    Rebeggiani, S.; Wagner, M.; Mazal, J.; Rosén, B.-G.; Dahlén, M.

    2018-06-01

    Surface finish plays a major role on perceived product quality, and is the first thing a potential buyer sees. Today end-of-line repairs of the body of cars and trucks are inevitably to secure required surface quality. Defects that occur in the paint shop, like dust particles, are eliminated by manual sanding/polishing which lead to other types of defects when the last polishing step is not performed correctly or not fully completed. One of those defects is known as ‘polishing roses’ or holograms, which are incredibly hard to detect in artificial light but are clearly visible in sunlight. This paper will present the first tests with a measurement set-up newly developed to measure and analyse polishing roses. The results showed good correlations to human visual evaluations where repaired panels were estimated based on the defects’ intensity, severity and viewing angle.

  5. Theory of Defects in Semiconductors

    CERN Document Server

    Drabold, David A

    2007-01-01

    Semiconductor science and technology is the art of defect engineering. The theoretical modeling of defects has improved dramatically over the past decade. These tools are now applied to a wide range of materials issues: quantum dots, buckyballs, spintronics, interfaces, amorphous systems, and many others. This volume presents a coherent and detailed description of the field, and brings together leaders in theoretical research. Today's state-of-the-art, as well as tomorrow’s tools, are discussed: the supercell-pseudopotential method, the GW formalism,Quantum Monte Carlo, learn-on-the-fly molecular dynamics, finite-temperature treatments, etc. A wealth of applications are included, from point defects to wafer bonding or the propagation of dislocation.

  6. Defect CFTs and holographic multiverse

    Energy Technology Data Exchange (ETDEWEB)

    Fiol, Bartomeu, E-mail: bfiol@ub.edu [Departament de Física Fonamental i Institut de Ciències del Cosmos, Universitat de Barcelona, Martí i Franquès 1, 08193 Barcelona (Spain)

    2010-07-01

    We investigate some aspects of a recent proposal for a holographic description of the multiverse. Specifically, we focus on the implications on the suggested duality of the fluctuations of a bubble separating two universes with different cosmological constants. We do so by considering a similar problem in a 2+1 CFT with a codimension one defect, obtained by an M5-brane probe embedding in AdS{sub 4} × S{sup 7}, and studying its spectrum of fluctuations. Our results suggest that the kind of behavior required by the spectrum of bubble fluctuations is not likely to take place in defect CFTs with an AdS dual, although it might be possible if the defect supports a non-unitary theory.

  7. Defect CFTs and holographic multiverse

    International Nuclear Information System (INIS)

    Fiol, Bartomeu

    2010-01-01

    We investigate some aspects of a recent proposal for a holographic description of the multiverse. Specifically, we focus on the implications on the suggested duality of the fluctuations of a bubble separating two universes with different cosmological constants. We do so by considering a similar problem in a 2+1 CFT with a codimension one defect, obtained by an M5-brane probe embedding in AdS 4 × S 7 , and studying its spectrum of fluctuations. Our results suggest that the kind of behavior required by the spectrum of bubble fluctuations is not likely to take place in defect CFTs with an AdS dual, although it might be possible if the defect supports a non-unitary theory

  8. Rail inspection of RCF defects

    Directory of Open Access Journals (Sweden)

    Z. Popović

    2013-10-01

    Full Text Available Rail defects due to rolling contact fatigue (RCF threaten the traffic safety around the world. That hazard is more distinct on railways without adequate maintenance strategy. Realization of interoperability of European railway network demands from every infrastructure manager to have a maintenance plan for the infrastructure subsystem. Besides that, this plan includes rail inspection and strategy against RCF defects. This paper emphasizes the importance of rail inspection and early detection of RCF because the most of RCF crack should be removed in rail grinding campaigns (preventive, cyclical and corrective activities during the whole rail service life.

  9. Defect characterization with positron annihilation

    International Nuclear Information System (INIS)

    Granatelli, L.; Lynn, K.G.

    1980-01-01

    Positron annihilation in metal crystals is reviewed. A brief introduction to the positron annihilation technique is presented first. Then the ability of the positron technique to perform microstructural characterization of four types of lattice defects (vacancies, voids, dislocations, grain boundaries) is discussed. It is frequently not possible to obtain samples that contain only one type of defect in nonnegligible concentrations. Such situations exist for some alloys and for fatigued metal samples. Finally, the current limitations and some future prospects of the technique are presented. 79 references, 14 figures, 1 table

  10. Protein and leucine metabolism in maple syrup urine disease

    International Nuclear Information System (INIS)

    Thompson, G.N.; Bresson, J.L.; Pacy, P.J.; Bonnefont, J.P.; Walter, J.H.; Leonard, J.V.; Saudubray, J.M.; Halliday, D.

    1990-01-01

    Constant infusions of [13C]leucine and [2H5]phenylalanine were used to trace leucine and protein kinetics, respectively, in seven children with maple syrup urine disease (MSUD) and eleven controls matched for age and dietary protein intake. Despite significant elevations of plasma leucine (mean 351 mumol/l, range 224-477) in MSUD subjects, mean whole body protein synthesis [3.78 +/- 0.42 (SD) g.kg-1. 24 h-1] and catabolism (4.07 +/- 0.46) were similar to control values (3.69 +/- 0.50 and 4.09 +/- 0.50, respectively). The relationship between phenylalanine and leucine fluxes was also similar in MSUD subjects (mean phenylalanine-leucine flux ratio 0.35 +/- 0.07) and previously reported adult controls (0.33 +/- 0.02). Leucine oxidation was undetectable in four of the MSUD subjects and very low in the other three (less than 4 mumol.kg-1.h-1; controls 13-20). These results show that persistent elevation in leucine concentration has no effect on protein synthesis. The marked disturbance in leucine metabolism in MSUD did not alter the relationship between rates of catabolism of protein to phenylalanine and leucine, which provides further support for the validity of the use of a single amino acid to trace whole body protein metabolism. The minimal leucine oxidation in MSUD differs from findings in other inborn metabolic errors and indicates that in patients with classical MSUD there is no significant route of leucine disposal other than through protein synthesis

  11. Association Between Newborn Metabolic Profiles and Pediatric Kidney Disease

    Directory of Open Access Journals (Sweden)

    Manish M. Sood

    2018-05-01

    Full Text Available Introduction: Metabolomics offers considerable promise in early disease detection. We set out to test the hypothesis that routine newborn metabolic profiles at birth, obtained through screening for inborn errors of metabolism, would be associated with kidney disease and add incremental information to known clinical risk factors. Methods: We conducted a population-level cohort study in Ontario, Canada, using metabolic profiles from 1,288,905 newborns from 2006 to 2015. The primary outcome was chronic kidney disease (CKD or dialysis. Individual metabolites and their ratio combinations were examined by logistic regression after adjustment for established risk factors for kidney disease and incremental risk prediction measured. Results: CKD occurred in 2086 (0.16%, median time 612 days and dialysis in 641 (0.05%, median time 99 days infants and children. Individual metabolites consisted of amino acids, acylcarnitines, markers of fatty acid oxidation, and others. Base models incorporating clinical risk factors only provided c-statistics of 0.61 for CKD and 0.70 for dialysis. The addition of identified metabolites to risk prediciton models resulted in significant incremental improvement in the performance of both models (CKD model: c-statistic 0.66 NRI 0.36 IDI 0.04, dialysis model: c-statistic 0.77 NRI 0.57 IDI 0.09. This was consistent after internal validation using bootstrapping and a sensitivity analysis excluding outcomes within the first 30 days. Conclusion: Routinely collected screening metabolites at birth are associated with CKD and the need for dialytic therapies in infants and children, and add incremental information to traditional clinical risk factors. Keywords: chronic kidney disease, dialysis, end-stage kidney disease, metabolomics, newborn screening, pediatric, renal failure

  12. Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency

    Directory of Open Access Journals (Sweden)

    Peter J. McGuire

    2014-02-01

    types of inborn errors of metabolism.

  13. Genetics of homocysteine metabolism and associated disorders

    Directory of Open Access Journals (Sweden)

    S. Brustolin

    2010-01-01

    Full Text Available Homocysteine is a sulfur-containing amino acid derived from the metabolism of methionine, an essential amino acid, and is metabolized by one of two pathways: remethylation or transsulfuration. Abnormalities of these pathways lead to hyperhomocysteinemia. Hyperhomocysteinemia is observed in approximately 5% of the general population and is associated with an increased risk for many disorders, including vascular and neurodegenerative diseases, autoimmune disorders, birth defects, diabetes, renal disease, osteoporosis, neuropsychiatric disorders, and cancer. We review here the correlation between homocysteine metabolism and the disorders described above with genetic variants on genes coding for enzymes of homocysteine metabolism relevant to clinical practice, especially common variants of the MTHFR gene, 677C>T and 1298A>C. We also discuss the management of hyperhomocysteinemia with folic acid supplementation and fortification of folic acid and the impact of a decrease in the prevalence of congenital anomalies and a decline in the incidence of stroke mortality.

  14. Genetic Variant in Flavin-Containing Monooxygenase 3 Alters Lipid Metabolism in Laying Hens in a Diet-Specific Manner

    OpenAIRE

    Wang, Jing; Long, Cheng; Zhang, Haijun; Zhang, Yanan; Wang, Hao; Yue, Hongyuan; Wang, Xiaocui; Wu, Shugeng; Qi, Guanghai

    2016-01-01

    Genetic variant T329S in flavin-containing monooxygenase 3 (FMO3) impairs trimethylamine (TMA) metabolism in birds. The TMA metabolism that under complex genetic and dietary regulation, closely linked to cardiovascular disease risk. We determined whether the genetic defects in TMA metabolism may change other metabolic traits in birds, determined whether the genetic effects depend on diets, and to identify genes or gene pathways that underlie the metabolic alteration induced by genetic and die...

  15. Successful intrauterine treatment of a patient with cobalamin C defect

    Directory of Open Access Journals (Sweden)

    Friedrich K. Trefz

    2016-03-01

    Full Text Available Cobalamin C (cblC defect is an inherited autosomal recessive disorder that affects cobalamin metabolism. Patients are treated with hydroxycobalamin to ameliorate the clinical features of early-onset disease and prevent clinical symptoms in late-onset disease. Here we describe a patient in whom prenatal maternal treatment with 30 mg/week hydroxycobalamin and 5 mg/day folic acid from week 15 of pregnancy prevented disease manifestation in a girl who is now 11 years old with normal IQ and only mild ophthalmic findings. The affected older sister received postnatal treatment only and is severely intellectually disabled with severe ophthalmic symptoms. This case highlights the potential of early, high-dose intrauterine treatment in a fetus affected by the cblC defect.

  16. Neural tube defects – recent advances, unsolved questions and controversies

    Science.gov (United States)

    Copp, Andrew J.; Stanier, Philip; Greene, Nicholas D. E.

    2014-01-01

    Neural tube defects (NTDs) are severe congenital malformations affecting around 1 in every 1000 pregnancies. Here we review recent advances and currently unsolved issues in the NTD field. An innovation in clinical management has come from the demonstration that closure of open spina bifida lesions in utero can diminish neurological dysfunction in children. Primary prevention by folic acid has been enhanced through introduction of mandatory food fortification in some countries, although not yet in UK. Genetic predisposition comprises the majority of NTD risk, and genes that regulate folate one-carbon metabolism and planar cell polarity have been strongly implicated. The sequence of human neural tube closure events remains controversial, but study of mouse NTD models shows that anencephaly, open spina bifida and craniorachischisis result from failure of primary neurulation, while skin-covered spinal dysraphism results from defective secondary neurulation. Other ‘NTD’ malformations, such as encephalocele, are likely to be post-neurulation disorders. PMID:23790957

  17. What Are Congenital Heart Defects?

    Science.gov (United States)

    ... a baby with a congenital heart defect. Family history and genetics Congenital heart disease is not usually passed along ... you or your child to a specialist in genetic testing. Cardiac MRI to diagnose a ... Factors to review family history, smoking, and medicines that increase your risk of ...

  18. Nuclear Pasta: Topology and Defects

    Science.gov (United States)

    da Silva Schneider, Andre; Horowitz, Charles; Berry, Don; Caplan, Matt; Briggs, Christian

    2015-04-01

    A layer of complex non-uniform phases of matter known as nuclear pasta is expected to exist at the base of the crust of neutron stars. Using large scale molecular dynamics we study the topology of some pasta shapes, the formation of defects and how these may affect properties of neutron star crusts.

  19. Defect branes as Alice strings

    International Nuclear Information System (INIS)

    Okada, Takashi; Sakatani, Yuho

    2015-01-01

    There exist various defect-brane backgrounds in supergravity theories which arise as the low energy limit of string theories. These backgrounds typically have non-trivial monodromies, and if we move a charged probe around the center of a defect, its charge will be changed by the action of the monodromy. During the process, the charge conservation law seems to be violated. In this paper, to resolve this puzzle, we examine a dynamics of the charge changing process and show that the missing charge of the probe is transferred to the background. We then explicitly construct the resultant background after the charge transfer process by utilizing dualities. This background has the same monodromy as the original defect brane, but has an additional charge which does not have any localized source. In the literature, such a charge without localized source is known to appear in the presence of Alice strings. We argue that defect branes can in fact be regarded as a realization of Alice strings in string theory and examine the charge transfer process from that perspective.

  20. Defect branes as Alice strings

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Takashi [Theoretical Biology Laboratory, RIKEN,Wako 351-0198 (Japan); Sakatani, Yuho [Department of Physics and Astronomy,Seoul National University, Seoul 151-747 (Korea, Republic of)

    2015-03-25

    There exist various defect-brane backgrounds in supergravity theories which arise as the low energy limit of string theories. These backgrounds typically have non-trivial monodromies, and if we move a charged probe around the center of a defect, its charge will be changed by the action of the monodromy. During the process, the charge conservation law seems to be violated. In this paper, to resolve this puzzle, we examine a dynamics of the charge changing process and show that the missing charge of the probe is transferred to the background. We then explicitly construct the resultant background after the charge transfer process by utilizing dualities. This background has the same monodromy as the original defect brane, but has an additional charge which does not have any localized source. In the literature, such a charge without localized source is known to appear in the presence of Alice strings. We argue that defect branes can in fact be regarded as a realization of Alice strings in string theory and examine the charge transfer process from that perspective.

  1. Ocular defects in cerebral palsy

    Directory of Open Access Journals (Sweden)

    Katoch Sabita

    2007-01-01

    Full Text Available There is a high prevalence of ocular defects in children with developmental disabilities. This study evaluated visual disability in a group of 200 cerebral palsy (CP patients and found that 68% of the children had significant visual morbidity. These findings emphasize the need for an early ocular examination in patients with CP.

  2. Characterization of point defects in monolayer arsenene

    Science.gov (United States)

    Liang, Xiongyi; Ng, Siu-Pang; Ding, Ning; Wu, Chi-Man Lawrence

    2018-06-01

    Topological defects that are inevitably found in 2D materials can dramatically affect their properties. Using density functional theory (DFT) calculations and ab initio molecular dynamics (AIMD) method, the structural, thermodynamic, electronic and magnetic properties of six types of typical point defects in arsenene, i.e. the Stone-Wales defect, single and double vacancies and adatoms, were systemically studied. It was found that these defects were all more easily generated in arsenene with lower formation energies than those with graphene and silicene. Stone-Wales defects can be transformed from pristine arsenene by overcoming a barrier of 2.19 eV and single vacancy defects tend to coalesce into double vacancy defects by diffusion. However, a type of adatom defect does not exhibit kinetic stability at room temperature. In addition, SV defects and another type of adatom defect can remarkably affect the electronic and magnetic properties of arsenene, e.g. they can introduce localized states near the Fermi level, as well as a strongly local magnetic moment due to dangling bond and unpaired electron. Furthermore, the simulated scanning tunneling microscopy (STM) and Raman spectroscopy were computed and the types of point defects can be fully characterized by correlating the STM images and Raman spectra to the defective atomistic structures. The results provide significant insights to the effect of defects in arsenene for potential applications, as well as identifications of two helpful tools (STM and Raman spectroscopy) to distinguish the type of defects in arsenene for future experiments.

  3. Nanocarbon: Defect Architectures and Properties

    Science.gov (United States)

    Vuong, Amanda

    The allotropes of carbon make its solid phases amongst the most diverse of any element. It can occur naturally as graphite and diamond, which have very different properties that make them suitable for a wide range of technological and commercial purposes. Recent developments in synthetic carbon include Highly Oriented Pyrolytic Graphite (HOPG) and nano-carbons, such as fullerenes, nanotubes and graphene. The main industrial application of bulk graphite is as an electrode material in steel production, but in purified nuclear graphite form, it is also used as a moderator in Advanced Gas-cooled Reactors across the United Kingdom. Both graphene and graphite are damaged over time when subjected to bombardment by electrons, neutrons or ions, and these have a wide range of effects on their physical and electrical properties, depending on the radiation flux and temperature. This research focuses on intrinsic defects in graphene and dimensional change in nuclear graphite. The method used here is computational chemistry, which complements physical experiments. Techniques used comprise of density functional theory (DFT) and molecular dynamics (MD), which are discussed in chapter 2 and chapter 3, respectively. The succeeding chapters describe the results of simulations performed to model defects in graphene and graphite. Chapter 4 presents the results of ab initio DFT calculations performed to investigate vacancy complexes that are formed in AA stacked bilayer graphene. In AB stacking, carbon atoms surrounding the lattice vacancies can form interlayer structures with sp2 bonding that are lower in energy compared to in-plane reconstructions. From the investigation of AA stacking, sp2 interlayer bonding of adjacent multivacancy defects in registry creates a type of stable sp2 bonded wormhole between the layers. Also, a new class of mezzanine structure characterised by sp3 interlayer bonding, resembling a prismatic vacancy loop has also been identified. The mezzanine, which is a

  4. Mitochondrial metabolism in hematopoietic stem cells requires functional FOXO3

    Science.gov (United States)

    Rimmelé, Pauline; Liang, Raymond; Bigarella, Carolina L; Kocabas, Fatih; Xie, Jingjing; Serasinghe, Madhavika N; Chipuk, Jerry; Sadek, Hesham; Zhang, Cheng Cheng; Ghaffari, Saghi

    2015-01-01

    Hematopoietic stem cells (HSC) are primarily dormant but have the potential to become highly active on demand to reconstitute blood. This requires a swift metabolic switch from glycolysis to mitochondrial oxidative phosphorylation. Maintenance of low levels of reactive oxygen species (ROS), a by-product of mitochondrial metabolism, is also necessary for sustaining HSC dormancy. Little is known about mechanisms that integrate energy metabolism with hematopoietic stem cell homeostasis. Here, we identify the transcription factor FOXO3 as a new regulator of metabolic adaptation of HSC. ROS are elevated in Foxo3−/− HSC that are defective in their activity. We show that Foxo3−/− HSC are impaired in mitochondrial metabolism independent of ROS levels. These defects are associated with altered expression of mitochondrial/metabolic genes in Foxo3−/− hematopoietic stem and progenitor cells (HSPC). We further show that defects of Foxo3−/− HSC long-term repopulation activity are independent of ROS or mTOR signaling. Our results point to FOXO3 as a potential node that couples mitochondrial metabolism with HSC homeostasis. These findings have critical implications for mechanisms that promote malignant transformation and aging of blood stem and progenitor cells. PMID:26209246

  5. Fibrous metaphyseal defect (fibrous cortical defect, non-ossifying fibroma)

    International Nuclear Information System (INIS)

    Freyschmidt, J.; Saure, D.; Dammenhain, S.

    1981-01-01

    Fibrous cortical defect and nonossifying fibromas can be classified together as fibrous metaphyseal defects (FMD) since they have the same pahtological substrate, with a tendency to the same localisation around the knee, and occuring at the same age. They have a tendency to spontaneous healing, are clinically silent and are usually discovered accidentally during radiological examination. A radiological survey fo 5.674 metaphyseal regions in the upper and lower extremities of 2.065 unselected patients aged one to 20 years revealed an incidence of 1.8%; exlcusive examination of the distal femur showed an incidence of 2.7%. 96% of all lesions were in the lower extremities and only 4% in the upper. The marked discrepancy in the incidence rate between American and German publications is discussed. (orig.) [de

  6. Oral cancer cells may rewire alternative metabolic pathways to survive from siRNA silencing of metabolic enzymes

    International Nuclear Information System (INIS)

    Zhang, Min; Chai, Yang D; Brumbaugh, Jeffrey; Liu, Xiaojun; Rabii, Ramin; Feng, Sizhe; Misuno, Kaori; Messadi, Diana; Hu, Shen

    2014-01-01

    Cancer cells may undergo metabolic adaptations that support their growth as well as drug resistance properties. The purpose of this study is to test if oral cancer cells can overcome the metabolic defects introduced by using small interfering RNA (siRNA) to knock down their expression of important metabolic enzymes. UM1 and UM2 oral cancer cells were transfected with siRNA to transketolase (TKT) or siRNA to adenylate kinase (AK2), and Western blotting was used to confirm the knockdown. Cellular uptake of glucose and glutamine and production of lactate were compared between the cancer cells with either TKT or AK2 knockdown and those transfected with control siRNA. Statistical analysis was performed with student T-test. Despite the defect in the pentose phosphate pathway caused by siRNA knockdown of TKT, the survived UM1 or UM2 cells utilized more glucose and glutamine and secreted a significantly higher amount of lactate than the cells transferred with control siRNA. We also demonstrated that siRNA knockdown of AK2 constrained the proliferation of UM1 and UM2 cells but similarly led to an increased uptake of glucose/glutamine and production of lactate by the UM1 or UM2 cells survived from siRNA silencing of AK2. Our results indicate that the metabolic defects introduced by siRNA silencing of metabolic enzymes TKT or AK2 may be compensated by alternative feedback metabolic mechanisms, suggesting that cancer cells may overcome single defective pathways through secondary metabolic network adaptations. The highly robust nature of oral cancer cell metabolism implies that a systematic medical approach targeting multiple metabolic pathways may be needed to accomplish the continued improvement of cancer treatment

  7. Predicting internal red oak (Quercus rubra) log defect features using surface defect defect measurements

    Science.gov (United States)

    R. Edward. Thomas

    2013-01-01

    Determining the defects located within a log is crucial to understanding the tree/log resource for efficient processing. However, existing means of doing this non-destructively requires the use of expensive x-ray/CT (computerized tomography), MRI (magnetic resonance imaging), or microwave technology. These methods do not lend themselves to fast, efficient, and cost-...

