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Sample records for include enzyme replacement

  1. Enzyme Replacement Therapy for Fabry Disease

    Directory of Open Access Journals (Sweden)

    Maria Dolores Sanchez-Niño PhD

    2016-11-01

    Full Text Available Fabry disease is a rare X-linked disease caused by the deficiency of α-galactosidase that leads to the accumulation of abnormal glycolipid. Untreated patients develop potentially lethal complications by age 30 to 50 years. Enzyme replacement therapy is the current standard of therapy for Fabry disease. Two formulations of recombinant human α-galactosidase A (agalsidase are available in most markets: agalsidase-α and agalsidase-β, allowing a choice of therapy. However, the US Food and Drug Administration rejected the application for commercialization of agalsidase-α. The main difference between the 2 enzymes is the dose. The label dose for agalsidase-α is 0.2 mg/kg/2 weeks, while the dose for agalsidase-β is 1.0 mg/kg/2 weeks. Recent evidence suggests a dose-dependent effect of enzyme replacement therapy and agalsidase-β is 1.0 mg/kg/2 weeks, which has been shown to reduce the occurrence of hard end points (severe renal and cardiac events, stroke, and death. In addition, patients with Fabry disease who have developed tissue injury should receive coadjuvant tissue protective therapy, together with enzyme replacement therapy, to limit nonspecific progression of the tissue injury. It is likely that in the near future, additional oral drugs become available to treat Fabry disease, such as chaperones or substrate reduction therapy.

  2. Enzyme replacement therapy for murine hypophosphatasia.

    Science.gov (United States)

    Millán, José Luis; Narisawa, Sonoko; Lemire, Isabelle; Loisel, Thomas P; Boileau, Guy; Leonard, Pierre; Gramatikova, Svetlana; Terkeltaub, Robert; Camacho, Nancy Pleshko; McKee, Marc D; Crine, Philippe; Whyte, Michael P

    2008-06-01

    Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5'-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment. Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2-/-), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, microCT, and histomorphometry. Akp2-/- mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2-/- mice.

  3. Enzyme Replacement Therapy for Murine Hypophosphatasia*

    Science.gov (United States)

    Millán, José Luis; Narisawa, Sonoko; Lemire, Isabelle; Loisel, Thomas P; Boileau, Guy; Leonard, Pierre; Gramatikova, Svetlana; Terkeltaub, Robert; Camacho, Nancy Pleshko; McKee, Marc D; Crine, Philippe; Whyte, Michael P

    2008-01-01

    Introduction Hypophosphatasia (HPP) is the inborn error of metabolism that features rickets or osteomalacia caused by loss-of-function mutation(s) within the gene that encodes the tissue-nonspecific isozyme of alkaline phosphatase (TNALP). Consequently, natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5`-phosphate (PLP), a co-factor form of vitamin B6. Babies with the infantile form of HPP often die with severe rickets and sometimes hypercalcemia and vitamin B6-dependent seizures. There is no established medical treatment. Materials and Methods Human TNALP was bioengineered with the C terminus extended by the Fc region of human IgG for one-step purification and a deca-aspartate sequence (D10) for targeting to mineralizing tissue (sALP-FcD10). TNALP-null mice (Akp2−/−), an excellent model for infantile HPP, were treated from birth using sALP-FcD10. Short-term and long-term efficacy studies consisted of once daily subcutaneous injections of 1, 2, or 8.2 mg/kg sALP-FcD10 for 15, 19, and 15 or 52 days, respectively. We assessed survival and growth rates, circulating levels of sALP-FcD10 activity, calcium, PPi, and pyridoxal, as well as skeletal and dental manifestations using radiography, μCT, and histomorphometry. Results Akp2−/− mice receiving high-dose sALP-FcD10 grew normally and appeared well without skeletal or dental disease or epilepsy. Plasma calcium, PPi, and pyridoxal concentrations remained in their normal ranges. We found no evidence of significant skeletal or dental disease. Conclusions Enzyme replacement using a bone-targeted, recombinant form of human TNALP prevents infantile HPP in Akp2−/− mice. PMID:18086009

  4. Pancreatic enzyme replacement therapy for people with cystic fibrosis.

    Science.gov (United States)

    Somaraju, Usha Rani; Solis-Moya, Arturo

    2016-11-23

    Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One

  5. Enzyme replacement and substrate reduction therapy for Gaucher disease.

    Science.gov (United States)

    Shemesh, Elad; Deroma, Laura; Bembi, Bruno; Deegan, Patrick; Hollak, Carla; Weinreb, Neal J; Cox, Timothy M

    2015-03-27

    Gaucher disease, a rare disorder, is caused by inherited deficiency of the enzyme glucocerebrosidase. It is unique among the ultra-orphan disorders in that four treatments are currently approved by various regulatory authorities for use in routine clinical practice. Hitherto, because of the relatively few people affected worldwide, many of whom started therapy during a prolonged period when there were essentially no alternatives to imiglucerase, these treatments have not been systematically evaluated in studies such as randomized controlled trials now considered necessary to generate the highest level of clinical evidence. To summarize all available randomized controlled study data on the efficacy and safety of enzyme replacement therapies and substrate reduction therapy for treating Gaucher disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Additional searches were conducted on ClinicalTrials.gov for any ongoing studies with potential interim results, and through PubMed. We also searched the reference lists of relevant articles and reviews.Date of last search: 07 August 2014. All randomized and quasi-randomized controlled studies (including open-label studies and cross-over studies) assessing enzyme replacement therapy or substrate reduction therapy, or both, in all types of Gaucher disease were included. Two authors independently assessed the risk of bias in the included studies, and extracted relevant data. Of the 488 studies retrieved by the electronic searches, eight met the inclusion criteria and were analysed (300 participants). Response parameters were restricted to haemoglobin concentration, platelet count, spleen and liver volume and serum biomarkers (chitotriosidase and CCL18). Only one publication reported a 'low risk of bias' score in all parameters assessed, and all studies included were randomized.Four studies reported the responses to enzyme replacement therapy of previously

  6. Enzyme replacement therapy for infantile-onset Pompe disease.

    Science.gov (United States)

    Chen, Min; Zhang, Lingli; Quan, Shuyan

    2017-11-20

    ) that fulfilled the selection criteria, comparing different doses of alglucosidase alfa. The trial provided low-quality evidence (this was a small trial, there were no numerical results available by dose group, random sequence generation and allocation concealment were unclear, and there was a lack of blinding). The duration of alglucosidase alfa treatment ranged from 52 weeks (the length of the original study) to up to three years (including the extended phase of the trial), with a median duration of treatment being 2.3 years.The trial only reported that clinical responses including cardiac function and motor development, as well as the proportion of children that were free of invasive ventilation, were similar in the 20 mg/kg every two weeks and the 40 mg/kg every two weeks groups (low-quality evidence). Long-term alglucosidase alfa treatment markedly extended survival as well as ventilation-free survival and improved cardiomyopathy (low-quality evidence). In relation to the number of children experiencing one or more infusion-related events, there was no significant difference between dose groups, risk ratio 0.83 (95% confidence interval 0.40 to 1.76) (low-quality of evidence). However, of note, at 52 weeks, five children in the 20 mg/kg every two weeks dose group experienced a total of 41 mild or moderate (none severe) infusion-related events and the six children in the 40 mg/kg every two weeks dose group experienced a total of 123 infusion-related events. By the end of the extended phase of the trial, five children in the 20 mg/kg every two weeks dose group experienced a total of 47 infusion-related events and the six children in the 40 mg/kg every two weeks dose group experienced a total of 177 infusion-related events. The trial was supported by the Genzyme Corporation. The search found no trials comparing the effectiveness and safety of enzyme replacement therapy to another intervention, no intervention or placebo. One small randomized controlled trial provided

  7. Enzyme replacement therapy for alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J

    2013-01-01

    Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly...

  8. Effect of Palm Kernel Cake Replacement and Enzyme ...

    African Journals Online (AJOL)

    A feeding trial which lasted for twelve weeks was conducted to study the performance of finisher pigs fed five different levels of palm kernel cake replacement for maize (0%, 40%, 40%, 60%, 60%) in a maize-palm kernel cake based ration with or without enzyme supplementation. It was a completely randomized design ...

  9. Enzyme replacement therapy in Fabry disease, towards individualized treatment

    NARCIS (Netherlands)

    Arends, M.

    2017-01-01

    Fabry disease is a very heterogeneous disorder for which expensive enzyme replacement therapy is available since more than 15 years. Because of the variety of symptoms and disease course, individual choices need to be made to improve the appropriate use of therapy. Supported by ZONWM, we have been

  10. Strategies for replacement of obsolete equipment - including reverse engineering

    International Nuclear Information System (INIS)

    Irish, C.S.

    2000-01-01

    The presentation shall detail the challenges facing nuclear power plants with the replacement of obsolete equipment and the strategies used to overcome those challenges. The presentation will outline the common equipment types which are either obsolete or are becoming obsolete, with a focus on safety related components. The four options of the obsolete equipment replacement philosophy will be presented with replacement examples from each of the options shown for discussion purposes. Detailed examples from each of the four obsolete equipment replacement options of: commercially available equivalent component; modification of a commercial available component; reverse engineering of the original component; and finally, design changes using a new component, shall be presented to evaluate the advantages and disadvantages of each option. The presentation will include the technical challenges, cost and schedule concerns for each of the four options. Emphasis will be placed on the technological challenges associated with replacing old and obsolete equipment. The following is a bullet list of the challenges which will be discussed: Missing, misleading or no information on the original component; Acquiring information from the original equipment manufacturer and the plant; Using a sample component for the replacement evaluation and or reverse engineering; and Reverse engineering old equipment with newly available discrete components. The presentation will include the equivalency documentation using the EPRI guidelines when replacing an original component with a different yet form, fit and functional equivalent component. The presentation will conclude with a discussion of the advantages and disadvantages of the replacement of the obsolete component with a form, fit and functional equivalent component vs. the replacement of the original component with a new component with today's technology. (author)

  11. Strategies for replacement of obsolete equipment, including reverse engineering

    International Nuclear Information System (INIS)

    Irish, C.S.

    2003-01-01

    The presentation shall detail the challenges facing nuclear power plants with the replacement of obsolete equipment and the strategies used to overcome those challenges. The presentation will outline the common equipment types which are either obsolete or are becoming obsolete, with a focus on safety related components. The four options of the obsolete equipment replacement philosophy will be presented with replacement examples from each of the options shown for discussion purposes. Detailed examples from each of the four obsolete equipment replacement options of, (1) commercially available equivalent component, (2) modification of a commercial available component, (3) reverse engineering of the original component and finally (4) design changes using a new component, shall be presented to evaluate the advantages and disadvantages of each option. The presentation will include the technical challenges, cost and schedule concerns for each of the four options. Emphasis will be placed on the technological challenges associated with replacing old and obsolete equipment. The following is a bullet list of the challenges which will be discussed: 1) Missing, misleading or no information on the original component. 2) Acquiring information from the original equipment manufacturer and the plant. 3) Using a sample component for the replacement evaluation and or reverse engineering. 4) Reverse engineering old equipment with newly available discrete components. The presentation will include the equivalency documentation using the EPRI guidelines when replacing an original component with a different yet form, fit and functional equivalent component. The presentation will conclude with a discussion of the advantages and disadvantages of the replacement of the obsolete component with a form, fit and functional equivalent component vs. the replacement of the original component with a new component with today's technology. (author)

  12. Model for Quantitative Evaluation of Enzyme Replacement Treatment

    Directory of Open Access Journals (Sweden)

    Radeva B.

    2009-12-01

    Full Text Available Gaucher disease is the most frequent lysosomal disorder. Its enzyme replacement treatment was the new progress of modern biotechnology, successfully used in the last years. The evaluation of optimal dose of each patient is important due to health and economical reasons. The enzyme replacement is the most expensive treatment. It must be held continuously and without interruption. Since 2001, the enzyme replacement therapy with Cerezyme*Genzyme was formally introduced in Bulgaria, but after some time it was interrupted for 1-2 months. The dose of the patients was not optimal. The aim of our work is to find a mathematical model for quantitative evaluation of ERT of Gaucher disease. The model applies a kind of software called "Statistika 6" via the input of the individual data of 5-year-old children having the Gaucher disease treated with Cerezyme. The output results of the model gave possibilities for quantitative evaluation of the individual trends in the development of the disease of each child and its correlation. On the basis of this results, we might recommend suitable changes in ERT.

  13. 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

  14. Parental experience of enzyme replacement therapy for Hunter syndrome.

    Science.gov (United States)

    Buraczewska, M; O'Leary, D; Walsh, O; Monavari, A; Crushell, E

    2013-04-01

    We aimed to establish the profile of Irish patients with Hunter Syndrome (Mucopolysaccharidosis type II, MPS II) receiving weekly intravenous Enzyme Replacement Therapy (ERT) with recombinant iduronate-2-sulfatase and to assess the social impact and parental opinion of ERT through the use of a parental questionnaire. Nine patients aged 3.5- 14 years have received a mean of 2 (range 0.5-3.5) years of ERT. Treatment was associated with clinical improvements from baseline in hepatosplenomegaly in 6/7 (85%) respiratory manifestations in 4/6 (67%) and a mean reduction in urinary glycosaminoglycan excretion of 62%. Changes noted by parents included increased energy 3/9 (33%) and softening of skin, hair and facial features 8/9 (89%). Parents report that seven hours weekly were spent on hospitalizations for ERT. Parental employment was adversely affected in 8 (89%) families. One day of school/preschool (20%) was lost every week for 8 (89%) children. All parents believed the benefits of ERT out-weigh the difficulties involved. All families would welcome the introduction of home based therapy. In conclusion the social and educational burden of hospital-based ERT on these children and their families is significant. The introduction of home-based therapy is likely to improve overall quality of life for MPSII patients and their families.