  8. Positron lifetime calculation for defects and defect clusters in graphite

    International Nuclear Information System (INIS)

    Onitsuka, T.; Ohkubo, H.; Takenaka, M.; Tsukuda, N.; Kuramoto, E.

    2000-01-01

    Calculations of positron lifetime have been made for vacancy type defects in graphite and compared with experimental results. Defect structures were obtained in a model graphite lattice after including relaxation of whole lattice as determined by the molecular dynamics method, where the interatomic potential given by Pablo Andribet, Dominguez-Vazguez, Mari Carmen Perez-Martin, Alonso, Jimenez-Rodriguez [Nucl. Instrum. and Meth. 115 (1996) 501] was used. For the defect structures obtained via lattice relaxation positron lifetime was calculated under the so-called atomic superposition method. Positron lifetimes 204 and 222 ps were obtained for the graphite matrix and a single vacancy, respectively, which can be compared with the experimental results 208 and 233 ps. For planar vacancy clusters, e.g., vacancy loops, lifetime calculation was also made and indicated that lifetime increases with the number of vacancies in a cluster. This is consistent with the experimental result in the region of higher annealing temperature (above 1200 deg. C), where the increase of positron lifetime is seen, probably corresponding to the clustering of mobile vacancies

  9. Capillary recruitment is impaired in essential hypertension and relates to insulin's metabolic and vascular actions

    NARCIS (Netherlands)

    Serne, EH; Gans, ROB; ter Maaten, JC; ter Wee, PM; Donker, AM; Stehouwer, CDA

    Objective: In patients with essential hypertension, defects in both the metabolic and vascular actions of insulin have been described. Impaired microvascular function, a well-established abnormality in essential hypertension, may explain part of these defects. In the present study we investigated

  10. Charged Semiconductor Defects Structure, Thermodynamics and Diffusion

    CERN Document Server

    Seebauer, Edmund G

    2009-01-01

    The technologically useful properties of a solid often depend upon the types and concentrations of the defects it contains. Not surprisingly, defects in semiconductors have been studied for many years, in many cases with a view towards controlling their behavior through various forms of "defect engineering." For example, in the bulk, charging significantly affects the total concentration of defects that are available to mediate phenomena such as solid-state diffusion. Surface defects play an important role in mediating surface mass transport during high temperature processing steps such as epitaxial film deposition, diffusional smoothing in reflow, and nanostructure formation in memory device fabrication. Charged Semiconductor Defects details the current state of knowledge regarding the properties of the ionized defects that can affect the behavior of advanced transistors, photo-active devices, catalysts, and sensors. Features: Group IV, III-V, and oxide semiconductors; Intrinsic and extrinsic defects; and, P...

  11. Automatic classification of blank substrate defects

    Science.gov (United States)

    Boettiger, Tom; Buck, Peter; Paninjath, Sankaranarayanan; Pereira, Mark; Ronald, Rob; Rost, Dan; Samir, Bhamidipati

    2014-10-01

    Mask preparation stages are crucial in mask manufacturing, since this mask is to later act as a template for considerable number of dies on wafer. Defects on the initial blank substrate, and subsequent cleaned and coated substrates, can have a profound impact on the usability of the finished mask. This emphasizes the need for early and accurate identification of blank substrate defects and the risk they pose to the patterned reticle. While Automatic Defect Classification (ADC) is a well-developed technology for inspection and analysis of defects on patterned wafers and masks in the semiconductors industry, ADC for mask blanks is still in the early stages of adoption and development. Calibre ADC is a powerful analysis tool for fast, accurate, consistent and automatic classification of defects on mask blanks. Accurate, automated classification of mask blanks leads to better usability of blanks by enabling defect avoidance technologies during mask writing. Detailed information on blank defects can help to select appropriate job-decks to be written on the mask by defect avoidance tools [1][4][5]. Smart algorithms separate critical defects from the potentially large number of non-critical defects or false defects detected at various stages during mask blank preparation. Mechanisms used by Calibre ADC to identify and characterize defects include defect location and size, signal polarity (dark, bright) in both transmitted and reflected review images, distinguishing defect signals from background noise in defect images. The Calibre ADC engine then uses a decision tree to translate this information into a defect classification code. Using this automated process improves classification accuracy, repeatability and speed, while avoiding the subjectivity of human judgment compared to the alternative of manual defect classification by trained personnel [2]. This paper focuses on the results from the evaluation of Automatic Defect Classification (ADC) product at MP Mask

  12. Sphingolipid metabolism diseases.

    Science.gov (United States)

    Kolter, Thomas; Sandhoff, Konrad

    2006-12-01

    Human diseases caused by alterations in the metabolism of sphingolipids or glycosphingolipids are mainly disorders of the degradation of these compounds. The sphingolipidoses are a group of monogenic inherited diseases caused by defects in the system of lysosomal sphingolipid degradation, with subsequent accumulation of non-degradable storage material in one or more organs. Most sphingolipidoses are associated with high mortality. Both, the ratio of substrate influx into the lysosomes and the reduced degradative capacity can be addressed by therapeutic approaches. In addition to symptomatic treatments, the current strategies for restoration of the reduced substrate degradation within the lysosome are enzyme replacement therapy (ERT), cell-mediated therapy (CMT) including bone marrow transplantation (BMT) and cell-mediated "cross correction", gene therapy, and enzyme-enhancement therapy with chemical chaperones. The reduction of substrate influx into the lysosomes can be achieved by substrate reduction therapy. Patients suffering from the attenuated form (type 1) of Gaucher disease and from Fabry disease have been successfully treated with ERT.

  13. Cooperation and Defection in Ghetto

    Science.gov (United States)

    Kułakowski, Krzysztof

    We consider ghetto as a community of people ruled against their will by an external power. Members of the community feel that their laws are broken. However, attempts to leave ghetto makes their situation worse. We discuss the relation of the ghetto inhabitants to the ruling power in context of their needs, organized according to the Maslow hierarchy. Decisions how to satisfy successive needs are undertaken in cooperation with or defection the ruling power. This issue allows to construct the tree of decisions and to adopt the pruning technique from the game theory. Dynamics of decisions can be described within the formalism of fundamental equations. The result is that the strategy of defection is stabilized by the estimated payoff.

  14. Topological defects in open string field theory

    Science.gov (United States)

    Kojita, Toshiko; Maccaferri, Carlo; Masuda, Toru; Schnabl, Martin

    2018-04-01

    We show how conformal field theory topological defects can relate solutions of open string field theory for different boundary conditions. To this end we generalize the results of Graham and Watts to include the action of defects on boundary condition changing fields. Special care is devoted to the general case when nontrivial multiplicities arise upon defect action. Surprisingly the fusion algebra of defects is realized on open string fields only up to a (star algebra) isomorphism.

  15. Various Stone-Wales defects in phagraphene

    Science.gov (United States)

    Openov, L. A.; Podlivaev, A. I.

    2016-08-01

    Various Stone-Wales defects in phagraphene, which is a graphene allotrope, predicted recently are studied in terms of the nonorthogonal tight-binding model. The energies of the defect formation and the heights of energy barriers preventing the formation and annealing of the defects are found. Corresponding frequency factors in the Arrhenius formula are calculated. The evolution of the defect structure is studied in the real-time mode using the molecular dynamics method.

  16. Iatrogenic Urethral Defect Repairment: A Case Report

    Directory of Open Access Journals (Sweden)

    Ulas Fidan

    2013-10-01

    Full Text Available    Iatrogenic urethral defect is a complication that occurs after vaginal surgical procedures. Many surgical methods according to place of defect are described in case of injury of urethra. In this article, we reported the repairment of distal urethral defect with the help of greft taken from labia minor. This defect is made by the excision of the granulation tissue that occurred after chronic paraurethral  gland infection.

  17. Defect relaxation in disordered materials

    International Nuclear Information System (INIS)

    Crandell, R.S.

    1989-01-01

    Using an exponential distribution of activation barriers, annealing data for metastable effects in hydrogenated amorphous silicon, a-Si:H, are quantitatively explained. This includes the stretched exponential time dependence of annealing and a Meyer-Neldel rule for the annealing time constant. An exponential distribution of annealing energies arises because defects are frozen in during growth at high temperature. Mechanisms that lead to an exponential distribution of annealing energies are weak bond-breaking and charge trapping

  18. Curvature-Controlled Topological Defects

    Directory of Open Access Journals (Sweden)

    Luka Mesarec

    2017-05-01

    Full Text Available Effectively, two-dimensional (2D closed films exhibiting in-plane orientational ordering (ordered shells might be instrumental for the realization of scaled crystals. In them, ordered shells are expected to play the role of atoms. Furthermore, topological defects (TDs within them would determine their valence. Namely, bonding among shells within an isotropic liquid matrix could be established via appropriate nano-binders (i.e., linkers which tend to be attached to the cores of TDs exploiting the defect core replacement mechanism. Consequently, by varying configurations of TDs one could nucleate growth of scaled crystals displaying different symmetries. For this purpose, it is of interest to develop a simple and robust mechanism via which one could control the position and number of TDs in such atoms. In this paper, we use a minimal mesoscopic model, where variational parameters are the 2D curvature tensor and the 2D orientational tensor order parameter. We demonstrate numerically the efficiency of the effective topological defect cancellation mechanism to predict positional assembling of TDs in ordered films characterized by spatially nonhomogeneous Gaussian curvature. Furthermore, we show how one could efficiently switch among qualitatively different structures by using a relative volume v of ordered shells, which represents a relatively simple naturally accessible control parameter.

  19. Defect grating modes as superimposed grating states

    NARCIS (Netherlands)

    van Groesen, Embrecht W.C.; Sopaheluwakan, A.; Andonowati, A.; de Ridder, R.M; de Ridder, R.M.; Altena, G; Altena, G.; Geuzebroek, D.H.; Geuzenboek, D.; Dekker, R.; Dekker, R

    2003-01-01

    For a symmetric grating structure with a defect, we show that a fully transmitted defect mode in the band gap can be obtained as a superposition of two steady states: an amplified and an attenuated defect state. Without scanning the whole band gap by transmission calculations, this simplifies the

  20. Disc defect classification for optical disc drives

    NARCIS (Netherlands)

    Helvoirt, van J.; Leenknegt, G.A.L.; Steinbuch, M.; Goossens, H.J.

    2005-01-01

    Optical disc drives are subject to various disturbances and faults. A special type of fault is the so-called disc defect. In this paper we present an approach for disc defect classification. It is based on hierarchical clustering of measured signals that are affected by disc defects. The

  1. Metastable and bistable defects in silicon

    International Nuclear Information System (INIS)

    Mukashev, Bulat N; Abdullin, Kh A; Gorelkinskii, Yurii V

    2000-01-01

    Existing data on the properties and structure of metastable and bistable defects in silicon are analyzed. Primary radiation-induced defects (vacancies, self-interstitial atoms, and Frenkel pairs), complexes of oxygen, carbon, hydrogen, and other impurity atoms and defects with negative correlation energy are considered. (reviews of topical problems)

  2. Photographic guide of selected external defect indicators and associated internal defects in sugar maple

    Science.gov (United States)

    Everette D. Rast; John A. Beaton; David L. Sonderman

    1991-01-01

    To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for sugar maple. Eleven types of external...

  3. Photographic guide of selected external defect indicators and associated internal defects in yellow-poplar

    Science.gov (United States)

    Everette D. Rast; John A. Beaton; David L. Sonderman

    1991-01-01

    To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow-poplar. Twelve types of external...

  4. Photographic guide of selected external defect indicators and associated internal defects in yellow birch

    Science.gov (United States)

    Everette D. Rast; John A. Beaton; David L. Sonderman

    1991-01-01

    To properly classify or grade logs or trees, one must be able to correctly identify defect indicators and assess the effect of the underlying defect on possible end products. This guide assists the individual in identifying the surface defect indicator and shows the progressive stages of the defect throughout its development for yellow birch. Eleven types of external...

  5. Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea); Kim, Eung Yeop [Yonsei University College of Medicine, Department of Radiology, Research Institute of Radiological Science, Brain Korea 21 Project for Medical Science, Seoul (Korea); Lee, Young-Mock; Lee, Joon Soo [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Kim, Heung Dong [Yonsei University College of Medicine, Department of Pediatrics, Pediatric Epilepsy Clinics, Severance Children' s Hospital, Brain Research Institute, Seoul (Korea); Yonsei University College of Medicine, Department of Pediatrics, Seoul (Korea)

    2008-08-15

    Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

  6. Neuroradiologic findings in children with mitochondrial disorder: correlation with mitochondrial respiratory chain defects

    International Nuclear Information System (INIS)

    Kim, Jinna; Lee, Seung-Koo; Kim, Dong Ik; Kim, Eung Yeop; Lee, Young-Mock; Lee, Joon Soo; Kim, Heung Dong

    2008-01-01

    Mitochondrial disorders are a heterogeneous group of disorders affecting energy metabolism that can present at any age with a wide variety of clinical symptoms. We investigated brain magnetic resonance (MR) findings in 40 children with defects of the mitochondrial respiratory chain (MRC) complex and correlated them with the type of MRC defects. Enrolled were 40 children with MRC defects in biochemical enzyme assay of the muscle specimen. Twenty-one children were found to have classical syndromes of mitochondrial disorders and 19 children presented nonspecific mitochondrial encephalomyopathies. Their brain MR imaging findings were retrospectively reviewed and correlated with the biochemical defect in the MRC complex. Children with MRC defects showed various neuroradiologic features on brain MR imaging that resulted from a complex genetic background and a heterogeneous phenotype. Rapid progression of atrophy involving all structures of the brain with variable involvement of deep gray and white matter are the most frequent MR findings in children with MRC defects in both classical syndromes of mitochondrial disorder and nonspecific mitochondrial encephalomyopathies. The type of biochemical defect in the MRC complex enzyme did not correlate with brain MR findings in child patients. (orig.)

  7. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. Normally your enzymes break carbohydrates down into glucose (a type of sugar). If ...

  8. Comprehensive metabolic panel

    Science.gov (United States)

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - blood. In: ... Tests and Diagnostic Procedures . 6th ed. St Louis, MO: ...

  9. Concurrence of metaphyseal fibrous defect and osteosarcoma

    International Nuclear Information System (INIS)

    Kyriakos, M.; Murphy, W.A.

    1981-01-01

    The case of a 15-year-old girl with juxtaposition of a femoral metaphyseal fibrous defect (fibrous cortical defect) and an osteosarcoma is reported. Despite the relatively common occurrence of metaphyseal fibrous defects, their reported association with other bone tumors is exceedingly rare. Only two previous acceptable examples of this association were found. Reports of malignant transformation of metaphyseal fibrous defect were reviewed and rejected because they lacked convincing radiologic or histopathologic evidence of a pre-existent benign fibrous lesion. The finding of a malignant bone tumor in association with a metaphyseal fibrous defect appears to be a chance occurrence. (orig.)

  10. Inherited metabolic liver diseases in infants and children: an overview

    Directory of Open Access Journals (Sweden)

    Ivo Barić

    2013-10-01

    Full Text Available Inborn errors of metabolism, which affect the liver are a large, continuously increasing group of diseases. Their clinical onset can occur at any age, from intrauterine period presenting as liver failure already at birth to late adulthood. Inherited metabolic disorders must be considered in differential diagnosis of every unexplained liver disease. Specific diagnostic work-up for either their confirmation or exclusion should start immediately since any postponing can result in delayed diagnosis and death or irreversible disability. This can be particularly painful while many inherited metabolic liver diseases are relatively easily treatable if diagnosed on time, for instance galactosemia or hereditary fructose intolerance by simple dietary means. Any unexplained liver disease, even one looking initially benign, should be considered as a potential liver failure and therefore should deserve proper attention. Diagnosis in neonates is additionally complicated because of the factors which can mask liver disease, such as physiological neonatal jaundice, normally relatively enlarged liver and increased transaminases at that age. In everyday practice, in order to reveal the etiology, it is useful to classify and distinguish some clinical patterns which, together with a few routine, widely available laboratory tests (aminotransferases, prothrombine time, albumin, gammaGT, total and conjugated bilirubin, ammonia, alkaline phosphatase and glucose make the search for the cause much easier. These patterns are isolated hyperbilirubinemia, syndrome of cholestasis in early infancy, hepatocellular jaundice, Reye syndrome, portal cirrhosis and isolated hepatomegaly. Despite the fact that some diseases can present with more than one pattern (for instance, alpha-1-antitrypsin deficiency as infantile cholestasis, but also as hepatocellular jaundice, and that in some disesases one pattern can evolve into another (for instance, Wilson disease from hepatocellular

  11. Areva solutions for management of defective fuel

    International Nuclear Information System (INIS)

    Morlaes, I.; Vo Van, V.

    2014-01-01

    Defective fuel management is a major challenge for nuclear operators when all fuel must be long-term managed. This paper describes AREVA solutions for managing defective fuel. Transport AREVA performs shipments of defective fuel in Europe and proposes casks that are licensed for that purpose in Europe and in the USA. The paper presents the transport experience and the new European licensing approach of defective fuel transport. Dry Interim Storage AREVA is implementing the defective fuel storage in the USA, compliant with the Safety Authority's requirements. In Europe, AREVA is developing a new, more long-term oriented storage solution for defective fuel, the best available technology regarding safety requirements. The paper describes these storage solutions. Treatment Various types of defective fuel coming from around the world have been treated in the AREVA La Hague plant. Specific treatment procedures were developed when needed. The paper presents operational elements related to this experience. (authors)

  12. Point defects and atomic transport in crystals

    International Nuclear Information System (INIS)

    Lidiard, A.B.

    1981-02-01

    There are two principle aspects to the theory of atomic transport in crystals as caused by the action of point defects, namely (1) the calculation of relevant properties of the point defects (energies and other thermodynamic characteristics of the different possible defects, activation energies and other mobility parameters) and (2) the statistical mechanics of assemblies of defects, both equilibrium and non-equilibrium assemblies. In the five lectures given here both these aspects are touched on. The first two lectures are concerned with the calculation of relevant point defect properties, particularly in ionic crystals. The first lecture is more general, the second is concerned particularly with some recent calculations of the free volumes of formation of defects in various ionic solids; these solve a rather long-standing problem in this area. The remaining three lectures are concerned with the kinetic theory of defects mainly in relaxation, drift and diffusion situations

  13. Insulin secretion and insulin action in non-insulin-dependent diabetes mellitus: which defect is primary?

    Science.gov (United States)

    Reaven, G M

    1984-01-01

    Defects in both insulin secretion and insulin action exist in patients with non-insulin-dependent diabetes mellitus (NIDDM). The loss of the acute plasma insulin response to intravenous glucose is seen in patients with relatively mild degrees of fasting hyperglycemia, but patients with severe fasting hyperglycemia also demonstrate absolute hypoinsulinemia in response to an oral glucose challenge. In contrast, day-long circulating insulin levels are within normal limits even in severely hyperglycemic patients with NIDDM. The relationship between NIDDM and insulin action in NIDDM is less complex, and is a characteristic feature of the syndrome. This metabolic defect is independent of obesity, and the severity of the resistance to insulin-stimulated glucose uptake increases with magnitude of hyperglycemia. Control of hyperglycemia with exogenous insulin ameliorates the degree of insulin resistance, and reduction of insulin resistance with weight loss in obese patients with NIDDM leads to an enhanced insulin response. Since neither therapeutic intervention is capable of restoring all metabolic abnormalities to normal, these observations do not tell us which of these two defects is primarily responsible for the development of NIDDM. Similarly, the observation that most patients with impaired glucose tolerance are hyperinsulinemic and insulin resistant does not prove that insulin resistance is the primary defect in NIDDM. In conclusion, reduction in both insulin secretion and action is seen in patients with NIDDM, and the relationship between these two metabolic abnormalities is very complex.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Packing defects into ordered structures

    DEFF Research Database (Denmark)

    Bechstein, R.; Kristoffersen, Henrik Høgh; Vilhelmsen, L.B.

    2012-01-01

    . With the help of density functional theory calculations we develop a complete structural model for the entire strand and demonstrate these adstructures to be more stable than an equivalent amount of bulk defects such as Ti interstitials. We argue that strands can form particularly easy on stepped surfaces......We have studied vicinal TiO2(110) surfaces by high-resolution scanning tunneling microscopy and density functional theory calculations. On TiO2 surfaces characterized by a high density of ⟨11̅ 1⟩ steps, scanning tunneling microscopy reveals a high density of oxygen-deficient strandlike adstructures...

  15. Comparison of simultaneous and sequential SPECT imaging for discrimination tasks in assessment of cardiac defects.

    Science.gov (United States)

    Trott, C M; Ouyang, J; El Fakhri, G

    2010-11-21

    Simultaneous rest perfusion/fatty-acid metabolism studies have the potential to replace sequential rest/stress perfusion studies for the assessment of cardiac function. Simultaneous acquisition has the benefits of increased signal and lack of need for patient stress, but is complicated by cross-talk between the two radionuclide signals. We consider a simultaneous rest (99m)Tc-sestamibi/(123)I-BMIPP imaging protocol in place of the commonly used sequential rest/stress (99m)Tc-sestamibi protocol. The theoretical precision with which the severity of a cardiac defect and the transmural extent of infarct can be measured is computed for simultaneous and sequential SPECT imaging, and their performance is compared for discriminating (1) degrees of defect severity and (2) sub-endocardial from transmural defects. We consider cardiac infarcts for which reduced perfusion and metabolism are observed. From an information perspective, simultaneous imaging is found to yield comparable or improved performance compared with sequential imaging for discriminating both severity of defect and transmural extent of infarct, for three defects of differing location and size.

  16. Comparison of simultaneous and sequential SPECT imaging for discrimination tasks in assessment of cardiac defects

    International Nuclear Information System (INIS)

    Trott, C M; Ouyang, J; El Fakhri, G

    2010-01-01

    Simultaneous rest perfusion/fatty-acid metabolism studies have the potential to replace sequential rest/stress perfusion studies for the assessment of cardiac function. Simultaneous acquisition has the benefits of increased signal and lack of need for patient stress, but is complicated by cross-talk between the two radionuclide signals. We consider a simultaneous rest 99m Tc-sestamibi/ 123 I-BMIPP imaging protocol in place of the commonly used sequential rest/stress 99m Tc-sestamibi protocol. The theoretical precision with which the severity of a cardiac defect and the transmural extent of infarct can be measured is computed for simultaneous and sequential SPECT imaging, and their performance is compared for discriminating (1) degrees of defect severity and (2) sub-endocardial from transmural defects. We consider cardiac infarcts for which reduced perfusion and metabolism are observed. From an information perspective, simultaneous imaging is found to yield comparable or improved performance compared with sequential imaging for discriminating both severity of defect and transmural extent of infarct, for three defects of differing location and size.

  17. Collagen-derived markers of bone metabolism in osteogenesis imperfecta

    DEFF Research Database (Denmark)

    Lund, A M; Hansen, M; Kollerup, Gina Birgitte

    1998-01-01

    )] were measured in 78 osteogenesis imperfecta (OI) patients to investigate bone metabolism in vivo and relate marker concentrations to phenotype and in vitro collagen I defects, as shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). PICP and PINP were generally low...

  18. Magnetoencephalography signals are influenced by skull defects.

    Science.gov (United States)

    Lau, S; Flemming, L; Haueisen, J

    2014-08-01

    Magnetoencephalography (MEG) signals had previously been hypothesized to have negligible sensitivity to skull defects. The objective is to experimentally investigate the influence of conducting skull defects on MEG and EEG signals. A miniaturized electric dipole was implanted in vivo into rabbit brains. Simultaneous recording using 64-channel EEG and 16-channel MEG was conducted, first above the intact skull and then above a skull defect. Skull defects were filled with agar gels, which had been formulated to have tissue-like homogeneous conductivities. The dipole was moved beneath the skull defects, and measurements were taken at regularly spaced points. The EEG signal amplitude increased 2-10 times, whereas the MEG signal amplitude reduced by as much as 20%. The EEG signal amplitude deviated more when the source was under the edge of the defect, whereas the MEG signal amplitude deviated more when the source was central under the defect. The change in MEG field-map topography (relative difference measure, RDM(∗)=0.15) was geometrically related to the skull defect edge. MEG and EEG signals can be substantially affected by skull defects. MEG source modeling requires realistic volume conductor head models that incorporate skull defects. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Dopants and defects in semiconductors

    CERN Document Server

    McCluskey, Matthew D

    2012-01-01

    "The book goes beyond the usual textbook in that it provides more specific examples of real-world defect physics … The book will be most useful for beginning graduate students in materials science. … an easy reading, broad introductory overview of the field …"-Materials Today, July-August 2012"… well written, with clear, lucid explanations …"-Chemistry World"The scientific development towards the method of controllable doping transformed the erratic and not reproducible family of semiconductor materials into the truly wonderful basis of modern microelectronics. This book tells the remarkable success story and I recommend it!"-Hans J. Queisser, Max-Planck-Institute, Stuttgart, Germany"McCluskey and Haller have written an outstanding modern guide to this field that will be useful to newcomers, and also to active researchers who want to broaden their horizons, as a means to learn the capabilities and limitations of the many techniques that are used in semiconductor-defect science."-Professor Michael J....

  20. Late-onset ornithine transcarbamylase deficiency: An under recognized cause of metabolic encephalopathy

    Directory of Open Access Journals (Sweden)

    Eric T Rush

    2014-07-01

    Full Text Available Introduction: Ornithine transcarbamylase deficiency is the most common inherited disorder of the urea cycle, has a variable phenotype, and is caused by mutations in the OTC gene. We report three cases of ornithine transcarbamylase deficiency to illustrate the late-onset presentation of this disorder and provide strategies for diagnosis and treatment. The patients were maternal first cousins, presenting with hyperammonemia and obtundation. Urea cycle disorder was not initially suspected in the first patient, delaying diagnosis. Results: Sequencing of the OTC gene showed a novel missense mutation, c.563G > C (p.G188A. Numerous family members were found to carry this mutation, which shows a trend toward later onset. Each urea cycle disorder has its own unique pattern of biochemical abnormalities, which differ from non-metabolic causes of critical illness. Conclusion: Regardless of age, clinical suspicion of a urea cycle disorder is important in encephalopathic patients to ensure quick diagnosis and definitive treatment of the underlying inborn error of metabolism.

  1. Biotin deprivation impairs mitochondrial structure and function and has implications for inherited metabolic disorders.

    Science.gov (United States)

    Ochoa-Ruiz, Estefanía; Díaz-Ruiz, Rodrigo; Hernández-Vázquez, Alaín de J; Ibarra-González, Isabel; Ortiz-Plata, Alma; Rembao, Daniel; Ortega-Cuéllar, Daniel; Viollet, Benoit; Uribe-Carvajal, Salvador; Corella, José Ahmed; Velázquez-Arellano, Antonio

    2015-11-01

    Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. This is accompanied by diminished flow through the electron transport chain, augmented by deficient cytochrome c oxidase (complex IV) activity with decreased cytochromes and reduced oxidative phosphorylation. There was also severe mitochondrial damage accompanied by decrease of mitochondria, associated with toxic levels of propionyl CoA as shown by carnitine supplementation studies, which explains the apparently paradoxical mitochondrial diminution in the face of the energy sensor AMPK activation, known to induce mitochondria biogenesis. This idea was supported by experiments on AMPK knockout mouse embryonic fibroblasts (MEFs). The multifactorial ATP deficit also provides a plausible basis for the cardiomyopathy in patients with propionic acidemia, and other diseases.Additionally, systemic inflammation concomitant to the toxic state might explain our findings of enhanced IL-6, STAT3 and HIF-1α, associated with an increase of mitophagic BNIP3 and PINK proteins, which may further increase mitophagy. Together our results imply core mechanisms of energy deficit in several inherited metabolic disorders.

  2. Metabolic Mechanisms in Obesity and Type 2 Diabetes: Insights from Bariatric/Metabolic Surgery

    Directory of Open Access Journals (Sweden)

    Adriana Florinela Cătoi

    2015-11-01

    Full Text Available Obesity and the related diabetes epidemics represent a real concern worldwide. Bariatric/metabolic surgery emerged in last years as a valuable therapeutic option for obesity and related diseases, including type 2 diabetes mellitus (T2DM. The complicated network of mechanisms involved in obesity and T2DM have not completely defined yet. There is still a debate on which would be the first metabolic defect leading to metabolic deterioration: insulin resistance or hyperinsulinemia? Insight into the metabolic effects of bariatric/metabolic surgery has revealed that, beyond weight loss and food restriction, other mechanisms can be activated by the rearrangements of the gastrointestinal tract, such as the incretinic/anti-incretinic system, changes in bile acid composition and flow, and modifications of gut microbiota; all of them possibly involved in the remission of T2DM. The complete elucidation of these mechanisms will lead to a better understanding of the pathogenesis of this disease. Our aim was to review some of the metabolic mechanisms involved in the development of T2DM in obese patients as well as in the remission of this condition in patients submitted to bariatric/metabolic surgery.

  3. Modeling human Coenzyme A synthase mutation in yeast reveals altered mitochondrial function, lipid content and iron metabolism

    Directory of Open Access Journals (Sweden)

    Camilla Ceccatelli Berti

    2015-04-01

    Full Text Available Mutations in nuclear genes associated with defective coenzyme A biosynthesis have been identified as responsible for some forms of neurodegeneration with brain iron accumulation (NBIA, namely PKAN and CoPAN. PKAN are defined by mutations in PANK2, encoding the pantothenate kinase 2 enzyme, that account for about 50% of cases of NBIA, whereas mutations in CoA synthase COASY have been recently reported as the second inborn error of CoA synthesis leading to CoPAN. As reported previously, yeast cells expressing the pathogenic mutation exhibited a temperature-sensitive growth defect in the absence of pantothenate and a reduced CoA content. Additional characterization revealed decreased oxygen consumption, reduced activities of mitochondrial respiratory complexes, higher iron content, increased sensitivity to oxidative stress and reduced amount of lipid droplets, thus partially recapitulating the phenotypes found in patients and establishing yeast as a potential model to clarify the pathogenesis underlying PKAN and CoPAN diseases.

  4. Effects of in-cascade defect clustering on near-term defect evolution

    Energy Technology Data Exchange (ETDEWEB)

    Heinisch, H.L. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-08-01

    The effects of in-cascade defect clustering on the nature of the subsequent defect population are being studied using stochastic annealing simulations applied to cascades generated in molecular dynamics (MD) simulations. The results of the simulations illustrates the strong influence of the defect configuration existing in the primary damage state on subsequent defect evolution. The large differences in mobility and stability of vacancy and interstitial defects and the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades have been shown to be significant factors affecting the evolution of the defect distribution. In recent work, the effects of initial cluster sizes appear to be extremely important.

  5. A metabolic signature of long life in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Viney Jonathan M

    2010-02-01

    Full Text Available Abstract Background Many Caenorhabditis elegans mutations increase longevity and much evidence suggests that they do so at least partly via changes in metabolism. However, up until now there has been no systematic investigation of how the metabolic networks of long-lived mutants differ from those of normal worms. Metabolomic technologies, that permit the analysis of many untargeted metabolites in parallel, now make this possible. Here we use one of these, 1H nuclear magnetic resonance spectroscopy, to investigate what makes long-lived worms metabolically distinctive. Results We examined three classes of long-lived worms: dauer larvae, adult Insulin/IGF-1 signalling (IIS-defective mutants, and a translation-defective mutant. Surprisingly, these ostensibly different long-lived worms share a common metabolic signature, dominated by shifts in carbohydrate and amino acid metabolism. In addition the dauer larvae, uniquely, had elevated levels of modified amino acids (hydroxyproline and phosphoserine. We interrogated existing gene expression data in order to integrate functional (metabolite-level changes with transcriptional changes at a pathway level. Conclusions The observed metabolic responses could be explained to a large degree by upregulation of gluconeogenesis and the glyoxylate shunt as well as changes in amino acid catabolism. These responses point to new possible mechanisms of longevity assurance in worms. The metabolic changes observed in dauer larvae can be explained by the existence of high levels of autophagy leading to recycling of cellular components. See associated minireview: http://jbiol.com/content/9/1/7

  6. Positron annihilation spectroscopy in defects of semiconductors

    International Nuclear Information System (INIS)

    Fujinami, Masanori

    2002-01-01

    Interaction of positron and defects, application to research of defects of semiconductor and defects on the surface of semiconductor are explained. Cz (Czochralski)-Si single crystal with 10 18 cm -3 impurity oxygen was introduced defects by electron irradiation and the positron lifetime was measured at 90K after annealing. The defect size and recovery temperature were determined by the lifetime measurement. The distribution of defects in the depth direction is shown by S-E curve. The chemical state analysis is possible by CBS (Coincidence Doppler Broadening) spectra. The application to silicon-implanted (100 keV, 2x10 15 cm -2 ) silicon and oxygen-implanted (180 keV, 2x10 15 cm -2 ) silicon are stated. On the oxygen-implanted silicon, the main product was V2 after implantation, V 6 O 2 at 600degC and V 10 O 6 at 800degC. (S.Y.)

  7. Perception of risk from automobile safety defects.

    Science.gov (United States)

    Slovic, P; MacGregor, D; Kraus, N N

    1987-10-01

    Descriptions of safety engineering defects of the kind that compel automobile manufacturers to initiate a recall campaign were evaluated by individuals on a set of risk characteristic scales that included overall vehicle riskiness, manufacturer's ability to anticipate the defect, importance for vehicle operation, severity of consequences and likelihood of compliance with a recall notice. A factor analysis of the risk characteristics indicated that judgments could be summarized in terms of two composite scales, one representing the uncontrollability of the damage the safety defect might cause and the other representing the foreseeability of the defect by the manufacturer. Motor vehicle defects were found to be highly diverse in terms of the perceived qualities of their risks. Location of individual defects within the factor space was closely associated with perceived riskiness, perceived likelihood of purchasing another car from the same manufacturer, perceived likelihood of compliance with a recall notice, and actual compliance rates.

  8. Automatic classification of defects in weld pipe

    International Nuclear Information System (INIS)

    Anuar Mikdad Muad; Mohd Ashhar Hj Khalid; Abdul Aziz Mohamad; Abu Bakar Mhd Ghazali; Abdul Razak Hamzah

    2000-01-01

    With the advancement of computer imaging technology, the image on hard radiographic film can be digitized and stored in a computer and the manual process of defect recognition and classification may be replace by the computer. In this paper a computerized method for automatic detection and classification of common defects in film radiography of weld pipe is described. The detection and classification processes consist of automatic selection of interest area on the image and then classify common defects using image processing and special algorithms. Analysis of the attributes of each defect such as area, size, shape and orientation are carried out by the feature analysis process. These attributes reveal the type of each defect. These methods of defect classification result in high success rate. Our experience showed that sharp film images produced better results

  9. Strained interface defects in silicon nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Benjamin G.; Stradins, Paul [National Center for Photovoltaics, National Renewable Energy Laboratory, Golden, CO (United States); Hiller, Daniel; Zacharias, Margit [IMTEK - Faculty of Engineering, Albert-Ludwigs-University Freiburg (Germany); Luo, Jun-Wei; Beard, Matthew C. [Chemical and Materials Science, National Renewable Energy Laboratory, Golden, CO (United States); Semonin, Octavi E. [Chemical and Materials Science, National Renewable Energy Laboratory, Golden, CO (United States); Department of Physics, University of Colorado, Boulder, CO (United States)

    2012-08-07

    The surface of silicon nanocrystals embedded in an oxide matrix can contain numerous interface defects. These defects strongly affect the nanocrystals' photoluminescence efficiency and optical absorption. Dangling-bond defects are nearly eliminated by H{sub 2} passivation, thus decreasing absorption below the quantum-confined bandgap and enhancing PL efficiency by an order of magnitude. However, there remain numerous other defects seen in absorption by photothermal deflection spectroscopy; these defects cause non-radiative recombination that limits the PL efficiency to <15%. Using atomistic pseudopotential simulations, we attribute these defects to two specific types of distorted bonds: Si-Si and bridging Si-O-Si bonds between two Si atoms at the nanocrystal surface. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. Altering graphene line defect properties using chemistry

    Science.gov (United States)

    Vasudevan, Smitha; White, Carter; Gunlycke, Daniel

    2012-02-01

    First-principles calculations are presented of a fundamental topological line defect in graphene that was observed and reported in Nature Nanotech. 5, 326 (2010). These calculations show that atoms and smaller molecules can bind covalently to the surface in the vicinity of the graphene line defect. It is also shown that the chemistry at the line defect has a strong effect on its electronic and magnetic properties, e.g. the ferromagnetically aligned moments along the line defect can be quenched by some adsorbates. The strong effect of the adsorbates on the line defect properties can be understood by examining how these adsorbates affect the boundary-localized states in the vicinity of the Fermi level. We also expect that the line defect chemistry will significantly affect the scattering properties of incident low-energy particles approaching it from graphene.

  11. Primordial inhomogeneities from massive defects during inflation

    Energy Technology Data Exchange (ETDEWEB)

    Firouzjahi, Hassan; Karami, Asieh; Rostami, Tahereh, E-mail: firouz@ipm.ir, E-mail: karami@ipm.ir, E-mail: t.rostami@ipm.ir [School of Astronomy, Institute for Research in Fundamental Sciences (IPM), P.O. Box 19395-5531, Tehran (Iran, Islamic Republic of)

    2016-10-01

    We consider the imprints of local massive defects, such as a black hole or a massive monopole, during inflation. The massive defect breaks the background homogeneity. We consider the limit that the physical Schwarzschild radius of the defect is much smaller than the inflationary Hubble radius so a perturbative analysis is allowed. The inhomogeneities induced in scalar and gravitational wave power spectrum are calculated. We obtain the amplitudes of dipole, quadrupole and octupole anisotropies in curvature perturbation power spectrum and identify the relative configuration of the defect to CMB sphere in which large observable dipole asymmetry can be generated. We observe a curious reflection symmetry in which the configuration where the defect is inside the CMB comoving sphere has the same inhomogeneous variance as its mirror configuration where the defect is outside the CMB sphere.

  12. Automatic classification of defects in weld pipe

    International Nuclear Information System (INIS)

    Anuar Mikdad Muad; Mohd Ashhar Khalid; Abdul Aziz Mohamad; Abu Bakar Mhd Ghazali; Abdul Razak Hamzah

    2001-01-01

    With the advancement of computer imaging technology, the image on hard radiographic film can be digitized and stored in a computer and the manual process of defect recognition and classification may be replaced by the computer. In this paper, a computerized method for automatic detection and classification of common defects in film radiography of weld pipe is described. The detection and classification processes consist of automatic selection of interest area on the image and then classify common defects using image processing and special algorithms. Analysis of the attributes of each defect such area, size, shape and orientation are carried out by the feature analysis process. These attributes reveal the type of each defect. These methods of defect classification result in high success rate. Our experience showed that sharp film images produced better results. (Author)

  13. Little string origin of surface defects

    Energy Technology Data Exchange (ETDEWEB)

    Haouzi, Nathan; Schmid, Christian [Center for Theoretical Physics, University of California, Berkeley,LeConte Hall, Berkeley (United States)

    2017-05-16

    We derive a large class of codimension-two defects of 4d N=4 Super Yang-Mills (SYM) theory from the (2,0) little string. The origin of the little string is type IIB theory compactified on an ADE singularity. The defects are D-branes wrapping the 2-cycles of the singularity. We use this construction to make contact with the description of SYM defects due to Gukov and Witten https://arxiv.org/abs/hep-th/0612073. Furthermore, we provide a geometric perspective on the nilpotent orbit classification of codimension-two defects, and the connection to ADE-type Toda CFT. The only data needed to specify the defects is a set of weights of the algebra obeying certain constraints, which we give explicitly. We highlight the differences between the defect classification in the little string theory and its (2,0) CFT limit.

  14. Agricultural Compounds in Water and Birth Defects.

    Science.gov (United States)

    Brender, Jean D; Weyer, Peter J

    2016-06-01

    Agricultural compounds have been detected in drinking water, some of which are teratogens in animal models. The most commonly detected agricultural compounds in drinking water include nitrate, atrazine, and desethylatrazine. Arsenic can also be an agricultural contaminant, although arsenic often originates from geologic sources. Nitrate has been the most studied agricultural compound in relation to prenatal exposure and birth defects. In several case-control studies published since 2000, women giving birth to babies with neural tube defects, oral clefts, and limb deficiencies were more likely than control mothers to be exposed to higher concentrations of drinking water nitrate during pregnancy. Higher concentrations of atrazine in drinking water have been associated with abdominal defects, gastroschisis, and other defects. Elevated arsenic in drinking water has also been associated with birth defects. Since these compounds often occur as mixtures, it is suggested that future research focus on the impact of mixtures, such as nitrate and atrazine, on birth defects.