  15. JCL Roundtable: enzyme replacement therapy for lipid storage disorders.

    Science.gov (United States)

    Brown, W Virgil; Desnick, Robert J; Grabowski, Gregory A

    2014-01-01

    There are several inherited disorders that involve abnormal storage of lipids in tissues leading to severe compromise of organs. Sadly, these are often accompanied by lifelong morbidity and early mortality. Disorders such as Gaucher, Fabry, and lysosomal acid lipase deficiencies (Wolman and cholesteryl ester storage diseases) have been known for many years, and provide a difficult and frustrating set of problems for patients, their families, and their physicians. With recombinant methods of protein synthesis, it is now possible to literally replace the defective enzymes that underlie the basic pathophysiology of many such disorders. The delivery of these enzymes into the affected cells is possible because of their location in the lysosomes where the natural degradation of their lipid substrates occurs. I have asked 2 well-known investigators to join us for this Roundtable. These are professors who have been involved with the research that has made this type of therapy possible and who have participated in the clinical trials that demonstrated the value of enzyme replacement therapy. They are Dr. Robert Desnick, dean of Genetic and Genomic Medicine and professor and chairman emeritus of the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai in New York City, and Dr. Gregory Grabowski, professor of Microbiology, Biochemistry, and Pediatrics, at the University of Cincinnati College of Medicine. Dr. Grabowski recently retired from that school to become the chief science officer of Synageva, a company involved in producing enzymes for this type of therapy. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  16. Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

    Science.gov (United States)

    Tong, Wenyong; Dwyer, Chrissa A; Thacker, Bryan E; Glass, Charles A; Brown, Jillian R; Hamill, Kristina; Moremen, Kelley W; Sarrazin, Stéphane; Gordts, Philip L S M; Dozier, Lara E; Patrick, Gentry N; Tor, Yitzhak; Esko, Jeffrey D

    2017-12-06

    Iduronidase (IDUA)-deficient mice accumulate glycosaminoglycans in cells and tissues and exhibit many of the same neuropathological symptoms of patients suffering from Mucopolysaccharidosis I. Intravenous enzyme-replacement therapy for Mucopolysaccharidosis I ameliorates glycosaminoglycan storage and many of the somatic aspects of the disease but fails to treat neurological symptoms due to poor transport across the blood-brain barrier. In this study, we examined the delivery of IDUA conjugated to guanidinoneomycin (GNeo), a molecular transporter. GNeo-IDUA and IDUA injected intravenously resulted in reduced hepatic glycosaminoglycan accumulation but had no effect in the brain due to fast clearance from the circulation. In contrast, intranasally administered GNeo-IDUA entered the brain rapidly. Repetitive intranasal treatment with GNeo-IDUA reduced glycosaminoglycan storage, lysosome size and number, and neurodegenerative astrogliosis in the olfactory bulb and primary somatosensory cortex, whereas IDUA was less effective. The enhanced efficacy of GNeo-IDUA was not the result of increased nose-to-brain delivery or enzyme stability, but rather due to more efficient uptake into neurons and astrocytes. GNeo conjugation also enhanced glycosaminoglycan clearance by intranasally delivered sulfamidase to the brain of sulfamidase-deficient mice, a model of Mucopolysaccharidosis IIIA. These findings suggest the general utility of the guanidinoglycoside-based delivery system for restoring missing lysosomal enzymes in the brain. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  17. Cerebral magnetic resonance findings during enzyme replacement therapy in mucopolysaccharidosis

    International Nuclear Information System (INIS)

    Matsubara, Yoshiko; Miyazaki, Osamu; Nosaka, Shunsuke; Kosuga, Motomichi; Okuyama, Torayuki

    2017-01-01

    Although enzyme replacement therapy (ERT) is an effective treatment for mucopolysaccharidosis (MPS) types I, II, IVA and VI, its effectiveness in children with central nervous system (CNS) disorders is said to be poor because the blood-brain barrier cannot be penetrated by ERT drugs. To assess CNS involvement in mucopolysaccharidosis at the start of enzyme replacement therapy and to investigate the time course of ERT in the central nervous system. We performed brain MRI in 17 children and young adults who underwent ERT. The clinical severity was classified as attenuated or severe by a specialist pediatrician, based on the clinical symptoms and genotypes. At the start of ERT, we scored nine parameters using two- or three-point scales based on the severity of the disease revealed on MRI scans. After the start of ERT, we compared the initial and follow-up MRI scans, and classified the findings as no change, improved or worse. We then compared the results with the changes in clinical findings. At the start of ERT, comparison of the clinical symptoms and image scores revealed differences between severe and attenuated mucopolysaccharidosis. The scores in patients with severe MPS ranged from 9 to 16 (mean 12.2); for patients with attenuated MPS, they ranged from 2 to 11 (mean 6.4). Images of the four patients with severe MPS showed ventricular dilation and brain atrophy. Such findings were made in only 2 of 13 patients with attenuated MPS. The results after the start of ERT showed that 11/17 (65%) patients manifested improvement or no change. All five patients with MPS I experienced improvement in some regions. There were no new lesions. One patient with MPS II experienced worsening of his CNS symptoms, and his MRI findings revealed more severe ventricular dilation, brain atrophy and white matter lesions. Ventricular dilation and brain atrophy on imaging studies might represent useful markers in predicting the severity of mucopolysaccharidosis and worsening of CNS

  18. Cerebral magnetic resonance findings during enzyme replacement therapy in mucopolysaccharidosis

    Energy Technology Data Exchange (ETDEWEB)

    Matsubara, Yoshiko [Division of Radiology, National Center for Child Health and Development, Tokyo (Japan); Hiroshima University, Department of Diagnostic Radiology, Hiroshima (Japan); Miyazaki, Osamu; Nosaka, Shunsuke [Division of Radiology, National Center for Child Health and Development, Tokyo (Japan); Kosuga, Motomichi [Division of Medical Genetics, National Center for Child Health and Development, Tokyo (Japan); Okuyama, Torayuki [Department of Clinical Laboratory Medicine, National Center for Child Health and Development, Tokyo (Japan)

    2017-11-15

    Although enzyme replacement therapy (ERT) is an effective treatment for mucopolysaccharidosis (MPS) types I, II, IVA and VI, its effectiveness in children with central nervous system (CNS) disorders is said to be poor because the blood-brain barrier cannot be penetrated by ERT drugs. To assess CNS involvement in mucopolysaccharidosis at the start of enzyme replacement therapy and to investigate the time course of ERT in the central nervous system. We performed brain MRI in 17 children and young adults who underwent ERT. The clinical severity was classified as attenuated or severe by a specialist pediatrician, based on the clinical symptoms and genotypes. At the start of ERT, we scored nine parameters using two- or three-point scales based on the severity of the disease revealed on MRI scans. After the start of ERT, we compared the initial and follow-up MRI scans, and classified the findings as no change, improved or worse. We then compared the results with the changes in clinical findings. At the start of ERT, comparison of the clinical symptoms and image scores revealed differences between severe and attenuated mucopolysaccharidosis. The scores in patients with severe MPS ranged from 9 to 16 (mean 12.2); for patients with attenuated MPS, they ranged from 2 to 11 (mean 6.4). Images of the four patients with severe MPS showed ventricular dilation and brain atrophy. Such findings were made in only 2 of 13 patients with attenuated MPS. The results after the start of ERT showed that 11/17 (65%) patients manifested improvement or no change. All five patients with MPS I experienced improvement in some regions. There were no new lesions. One patient with MPS II experienced worsening of his CNS symptoms, and his MRI findings revealed more severe ventricular dilation, brain atrophy and white matter lesions. Ventricular dilation and brain atrophy on imaging studies might represent useful markers in predicting the severity of mucopolysaccharidosis and worsening of CNS

  19. Modelling Gaucher disease progression: long-term enzyme replacement therapy reduces the incidence of splenectomy and bone complications

    NARCIS (Netherlands)

    van Dussen, Laura; Biegstraaten, Marieke; Dijkgraaf, Marcel Gw; Hollak, Carla Em

    2014-01-01

    Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on

  20. Interruption of enzyme replacement therapy in Gaucher disease.

    Science.gov (United States)

    Goldblatt, J; Fletcher, J M; McGill, J; Szer, J; Wilson, M

    2016-05-25

    In Australia, 58 patients with Gaucher disease were managed by a Gaucher Disease Advisory Committee (GDAC) through a centrally adminis-tered national programme, the Life Savings Drug Program (LSDP). In June 2009, Genzyme Corporation, which manufactures imiglucerase (Cerezyme), the only enzyme replacement therapy (ERT) registered for the treatment of Gaucher disease in Australia at that time, announced that due to a viral contamination problem there would be no further shipments of Cerezyme to Australia prior to the end of 2009. The GDAC allocated available drug supplies in order to maintain treatment to those most in need on a hierarchal clinical severity basis. A cohort of 24 patients with Type 1 Gaucher disease was withdrawn from therapy, 22 of whom had no discernible clinically significant adverse effects when reviewed off therapy for up to 6 months. In this paper, we review the course of 20 of the patients who have been on imiglucerase for periods of at least 24 months after the end of their 'drug holiday'. No patient experienced a bone crisis nor clinical nor magnetic resonance imaging evidence of new avascular necrosis events during this period. Two years after recommencing ERT after a 6-month drug holiday, no patient had developed an overt irreversible complication of their Gaucher disease, with the majority returning to their previous clinical status.

  1. COMPARING THE ENZYME REPLACEMENT THERAPY COST IN POST PANCREATECTOMY PATIENTS DUE TO PANCREATIC TUMOR AND CHRONIC PANCREATITIS.

    Science.gov (United States)

    Fragoso, Anna Victoria; Pedroso, Martha Regina; Herman, Paulo; Montagnini, André Luis

    2016-01-01

    Among late postoperative complications of pancreatectomy are the exocrine and endocrine pancreatic insufficiencies. The presence of exocrine pancreatic insufficiency imposes, as standard treatment, pancreatic enzyme replacement. Patients with chronic pancreatitis, with intractable pain or any complications with surgical treatment, are likely to present exocrine pancreatic insufficiency or have this condition worsened requiring adequate dose of pancreatic enzymes. The aim of this study is to compare the required dose of pancreatic enzyme and the enzyme replacement cost in post pancreatectomy patients with and without chronic pancreatitis. Observational cross-sectional study. In the first half of 2015 patients treated at the clinic of the Department of Gastrointestinal Surgery at Hospital das Clínicas, Universidade de São Paulo, Brazil, who underwent pancreatectomy for at least 6 months and in use of enzyme replacement therapy were included in this series. The study was approved by the Research Ethics Committee. The patients were divided into two groups according to the presence or absence of chronic pancreatitis prior to pancreatic surgery. For this study, Ptreatment was R$ 2150.5 ± 729.39; R$ 2118.18 ± 731.02 in patients without pancreatitis and R$ 2217.74 ± 736.30 in patients with pancreatitis. There was no statistically significant difference in the cost of treatment of enzyme replacement post pancreatectomy in patients with or without chronic pancreatitis prior to surgical indication.

  2. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease

    DEFF Research Database (Denmark)

    Biegstraaten, Marieke; Arngrímsson, Reynir; Barbey, Frederic

    2015-01-01

    INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed ...

  3. Engineering of GlcNAc-1-Phosphotransferase for Production of Highly Phosphorylated Lysosomal Enzymes for Enzyme Replacement Therapy.

    Science.gov (United States)

    Liu, Lin; Lee, Wang-Sik; Doray, Balraj; Kornfeld, Stuart

    2017-06-16

    Several lysosomal enzymes currently used for enzyme replacement therapy in patients with lysosomal storage diseases contain very low levels of mannose 6-phosphate, limiting their uptake via mannose 6-phosphate receptors on the surface of the deficient cells. These enzymes are produced at high levels by mammalian cells and depend on endogenous GlcNAc-1-phosphotransferase α/β precursor to phosphorylate the mannose residues on their glycan chains. We show that co-expression of an engineered truncated GlcNAc-1-phosphotransferase α/β precursor and the lysosomal enzyme of interest in the producing cells resulted in markedly increased phosphorylation and cellular uptake of the secreted lysosomal enzyme. This method also results in the production of highly phosphorylated acid β-glucocerebrosidase, a lysosomal enzyme that normally has just trace amounts of this modification.