  15. Coherent defects in superconducting circuits

    International Nuclear Information System (INIS)

    Mueller, Clemens

    2011-01-01

    The interaction of superconducting circuits with additional quantum systems is a topic that has found extensive study in the recent past. In the limit where the added system are incoherent, this is the standard field of decoherence and the system dynamics can be described by a simple master equation. In the other limit however, when the additional parts are coherent, the resulting time-evolution can become more complicated. In this thesis we have investigated the interaction of superconducting circuits with coherent and incoherent two-level defects. We have shown theoretical calculations characterizing this interaction for all relevant parameter regimes. In the weak coupling limit, the interaction can be described in an effective bath picture, where the TLS act as parts of a large, decohering environment. For strong coupling, however, the coherent dynamics of the full coupled system has to be considered. We show the calculations of the coupled time-evolution and again characterize the interaction by an effective decoherence rate. We also used experimental data to characterize the microscopic origin of the defects and the details of their interaction with the circuits. The results obtained by analyzing spectroscopic data allow us to place strong constraint on several microscopic models for the observed TLS. However, these calculations are not yet fully conclusive as to the physical nature of the TLS. We propose additional experiments to fully characterize the interaction part of the Hamiltonian, thus providing the answer to the question of the physical origin of the coupling. Additionally we have developed a method to directly drive individual defect states via virtual excitation of the qubit. This method allows one to directly probe the properties of single TLS and possibly make use of their superior coherence times for quantum information purposes. The last part of this thesis provided a way for a possible implementation of geometric quantum computation in

  16. Effects of mass defect in atomic clocks

    Science.gov (United States)

    Taichenachev, A. V.; Yudin, V. I.

    2018-01-01

    We consider some implications of the mass defect on the frequency of atomic transitions. We have found that some well-known frequency shifts (such as gravitational and quadratic Doppler shifts) can be interpreted as consequences of the mass defect, i.e., without the need for the concept of time dilation used in special and general relativity theories. Moreover, we show that the inclusion of the mass defect leads to previously unknown shifts for clocks based on trapped ions..

  17. Phosphorous–vacancy–oxygen defects in silicon

    KAUST Repository

    Wang, Hao

    2013-07-30

    Electronic structure calculations employing the hybrid functional approach are used to gain fundamental insight in the interaction of phosphorous with oxygen interstitials and vacancies in silicon. It recently has been proposed, based on a binding energy analysis, that phosphorous–vacancy–oxygen defects may form. In the present study we investigate the stability of this defect as a function of the Fermi energy for the possible charge states. Spin polarization is found to be essential for the charge neutral defect.

  18. Research In Diagnosing Bearing Defects From Vibrations

    Science.gov (United States)

    Zoladz, T.; Earhart, E.; Fiorucci, T.

    1995-01-01

    Report describes research in bearing-defect signature analysis - use of vibration-signal analysis to diagnose defects in roller and ball bearings. Experiments performed on bearings in good condition and other bearings in which various parts scratched to provide known defects correlated with vibration signals. Experiments performed on highly instrumented motor-driven rotor assembly at speeds up to 10,050 r/min, using accelerometers, velocity probes, and proximity sensors mounted at various locations on assembly to measure vibrations.

  19. Thermophysical spectroscopy of defect states in silicon

    International Nuclear Information System (INIS)

    Igamberdyev, Kh.T.; Mamadalimov, A.T.; Khabibullaev, P.K.

    1989-01-01

    The present work deals with analyzing the possibilities of using the non-traditional thermophysical methods to study a defect structure in silicon. For this purpose, the temperature dependences of thermophysical properties of defect silicon are investigated. A number of new, earlier unknown physical phenomena in silicon are obtained, and their interpretation has enabled one to establish the main physical mechanisms of formation of deep defect states in silicon

  20. Renyi entropy and conformal defects

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Lorenzo [Humboldt-Univ. Berlin (Germany). Inst. fuer Physik; Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik; Meineri, Marco [Scuola Normale Superiore, Pisa (Italy); Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Istituto Nazionale di Fisica Nucleare, Pisa (Italy); Myers, Robert C. [Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Smolkin, Michael [California Univ., Berkely, CA (United States). Center for Theoretical Physics and Department of Physics

    2016-04-18

    We propose a field theoretic framework for calculating the dependence of Renyi entropies on the shape of the entangling surface in a conformal field theory. Our approach rests on regarding the corresponding twist operator as a conformal defect and in particular, we define the displacement operator which implements small local deformations of the entangling surface. We identify a simple constraint between the coefficient defining the two-point function of the displacement operator and the conformal weight of the twist operator, which consolidates a number of distinct conjectures on the shape dependence of the Renyi entropy. As an example, using this approach, we examine a conjecture regarding the universal coefficient associated with a conical singularity in the entangling surface for CFTs in any number of spacetime dimensions. We also provide a general formula for the second order variation of the Renyi entropy arising from small deformations of a spherical entangling surface, extending Mezei's results for the entanglement entropy.

  1. Universe as a topological defect

    International Nuclear Information System (INIS)

    Anabalon, Andres; Willison, Steven; Zanelli, Jorge

    2008-01-01

    Four-dimensional Einstein's general relativity is shown to arise from a gauge theory for the conformal group, SO(4,2). The theory is constructed from a topological dimensional reduction of the six-dimensional Euler density integrated over a manifold with a four-dimensional topological defect. The resulting action is a four-dimensional theory defined by a gauged Wess-Zumino-Witten term. An ansatz is found which reduces the full set of field equations to those of Einstein's general relativity. When the same ansatz is replaced in the action, the gauged WZW term reduces to the Einstein-Hilbert action. Furthermore, the unique coupling constant in the action can be shown to take integer values if the fields are allowed to be analytically continued to complex values

  2. Neural Tube Defects and Pregnancy

    Directory of Open Access Journals (Sweden)

    Emine Çoşar

    2009-09-01

    Full Text Available OBJECTIVE: Neural tube defects are congenital malformations those mostly causing life-long morbidities. They are prevented by the periconseptional folic acid usage and prenatal diagnostic methods. MATERIALS-METHODS: Pregnants from Afyonkarahisar and neighbourhood cities applied to our hospital and determined NTD, were investigated. RESULTS: In our obstetrics clinic 1403 delivery were made and 43 of them had fetus with NTD. Among these fetuses 41.3% had meningomyelocel, 17.4% had meningocel, 21.7% had encephalocel, 8.7% had unencephali and 4.3% had iniencephali. CONCLUSION: Incidence of NTD is high in our region and geographic region, nutrition and other socioeconomic factors may be related to the high incidence. Education of the mother and periconceptional folic acid usage may reduce teh incidence of NTD.

  3. Renyi entropy and conformal defects

    International Nuclear Information System (INIS)

    Bianchi, Lorenzo; Myers, Robert C.; Smolkin, Michael

    2016-01-01

    We propose a field theoretic framework for calculating the dependence of Renyi entropies on the shape of the entangling surface in a conformal field theory. Our approach rests on regarding the corresponding twist operator as a conformal defect and in particular, we define the displacement operator which implements small local deformations of the entangling surface. We identify a simple constraint between the coefficient defining the two-point function of the displacement operator and the conformal weight of the twist operator, which consolidates a number of distinct conjectures on the shape dependence of the Renyi entropy. As an example, using this approach, we examine a conjecture regarding the universal coefficient associated with a conical singularity in the entangling surface for CFTs in any number of spacetime dimensions. We also provide a general formula for the second order variation of the Renyi entropy arising from small deformations of a spherical entangling surface, extending Mezei's results for the entanglement entropy.

  4. INO80 Chromatin Remodeling Coordinates Metabolic Homeostasis with Cell Division

    Directory of Open Access Journals (Sweden)

    Graeme J. Gowans

    2018-01-01

    Full Text Available Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the yeast metabolic cycle (YMC. Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here, we demonstrate that the INO80 chromatin-remodeling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC1-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin to restrict proliferation to metabolically optimal states.

  5. Paternal occupation and birth defects: findings from the National Birth Defects Prevention Study.

    NARCIS (Netherlands)

    Desrosiers, T.A.; Herring, A.H.; Shapira, S.K.; Hooiveld, M.; Luben, T.J.; Herdt-Losavio, M.L.; Lin, S.; Olshan, A.F.

    2012-01-01

    Objectives: Several epidemiological studies have suggested that certain paternal occupations may be associated with an increased prevalence of birth defects in offspring. Using data from the National Birth Defects Prevention Study, the authors investigated the association between paternal occupation

  6. Defining defect specifications to optimize photomask production and requalification

    Science.gov (United States)

    Fiekowsky, Peter

    2006-10-01

    Reducing defect repairs and accelerating defect analysis is becoming more important as the total cost of defect repairs on advanced masks increases. Photomask defect specs based on printability, as measured on AIMS microscopes has been used for years, but the fundamental defect spec is still the defect size, as measured on the photomask, requiring the repair of many unprintable defects. ADAS, the Automated Defect Analysis System from AVI is now available in most advanced mask shops. It makes the use of pure printability specs, or "Optimal Defect Specs" practical. This software uses advanced algorithms to eliminate false defects caused by approximations in the inspection algorithm, classify each defect, simulate each defect and disposition each defect based on its printability and location. This paper defines "optimal defect specs", explains why they are now practical and economic, gives a method of determining them and provides accuracy data.

  7. Modeling the relationships among internal defect features and external Appalachian hardwood log defect indicators

    Science.gov (United States)

    R. Edward. Thomas

    2009-01-01

    As a hardwood tree grows and develops, surface defects such as branch stubs and wounds are overgrown. Evidence of these defects remain on the log surface for decades and in many instances for the life of the tree. As the tree grows the defect is encapsulated or grown over by new wood. During this process the appearance of the defect in the tree's bark changes. The...

  8. Acute fatal metabolic complications in alkaptonuria.

    Science.gov (United States)

    Davison, A S; Milan, A M; Gallagher, J A; Ranganath, L R

    2016-03-01

    Alkaptonuria (AKU) is a rare inherited metabolic disorder of tyrosine metabolism that results from a defect in an enzyme called homogentisate 1,2-dioxygenase. The result of this is that homogentisic acid (HGA) accumulates in the body. HGA is central to the pathophysiology of this disease and the consequences observed; these include spondyloarthropathy, rupture of ligaments/muscle/tendons, valvular heart disease including aortic stenosis and renal stones. While AKU is considered to be a chronic progressive disorder, it is clear from published case reports that fatal acute metabolic complications can also occur. These include oxidative haemolysis and methaemoglobinaemia. The exact mechanisms underlying the latter are not clear, but it is proposed that disordered metabolism within the red blood cell is responsible for favouring a pro-oxidant environment that leads to the life threatening complications observed. Herein the role of red blood cell in maintaining the redox state of the body is reviewed in the context of AKU. In addition previously reported therapeutic strategies are discussed, specifically with respect to why reported treatments had little therapeutic effect. The potential use of nitisinone for the management of patients suffering from the acute metabolic decompensation in AKU is proposed as an alternative strategy.

  9. Frequency of cardiac defects among children at echocardiography centre in a teaching hospital

    International Nuclear Information System (INIS)

    Malik, A.S.; Majeed, R.; Channer, M.S.; Saleem, M.I.

    2010-01-01

    Objective: To assess frequency of cardiac defects among children from birth to 12 years of age on each Methodology: A cross sectional study was conducted at echocardiography centre in coronary care unit at Bahawal Victoria Hby Paediatric Transthoracic echo probe; 2-D colour Doppler, Acuson CV-70 and Niemo-30 echocardiography machines. Mothers of children with cardiac defects were interviewed at the echocardiography centre. Variables included were A- Muscular plus Vascular defects; B- Valvular defects; C-Pericardial effusion; D- Dextrocardia and E- Congestive cardiac failure. History of children for sore throat followed by joint pains; history of mothers for drug intake (antihypertensive, antipyretic, anti-emetic, hypoglycaemic) as well as chronic diseases (diabetes mellitus, hypertension, anaemia) during pregnancy were surveyed. Parity of mothers, their cousin marriages, and family socio-economic status was also inquired. The results were tabulated, analyzed and finally subjected to suitable test of significant (SR of proportion) to find out statistical significant if any. Results: It was found that out of 150 patients, 76 (50.66%) were suffering from Cardiac muscular and Vascular defects, 61 (40.66%) Valvular defects, 7 (4.66%) Pericardial effusion, 2 (1.33%) Dextrocardia and 4 (2.66%) from Congestive Cardiac Failure. According to age, 54 (36%) were from birth to 3 years of age and 51 (34%) from 10 to 12 years. There was history of Rheumatic fever among 45 (30%) children. There were 106 (70.6%) children from lower socio-economic class and 79 (52.6%) parents had history of cousin marriages. Conclusion: Frequency of cardiac defects was more in children of male sex, lower socio-economic group, from birth to three years age and children from primipara mothers in our specified locality. Rheumatic fever, cousin's marriage, and prescribed drugs intake during pregnancy (for metabolic and hormonal disorders) were other contributors to cardiac defects. (author)

  10. Dental enamel defects predict adolescent health indicators: A cohort study among the Tsimane' of Bolivia.

    Science.gov (United States)

    Masterson, Erin E; Fitzpatrick, Annette L; Enquobahrie, Daniel A; Mancl, Lloyd A; Eisenberg, Dan T A; Conde, Esther; Hujoel, Philippe P

    2018-05-01

    Bioarchaeological findings have linked defective enamel formation in preadulthood with adult mortality. We investigated how defective enamel formation in infancy and childhood is associated with risk factors for adult morbidity and mortality in adolescents. This cohort study of 349 Amerindian adolescents (10-17 years of age) related extent of enamel defects on the central maxillary incisors (none, less than 1/3, 1/3 to 2/3, more than 2/3) to adolescent anthropometrics (height, weight) and biomarkers (hemoglobin, glycated hemoglobin, white blood cell count, and blood pressure). Risk differences and 95% confidence intervals were estimated using multiple linear regression. Enamel defects and stunted growth were compared in their ability to predict adolescent health indicators using log-binomial regression and receiver operating characteristics (ROCs). Greater extent of defective enamel formation on the tooth surface was associated with shorter height (-1.35 cm, 95% CI: -2.17, -0.53), lower weight (-0.98 kg, 95% CI: -1.70, -0.26), lower hemoglobin (-0.36 g/dL, 95% CI: -0.59, -0.13), lower glycated hemoglobin (-0.04 %A 1c , 95% CI: -0.08, -0.00008), and higher white blood cell count (0.74 10 9 /L, 95% CI: 0.35, 1.14) in adolescence. Extent of enamel defects and stunted growth independently performed similarly as risk factors for adverse adolescent outcomes, including anemia, prediabetes/type II diabetes, elevated WBC count, prehypertension/hypertension, and metabolic health. Defective enamel formation in infancy and childhood predicted adolescent health outcomes and may be primarily associated with infection. Extent of enamel defects and stunted growth may be equally predictive of adverse adolescent health outcomes. © 2018 Wiley Periodicals, Inc.

  11. Failures and Defects in the Building Process

    DEFF Research Database (Denmark)

    Jørgensen, Kirsten

    2009-01-01

    Function failures, defects, mistakes and poor communication are major problems for the construction sector. As the empirical element in the research, a large construction site was observed from the very start to the very end and all failures and defects of a certain size were recorded and analysed...

  12. Treatment of osteochondral defects of the talus

    NARCIS (Netherlands)

    van Bergen, C. J. A.; de Leeuw, P. A. J.; van Dijk, C. N.

    2008-01-01

    This review article provides a current concepts overview of osteochondral defects of the talus, with special emphasis on treatment options, their indications and future developments. Osteochondral defects of the talar dome are mostly caused by a traumatic event. They may lead to deep ankle pain on

  13. Indicators for Building Process without Final Defects -

    DEFF Research Database (Denmark)

    Jørgensen, Kirsten; Rasmussen, Grane Mikael Gregaard; Thuesen, Christian Langhoff

    2011-01-01

    This article introduces the preliminary data analysis, as well as the underlying theories and methods for identifying the indicators for building process without final defects. Since 2004, the Benchmark Centre for the Danish Construction Sector (BEC) has collected information about legal defects...

  14. Positron analysis of defects in metals

    NARCIS (Netherlands)

    van Veen, A.; Kruseman, A.C.; Schut, H.; Mijnarends, P.E.; Kooi, B.J.; de Hosson, J.T.M.; Jean, YC; Eldrup, M; Schrader, DM; West, RN

    1997-01-01

    New methods are discussed to improve defect analysis. The first method employs mapping of two shape parameters, S and W, of the positron annihilation photopeak. It is demonstrated that the combined use of S and W allows to a better discrimination of defects. The other method is based on background

  15. Defect structure of electrodeposited chromium layers

    International Nuclear Information System (INIS)

    Marek, T.; Suevegh, K.; Vertes, A.; El-Sharif, M.; McDougall, J.; Chisolm, C.U.

    2000-01-01

    Positron annihilation spectroscopy was applied to study the effects of pre-treatment and composition of substrates on the quality and defect structure of electrodeposited thick chromium coatings. The results show that both parameters are important, and a scenario is proposed why the mechanically polished substrate gives more defective film than the electro polished one.

  16. Defect structure of electrodeposited chromium layers

    Energy Technology Data Exchange (ETDEWEB)

    Marek, T. E-mail: marek@para.chem.elte.hu; Suevegh, K.; Vertes, A.; El-Sharif, M.; McDougall, J.; Chisolm, C.U

    2000-06-01

    Positron annihilation spectroscopy was applied to study the effects of pre-treatment and composition of substrates on the quality and defect structure of electrodeposited thick chromium coatings. The results show that both parameters are important, and a scenario is proposed why the mechanically polished substrate gives more defective film than the electro polished one.

  17. Birth defects in children with newborn encephalopathy

    NARCIS (Netherlands)

    Felix, JF; Badawi, N; Kurinczuk, JJ; Bower, C; Keogh, JM; Pemberton, PJ

    2000-01-01

    This study was designed to investigate birth defects found in association with newborn encephalopathy. All possible birth defects were ascertained in a population-based study of 276 term infants with moderate or severe encephalopathy and 564 unmatched term control infants. A strong association

  18. Iodide-trapping defect of the thyroid

    International Nuclear Information System (INIS)

    Pannall, P.R.; Steyn, A.F.; Van Reenen, O.

    1978-01-01

    We describe a grossly hypothyroid 50-year-old woman, mentally retarded since birth. On the basis of her history of recurrent goitre, absence of 131 I neck uptake and a low saliva/plasma 131 I ratio, congenital hypothyroidism due to a defect of the iodide-trapping mechanism was diagnosed. Other family members studied did not have the defect

  19. Impurity Role In Mechanically Induced Defects

    International Nuclear Information System (INIS)

    Howell, R.H.; Asoka-Kumar, P.; Hartley, J.; Sterne, P.

    2000-01-01

    An improved understanding of dislocation dynamics and interactions is an outstanding problem in the multi scale modeling of materials properties, and is the current focus of major theoretical efforts world wide. We have developed experimental and theoretical tools that will enable us to measure and calculate quantities defined by the defect structure. Unique to the measurements is a new spectroscopy that determines the detailed elemental composition at the defect site. The measurements are based on positron annihilation spectroscopy performed with a 3 MeV positron beam [1]. Positron annihilation spectroscopy is highly sensitive to dislocations and associated defects and can provide unique elements of the defect size and structure. Performing this spectroscopy with a highly penetrating positron beam enables flexibility in sample handling. Experiments on fatigued and stressed samples have been done and in situ measurement capabilities have been developed. We have recently performed significant upgrades to the accelerator operation and novel new experiments have been performed [2-4] To relate the spectrographic results and the detailed structure of a defect requires detailed calculations. Measurements are coupled with calculated results based on a description of positions of atoms at the defect. This gives an atomistic view of dislocations and associated defects including impurity interactions. Our ability to probe impurity interactions is a unique contribution to defect understanding not easily addressed by other atomistic spectroscopies

  20. Hypoglycaemia related to inherited metabolic diseases in adults

    Directory of Open Access Journals (Sweden)

    Douillard Claire

    2012-05-01

    Full Text Available Abstract In non-diabetic adult patients, hypoglycaemia may be related to drugs, critical illness, cortisol or glucagon insufficiency, non-islet cell tumour, insulinoma, or it may be surreptitious. Nevertheless, some hypoglycaemic episodes remain unexplained, and inborn errors of metabolism (IEM should be considered, particularly in cases of multisystemic involvement. In children, IEM are considered a differential diagnosis in cases of hypoglycaemia. In adulthood, IEM-related hypoglycaemia can persist in a previously diagnosed childhood disease. Hypoglycaemia may sometimes be a presenting sign of the IEM. Short stature, hepatomegaly, hypogonadism, dysmorphia or muscular symptoms are signs suggestive of IEM-related hypoglycaemia. In both adults and children, hypoglycaemia can be clinically classified according to its timing. Postprandial hypoglycaemia can be an indicator of either endogenous hyperinsulinism linked to non-insulinoma pancreatogenic hypoglycaemia syndrome (NIPHS, unknown incidence in adults or very rarely, inherited fructose intolerance. Glucokinase-activating mutations (one family are the only genetic disorder responsible for NIPH in adults that has been clearly identified so far. Exercise-induced hyperinsulinism is linked to an activating mutation of the monocarboxylate transporter 1 (one family. Fasting hypoglycaemia may be caused by IEM that were already diagnosed in childhood and persist into adulthood: glycogen storage disease (GSD type I, III, 0, VI and IX; glucose transporter 2 deficiency; fatty acid oxidation; ketogenesis disorders; and gluconeogenesis disorders. Fasting hypoglycaemia in adulthood can also be a rare presenting sign of an IEM, especially in GSD type III, fatty acid oxidation [medium-chain acyl-CoA dehydrogenase (MCAD, ketogenesis disorders (3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA lyase deficiency, and gluconeogenesis disorders (fructose-1,6-biphosphatase deficiency].