  4. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    Science.gov (United States)

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

  5. Replacement of traditional seawater-soluble pigments by starch and hydrolytic enzymes in polishing antifouling coatings

    DEFF Research Database (Denmark)

    Olsen, Søren Martin; Pedersen, L. T.; Dam-Johansen, Kim

    2010-01-01

    The use of starch and hydrolytic enzymes as replacement for traditional polishing pigments (e.g., Cu2O and ZnO) in antifouling coatings has been investigated. The enzymes facilitate a slow conversion of water-insoluble starch into water-soluble glucose, and dissolution of glucose causes the devel......The use of starch and hydrolytic enzymes as replacement for traditional polishing pigments (e.g., Cu2O and ZnO) in antifouling coatings has been investigated. The enzymes facilitate a slow conversion of water-insoluble starch into water-soluble glucose, and dissolution of glucose causes...... the development of a leached (porous) layer in the wetted, outermost part of the coating. Subsequent water-binder interaction at the pore walls gives rise to polishing, in a manner similar to that of conventional antifouling coatings. Different starch types have been evaluated and classified as potential coating...

  6. COMPARING THE ENZYME REPLACEMENT THERAPY COST IN POST PANCREATECTOMY PATIENTS DUE TO PANCREATIC TUMOR AND CHRONIC PANCREATITIS

    Directory of Open Access Journals (Sweden)

    Anna Victoria FRAGOSO

    Full Text Available ABSTRACT Background - Among late postoperative complications of pancreatectomy are the exocrine and endocrine pancreatic insufficiencies. The presence of exocrine pancreatic insufficiency imposes, as standard treatment, pancreatic enzyme replacement. Patients with chronic pancreatitis, with intractable pain or any complications with surgical treatment, are likely to present exocrine pancreatic insufficiency or have this condition worsened requiring adequate dose of pancreatic enzymes. Objective - The aim of this study is to compare the required dose of pancreatic enzyme and the enzyme replacement cost in post pancreatectomy patients with and without chronic pancreatitis. Methods - Observational cross-sectional study. In the first half of 2015 patients treated at the clinic of the Department of Gastrointestinal Surgery at Hospital das Clínicas, Universidade de São Paulo, Brazil, who underwent pancreatectomy for at least 6 months and in use of enzyme replacement therapy were included in this series. The study was approved by the Research Ethics Committee. The patients were divided into two groups according to the presence or absence of chronic pancreatitis prior to pancreatic surgery. For this study, P<0.05 was considered statistically significant. Results - The annual cost of the treatment was R$ 2150.5 ± 729.39; R$ 2118.18 ± 731.02 in patients without pancreatitis and R$ 2217.74 ± 736.30 in patients with pancreatitis. Conclusion - There was no statistically significant difference in the cost of treatment of enzyme replacement post pancreatectomy in patients with or without chronic pancreatitis prior to surgical indication.

  7. Resolution of Hydronephrosis in a Patient With Mucopolysaccharidosis Type II With Enzyme Replacement Therapy.

    Science.gov (United States)

    Nishiyama, Kei; Imai, Takashi; Ohkubo, Kazuhiro; Sanefuji, Masafumi; Takada, Hidetoshi

    2017-03-01

    Mucopolysaccharidosis type II (MPS II) is caused by deficiency of lysosomal enzyme iduronate-2-sulfatase. Insufficient activity of the enzyme results in accumulation of glycosaminoglycans leading to progressive multisystem pathologies. MPS II is less likely to be complicated by kidney and urinary tract problems. We report a boy with MPS II, who developed left hydronephrosis. His hydronephrosis improved after starting enzyme replacement therapy. It was suggested that MPS II was closely associated with the pathogenesis of hydronephrosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports.

    Science.gov (United States)

    Amato, Dominick; Patterson, Mary Anne

    2018-01-27

    Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods. We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy. While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy

  9. Histologic findings of femoral heads from patients with Gaucher disease treated with enzyme replacement.

    Science.gov (United States)

    Lebel, Ehud; Elstein, Deborah; Peleg, Ariel; Reinus, Constantine; Zimran, Ari; Amir, Gail

    2013-07-01

    To assess correlations of patient demographics, including enzyme replacement therapy (ERT) with bone histology, to facilitate decisions of whether and when to perform hip replacement surgery in patients with Gaucher disease. We examined the histology of surgically removed femoral heads and categorized findings by the presence or extent of osteonecrosis, Gaucher cell (GC) infiltration, and bone regeneration qualifiers using a tripartite histology-based scoring system. Twenty-two patients with 26 bone specimens were evaluated. Seventeen patients (77%) were splenectomized, 16 (73%) received ERT, and 12 (55%) had the putatively milder genotype (N370S/N370S), with the rest putatively at increased risk for skeletal disease (N370S/other). The 3 histology subscores were applicable to all specimens. Osteonecrotic bone was seen in 19 of 26 (73%); osteoarthritis was seen in all cartilage specimens. Gaucher cell infiltration was not correlated with demographics or disease severity. A trend was noted between reduced GC infiltration and ERT (ρ = 0.407), but regeneration qualifiers were not correlated with ERT or other features. Histologic findings of GC infiltration and bone regeneration qualifiers did not correlate with demographics or with exposure to ERT. Most specimens unexpectedly showed good regenerative responses to osteonecrosis despite heavy GC infiltration.

  10. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis.

    Science.gov (United States)

    de la Iglesia-García, Daniel; Huang, Wei; Szatmary, Peter; Baston-Rey, Iria; Gonzalez-Lopez, Jaime; Prada-Ramallal, Guillermo; Mukherjee, Rajarshi; Nunes, Quentin M; Domínguez-Muñoz, J Enrique; Sutton, Robert

    2017-08-01

    The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, pregression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  11. Guidelines to start enzyme replacement therapy in classic Fabry Disease patients in Latin America

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2017-01-01

    Full Text Available Introduction: Fabry disease is a rare inherited X-linked disorder resulting from the absence or deficient activity of the α-galactosidase A enzyme. Objetive: To provide the first guideline on the best time to start enzyme replacement therapy to treat classic Fabry disease, based on the knowledge and experience of experts from ten Latin American countries: Argentina, Brazil, Colombia, Costa Rica, Chile, Ecuador, Mexico, Peru, Uruguay and Venezuela. Methods: The project coordinator designed a survey based on the criteria for starting the treatment which are established in different international guidelines published to date. This document was later sent to all the participants for its evaluation. Results: Fifty experts responded to the survey, whose criteria was divided into 5 sections according to specialty, and they arrived at a consensus. Discussion: The criteria for an early treatment were defined given the growing evidence of a better response and prognosis associated with it. Conclusion: We believe that the importance of this guideline relies on the participation of experts from ten Latin American countries. However, as it deals with a systemic disease whose physiopathological mechanisms and complications are still being described, some manifestations have not been included in the criteria, making it necessary to revise this guideline in order to report any changes that may arise in the future.