  1. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects

    NARCIS (Netherlands)

    Smedts, H.P.M.; Rakhshandehroo, M.; Verkleij-Hagoort, A.C.; Vries, de J.H.M.; Ottenkamp, J.; Steegers, E.A.P.; Steegers-Theunissen, R.P.M.

    2008-01-01

    With the exception of studies on folic acid, little evidence is available concerning other nutrients in the pathogenesis of congenital heart defects (CHDs). Fatty acids play a central role in embryonic development, and the B-vitamins riboflavin and nicotinamide are co-enzymes in lipid metabolism.

  2. Epigenetic profiles in children with a neural tube defect; a case-control study in two populations

    NARCIS (Netherlands)

    L. Stolk (Lisette); M.I. Both (Marieke); N.H. van Mill (Nina); M.M.P.J. Verbiest (Michael); P.H.C. Eilers (Paul); H. Zhu (Huiping); L. Suarez (Lucina); A.G. Uitterlinden (André); R.P.M. Steegers-Theunissen (Régine)

    2013-01-01

    textabstractFolate deficiency is implicated in the causation of neural tube defects (NTDs). The preventive effect of periconceptional folic acid supplement use is partially explained by the treatment of a deranged folate-dependent one carbon metabolism, which provides methyl groups for

  3. Defect-Tolerant Monolayer Transition Metal Dichalcogenides

    DEFF Research Database (Denmark)

    Pandey, Mohnish; Rasmussen, Filip Anselm; Kuhar, Korina

    2016-01-01

    Localized electronic states formed inside the band gap of a semiconductor due to crystal defects can be detrimental to the material's optoelectronic properties. Semiconductors with a lower tendency to form defect induced deep gap states are termed defect-tolerant. Here we provide a systematic first...... the gap. These ideas are made quantitative by introducing a descriptor that measures the degree of similarity of the conduction and valence band manifolds. Finally, the study is generalized to nonpolar nanoribbons of the TMDs where we find that only the defect sensitive materials form edge states within......-principles investigation of defect tolerance in 29 monolayer transition metal dichalcogenides (TMDs) of interest for nanoscale optoelectronics. We find that the TMDs based on group VI and X metals form deep gap states upon creation of a chalcogen (S, Se, Te) vacancy, while the TMDs based on group IV metals form only...

  4. Teratology: from science to birth defects prevention.

    Science.gov (United States)

    Rasmussen, Sonja A; Erickson, J David; Reef, Susan E; Ross, Danielle S

    2009-01-01

    One of the goals of birth defects research is to better understand risk or preventive factors for birth defects so that strategies for prevention can be developed. In this article, we have selected four areas of birth defects research that have led to the development of prevention strategies. These areas include rubella virus as a cause of congenital rubella syndrome, folic acid as a preventive factor for neural tube defects, cytomegalovirus infection as a cause of birth defects and developmental disabilities, and alcohol as a cause of fetal alcohol spectrum disorders. For each of these areas, we review key clinical and research findings that led to the identification of the risk or preventive factor, milestones in the development of prevention strategies, and the progress made thus far toward prevention.

  5. Defective Reduction in Frozen Pie Manufacturing Process

    Science.gov (United States)

    Nooted, Oranuch; Tangjitsitcharoen, Somkiat

    2017-06-01

    The frozen pie production has a lot of defects resulting in high production cost. Failure mode and effect analysis (FMEA) technique has been applied to improve the frozen pie process. Pareto chart is also used to determine the major defects of frozen pie. There are 3 main processes that cause the defects which are the 1st freezing to glazing process, the forming process, and the folding process. The Risk Priority Number (RPN) obtained from FMEA is analyzed to reduce the defects. If RPN of each cause exceeds 45, the process will be considered to be improved and selected for the corrective and preventive actions. The results showed that RPN values decreased after the correction. Therefore, the implementation of FMEA technique can help to improve the performance of frozen pie process and reduce the defects approximately 51.9%.

  6. Defect accumulation under cascade damage conditions

    DEFF Research Database (Denmark)

    Trinkaus, H.; Singh, B.N.; Woo, C.H.

    1994-01-01

    in terms of this reaction kinetics taking into account cluster production, dissociation, migration and annihilation at extended sinks. Microstructural features which are characteristic of cascade damage and cannot be explained in terms of the conventional single defect reaction kinetics are emphasized......There is now ample evidence from both experimental and computer simulation studies that in displacement cascades not only intense recombination takes place but also efficient clustering of both self-interstitial atoms (SIAs) and vacancies. The size distributions of the two types of defects produced...... reactions kinetics associated with the specific features of cascade damage is described, with emphasis on asymmetries between SIA and vacancy type defects concerning their production, stability, mobility and interactions with other defects. Defect accumulation under cascade damage conditions is discussed...

  7. Defect pin behaviour in the DFR

    International Nuclear Information System (INIS)

    Sloss, W.M.; Bagley, K.Q.; Edmonds, E.; Potter, P.E.

    1979-01-01

    A program of defective fuel pin irradiations has been carried out in the DFR. This program employed fuel pins which had failed during previous irradiations (natural defects) and pins in which simulated failures (artificial defects) had been induced prior to irradiation or during an intermediate examination stage at moderate or substantial burnups. The artificial defects simulated longitudinal ruptures and were normally located at positions near the top, middle and bottom of the pin where clad temperatures were 450, 540 and 630 0 C respectively. The fuel was mixed U-Pu oxide, and fuel form, stoichiometry, clad type, pin diameter, linear rating, and burnup were among the variables examined. The defect pin tests were normally carried out in single pin or trefoil type vehicles. After irradiation all the pins were subjected to the normal nondestructive examination procedures and the visual, radiographic, gamma-scanning, and dimensional change results are presented. Several pins were destructively examined and the metallographic data are discussed

  8. Tritium releases, birth defects and infant deaths

    International Nuclear Information System (INIS)

    1991-01-01

    The AECB has published a report 'Tritium releases from the Pickering Nuclear Generating Station and Birth Defects and Infant Mortality in Nearby Communities 1971-1988' (report number INFO-0401). This presents the results of a detailed analysis of deaths and birth defects occurring in infants born to mothers living in the area (25 Km radius) of the Pickering nuclear power plant, over an 18-year period. The analysis looked at the frequency of these defects and deaths in comparison to the general rate for Ontario, and also in relation to airborne and waterborne releases of tritium from the power plant. The overall conclusion was that the rates of infant death and birth defects were generally not higher in the study population than in all of Ontario. There was no prevalent relationship between these deaths and defects and tritium releases measured either at the power plant or by ground monitoring stations t some distance from the facility

  9. CHANGING OF THE BIOCHEMICAL INDICES ON REGENERATION OF EXPERIMENTAL DEFECT OF THE MANDIBLE BONE

    Directory of Open Access Journals (Sweden)

    A. Borysenko

    2012-09-01

    Full Text Available Summary. The results of an experimental biochemical investigation on the influence of the proposed drug composition for the experimental mandible bone defect regeneration in rats were presented. The high efficiency and osteoregenerative properties of this paste were shown. The experimental investigations showed that the proposed drug composition exerts a considerable normalization influence upon the biochemical indicators of bone mineral metabolism, comparable to Collapan influence.

  10. Wafer plane inspection for advanced reticle defects

    Science.gov (United States)

    Nagpal, Rajesh; Ghadiali, Firoz; Kim, Jun; Huang, Tracy; Pang, Song

    2008-05-01

    Readiness of new mask defect inspection technology is one of the key enablers for insertion & transition of the next generation technology from development into production. High volume production in mask shops and wafer fabs demands a reticle inspection system with superior sensitivity complemented by a low false defect rate to ensure fast turnaround of reticle repair and defect disposition (W. Chou et al 2007). Wafer Plane Inspection (WPI) is a novel approach to mask defect inspection, complementing the high resolution inspection capabilities of the TeraScanHR defect inspection system. WPI is accomplished by using the high resolution mask images to construct a physical mask model (D. Pettibone et al 1999). This mask model is then used to create the mask image in the wafer aerial plane. A threshold model is applied to enhance the inspectability of printing defects. WPI can eliminate the mask restrictions imposed on OPC solutions by inspection tool limitations in the past. Historically, minimum image restrictions were required to avoid nuisance inspection stops and/or subsequent loss of sensitivity to defects. WPI has the potential to eliminate these limitations by moving the mask defect inspections to the wafer plane. This paper outlines Wafer Plane Inspection technology, and explores the application of this technology to advanced reticle inspection. A total of twelve representative critical layers were inspected using WPI die-to-die mode. The results from scanning these advanced reticles have shown that applying WPI with a pixel size of 90nm (WPI P90) captures all the defects of interest (DOI) with low false defect detection rates. In validating CD predictions, the delta CDs from WPI are compared against Aerial Imaging Measurement System (AIMS), where a good correlation is established between WPI and AIMSTM.

  11. Mitochondrial respiratory chain Complex I defects in Fanconi anemia complementation group A.

    Science.gov (United States)

    Ravera, Silvia; Vaccaro, Daniele; Cuccarolo, Paola; Columbaro, Marta; Capanni, Cristina; Bartolucci, Martina; Panfoli, Isabella; Morelli, Alessandro; Dufour, Carlo; Cappelli, Enrico; Degan, Paolo

    2013-10-01

    Fanconi anemia (FA) is a rare and complex inherited blood disorder of the child. At least 15 genes are associated with the disease. The highest frequency of mutations belongs to groups A, C and G. Genetic instability and cytokine hypersensitivity support the selection of leukemic over non-leukemic stem cells. FA cellular phenotype is characterized by alterations in red-ox state, mitochondrial functionality and energy metabolism as reported in the past however a clear picture of the altered biochemical phenotype in FA is still elusive and the final biochemical defect(s) still unknown. Here we report an analysis of the respiratory fluxes in FANCA primary fibroblasts, lymphocytes and lymphoblasts. FANCA mutants show defective respiration through Complex I, diminished ATP production and metabolic sufferance with an increased AMP/ATP ratio. Respiration in FANCC mutants is normal. Treatment with N-acetyl-cysteine (NAC) restores oxygen consumption to normal level. Defective respiration in FANCA mutants appear correlated with the FA pro-oxidative phenotype which is consistent with the altered morphology of FANCA mitochondria. Electron microscopy measures indeed show profound alterations in mitochondrial ultrastructure and shape. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. A proposed defect tracking model for classifying the inserted defect reports to enhance software quality control.

    Science.gov (United States)

    Sultan, Torky; Khedr, Ayman E; Sayed, Mostafa

    2013-01-01

    NONE DECLARED Defect tracking systems play an important role in the software development organizations as they can store historical information about defects. There are many research in defect tracking models and systems to enhance their capabilities to be more specifically tracking, and were adopted with new technology. Furthermore, there are different studies in classifying bugs in a step by step method to have clear perception and applicable method in detecting such bugs. This paper shows a new proposed defect tracking model for the purpose of classifying the inserted defects reports in a step by step method for more enhancement of the software quality.

  13. How to 'visualize' lattice defects

    International Nuclear Information System (INIS)

    Doi, Kenji

    1974-01-01

    Methods to recognize objects are discussed. In case of optics, lenses are used, and light from objects passing through the lenses focuses on focal planes. The amplitude of light on the focal planes in given as a function of the structure factor of scattering light from objects, images of objects are made on image planes. In case of X-ray or neutron diffraction, lenses which make images by X-ray or neutrons can not be made, accordingly images cannot be obtained. Images can be seen with electron microscopes. By X-ray or thermal neutron diffraction, intensity on focal planes in observed, and the defects to be studied are recognized as diffuse scattering. Since it is necessary to minimize aberration in case of image observation with electron microscopes, slits are used to utilize electron beam near optical axis exclusively. Therefore large resolving power cannot be expected. The information concerning structure obtained from focal planes is of statistical nature, and that from image planes is local information. The principle of neutron topography, by which the informations concerning local points are obtained, is explained. A photograph of LiF irradiated by 0.5 MeV proton beam was taken by the topographic method, and shown in this paper. (Kato, T.)

  14. Metabolism and disease

    National Research Council Canada - National Science Library

    Grodzicker, Terri; Stewart, David J; Stillman, Bruce

    2011-01-01

    ...), cellular, organ system (cardiovascular, bone), and organismal (timing and life span) scales. Diseases impacted by metabolic imbalance or dysregulation that were covered in detail included diabetes, obesity, metabolic syndrome, and cancer...

  15. Characterization of the structure and chemistry of defects in materials

    International Nuclear Information System (INIS)

    Larson, B.C.; Ruehle, M.; Seidman, D.N.

    1988-01-01

    Research programs, presented at the materials research symposium, on defects in materials are presented. Major areas include: point defects, defect aggregates, and ordering; defects in non-metals and semiconductors; atomic resolution imaging of defects; and gain boundaries, interfaces, and layered materials. Individual projects are processed separately for the data bases

  16. A Role for Cytosolic Fumarate Hydratase in Urea Cycle Metabolism and Renal Neoplasia

    Directory of Open Access Journals (Sweden)

    Julie Adam

    2013-05-01

    Full Text Available The identification of mutated metabolic enzymes in hereditary cancer syndromes has established a direct link between metabolic dysregulation and cancer. Mutations in the Krebs cycle enzyme, fumarate hydratase (FH, predispose affected individuals to leiomyomas, renal cysts, and cancers, though the respective pathogenic roles of mitochondrial and cytosolic FH isoforms remain undefined. On the basis of comprehensive metabolomic analyses, we demonstrate that FH1-deficient cells and tissues exhibit defects in the urea cycle/arginine metabolism. Remarkably, transgenic re-expression of cytosolic FH ameliorated both renal cyst development and urea cycle defects associated with renal-specific FH1 deletion in mice. Furthermore, acute arginine depletion significantly reduced the viability of FH1-deficient cells in comparison to controls. Our findings highlight the importance of extramitochondrial metabolic pathways in FH-associated oncogenesis and the urea cycle/arginine metabolism as a potential therapeutic target.

  17. Distribution of defects in wind turbine blades and reliability assessment of blades containing defects

    DEFF Research Database (Denmark)

    Stensgaard Toft, Henrik; Branner, Kim; Berring, Peter

    2009-01-01

    on the assumption that one error in the production process tends to trigger several defects. For both models additional information about number, type and size of the defects is included as stochastic variables. The probability of failure for a wind turbine blade will not only depend on variations in the material......In the present paper two stochastic models for the distribution of defects in wind turbine blades are proposed. The first model assumes that the individual defects are completely randomly distributed in the blade. The second model assumes that the defects occur in clusters of different size based...... properties and the load but also on potential defects in the blades. As a numerical example the probability of failure is calculated for the main spar both with and without defects in terms of delaminations. The delaminations increase the probability of failure compared to a perfect blade, but by applying...

  18. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

    The International Metabolic Engineering Society (IMES) and the Society for Biological Engineering (SBE), both technological communities of the American Institute of Chemical Engineers (AIChE), hosted the Metabolic Engineering X Conference (ME-X) on June 15-19, 2014 at the Westin Bayshore in Vancouver, British Columbia. It attracted 395 metabolic engineers from academia, industry and government from around the globe.

  19. Developmental dental defects in children exposed to PCBs

    Energy Technology Data Exchange (ETDEWEB)

    Jan, J. [Ljubljana Univ. (Slovenia). Fac. of Medicine; Sovcikova, E.; Kovrizhnykh, I.; Wimmerova, S.; Trnovec, T. [Slovak Medical Univ., Bratislava (Slovakia). Inst. of Preventive and Clinical Medicine; Kocan, A. [Institute of Preventive and Clinical Medicine, Bratislava (Slovakia). Dept. of Toxic Organic Pollutants

    2004-09-15

    Developing enamel is sensitive to a wide range of local and systemic disturbances. Because of the absolute metabolic stability of its structure, changes in enamel during its development are permanent in nature. Polychlorinated biphenyls (PCB) have been shown to disturb tooth development in experimental animals, but only limited amounts of data exist on their adverse effects in humans. Dental changes such as mottled, chipped, carious, and neonatal teeth have been reported in accidentally exposed humans. Nevertheless, co-contamination with polychlorinated dibenzo-furans (PCDFs) was largely responsible for the overall toxicity4. Alaluusua et al. found that developmental dental defects were correlated with the total exposure to polychlorinated aromatic hydrocarbons via mother's milk. The correlation was strong with exposure to prevailing levels of polychlorinated dibenzo-p-dioxins (PCDD) and furans (PCDF) but weak with exposure to PCBs alone. In our previous study we have shown developmental dental defects in children exposed to PCBs alone6, suggesting that the developing human teeth are vulnerable to PCBs. In the Michalovce region of eastern Slovakia, PCBs from a chemical plant manufacturing Delors contaminated the surrounding district7. The total serum PCB levels in samples from the general population there exceeded by several times the background levels in subjects living in a comparable unexposed Svidnik district. PCB levels in breast milk samples in the Michalovce region were the highest in Slovakia. Levels of toxic polychlorinated aromatics (PCDFs, PCNs, and planar PCBs) in technical Delors were high. The aim of this study was to evaluate the effects of long-term exposure to PCBs, measured at the individual level, on developmental dental defects in children in eastern Slovakia.

  20. Professor John Scott, folate and neural tube defects.

    Science.gov (United States)

    Hoffbrand, A Victor

    2014-02-01

    John Scott (1940-2013) was born in Dublin where he was to spend the rest of his career, both as an undergraduate and subsequently Professor of Biochemistry and Nutrition at Trinity College. His research with the talented group of scientists and clinicians that he led has had a substantial impact on our understanding of folate metabolism, mechanisms of its catabolism and deficiency. His research established the leading theory of folate involvement with vitamin B12 in the pathogenesis of vitamin B12 neuropathy. He helped to establish the normal daily intake of folate and the increased requirements needed either in food or as a supplement before and during pregnancy to prevent neural tube defects. He also suggested a dietary supplement of vitamin B12 before and during pregnancy to reduce the risk of neural tube defects. It would be an appropriate epitaph if fortification of food with folic acid became mandatory in the UK and Ireland, as it is in over 70 other countries. © 2013 John Wiley & Sons Ltd.

  1. Reduction in Defect Content in ODS Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Ritherdon, J.; Jones, A.R.

    2000-02-01

    The work detailed within this report is a continuation of earlier work that was carried out under contract number IDX-SY382V. The earlier work comprised a literature review of the sources and types of defects found principally in Fe-based ODS alloys together with a series of experiments designed to identify defects in ODS Fe{sub 3}Al material and recommend methods of defect reduction. Defects found in the Mechanically Alloyed (MA) ODS Fe{sub 3}Al included regions of incomplete MA, porosity, intrusions and fine-grained stringers. Some defects tended to be found in association with one another e.g. intrusions and fine-grained stringers. Preliminary powder separation experiments were also performed. The scope and objectives of the present work were laid out in the technical proposal ``Reduction in Defect Content in ODS Alloys--II'' which formed the basis of amendment 3 of the current contract. The current studies were devised in the context of the preceding work with a view to extending and concluding certain experiments while exploring new avenues of investigation of defect control and reduction where appropriate. All work proposed was within the context of achieving an ODS Fe{sub 3}Al alloy of improved overall quality and potential creep performance (particularly) in the consolidated, release condition. The interim outturn of the experimental work performed is also reported.

  2. Modeling of Powder Bed Manufacturing Defects

    Science.gov (United States)

    Mindt, H.-W.; Desmaison, O.; Megahed, M.; Peralta, A.; Neumann, J.

    2018-01-01

    Powder bed additive manufacturing offers unmatched capabilities. The deposition resolution achieved is extremely high enabling the production of innovative functional products and materials. Achieving the desired final quality is, however, hampered by many potential defects that have to be managed in due course of the manufacturing process. Defects observed in products manufactured via powder bed fusion have been studied experimentally. In this effort we have relied on experiments reported in the literature and—when experimental data were not sufficient—we have performed additional experiments providing an extended foundation for defect analysis. There is large interest in reducing the effort and cost of additive manufacturing process qualification and certification using integrated computational material engineering. A prerequisite is, however, that numerical methods can indeed capture defects. A multiscale multiphysics platform is developed and applied to predict and explain the origin of several defects that have been observed experimentally during laser-based powder bed fusion processes. The models utilized are briefly introduced. The ability of the models to capture the observed defects is verified. The root cause of the defects is explained by analyzing the numerical results thus confirming the ability of numerical methods to provide a foundation for rapid process qualification.

  3. Extrusion product defects: a statistical study

    International Nuclear Information System (INIS)

    Qamar, S.Z.; Arif, A.F.M.; Sheikh, A.K.

    2003-01-01

    In any manufacturing environment, defects resulting in rework or rejection are directly related to product cost and quality, and indirectly linked with process, tooling and product design. An analysis of product defects is therefore integral to any attempt at improving productivity, efficiency and quality. Commercial aluminum extrusion is generally a hot working process and consists of a series of different but integrated operations: billet preheating and sizing, die set and container preheating, billet loading and deformation, product sizing and stretching/roll-correction, age hardening, and painting/anodizing. Product defects can be traced back to problems in billet material and preparation, die and die set design and maintenance, process variable aberrations (ram speed, extrusion pressure, container temperature, etc), and post-extrusion treatment (age hardening, painting/anodizing, etc). The current paper attempts to analyze statistically the product defects commonly encountered in a commercial hot aluminum extrusion setup. Real-world rejection data, covering a period of nine years, has been researched and collected from a local structural aluminum extrusion facility. Rejection probabilities have been calculated for all the defects studied. The nine-year rejection data have been statistically analyzed on the basis of (i) an overall breakdown of defects, (ii) year-wise rejection behavior, (iii) breakdown of defects in each of three cost centers: press, anodizing, and painting. (author)

  4. Exploring atomic defects in molybdenum disulphide monolayers

    KAUST Repository

    Hong, Jinhua; Hu, Zhixin; Probert, Matt; Li, Kun; Lv, Danhui; Yang, Xinan; Gu, Lin; Mao, Nannan; Feng, Qingliang; Xie, Liming; Zhang, Jin; Wu, Dianzhong; Zhang, Zhiyong; Jin, Chuanhong; Ji, Wei; Zhang, Xixiang; Yuan, Jun; Zhang, Ze

    2015-01-01

    Defects usually play an important role in tailoring various properties of two-dimensional materials. Defects in two-dimensional monolayer molybdenum disulphide may be responsible for large variation of electric and optical properties. Here we present a comprehensive joint experiment-theory investigation of point defects in monolayer molybdenum disulphide prepared by mechanical exfoliation, physical and chemical vapour deposition. Defect species are systematically identified and their concentrations determined by aberration-corrected scanning transmission electron microscopy, and also studied by ab-initio calculation. Defect density up to 3.5 × 10 13 cm '2 is found and the dominant category of defects changes from sulphur vacancy in mechanical exfoliation and chemical vapour deposition samples to molybdenum antisite in physical vapour deposition samples. Influence of defects on electronic structure and charge-carrier mobility are predicted by calculation and observed by electric transport measurement. In light of these results, the growth of ultra-high-quality monolayer molybdenum disulphide appears a primary task for the community pursuing high-performance electronic devices.

  5. Platelet rich fibrin in jaw defects

    Science.gov (United States)

    Nica, Diana; Ianes, Emilia; Pricop, Marius

    2016-03-01

    Platelet rich fibrin (PRF) is a tissue product of autologous origin abundant in growth factors, widely used in regenerative procedures. Aim of the study: Evaluation of the regenerative effect of PRF added in the bony defects (after tooth removal or after cystectomy) Material and methods: The comparative nonrandomized study included 22 patients divided into 2 groups. The first group (the test group) included 10 patients where the bony defects were treated without any harvesting material. The second group included 12 patients where the bony defects were filled with PRF. The bony defect design was not critical, with one to two walls missing. After the surgeries, a close clinically monitoring was carried out. The selected cases were investigated using both cone beam computer tomography (CBCT) and radiographic techniques after 10 weeks postoperatively. Results: Faster bone regeneration was observed in the bony defects filled with PRF comparing with the not grafted bony defects. Conclusions: PRF added in the bony defects accelerates the bone regeneration. This simplifies the surgical procedures and decreases the economic costs.

  6. Exploring atomic defects in molybdenum disulphide monolayers

    KAUST Repository

    Hong, Jinhua

    2015-02-19

    Defects usually play an important role in tailoring various properties of two-dimensional materials. Defects in two-dimensional monolayer molybdenum disulphide may be responsible for large variation of electric and optical properties. Here we present a comprehensive joint experiment-theory investigation of point defects in monolayer molybdenum disulphide prepared by mechanical exfoliation, physical and chemical vapour deposition. Defect species are systematically identified and their concentrations determined by aberration-corrected scanning transmission electron microscopy, and also studied by ab-initio calculation. Defect density up to 3.5 × 10 13 cm \\'2 is found and the dominant category of defects changes from sulphur vacancy in mechanical exfoliation and chemical vapour deposition samples to molybdenum antisite in physical vapour deposition samples. Influence of defects on electronic structure and charge-carrier mobility are predicted by calculation and observed by electric transport measurement. In light of these results, the growth of ultra-high-quality monolayer molybdenum disulphide appears a primary task for the community pursuing high-performance electronic devices.

  7. Defect Chemistry of Oxides for Energy Applications.

    Science.gov (United States)

    Schweke, Danielle; Mordehovitz, Yuval; Halabi, Mahdi; Shelly, Lee; Hayun, Shmuel

    2018-05-31

    Oxides are widely used for energy applications, as solid electrolytes in various solid oxide fuel cell devices or as catalysts (often associated with noble metal particles) for numerous reactions involving oxidation or reduction. Defects are the major factors governing the efficiency of a given oxide for the above applications. In this paper, the common defects in oxide systems and external factors influencing the defect concentration and distribution are presented, with special emphasis on ceria (CeO 2 ) based materials. It is shown that the behavior of a variety of oxide systems with respect to properties relevant for energy applications (conductivity and catalytic activity) can be rationalized by general considerations about the type and concentration of defects in the specific system. A new method based on transmission electron microscopy (TEM), recently reported by the authors for mapping space charge defects and measuring space charge potentials, is shown to be of potential importance for understanding conductivity mechanisms in oxides. The influence of defects on gas-surface reactions is exemplified on the interaction of CO 2 and H 2 O with ceria, by correlating between the defect distribution in the material and its adsorption capacity or splitting efficiency. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Interdisciplinary Management of an Isolated Intrabony Defect

    Directory of Open Access Journals (Sweden)

    Sheetal Ghivari

    2014-01-01

    Full Text Available The treatment of intrabony defects is a real challenge in molar teeth as it is chronic, slowly progressing disease which needs timely intervention. Periodontal inflammation associated with intrabony defect is not a separate entity as it secondarily affects the pulp causing retrograde pulpitis. However, treatment of these lesions will be complicated due to extensive bone loss. The tooth was endodontically treated followed by periodontal surgery to eliminate the deep periodontal pocket and promote bone fill in osseous defect. PepGen P-15 composited with platelet rich plasma was utilized for enhancing bone formation. The combination of these graft materials provides synergistic effect on bone regeneration.

  9. Mass defect effects in atomic clocks

    Science.gov (United States)

    Yudin, Valeriy; Taichenachev, Alexey

    2018-03-01

    We consider some implications of the mass defect on the frequency of atomic transitions. We have found that some well-known frequency shifts (the gravitational shift and motion-induced shifts such as quadratic Doppler and micromotion shifts) can be interpreted as consequences of the mass defect in quantum atomic physics, i.e. without the need for the concept of time dilation used in special and general relativity theories. Moreover, we show that the inclusion of the mass defect leads to previously unknown shifts for clocks based on trapped ions.

  10. Tibial and fibular developmental fields defects

    International Nuclear Information System (INIS)

    Khoury, N.J.; Haddad, M.C.; Hourani, M.H.

    1999-01-01

    Malformations of the lower limbs are rare and heterogeneous anomalies. To explain the diversity and complexity of these abnormalities, authors introduced the concept of tibial and fibular developmental fields. Defects in these fields are responsible for different malformations, which have been described, to our knowledge, in only one report in the radiology literature. We present a case of a newborn with femoral bifurcation, absent fibulae and talar bones, ankle and foot malformations, and associated atrial septal defect. Our case is an example of defects in both fibular and tibial developmental fields. (orig.)

  11. Study of irradiation induced defects in silicon

    International Nuclear Information System (INIS)

    Pal, Gayatri; Sebastian, K.C.; Somayajulu, D.R.S.; Chintalapudi, S.N.

    2000-01-01

    Pure high resistivity (6000 ohm-cm) silicon wafers were recoil implanted with 1.8 MeV 111 In ions. As-irradiated wafers showed a 13 MHz quadrupole interaction frequency, which was not observed earlier. The annealing behaviour of these defects in the implanted wafers was studied between room temperature and 1073 K. At different annealing temperatures two more interaction frequencies corresponding to defect complexes D2 and D3 are observed. Even though the experimental conditions were different, these are identical to the earlier reported ones. Based on an empirical point charge model calculation, an attempt is made to identify the configuration of these defect complexes. (author)

  12. Dimensions of defects determined by radiographical testing

    International Nuclear Information System (INIS)

    Oesterberg, J.

    Normally industrial radiography using x-rays or radionuclides gives information on the existence of defects in welds. These defects may in some instances be harmless, the size of the flaw is important. Radiography may be used for determining the thickness of the defect in many cases, by measuring the blackening of the photographic film used. The report gives a theoretical treatment of the problems and goes on to practical examples of the application. For flaws that have a width of at least 0.3 mm, a thickness of the order 0.1 mm can be determined with sufficient accuracy in materials 40 mm thick.(P.Aa.)

  13. Altered metabolism in cancer

    Directory of Open Access Journals (Sweden)

    Locasale Jason W

    2010-06-01

    Full Text Available Abstract Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs. See research article: http://www.biomedcentral.com/1752-0509/4/58/

  14. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds...... of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation....

  15. Knowledge of birth defects among nursing mothers in a developing ...

    African Journals Online (AJOL)

    sponsibility is placed on parents in the recognition of these defects. Objectives: The .... be prevented, detected, inherited or treated; and if they knew that folic ... could be used to prevent certain birth defects. ..... birth defects such as smoking.

  16. Vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association with Mayer-Rokitansky-Küster-Hauser syndrome in co-occurrence

    DEFF Research Database (Denmark)

    Bjørsum-Meyer, Thomas; Herlin, Morten; Qvist, Niels

    2016-01-01

    Background: The vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome are rare conditions. We aimed to present two cases with the vertebral defect, anal atresia, cardiac...... defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser co-occurrence from our local surgical center and through a systematic literature search detect published cases. Furthermore, we aimed to collect existing knowledge...... in the embryopathogenesis and genetics in order to discuss a possible link between the vertebral defect, anal atresia, cardiac defect, tracheoesophageal fistula/esophageal atresia, renal defect, and limb defect association and Mayer-Rokitansky-Küster-Hauser syndrome. Case presentation: Our first case was a white girl...

  17. Muscle Involvement in Preservation of Metabolic Flexibility by Treatment using n-3 PUFA or Rosiglitazone in Dietary-Obese Mice

    NARCIS (Netherlands)

    Medrikova, Dasa; Schothorst, van Evert; Bunschoten, Annelies; Flachs, Pavel; Kopecky, Jan; Keijer, Jaap

    2012-01-01

    Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the

  18. The effects of photobiomodulation on healing of bone defects in streptozotocin induced diabetic rats

    Science.gov (United States)

    Martinez Costa Lino, Maíra D.; Bastos de Carvalho, Fabíola; Ferreira Moraes, Michel; Augusto Cardoso, José; Pinheiro, Antônio L. B.; Maria Pedreira Ramalho, Luciana

    2011-03-01

    Previous studies have shown positive effects of Low level laser therapy (LLLT) on the repair of bone defects, but there are only a few that associates bone healing in the presence of a metabolic disorder as Diabetes Melitus and LLLT. The aim of this study was to assess histologically the effect of LLLT (AsGaAl), 780nm, 70mW, CW, Ø~0.4mm, 16J/cm2 per session) on the repair of surgical defects created in the femur of diabetic and non-diabetic Wistar Albinus rats. Surgical bone defects were created in 60 animals divided into four groups of 15 animals each: Group C (non-diabetic - control); Group CL (non-diabetic + LLLT); Group CD (diabetic); Group CDL (diabetic + LLLT). The animals on the irradiated group received 16 J/cm2 per session divided into four points around the defect, being the first irradiation immediately after surgery and repeated every 48h for 14 days. The animals were killed 15, 21 and 30 days after surgery. The results of the present investigation showed histological evidence of improved amount of collagen fibers at early stages of the bone healing (15 days) and increased amount of well organized bone trabeculae at the end of the experimental period (30 days) on irradiated animals, (diabetic and non-diabetic) compared to non irradiated ones. It is concluded that LLLT has a positive biomodulative effect on the healing process of bone defects, even when diabetes mellitus was present.

  19. Nucleic acid-based approaches to investigate microbial-related cheese quality defects

    Directory of Open Access Journals (Sweden)

    Daniel eO Sullivan

    2013-01-01

    Full Text Available AbstractThe microbial profile of cheese is a primary determinant of cheese quality. Microorganisms can contribute to aroma and taste defects, form biogenic amines, cause gas and secondary fermentation defects, and can contribute to cheese pinking and mineral deposition issues. These defects may be as a result of seasonality and the variability in the composition of the milk supplied, variations in cheese processing parameters, as well as the nature and number of the non-starter microorganisms which come from the milk or other environmental sources. Such defects can be responsible for production and product recall costs and thus represent a significant economic burden for the dairy industry worldwide. Traditional non-molecular approaches are often considered biased and have inherently slow turnaround times. Molecular techniques can provide early and rapid detection of defects that result from the presence of specific spoilage microbes and, ultimately, assist in enhancing cheese quality and reducing costs. Here we review the DNA-based methods that are available to detect/quantify spoilage bacteria, and relevant metabolic pathways, in cheeses and, in the process, highlight how these strategies can be employed to improve cheese quality and reduce the associated economic burden on cheese processors.

  20. Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis.

    Science.gov (United States)

    Ivanovski, Ivan; Ješić, Miloš; Ivanovski, Ana; Garavelli, Livia; Ivanovski, Petar

    2017-11-28

    The underlying pathophysiology of liver dysfunction in urea cycle disorders (UCDs) is still largely elusive. There is some evidence that the accumulation of urea cycle (UC) intermediates are toxic for hepatocyte mitochondria. It is possible that liver injury is directly caused by the toxicity of ammonia. The rarity of UCDs, the lack of checking of iron level in these patients, superficial knowledge of UC and an underestimation of the metabolic role of fumaric acid, are the main reasons that are responsible for the incomprehension of the mechanism of liver injury in patients suffering from UCDs. Owing to our routine clinical practice to screen for iron overload in severely ill neonates, with the focus on the newborns suffering from acute liver failure, we report a case of citrullinemia with neonatal liver failure and high blood parameters of iron overload. We hypothesize that the key is in the decreased-deficient fumaric acid production in the course of UC in UCDs that causes several sequentially intertwined metabolic disturbances with final result of liver iron overload. The presented hypothesis could be easily tested by examining the patients suffering from UCDs, for liver iron overload. This could be easily performed in countries with a high population and comprehensive national register for inborn errors of metabolism. Providing the hypothesis is correct, neonatal liver damage in patients having UCD can be prevented by the supplementation of pregnant women with fumaric or succinic acid, prepared in the form of iron supplementation pills. After birth, liver damage in patients having UCDs can be prevented by supplementation of these patients with zinc fumarate or zinc succinylate, as well.

  1. ILT based defect simulation of inspection images accurately predicts mask defect printability on wafer

    Science.gov (United States)

    Deep, Prakash; Paninjath, Sankaranarayanan; Pereira, Mark; Buck, Peter

    2016-05-01

    At advanced technology nodes mask complexity has been increased because of large-scale use of resolution enhancement technologies (RET) which includes Optical Proximity Correction (OPC), Inverse Lithography Technology (ILT) and Source Mask Optimization (SMO). The number of defects detected during inspection of such mask increased drastically and differentiation of critical and non-critical defects are more challenging, complex and time consuming. Because of significant defectivity of EUVL masks and non-availability of actinic inspection, it is important and also challenging to predict the criticality of defects for printability on wafer. This is one of the significant barriers for the adoption of EUVL for semiconductor manufacturing. Techniques to decide criticality of defects from images captured using non actinic inspection images is desired till actinic inspection is not available. High resolution inspection of photomask images detects many defects which are used for process and mask qualification. Repairing all defects is not practical and probably not required, however it's imperative to know which defects are severe enough to impact wafer before repair. Additionally, wafer printability check is always desired after repairing a defect. AIMSTM review is the industry standard for this, however doing AIMSTM review for all defects is expensive and very time consuming. Fast, accurate and an economical mechanism is desired which can predict defect printability on wafer accurately and quickly from images captured using high resolution inspection machine. Predicting defect printability from such images is challenging due to the fact that the high resolution images do not correlate with actual mask contours. The challenge is increased due to use of different optical condition during inspection other than actual scanner condition, and defects found in such images do not have correlation with actual impact on wafer. Our automated defect simulation tool predicts

  2. Non-invasive Assessments of Adipose Tissue Metabolism In Vitro.

    Science.gov (United States)

    Abbott, Rosalyn D; Borowsky, Francis E; Quinn, Kyle P; Bernstein, David L; Georgakoudi, Irene; Kaplan, David L

    2016-03-01

    Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with non-invasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored.

  3. Holographic entanglement entropy of surface defects

    Energy Technology Data Exchange (ETDEWEB)

    Gentle, Simon A.; Gutperle, Michael; Marasinou, Chrysostomos [Department of Physics and Astronomy, University of California,Los Angeles, CA 90095 (United States)

    2016-04-12

    We calculate the holographic entanglement entropy in type IIB supergravity solutions that are dual to half-BPS disorder-type surface defects in N=4 supersymmetric Yang-Mills theory. The entanglement entropy is calculated for a ball-shaped region bisected by a surface defect. Using the bubbling supergravity solutions we also compute the expectation value of the defect operator. Combining our result with the previously-calculated one-point function of the stress tensor in the presence of the defect, we adapt the calculation of Lewkowycz and Maldacena http://dx.doi.org/10.1007/JHEP05(2014)025 to obtain a second expression for the entanglement entropy. Our two expressions agree up to an additional term, whose possible origin and significance is discussed.

  4. Holographic entanglement entropy of surface defects

    International Nuclear Information System (INIS)

    Gentle, Simon A.; Gutperle, Michael; Marasinou, Chrysostomos

    2016-01-01

    We calculate the holographic entanglement entropy in type IIB supergravity solutions that are dual to half-BPS disorder-type surface defects in N=4 supersymmetric Yang-Mills theory. The entanglement entropy is calculated for a ball-shaped region bisected by a surface defect. Using the bubbling supergravity solutions we also compute the expectation value of the defect operator. Combining our result with the previously-calculated one-point function of the stress tensor in the presence of the defect, we adapt the calculation of Lewkowycz and Maldacena http://dx.doi.org/10.1007/JHEP05(2014)025 to obtain a second expression for the entanglement entropy. Our two expressions agree up to an additional term, whose possible origin and significance is discussed.

  5. Di-interstitial defect in silicon revisited

    International Nuclear Information System (INIS)

    Londos, C. A.; Antonaras, G.; Chroneos, A.

    2013-01-01

    Infrared spectroscopy was used to study the defect spectrum of Cz-Si samples following fast neutron irradiation. We mainly focus on the band at 533 cm −1 , which disappears from the spectra at ∼170 °C, exhibiting similar thermal stability with the Si-P6 electron paramagnetic resonance (EPR) spectrum previously correlated with the di-interstitial defect. The suggested structural model of this defect comprises of two self-interstitial atoms located symmetrically around a lattice site Si atom. The band anneals out following a first-order kinetics with an activation energy of 0.88 ± 0.3 eV. This value does not deviate considerably from previously quoted experimental and theoretical values for the di-interstitial defect. The present results indicate that the 533 cm −1 IR band originates from the same structure as that of the Si-P6 EPR spectrum

  6. Microcephaly and Other Birth Defects: Zika

    Science.gov (United States)

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Zika and Microcephaly Microcephaly is a birth defect in ... pregnancy or has stopped growing after birth. Congenital Zika Syndrome Congenital Zika syndrome is a unique pattern ...

  7. Ultrasonic determination of the size of defects

    International Nuclear Information System (INIS)

    Zetterwall, T.

    1989-01-01

    The paper presents results from a study of ultrasonic testing of materials. The main topic has been the determination of the size, length and deep, of cracks or defects in stainless steel plates. (K.A.E)

  8. Focal skin defect, limb anomalies and microphthalmia.

    NARCIS (Netherlands)

    Jackson, K.E.; Andersson, H.C.

    2004-01-01

    We describe two unrelated female patients with congenital single focal skin defects, unilateral microphthalmia and limb anomalies. Growth and psychomotor development were normal and no brain malformation was detected. Although eye and limb anomalies are commonly associated, clinical anophthalmia and

  9. Genetic Counseling for Congenital Heart Defects

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Genetic Counseling for Congenital Heart Defects Updated:Jan 19,2018 ... with congenital heart disease considers having children. Genetic counseling can help answer these questions and address your ...

  10. Reduction of Defects in Jewelry Manufacturing

    Science.gov (United States)

    Ayudhya, Phitchaya Phanomwan na; Tangjitsitcharoen, Somkiat

    2017-06-01

    The aim of this research was to reduce the defects of gem bracelet found during manufacturing process at a jewelry company. It was found that gem bracelet product has the highest rejects compared to the rejects found in ring, earring, and pendant products. Types of defect were classified by using Pareto Diagram consisting of gem falling, seam, unclean casting, impinge, and deformation. The causes of defect were analyzed by Cause and Effect Diagram and applied Failure Mode and Effects Analysis (FMEA) was applied during manufacturing processes. This research found that the improvement of manufacturing process could reduce the Risk Priority Number (RPN) and total of all defects by 48.70% and 48.89%, respectively.

  11. Dental Enamel Defects and Celiac Disease

    Science.gov (United States)

    ... Digestive System & How it Works Zollinger-Ellison Syndrome Dental Enamel Defects and Celiac Disease Celiac disease manifestations ... affecting any organ or body system. One manifestation—dental enamel defects—can help dentists and other health ...

  12. Creation of radiation defects in KCl crystals

    International Nuclear Information System (INIS)

    Lushchik, A.Ch.; Pung, L.A.; Khaldre, Yu.Yu.; Kolk, Yu.V.