  12. Overweight, insulin resistance and type II diabetes in type I Gaucher disease patients in relation to enzyme replacement therapy

    NARCIS (Netherlands)

    Langeveld, M.; de Fost, M.; Aerts, J. M. F. G.; Sauerwein, H. P.; Hollak, C. E. M.

    2008-01-01

    Type I Gaucher disease, a lysosomal storage disorder is associated with metabolic abnormalities such as high resting energy expenditure, low circulating adiponectin and peripheral insulin resistance. Treatment with enzyme replacement therapy (enzyme therapy) leads to a decrease in resting energy

  13. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition : A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Celine; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Kobold, Anneke C. Muller; Bandsma, Robert H.; van Hensbroek, Michael Boele; Voskuijl, Wieger P.

    Objective: To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design: We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth

  14. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Muller Kobold, Anneke C.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Voskuijl, Wieger P.

    2017-01-01

    Objective To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central

  15. Hearing loss in adult patients with Fabry disease treated with enzyme replacement therapy

    NARCIS (Netherlands)

    Suntjens, Eefje B.; Smid, Bouwien E.; Biegstraaten, Marieke; Dreschler, Wouter A.; Hollak, Carla E. M.; Linthorst, Gabor E.

    2015-01-01

    Data on prevalence, natural history, and effect of enzyme replacement therapy (ERT) on hearing loss (HL) in Fabry disease (FD) are scarce. This is a retrospective study with cross-sectional and longitudinal analyses. Low and high-frequency HL in the Dutch FD cohort was studied in four groups:

  16. Children with Pompe disease: clinical characteristics, peculiar features and effects of enzyme replacement therapy

    NARCIS (Netherlands)

    C.I. van Capelle (Carine)

    2014-01-01

    markdownabstract__Abstract__ Pompe disease is a metabolic myopathy. Since the first description of the disease in 1932 by J.C. Pompe,1 tremendous progress has been made from discovering the biochemical and genetic basis of the disease to developing enzyme replacement therapy (ERT). With this

  17. Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain

    NARCIS (Netherlands)

    Rombach, Saskia M.; Smid, Bouwien E.; Bouwman, Machtelt G.; Linthorst, Gabor E.; Dijkgraaf, Marcel G. W.; Hollak, Carla E. M.

    2013-01-01

    Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase A deficiency leading to renal, cardiac, cerebrovascular disease and premature death. Treatment with α-galactosidase A (enzyme replacement therapy, ERT) stabilises disease in some patients, but long term effectiveness

  18. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease

    DEFF Research Database (Denmark)

    Hughes, Derralynn A.; Nicholls, Kathleen; Shankar, Suma P.

    2017-01-01

    Background Fabry disease is an X-linked lysosomal storage disorder caused by GLA mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of lysosomal substrates. Migalastat, an oral pharmacological chaperone being developed as an alternative to intravenous enzyme replacement t...

  19. Enzyme replacement therapy for Fabry disease: some answers but more questions

    Directory of Open Access Journals (Sweden)

    Majid Alfadhel

    2011-02-01

    Full Text Available Majid Alfadhel1, Sandra Sirrs21Division of Biochemical Diseases, Department of Paediatrics, BC Children’s and Women’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2Adult Metabolic Diseases Clinic, Division of Endocrinology, Department of Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, BC, CanadaAbstract: Fabry disease (FD is a multisystem, X-linked disorder of glycosphingolipid metabolism caused by enzyme deficiency of α-galactosidase A. Affected patients have symptoms including acroparesthesias, angiokeratomas, and hypohidrosis. More serious manifestations include debilitating pain and gastrointestinal symptoms, proteinuria and gradual deterioration of renal function leading to end-stage renal disease, hypertrophic cardiomyopathy, and stroke. Heterozygous females may have symptoms as severe as males with the classic phenotype. Before 2001, treatment of patients with FD was supportive. The successful development of enzyme replacement therapy (ERT has been a great advancement in the treatment of patients with FD and can stabilize renal function and cardiac size, as well as improve pain and quality of life of patients with FD. In this review, we have provided a critical appraisal of the literature on the effects of ERT for FD. This analysis shows that data available on the treatment of FD are often derived from studies which are not controlled, rely on surrogate markers, and are of insufficient power to detect differences on hard clinical endpoints. Further studies of higher quality are needed to answer the questions that remain concerning the efficacy of ERT for FD.Keywords: Fabry disease, agalsidase α, agalsidase β, Replagal, Fabrazyme, critical appraisal, evidence-based medicine

  20. Fabry disease: the importance of the enzyme replacement therapy (TRE, treating quickly and efficiently

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2014-06-01

    Full Text Available Fabry Disease is a lysosomal disorder due to the absence or deficiency of the Alpha galactosidase A enzyme that causes a pathological accumulation of glycosphingolipids mainly in the endothelial cells, vascular smooth muscle cells and podocytes among others. Enzyme replacement therapy is the only option for a specific treatment at present. Increasing knowledge of the physiopathological mechanisms has changed the management of the disease and above all, when treatment should begin. At present, beginning treatment at an early age seems to be a way of preventing and in some cases reverting some of the signs and symptoms of Fabry disease.

  1. Some factors including radiation affecting the productivity of proteinase enzymes by mucor lamprosporus

    International Nuclear Information System (INIS)

    El-Kabbany, H.M.I.

    1996-01-01

    In the present time, great attention has been focused on the production of milk clotting enzymes from microbial source for use as remain substitute due to the increasing demands on rennin for cheese making and the prohibition of the slaughter of small calves. The present investigation included the isolation and identification of remin-like enzyme fungal producers from different egyptian food and soil samples. Different factors including gamma radiation affecting the capability of selected isolate to produce the enzyme was also included. Special attention has also given to study the effect of different purification methods of the produced enzyme. The properties of the purified enzyme were also investigated

  2. Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia.

    Science.gov (United States)

    McKee, M D; Nakano, Y; Masica, D L; Gray, J J; Lemire, I; Heft, R; Whyte, M P; Crine, P; Millán, J L

    2011-04-01

    Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2(-/-)) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B(6)-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2(-/-) mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD(10)). sALP-FcD(10) prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin--a marker of acellular cementum--was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2(-/-) mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life--where the majority of tooth root development occurs, including acellular cementum formation--could prevent the accelerated tooth loss seen in individuals with HPP.

  3. Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings.

    Science.gov (United States)

    Laraway, Sarah; Breen, Catherine; Mercer, Jean; Jones, Simon; Wraith, James E

    2013-07-01

    Enzyme replacement therapy is widely used as treatment for mucopolysaccharidosis I (MPS I), and there is evidence that this produces improvement in certain clinical domains. There does appear to be variation in the response of clinical features to treatment once these are established. In a reported sibling pair, when enzyme replacement therapy was commenced pre-symptomatically in the younger child, the natural history of the condition appeared to be affected. We present data from three siblings treated with enzyme replacement therapy at different ages which supports this finding. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century.

    Science.gov (United States)

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-09-07

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.

  5. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

    Science.gov (United States)

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-01-01

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy. PMID:25206255

  6. Response of women with Fabry disease to enzyme replacement therapy: comparison with men, using data from FOS--the Fabry Outcome Survey

    NARCIS (Netherlands)

    Hughes, Derralynn A.; Barba Romero, Miguel-Ángel; Hollak, Carla E. M.; Giugliani, Roberto; Deegan, Patrick B.

    2011-01-01

    Fabry disease (α-galactosidase A deficiency) is an X-linked disorder. Women who are heterozygous for disease-causing mutations often manifest signs and symptoms of Fabry disease, but most studies of the effects of enzyme replacement therapy (ERT) have included only men. To date, no direct comparison

  7. Towards the development of an enzyme replacement therapy for the metabolic disorder propionic acidemia

    Directory of Open Access Journals (Sweden)

    Mahnaz Darvish-Damavandi

    2016-09-01

    Full Text Available Propionic acidemia (PA is a life-threatening disease caused by the deficiency of a mitochondrial biotin-dependent enzyme known as propionyl coenzyme-A carboxylase (PCC. This enzyme is responsible for degrading the metabolic intermediate, propionyl coenzyme-A (PP-CoA, derived from multiple metabolic pathways. Currently, except for drastic surgical and dietary intervention that can only provide partial symptomatic relief, no other form of therapeutic option is available for this genetic disorder. Here, we examine a novel approach in protein delivery by specifically targeting and localizing our protein candidate of interest into the mitochondrial matrix of the cells. In order to test this concept of delivery, we have utilized cell penetrating peptides (CPPs and mitochondria targeting sequences (MTS to form specific fusion PCC protein, capable of translocating and localizing across cell membranes. In vitro delivery of our candidate fusion proteins, evaluated by confocal images and enzymatic activity assay, indicated effectiveness of this strategy. Therefore, it holds immense potential in creating a new paradigm in site-specific protein delivery and enzyme replacement therapeutic for PA.

  8. Successful switch from enzyme replacement therapy to miglustat in an adult patient with type 1 Gaucher disease: a case report.

    Science.gov (United States)

    Giuffrida, Gaetano; Lombardo, Rita; Di Francesco, Ernesto; Parrinello, Laura; Di Raimondo, Francesco; Fiumara, Agata

    2016-11-08

    Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy. We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no

  9. Antibody-mediated enzyme replacement therapy targeting both lysosomal and cytoplasmic glycogen in Pompe disease.

    Science.gov (United States)

    Yi, Haiqing; Sun, Tao; Armstrong, Dustin; Borneman, Scott; Yang, Chunyu; Austin, Stephanie; Kishnani, Priya S; Sun, Baodong

    2017-05-01

    Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers "cargo" proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2. We speculate that 3E10-mediated ERT with GAA will target both lysosomal and cytoplasmic glycogen in Pompe disease. A fusion protein (FabGAA) containing a humanized Fab fragment derived from the murine 3E10 antibody and the 110 kDa human GAA precursor was constructed and produced in CHO cells. Immunostaining with an anti-Fab antibody revealed that the Fab signals did not co-localize with the lysosomal marker LAMP2 in cultured L6 myoblasts or Pompe patient fibroblasts after incubation with FabGAA. Western blot with an anti-GAA antibody showed presence of the 150 kDa full-length FabGAA in the cell lysates, in addition to the 95- and 76 kDa processed forms of GAA that were also seen in the rhGAA-treated cells. Blocking of mannose-6-phosphate receptor with mannose-6-phosphate markedly reduced the 95- and the 76 kDa forms but not the 150 kDa form. In GAA-KO mice, FabGAA achieved similar treatment efficacy as rhGAA at an equal molar dose in reducing tissue glycogen contents. Our data suggest that FabGAA retains the ability of rhGAA to treat lysosomal glycogen accumulation and has the beneficial potential over rhGAA to reduce cytoplasmic glycogen storage in Pompe disease. FabGAA can be delivered to both the cytoplasm and lysosomes in cultured cells. FabGAA equally reduced lysosomal glycogen accumulation as rhGAA in GAA-KO mice. FabGAA has the beneficial potential over rhGAA to clear cytoplasmic glycogen. This study suggests a novel antibody-enzyme fusion protein therapy

  10. Pancreatic enzyme replacement therapy in cystic fibrosis: dose, variability and coefficient of fat absorption.

    Science.gov (United States)

    Calvo-Lerma, Joaquim; Martínez-Barona, Sandra; Masip, Etna; Fornés, Victoria; Ribes-Koninckx, Carmen

    2017-10-01

    Pancreatic enzyme replacement therapy (PERT) remains a backbone in the nutritional treatment of cystic fibrosis. Currently, there is a lack of an evidence-based tool that allows dose adjustment. To date, no studies have found an association between PERT dose and fat absorption. Therefore, the aim of the study was to assess the influence of both the PERT dose and the variability in this dose on the coefficient of fat absorption (CFA). This is a retrospective longitudinal study of 16 pediatric patients (192 food records) with three consecutive visits to the hospital over a twelve-month period. Dietary fat intake and PERT were assessed via a four-day food record and fat content in stools was determined by means of a three-day stool sample collection. A beta regression model was built to explain the association between the CFA and the interaction between the PERT dose (lipase units [LU]/g dietary fat) and the variability in the PERT dose (standard deviation [SD]). The coefficient of fat absorption increased with the PERT dose when the variability in the dose was low. In contrast, even at the highest PERT dose values, the CFA decreased when the variability was high. The confidence interval suggested an association, although the analysis was not statistically significant. The variability in the PERT dose adjustment should be taken into consideration when performing studies on PERT efficiency. A clinical goal should be the maintenance of a constant PERT dose rather than trying to obtain an optimal value.

  11. Gaucher disease: MR evaluation of bone marrow features during treatment with enzyme replacement

    International Nuclear Information System (INIS)

    Poll, L.W.; Koch, J.A.; Boerner, D.; Cohnen, M.; Jung, G.; Scherer, A.; Moedder, U.; Niederau, C.