    1981-01-01

    Optical and EPR methods were used to study the creation of anion and cation Frenkel defects in KCl crystals irradiated by X-ray and VUV-radiation. The decay of excitons with the creation of charged Frenkel defects (α and I centres) was detected and investigated at 4.2 K. The decay of excitons as well as the recombination of electrons with self-trapped holes leads to the creation of neutral Frenkel defects (F and H centres). The creation of Cl 3 - and Vsub(F) centres (cation vacancy is a component of these centres) by X-irradiation at 80 K proves the possibility of cation defects creation in KCl [ru

  13. Infrared computations of defect Schur indices

    Energy Technology Data Exchange (ETDEWEB)

    Córdova, Clay [School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr., Princeton, NJ (United States); Gaiotto, Davide [Perimeter Institute for Theoretical Physics,31 Caroline St., Waterloo, Ontario, N2L 2Y5 (Canada); Shao, Shu-Heng [Jefferson Physical Laboratory, Harvard University,17 Oxford St., Cambridge, MA (United States); School of Natural Sciences, Institute for Advanced Study,1 Einstein Dr., Princeton, NJ (United States)

    2016-11-18

    We conjecture a formula for the Schur index of four-dimensional N=2 theories in the presence of boundary conditions and/or line defects, in terms of the low-energy effective Seiberg-Witten description of the system together with massive BPS excitations. We test our proposal in a variety of examples for SU(2) gauge theories, either conformal or asymptotically free. We use the conjecture to compute these defect-enriched Schur indices for theories which lack a Lagrangian description, such as Argyres-Douglas theories. We demonstrate in various examples that line defect indices can be expressed as sums of characters of the associated two-dimensional chiral algebra and that for Argyres-Douglas theories the line defect OPE reduces in the index to the Verlinde algebra.

  14. Intrinsic defects in 3D printed materials

    OpenAIRE

    Bolton, Christopher; Dagastine, Raymond

    2015-01-01

    We discuss the impact of bulk structural defects on the coherence, phase and polarisation of light passing through transparent 3D printed materials fabricated using a variety of commercial print technologies.

  15. International conference on defects in insulating crystals

    International Nuclear Information System (INIS)

    1977-01-01

    Short summaries of conference papers are presented. Some of the conference topics included transport properties, defect levels, superionic conductors, radiation effects, John-Teller effect, electron-lattice interactions, and relaxed excited states

  16. Apparatus for locating defective nuclear fuel elements

    International Nuclear Information System (INIS)

    Lawrie, W.E.

    1979-01-01

    An ultrasonic search unit for locating defective fuel elements within a fuel assembly used in a water cooled nuclear reactor is presented. The unit is capable of freely traversing the restricted spaces between the fuel elements

  17. Point defects dynamics in a stress field

    International Nuclear Information System (INIS)

    Smetniansky de De Grande, Nelida.

    1989-01-01

    The dependence of anisotropic defect diffusion on stress is studied for a hexagonal close packed (hcp) material under irradiation and uniaxially stressed. The diffusion is described as a discrete process of thermally activated jumps. It is shown that the presence of an external stress field enhances the intrinsic anisotropic diffusion, being this variation determined by the defect dipole tensors' symmetry in the equilibrium and saddle point configurations. Also, the point defect diffusion equations to sinks, like edge dislocations and spherical cavities, are solved and the sink strengths are calculated. The conclusion is that the dynamics of the interaction between defects and sinks is controlled by the changes in diffusivity induced by stress fields. (Author) [es

  18. Genetics Home Reference: abdominal wall defect

    Science.gov (United States)

    ... are two main types of abdominal wall defects: omphalocele and gastroschisis . Omphalocele is an opening in the center of the ... covering the exposed organs in gastroschisis. Fetuses with omphalocele may grow slowly before birth (intrauterine growth retardation) ...

  19. Defect networks and supersymmetric loop operators

    Energy Technology Data Exchange (ETDEWEB)

    Bullimore, Mathew [Perimeter Institute for Theoretical Physics, 31 Caroline Street North, Waterloo, ON N2L 2Y5 (Canada)

    2015-02-10

    We consider topological defect networks with junctions in A{sub N−1} Toda CFT and the connection to supersymmetric loop operators in N=2 theories of class S on a four-sphere. Correlation functions in the presence of topological defect networks are computed by exploiting the monodromy of conformal blocks, generalising the notion of a Verlinde operator. Concentrating on a class of topological defects in A{sub 2} Toda theory, we find that the Verlinde operators generate an algebra whose structure is determined by a set of generalised skein relations that encode the representation theory of a quantum group. In the second half of the paper, we explore the dictionary between topological defect networks and supersymmetric loop operators in the N=2{sup ∗} theory by comparing to exact localisation computations. In this context, the the generalised skein relations are related to the operator product expansion of loop operators.

  20. Electronic structure of point defects in semiconductors

    International Nuclear Information System (INIS)

    Bruneval, Fabien

    2014-01-01

    This 'Habilitation a diriger des Recherches' memoir presents most of my scientific activities during the past 7 years, in the field of electronic structure calculations of defects in solids. Point defects (vacancies, interstitials, impurities) in functional materials are a key parameter to determine if these materials will actually fill the role they have been assigned or not. Indeed, the presence of defects cannot be avoided when the temperature is increased or when the material is subjected to external stresses, such as irradiation in the nuclear reactors and in artificial satellites with solar radiations. However, in many cases, defects are introduced in the materials on purpose to tune the electronic transport, optical or even magnetic properties. This procedure is called the doping of semiconductors, which is the foundation technique for transistors, diodes, or photovoltaic cells. However, doping is not always straightforward and unexpected features may occur, such as doping asymmetry or Fermi level pinning, which can only be explained by complex phenomena involving different types of defects or complexes of defects. In this context, the calculations of electronic structure ab initio is an ideal tool to complement the experimental observations, to gain the understanding of phenomena at the atomic level, and even to predict the properties of defects. The power of the ab initio calculations comes from their ability to describe any system of electrons and nuclei without any specific adjustment. But although there is a strong need for numerical simulations in this field, the ab initio calculations for defects are still under development as of today. The work presented in this memoir summarizes my contributions to methodological developments on this subject. These developments have followed two main tracks. The first topic is the better understanding of the unavoidable finite size effects. Indeed, defects in semiconductors or insulators are generally present in

  1. Elastic interaction energies of defect structures

    International Nuclear Information System (INIS)

    Seitz, E.; de Fontaine, D.

    1976-01-01

    The elastic strain energy between point defects and small disk-shaped clusters of defects are calculated to determine stable configurations. A distortion tensor of tetragonal symmetry is assigned to each impurity atom. The tetragonality ratio t is varied to cover needle-type (t greater than 1), spherical (t = 1) and disk-type (t less than 0) strain fields. To vary the elastic properties of the host material, Fe, Cu, Al, and V were chosen as examples. Computer calculations are based on the microscopic theory of elasticity which emphasizes calculations in discrete Fourier space. Pairs of point defects order along [001] for t less than 1 and along (001) for t = 1 for all host elements. For t greater than 1 fcc lattices and bcc lattices behave differently. It is shown that only certain three dimensional periodic arrangements of parallel and perpendicular disk-like defect clusters are realized for given tetragonality ratio t and host element

  2. Residual Defect Density in Random Disks Deposits.

    Science.gov (United States)

    Topic, Nikola; Pöschel, Thorsten; Gallas, Jason A C

    2015-08-03

    We investigate the residual distribution of structural defects in very tall packings of disks deposited randomly in large channels. By performing simulations involving the sedimentation of up to 50 × 10(9) particles we find all deposits to consistently show a non-zero residual density of defects obeying a characteristic power-law as a function of the channel width. This remarkable finding corrects the widespread belief that the density of defects should vanish algebraically with growing height. A non-zero residual density of defects implies a type of long-range spatial order in the packing, as opposed to only local ordering. In addition, we find deposits of particles to involve considerably less randomness than generally presumed.

  3. International conference on defects in insulating crystals

    Energy Technology Data Exchange (ETDEWEB)

    1977-01-01

    Short summaries of conference papers are presented. Some of the conference topics included transport properties, defect levels, superionic conductors, radiation effects, John-Teller effect, electron-lattice interactions, and relaxed excited states. (SDF)

  4. Filter paper saturated by urine sample in metabolic disorders detection by proton magnetic resonance spectroscopy.

    Science.gov (United States)

    Blasco, Hélène; Garrigue, Marie-Ange; De Vos, Aymeric; Antar, Catherine; Labarthe, François; Maillot, François; Andres, Christian R; Nadal-Desbarats, Lydie

    2010-02-01

    NMR spectroscopy of urine samples is able to diagnose many inborn errors of metabolism (IEM). However, urinary metabolites have a poor stability, requiring special care for routine analysis (storage of urine at -20 or -80 degrees C, fast transport). The aim of our study was to investigate the reliability of dried urine filter paper for urine storage and transport and to evaluate the ability of NMR to detect several IEM using this method. Urine samples from five healthy subjects were analyzed by (1)H NMR following different storage conditions (-20 vs 4 degrees C vs dried on filter paper) and at different time points (24 h, 48 h, 96 h, and 7 days). Urine pattern of fresh urine was considered as a reference. We analyzed the conservation of some amino acids and organic acids using Bland and Altman plot with intraclass correlation coefficient determination. Then, we evaluated the use of filter paper to detect four different IEM (methylmalonic and isovaleric acidurias, ornithine transcarbamylase deficiency, and cystinuria). Analysis of urine samples from healthy subjects revealed a high stability of studied molecules (ICC > 0.8) even after 7 days of storage on filter paper. Moreover, an excellent preservation of metabolites specifically accumulated in IEM was observed when analysis of dried urine filter paper was compared to fresh urine (coefficient of variation storage of dried urine on filter paper is reliable for (1)H NMR spectroscopy analysis. Preservation of urine molecules over time using that method is convenient for routine clinical practice.

  5. Diffuse scattering from crystals with point defects

    International Nuclear Information System (INIS)

    Andrushevsky, N.M.; Shchedrin, B.M.; Simonov, V.I.; Malakhova, L.F.

    2002-01-01

    The analytical expressions for calculating the intensities of X-ray diffuse scattering from a crystal of finite dimensions and monatomic substitutional, interstitial, or vacancy-type point defects have been derived. The method for the determination of the three-dimensional structure by experimental diffuse-scattering data from crystals with point defects having various concentrations is discussed and corresponding numerical algorithms are suggested

  6. [SOX2 defect and anophthalmia and microphthalmia].

    Science.gov (United States)

    Ye, Fu-xiang; Fan, Xian-qun

    2012-11-01

    As a severe congenital developmental disorder, anophthalmia and microphthalmia are usually accompanied with vision impairment and hypoevolutism of the orbit in the affected side. Many genes are involved in anophthalmia and microphthalmia, in which, SOX2 is an important one. The defect of SOX2 causes multiple system disorders, including anophthalmia and microphthalmia. We describe the relationship between the SOX2 defect and anophthalmia/microphthalmia, in order to offer some proposals for the differential diagnosis, treatment and research of anophthalmia and microphthalmia.

  7. Virtues and defects of peruvians colonial heritage

    OpenAIRE

    León, Ramón

    2014-01-01

    This communication reports a study in 691 students (414 women, 277 men, 16-60 years old), who were asked to rate (on a scale of 0 to 4) ten virtues and ten defects of an average Peruvian. The virtues considered were hard-working, honest, enterprising, ambitious, thrifty, sympathetic, creative, tidy, proud, and wel.organized; the defects were lazy, corrupt, conformist, fatalist, spendthrift, individualist, passive, envious, inhibited, talkative. They were asked too to rate the influence of col...

  8. Radioactive fallout and neural tube defects

    Directory of Open Access Journals (Sweden)

    Nejat Akar

    2015-10-01

    Full Text Available Possible link between radioactivity and the occurrence of neural tube defects is a long lasting debate since the Chernobyl nuclear fallout in 1986. A recent report on the incidence of neural defects in the west coast of USA, following Fukushima disaster, brought another evidence for effect of radioactive fallout on the occurrence of NTD’s. Here a literature review was performed focusing on this special subject.

  9. Dural sinus filling defect: intrasigmoid encephalocele

    Science.gov (United States)

    Karatag, Ozan; Cosar, Murat; Kizildag, Betul; Sen, Halil Murat

    2013-01-01

    Filling defects of dural venous sinuses are considered to be a challenging problem especially in case of symptomatic patients. Many lesions have to be ruled out such as sinus thrombosis, arachnoid granulations and tumours. Encephalocele into dural sinus is also a rare cause of these filling defects of dural sinuses. Here, we report an extremely rare case with spontaneous occult invagination of temporal brain tissue into the left sigmoid sinus and accompanying cerebellar ectopia. PMID:24311424

  10. Defect core detection in radiata pine logs

    International Nuclear Information System (INIS)

    Wallace, G.

    1993-01-01

    Internal defect cores in Pinus radiata logs arise primarily from the practice in New Zealand of pruning trees to increase the amount of clear wood. Realising the benefits of this practice when milling the logs is hampered by the lack of a practical method for detecting the defect cores. This report attempts to establish industry requirements for detections and examine techniques which may be suitable. Some trials of a novel technique are described. (author) 19 refs.; 11 figs

  11. Steroidogenic versus Metabolic Programming of Reproductive Neuroendocrine, Ovarian and Metabolic Dysfunctions.

    Science.gov (United States)

    Cardoso, Rodolfo C; Puttabyatappa, Muraly; Padmanabhan, Vasantha

    2015-01-01

    The susceptibility of the reproductive system to early exposure to steroid hormones has become a major concern in our modern societies. Human fetuses are at risk of abnormal programming via exposure to endocrine disrupting chemicals, inadvertent use of contraceptive pills during pregnancy, as well as from excess exposure to steroids due to disease states. Animal models provide an unparalleled resource to understand the developmental origin of diseases. In female sheep, prenatal exposure to testosterone excess results in an array of adult reproductive disorders that recapitulate those seen in women with polycystic ovary syndrome (PCOS), including disrupted neuroendocrine feedback mechanisms, increased pituitary sensitivity to gonadotropin-releasing hormone, luteinizing hormone excess, functional hyperandrogenism, and multifollicular ovarian morphology culminating in early reproductive failure. Prenatal testosterone treatment also leads to fetal growth retardation, insulin resistance, and hypertension. Mounting evidence suggests that developmental exposure to an improper steroidal/metabolic environment may mediate the programming of adult disorders in prenatal testosterone-treated females, and these defects are maintained or amplified by the postnatal sex steroid and metabolic milieu. This review addresses the steroidal and metabolic contributions to the development and maintenance of the PCOS phenotype in the prenatal testosterone-treated sheep model, including the effects of prenatal and postnatal treatment with an androgen antagonist or insulin sensitizer as potential strategies to prevent/ameliorate these dysfunctions. Insights obtained from these intervention strategies on the mechanisms underlying these defects are likely to have translational relevance to human PCOS. © 2015 S. Karger AG, Basel.

  12. EUV actinic defect inspection and defect printability at the sub-32 nm half pitch

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Sungmin; Kearney, Patrick; Wurm, Stefan; Goodwin, Frank; Han, Hakseung; Goldberg, Kenneth; Mochi, Iacopp; Gullikson, Eric M.

    2009-08-01

    Extreme ultraviolet (EUV) mask blanks with embedded phase defects were inspected with a reticle actinic inspection tool (AIT) and the Lasertec M7360. The Lasertec M7360, operated at SEMA TECH's Mask Blank Development Center (MBDC) in Albany, NY, has a sensitivity to multilayer defects down to 40-45 nm, which is not likely sufficient for mask blank development below the 32 nm half-pitch node. Phase defect printability was simulated to calculate the required defect sensitivity for a next generation blank inspection tool to support reticle development for the sub-32 nm half-pitch technology node. Defect mitigation technology is proposed to take advantage of mask blanks with some defects. This technology will reduce the cost of ownership of EUV mask blanks. This paper will also discuss the kind of infrastructure that will be required for the development and mass production stages.

  13. Characterization of lacunar defects by positrons annihilation

    International Nuclear Information System (INIS)

    Barthe, M.F.; Corbel, C.; Blondiaux, G.

    2003-01-01

    Among the nondestructive methods for the study of matter, the positrons annihilation method allows to sound the electronic structure of materials by measuring the annihilation characteristics. These characteristics depend on the electronic density as seen by the positon, and on the electron momentums distribution which annihilate with the positon. The positon is sensible to the coulombian potential variations inside a material and sounds preferentially the regions away from nuclei which represent potential wells. The lacunar-type defects (lack of nuclei) represent deep potential wells which can trap the positon up to temperatures close to the melting. This article describes the principles of this method and its application to the characterization of lacunar defects: 1 - positrons: matter probes (annihilation of electron-positon pairs, annihilation characteristics, positrons sources); 2 - positrons interactions in solids (implantation profiles, annihilation states, diffusion and trapping, positon lifetime spectrum: evolution with the concentration of defects); 3 - measurement of annihilation characteristics with two gamma photons (lifetime spectroscopy with the β + 22 Na isotope, spectroscopy of Doppler enlargement of the annihilation line); 4 - determination of the free volume of defects inside or at the surface of materials (annihilation signature in lacunar defects, lacuna, lacunar clusters and cavities, acceptors nature in semiconductors: ionic or lacunar, interface defects, precipitates in alloys); 5 - conclusions. (J.S.)

  14. Positron annihilation spectroscopy in defects of semiconductors

    CERN Document Server

    Fujinami, M

    2002-01-01

    Interaction of positron and defects, application to research of defects of semiconductor and defects on the surface of semiconductor are explained. Cz (Czochralski)-Si single crystal with 10 sup 1 sup 8 cm sup - sup 3 impurity oxygen was introduced defects by electron irradiation and the positron lifetime was measured at 90K after annealing. The defect size and recovery temperature were determined by the lifetime measurement. The distribution of defects in the depth direction is shown by S-E curve. The chemical state analysis is possible by CBS (Coincidence Doppler Broadening) spectra. The application to silicon-implanted (100 keV, 2x10 sup 1 sup 5 cm sup - sup 2) silicon and oxygen-implanted (180 keV, 2x10 sup 1 sup 5 cm sup - sup 2) silicon are stated. On the oxygen-implanted silicon, the main product was V2 after implantation, V sub 6 O sub 2 at 600degC and V sub 1 sub 0 O sub 6 at 800degC. (S.Y.)

  15. Reduction in Defect Content of ODS Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Ritherdon, J

    2001-05-15

    The work detailed within this report is a continuation of earlier work carried out under contract number 1DX-SY382V. The earlier work comprises a literature review of the sources and types of defects found principally in Fe-based ODS alloys as well as experimental work designed to identify defects in the prototype ODS-Fe{sub 3}Al alloy, deduce their origins and to recommend methods of defect reduction. The present work is an extension of the experimental work already reported and concentrates on means of reduction of defects already identified rather than the search for new defect types. This report also includes results gathered during powder separation trials, conducted by the University of Groningen, Netherlands and coordinated by the University of Liverpool, involving the separation of different metallic powders in terms of their differing densities. The scope and objectives of the present work were laid out in the technical proposal ''Reduction in Defect Content in ODS Alloys-III''. All the work proposed in the ''Statement of Work'' section of the technical proposal has been carried out and all work extra to the ''Statement of Work'' falls within the context of an ODS-Fe{sub 3}Al alloy of improved overall quality and potential creep performance in the consolidated form. The outturn of the experimental work performed is reported in the following sections.

  16. Secondary defects in non-metallic solids

    International Nuclear Information System (INIS)

    Ashbee, K.H.G.; Hobbs, L.W.

    1977-01-01

    This paper points out features of secondary defect formation which are peculiar to non-metallic solids (excluding elemental semiconductors). Most of the materials of interest are compounds of two or more (usually more or less ionic) atomic species, and immediate consequence of which is a need to maintain both stoichiometry (or accommodate non-stoichiometry) and order. Primary defects in these solids, whether produced thermally, chemically or by irradiation, seldom are present or aggregate in exactly stoichiometric proportions, and the resulting extending defect structures can be quite distinct from those found in metallic solids. Where stoichiometry is maintained, it is often convenient to describe extended defects in terms of alterations in the arrangement of 'molecular' units. The adoption of this procedure enables several novel features of extended defect structures in non-metals to be explained. There are several ways in which a range of non-stoichiometry can be accommodated, which include structural elimination of point defects, nucleation of new coherent phases of altered stoichiometry, and decomposition. (author)

  17. Defect assessment procedures at high temperature

    International Nuclear Information System (INIS)

    Ainsworth, R.A.

    1991-01-01

    A comprehensive assessment procedure for the high-temperature response of structures is being produced. The procedure is referred to as R5 and is written as a series of step-by-step instructions in a number of volumes. This paper considers in detail those parts of R5 which address the behaviour of defects. The defect assessment procedures may be applied to defects found in service, postulated defects, or defects formed during operation as a result of creep-fatigue loading. In the last case, a method is described for deducing from endurance data the number of cycles to initiate a crack of a specified size. Under steady loading, the creep crack tip parameter C * is used to assess crack growth. Under cyclic loading, the creep crack growth during dwell periods is stiell governed by C * but crack growth due to cyclic excursions must also be included. This cyclic crack growth is described by an effective stress intensity factor range. A feature of the R5 defect assessment procedures in that they are based on simplified methods and approximate reference stress methods are described which enable C * in a component to be evaluated. It is shown by comparison with theoretical calculations and experimental data that reliable estimates of C * and the associated crack growth are obtained provided realistic creep strain rate date are used in the reference stress approximation. (orig./HP)

  18. Congenital heart defects in Williams syndrome.

    Science.gov (United States)

    Yuan, Shi-Min

    2017-01-01

    Yuan SM. Congenital heart defects in Williams syndrome. Turk J Pediatr 2017; 59: 225-232. Williams syndrome (WS), also known as Williams-Beuren syndrome, is a rare genetic disorder involving multiple systems including the circulatory system. However, the etiologies of the associated congenital heart defects in WS patients have not been sufficiently elucidated and represent therapeutic challenges. The typical congenital heart defects in WS were supravalvar aortic stenosis, pulmonary stenosis (both valvular and peripheral), aortic coarctation and mitral valvar prolapse. The atypical cardiovascular anomalies include tetralogy of Fallot, atrial septal defects, aortic and mitral valvular insufficiencies, bicuspid aortic valves, ventricular septal defects, total anomalous pulmonary venous return, double chambered right ventricle, Ebstein anomaly and arterial anomalies. Deletion of the elastin gene on chromosome 7q11.23 leads to deficiency or abnormal deposition of elastin during cardiovascular development, thereby leading to widespread cardiovascular abnormalities in WS. In this article, the distribution, treatment and surgical outcomes of typical and atypical cardiac defects in WS are discussed.

  19. A novel inspection system for cosmetic defects

    Science.gov (United States)

    Hazra, S.; Roy, R.; Williams, D.; Aylmore, R.; Hollingdale, D.

    2013-12-01

    The appearance of automotive skin panels creates desirability for a product and differentiates it from the competition. Because of the importance of skin panels, considerable care is taken in minimizing defects such as the 'hollow' defect that occur around door-handle depressions. However, the inspection process is manual, subjective and time-consuming. This paper describes the development of an objective and inspection scheme for the 'hollow' defect. In this inspection process, the geometry of a panel is captured using a structured lighting system. The geometry data is subsequently analyzed by a purpose-built wavelet-based algorithm to identify the location of any defects that may be present and to estimate the perceived severity of the defects without user intervention. This paper describes and critically evaluates the behavior of this physically-based algorithm on an ideal and real geometry and compares its result to an actual audit. The results show that the algorithm is capable of objectively locating and classifying 'hollow' defects in actual panels.

  20. Elucidating the Metabolic Plasticity of Cancer: Mitochondrial Reprogramming and Hybrid Metabolic States

    Directory of Open Access Journals (Sweden)

    Dongya Jia

    2018-03-01

    Full Text Available Aerobic glycolysis, also referred to as the Warburg effect, has been regarded as the dominant metabolic phenotype in cancer cells for a long time. More recently, it has been shown that mitochondria in most tumors are not defective in their ability to carry out oxidative phosphorylation (OXPHOS. Instead, in highly aggressive cancer cells, mitochondrial energy pathways are reprogrammed to meet the challenges of high energy demand, better utilization of available fuels and macromolecular synthesis for rapid cell division and migration. Mitochondrial energy reprogramming is also involved in the regulation of oncogenic pathways via mitochondria-to-nucleus retrograde signaling and post-translational modification of oncoproteins. In addition, neoplastic mitochondria can engage in crosstalk with the tumor microenvironment. For example, signals from cancer-associated fibroblasts can drive tumor mitochondria to utilize OXPHOS, a process known as the reverse Warburg effect. Emerging evidence shows that cancer cells can acquire a hybrid glycolysis/OXPHOS phenotype in which both glycolysis and OXPHOS can be utilized for energy production and biomass synthesis. The hybrid glycolysis/OXPHOS phenotype facilitates metabolic plasticity of cancer cells and may be specifically associated with metastasis and therapy-resistance. Moreover, cancer cells can switch their metabolism phenotypes in response to external stimuli for better survival. Taking into account the metabolic heterogeneity and plasticity of cancer cells, therapies targeting cancer metabolic dependency in principle can be made more effective.

  1. Multiscale crystal defect dynamics: A coarse-grained lattice defect model based on crystal microstructure

    Science.gov (United States)

    Lyu, Dandan; Li, Shaofan

    2017-10-01

    Crystal defects have microstructure, and this microstructure should be related to the microstructure of the original crystal. Hence each type of crystals may have similar defects due to the same failure mechanism originated from the same microstructure, if they are under the same loading conditions. In this work, we propose a multiscale crystal defect dynamics (MCDD) model that models defects by considering its intrinsic microstructure derived from the microstructure or material genome of the original perfect crystal. The main novelties of present work are: (1) the discrete exterior calculus and algebraic topology theory are used to construct a scale-up (coarse-grained) dual lattice model for crystal defects, which may represent all possible defect modes inside a crystal; (2) a higher order Cauchy-Born rule (up to the fourth order) is adopted to construct atomistic-informed constitutive relations for various defect process zones, and (3) an hierarchical strain gradient theory based finite element formulation is developed to support an hierarchical multiscale cohesive (process) zone model for various defects in a unified formulation. The efficiency of MCDD computational algorithm allows us to simulate dynamic defect evolution at large scale while taking into account atomistic interaction. The MCDD model has been validated by comparing of the results of MCDD simulations with that of molecular dynamics (MD) in the cases of nanoindentation and uniaxial tension. Numerical simulations have shown that MCDD model can predict dislocation nucleation induced instability and inelastic deformation, and thus it may provide an alternative solution to study crystal plasticity.

  2. Some aspects of copper metabolism in Brindled mice

    International Nuclear Information System (INIS)

    Prins, H.W.

    1981-01-01

    The semi-dominant X-linked mutation in Brindled mice causes a severe copper deficiency of which the hemizygous Brindled mice die between 14 and 21 days post partum. Previously, in analogy to Menkes' disease in man, the primary defect in mutated Brindled mice has been described as a block in the resorption of alimentary copper, i.e., the transport of copper from the intestinal lumen into the portal blood circulation. During this research it became clear that the impaired resorption of alimentary copper is only a part of a more general aberration of copper metabolism in epithelioid cells. Tracer techniques using 64 Cu are used for metabolism studies. (Auth.)

  3. [Menopause and metabolic syndrome].

    Science.gov (United States)

    Meirelles, Ricardo M R

    2014-03-01

    The incidence of cardiovascular disease increases considerably after the menopause. One reason for the increased cardiovascular risk seems to be determined by metabolic syndrome, in which all components (visceral obesity, dyslipidemia, hypertension, and glucose metabolism disorder) are associated with higher incidence of coronary artery disease. After menopause, metabolic syndrome is more prevalent than in premenopausal women, and may plays an important role in the occurrence of myocardial infarction and other atherosclerotic and cardiovascular morbidities. Obesity, an essential component of the metabolic syndrome, is also associated with increased incidence of breast, endometrial, bowel, esophagus, and kidney cancer. The treatment of metabolic syndrome is based on the change in lifestyle and, when necessary, the use of medication directed to its components. In the presence of symptoms of the climacteric syndrome, hormonal therapy, when indicated, will also contribute to the improvement of the metabolic syndrome.

  4. Mitochondrial dysfunction in fatty acid oxidation disorders: insights from human and animal studies

    OpenAIRE

    Wajner, Moacir; Amaral, Alexandre?Umpierrez

    2016-01-01

    Mitochondrial fatty acid oxidation (FAO) plays a pivotal role in maintaining body energy homoeostasis mainly during catabolic states. Oxidation of fatty acids requires approximately 25 proteins. Inherited defects of FAO have been identified in the majority of these proteins and constitute an important group of inborn errors of metabolism. Affected patients usually present with severe hepatopathy, cardiomyopathy and skeletal myopathy, whereas some patients may suffer acute and/or progressive e...

  5. Congenital malformations of hands and feet in Smith-Lemli-Opitz syndrome

    Directory of Open Access Journals (Sweden)

    N. A. Kovalenko-Klychkova

    2013-01-01

    Full Text Available Smith-Lemli-Opitz syndrome is rare genetic disorder with multiple limb malformations and neurological manifestation, caused by inborn defect of cholesterol metabolism. Congenital deformities of feet and hands are most common orthopedic symptoms in this syndrome. Description of a girl with Smith-Lemli-Opitz syndrome demonstrates specific features of this disorder and emphasize the importance of proper interpretation of orthopedic malformations for early diagnosis of genetic conditions.

  6. Metabolic syndrome and menopause

    OpenAIRE

    Jouyandeh, Zahra; Nayebzadeh, Farnaz; Qorbani, Mostafa; Asadi, Mojgan

    2013-01-01

    Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3) criteria t...

  7. [Metabolic functions and sport].

    Science.gov (United States)

    Riviere, Daniel

    2004-01-01

    Current epidemiological studies emphasize the increased of metabolic diseases of the adults, such as obesity, type-2 diabetes and metabolic syndromes. Even more worrying is the rising prevalence of obesity in children. It is due more to sedentariness, caused more by inactivity (television, video, games, etc.) than by overeating. Many studies have shown that regular physical activities benefit various bodily functions including metabolism. After dealing with the major benefits of physical exercise on some adult metabolic disorders, we focus on the prime role played by physical activity in combating the public health problem of childhood obesity.

  8. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

    Mathematical models of the cellular metabolism have a special interest within biotechnology. Many different kinds of commercially important products are derived from the cell factory, and metabolic engineering can be applied to improve existing production processes, as well as to make new processes...... availability of genomic information and powerful analytical techniques, mathematical models also serve as a tool for understanding the cellular metabolism and physiology....... available. Both stoichiometric and kinetic models have been used to investigate the metabolism, which has resulted in defining the optimal fermentation conditions, as well as in directing the genetic changes to be introduced in order to obtain a good producer strain or cell line. With the increasing...

  9. Gestational dating by metabolic profile at birth: a California cohort study.

    Science.gov (United States)

    Jelliffe-Pawlowski, Laura L; Norton, Mary E; Baer, Rebecca J; Santos, Nicole; Rutherford, George W

    2016-04-01

    Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (PTBs and term births. Using a linear discriminate analyses-derived linear function, we were able to sort PTBs and term births accurately with sensitivities and specificities of ≥95% in both the training and testing subsets. Assignment of a specific week of gestation in those identified as PTBs resulted in the correct assignment of week ±2 weeks in 89.8% of all newborns in the training and 91.7% of those in the testing subset. When PTB rates were modeled using the metabolic dating algorithm compared to fetal ultrasound, PTB rates were 7.15% vs 6.11% in the training subset and 7.31% vs 6.25% in the testing subset. When considered in combination with birthweight and hours of age at test, metabolic profile evaluated within 8 days of birth appears to be a useful measure of PTB and, among those born preterm, of specific week of gestation ±2 weeks. Dating by metabolic profile may be useful in instances where there is no fetal ultrasound due to lack of availability or late entry into care. Copyright © 2016 The Authors. Published

  10. Gestational dating by metabolic profile at birth: a California cohort study

    Science.gov (United States)

    Jelliffe-Pawlowski, Laura L.; Norton, Mary E.; Baer, Rebecca J.; Santos, Nicole; Rutherford, George W.

    2016-01-01

    Background Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. Objective We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (PTBs and term births. Using a linear discriminate analyses-derived linear function, we were able to sort PTBs and term births accurately with sensitivities and specificities of ≥95% in both the training and testing subsets. Assignment of a specific week of gestation in those identified as PTBs resulted in the correct assignment of week ±2 weeks in 89.8% of all newborns in the training and 91.7% of those in the testing subset. When PTB rates were modeled using the metabolic dating algorithm compared to fetal ultrasound, PTB rates were 7.15% vs 6.11% in the training subset and 7.31% vs 6.25% in the testing subset. Conclusion When considered in combination with birthweight and hours of age at test, metabolic profile evaluated within 8 days of birth appears to be a useful measure of PTB and, among those born preterm, of specific week of gestation ±2 weeks. Dating by metabolic profile may be useful in instances where there is no fetal ultrasound due to lack of availability or late entry into care. PMID

  11. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, J; Davis, E J

    1973-01-01

    The metabolism and metabolic effects of fluoroacetylcarnitine have been investigated. Carnitineacetyltransferase transfers the fluoro-acetyl group of fluoroacetylcarnitine nearly as rapidly to CoA as the acetyl group of acetylcarnitine. Fluorocitrate is then formed by citrate synthase, but this second reaction is relatively slow. The fluorocitrate formed intramitochondrially inhibits the metabolism of citrate. In heart and skeletal muscle mitochondria the accumulated citrate inhibits citrate synthesis and the ..beta..-oxidation of fatty acids. Free acetate is formed, presumably because accumulated acetyl-CoA is hydrolyzed. In liver mitochondria the accumulation of citrate leads to a relatively increased rate of ketogenesis. Increased ketogenesis is obtained also upon the addition of citrate to the reaction mixture.

  12. Logistic planning and control of reworking perishable production defectives

    NARCIS (Netherlands)

    R.H. Teunter (Ruud); S.D.P. Flapper

    2001-01-01

    textabstractWe consider a production line that is dedicated to a single product. Produced lots may be non-defective, reworkable defective, or non-reworkable defective. The production line switches between production and rework. After producing a fixed number (N) of lots, all reworkable defective

  13. Channeling studies of impurity-defect interactions in silicon

    International Nuclear Information System (INIS)

    Wiggers, L.W.

    1978-01-01

    This thesis deals with the mechanism of defect production and interaction of introduced defects with impurity atoms in silicon single crystals. Defects are created by irradiation with energetic light particles (.2 - 3 MeV H + or He + ions). Mostly simple defects like vacancies and interstitials are produced during bombardment. (Auth.)

  14. Observation of defects evolution in electronic materials

    Science.gov (United States)

    Jang, Jung Hun

    Advanced characterization techniques have been used to obtain a better understanding of the microstructure of electronic materials. The structural evolution, especially defects, has been investigated during the film growth and post-growth processes. Obtaining the relation between the defect evolution and growth/post-growth parameters is very important to obtain highly crystalline films. In this work, the growth and post-growth related defects in GaN, ZnO, strained-Si/SiGe films have been studied using several advanced characterization techniques. First of all, the growth of related defects in GaN and p-type ZnO films have been studied. The effect of growth parameters, such as growth temperature, gas flow rate, dopants used during the deposition, on the crystalline quality of the GaN and ZnO layers was investigated by high resolution X-ray diffraction (HRXRD) and transmission electron microscopy (TEM). In GaN films, it was found that the edge and mixed type threading dislocations were the dominant defects so that the only relevant figure of merit (FOM) for the crystalline quality should be the FWHM value of o-RC of the surface perpendicular plane which could be determined by a grazing incidence x-ray diffraction (GIXD) technique as shown in this work. The understanding of the relationship between the defect evolution and growth parameters allowed for the growth of high crystalline GaN films. For ZnO films, it was found that the degree of texture and crystalline quality of P-doped ZnO films decreased with increasing the phosphorus atomic percent. In addition, the result from the x-ray diffraction line profile analysis showed that the 0.5 at % P-doped ZnO film showed much higher microstrain than the 1.0 at % P-doped ZnO film, which indicated that the phosphorus atoms were segregated with increasing P atomic percentage. Finally, post-growth related defects in strained-Si/SiGe films were investigated. Postgrowth processes used in this work included high temperature N2

  15. Fatty acid metabolism: target for metabolic syndrome

    OpenAIRE

    Wakil, Salih J.; Abu-Elheiga, Lutfi A.

    2009-01-01

    Fatty acids are a major energy source and important constituents of membrane lipids, and they serve as cellular signaling molecules that play an important role in the etiology of the metabolic syndrome. Acetyl-CoA carboxylases 1 and 2 (ACC1 and ACC2) catalyze the synthesis of malonyl-CoA, the substrate for fatty acid synthesis and the regulator of fatty acid oxidation. They are highly regulated and play important roles in the energy metabolism of fatty acids in animals, including humans. They...

  16. Metabolic oxidative stress in cancer biology and therapy

    International Nuclear Information System (INIS)

    Spitz, Douglas R.

    2014-01-01

    Cancer cells (relative to normal cells) exhibit increased glycolysis and pentose cycle activity. These metabolic alterations were thought to arise from damage to the respiratory mechanism and cancer cells were thought to compensate for this defect by increasing glycolysis (Science 132:309). In addition to its role in ATP production, glucose metabolism results in the formation of pyruvate and NADPH which both play an integral role in peroxide detoxification (Ann. NY Acad. Sci. 899:349). Recently, cancer cells have been shown to have enhanced susceptibility to glucose deprivation-induced oxidative stress, relative to normal cells, that is mediated by reactive oxygen species (ROS; Biochem.J. 418:29-37). These results support the hypothesis that cancer cells may have a defect in mitochondrial respiration leading to increased steady-state levels of ROS (i.e., O 2 and H 2 O 2 ) and glucose metabolism may be increased to provide reducing equivalents to compensate for this defect. The application of these findings to developing new combined modality cancer therapy protocols will be discussed. (author)

  17. Congenital heart defects and extracardiac malformations.

    Science.gov (United States)

    Rosa, Rosana Cardoso M; Rosa, Rafael Fabiano M; Zen, Paulo Ricardo G; Paskulin, Giorgio Adriano

    2013-06-01

    To review the association between congenital heart defects and extracardiac malformations. Scientific articles were searched in the Medline, Lilacs, and SciELO databases, using the descriptors "congenital heart disease," "congenital heart defects," "congenital cardiac malformations," "extracardiac defects," and "extracardiac malformations." All case series that specifically explored the association between congenital heart defects and extracardiac malformations were included. Congenital heart diseases are responsible for about 40% of birth defects, being one of the most common and severe malformations. Extracardiac malformations are observed in 7 to 50% of the patients with congenital heart disease, bringing a greater risk of comorbidity and mortality and increasing the risks related to heart surgery. Different studies have attempted to assess the presence of extracardiac abnormalities in patients with congenital heart disease. Among the changes described, those of the urinary tract are more often reported. However, no study has evaluated all patients in the same way. Extracardiac abnormalities are frequent among patients with congenital heart disease, and patients with these alterations may present an increased risk of morbimortality. Therefore, some authors have been discussing the importance and cost-effectiveness of screening these children for other malformations by complementary exams.

  18. Ultrasonic NDE Simulation for Composite Manufacturing Defects

    Science.gov (United States)

    Leckey, Cara A. C.; Juarez, Peter D.

    2016-01-01

    The increased use of composites in aerospace components is expected to continue into the future. The large scale use of composites in aerospace necessitates the development of composite-appropriate nondestructive evaluation (NDE) methods to quantitatively characterize defects in as-manufactured parts and damage incurred during or post manufacturing. Ultrasonic techniques are one of the most common approaches for defect/damage detection in composite materials. One key technical challenge area included in NASA's Advanced Composite's Project is to develop optimized rapid inspection methods for composite materials. Common manufacturing defects in carbon fiber reinforced polymer (CFRP) composites include fiber waviness (in-plane and out-of-plane), porosity, and disbonds; among others. This paper is an overview of ongoing work to develop ultrasonic wavefield based methods for characterizing manufacturing waviness defects. The paper describes the development and implementation of a custom ultrasound simulation tool that is used to model ultrasonic wave interaction with in-plane fiber waviness (also known as marcelling). Wavefield data processing methods are applied to the simulation data to explore possible routes for quantitative defect characterization.

  19. Color Vision Defects in School Going Children

    Directory of Open Access Journals (Sweden)

    R K Shrestha

    2010-12-01

    Full Text Available Introduction: Color Vision defect can be observed in various diseases of optic nerve and retina and also a significant number of people suffer from the inherited condition of red and green color defect. Methods: A cross-sectional descritptive study was designed with purposive sampling of students from various schools of Kathmandu Valley. All children were subjected to color vision evaluation using Ishihara Isochromatic color plates along with other examination to rule out any other causes of color deficiency. Results: A total of 2001 students were examined, 1050 male students and 951 females with mean age of 10.35 (±2.75 and 10.54 (±2.72 respectively. Among the total students examined, 2.1% had some form of color vision defects. Of the male population , 3.9% had color vision defects while none of the female was found with the deficiency. Conclusions: The prelevance of color vision defect in Nepal is significant and comparable with the prelevance quoted in the studies from different countries. Keywords:color vision; congenital red green color effect; Nepal; prevalence.

  20. Imaging active topological defects in carbon nanotubes

    Science.gov (United States)

    Suenaga, Kazu; Wakabayashi, Hideaki; Koshino, Masanori; Sato, Yuta; Urita, Koki; Iijima, Sumio

    2007-06-01

    A single-walled carbon nanotube (SWNT) is a wrapped single graphene layer, and its plastic deformation should require active topological defects-non-hexagonal carbon rings that can migrate along the nanotube wall. Although in situ transmission electron microscopy (TEM) has been used to examine the deformation of SWNTs, these studies deal only with diameter changes and no atomistic mechanism has been elucidated experimentally. Theory predicts that some topological defects can form through the Stone-Wales transformation in SWNTs under tension at 2,000 K, and could act as a dislocation core. We demonstrate here, by means of high-resolution (HR)-TEM with atomic sensitivity, the first direct imaging of pentagon-heptagon pair defects found in an SWNT that was heated at 2,273 K. Moreover, our in situ HR-TEM observation reveals an accumulation of topological defects near the kink of a deformed nanotube. This result suggests that dislocation motions or active topological defects are indeed responsible for the plastic deformation of SWNTs.