    2001-01-01

    Purpose: Enzyme replacement therapy (ERT) arrests and reverses the hematological and visceral symptoms of adult Gaucher disease, the most frequent lysosomal storage disorder. There are only a few studies available evaluating bone disease during ERT. The aim of this study was to investigate the features of bone marrow (bm) by magnetic resonance imaging (MRI) in these patients during ERT. Materials and Methods: MRI was performed prospectively in thirty adult type I Gaucher patients before and during ERT with a mean follow-up of 3 years. Spin-echo sequences (T 1 /T 2 ) of the lower extremities were obtained and the reconversion (response) or lack of reconversion (non-response) to fatty marrow during treatment was analyzed. The morphological features of bm involvement, a homogeneous or non-homogeneous distribution of bm changes and focal bone lesions surrounded by a rim of reduced signal intensity (SI), were analyzed. Results: Infiltration of bm by Gaucher cells is characterized by a reduction of Sl on both T 1 - and T 2 -weighted sequences. Bone marrow responses were seen in 19 patients (63%) during treatment. Focal bone lesions, surrounded by a rim of reduced Sl, did not respond to ERT and correlated with a non-homogenous distribution of bone involvement and splenectomy. (orig.) [de

  12. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial.

    Science.gov (United States)

    Bartels, Rosalie H; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A; Mponda, John S; Muller Kobold, Anneke C; Bandsma, Robert H; Boele van Hensbroek, Michael; Voskuijl, Wieger P

    2017-11-01

    To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central Hospital in Malawi. All children received standard care; the intervention group also received PERT for 28 days. Children treated with PERT for 28 days did not gain more weight than controls (13.7 ± 9.0% in controls vs 15.3 ± 11.3% in PERT; P = .56). Exocrine pancreatic insufficiency was present in 83.1% of patients on admission and fecal elastase-1 levels increased during hospitalization mostly seen in children with nonedematous severe acute malnutrition (P Children who died had low fecal fatty acid split ratios at admission. Exocrine pancreatic insufficiency was not improved by PERT, but children receiving PERT were more likely to be discharged with every passing day (P = .02) compared with controls. PERT does not improve weight gain in severely malnourished children but does increase the rate of hospital discharge. Mortality was lower in patients on PERT, a finding that needs to be investigated in a larger cohort with stratification for edematous and nonedematous malnutrition. Mortality in severe acute malnutrition is associated with markers of poor digestive function. ISRCTN.com: 57423639. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Potential efficacy of enzyme replacement and substrate reduction therapy in three siblings with Gaucher disease type III

    NARCIS (Netherlands)

    Cox-Brinkman, J.; van Breemen, M. J.; van Maldegem, B. T.; Bour, L.; Donker, W. E.; Hollak, C. E. M.; Wijburg, F. A.; Aerts, J. M. F. G.

    2008-01-01

    We report three siblings with Gaucher disease type III, born between 1992 and 2004. During this period, new developments resulted in different potential therapies, changing clinical practice. The two eldest siblings received enzyme replacement therapy (ERT) from the age of 24 and 5 months

  14. Pancreatic Enzyme Therapy and Coefficient of Fat Absorption in Children and AdolReplacement escents With Cystic Fibrosis

    NARCIS (Netherlands)

    Woestenenk, Janna W; van der Ent, Cornelis K.; Houwen, Roderick H J; van der Ent, CK

    Objectives: Pancreatic enzyme replacement therapy (PERT) is the proven therapy to substantially reduce fat malabsorption in patients with cystic fibrosis (CF). Few details of the daily practice regarding PERT and the resulting coefficient of fat absorption (CFA) are known. We therefore recorded the

  15. Cost-effectiveness of enzyme replacement therapy with alglucosidase alfa in classic-infantile patients with Pompe disease

    NARCIS (Netherlands)

    T.A. Kanters (Tim A.); I Hoogenboom-Plug (Iris); M.P.M.H. Rutten-van Mölken (Maureen); W.K. Redekop (Ken); A.T. van der Ploeg (Ans); L. van Hakkaart-van Roijen (Leona)

    2014-01-01

    textabstractBackground: Infantile Pompe disease is a rare metabolic disease. Patients generally do not survive the first year of life. Enzyme replacement therapy (ERT) has proven to have substantial effects on survival in infantile Pompe disease. However, the costs of therapy are very high. In this

  16. Replacement

    Directory of Open Access Journals (Sweden)

    S. Radhakrishnan

    2014-03-01

    Full Text Available The fishmeal replaced with Spirulina platensis, Chlorella vulgaris and Azolla pinnata and the formulated diet fed to Macrobrachium rosenbergii postlarvae to assess the enhancement ability of non-enzymatic antioxidants (vitamin C and E, enzymatic antioxidants (superoxide dismutase (SOD and catalase (CAT and lipid peroxidation (LPx were analysed. In the present study, the S. platensis, C. vulgaris and A. pinnata inclusion diet fed groups had significant (P < 0.05 improvement in the levels of vitamins C and E in the hepatopancreas and muscle tissue. Among all the diets, the replacement materials in 50% incorporated feed fed groups showed better performance when compared with the control group in non-enzymatic antioxidant activity. The 50% fishmeal replacement (best performance diet fed groups taken for enzymatic antioxidant study, in SOD, CAT and LPx showed no significant increases when compared with the control group. Hence, the present results revealed that the formulated feed enhanced the vitamins C and E, the result of decreased level of enzymatic antioxidants (SOD, CAT and LPx revealed that these feeds are non-toxic and do not produce any stress to postlarvae. These ingredients can be used as an alternative protein source for sustainable Macrobrachium culture.

  17. Rapid replacement of Tangier Island bridges including lightweight and durable fiber-reinforced polymer deck systems.

    Science.gov (United States)

    2009-01-01

    Fiber-reinforced polymer (FRP) composite cellular deck systems were used as new bridge decks on two replacement bridges on Tangier Island, Virginia. The most important characteristics of this application were reduced self-weight and increased durabil...

  18. AB073. Classic infantile-onset Pompe disease: phenotypes and outcomes of 5 Vietnamese patients receiving enzyme replacement therapy

    Science.gov (United States)

    Nguyen, Khanh Ngoc; Do, Mai Thi Thanh; Can, Ngoc Thi Bich; Hwu, Wuh-Liang; Vu, Dung Chi

    2017-01-01

    Background Pompe disease (PD) or glycogen storage disease type II is a lysosomal storage disorder, caused by mutations of GAA gene which results in deficiency of acid alpha-glucosidase (GAA) enzyme that involves in metabolism of glycogen in the lysosomes. Its incidence is 1/14,000–1/100,000. PD is divided into three types: classic infantile onset, non-classic infantile onset, and late onset. Early enzyme replacement therapy (ERT) before developing respiratory distress may lead to good outcome. Since 2013, we have identified 16 cases with classic infantile-onset and 5 cases were treated with ERT. Herein, we describe phenotypes and outcomes of five infantile-onset PD patients who received ERT. Methods GAA enzyme assay was done at National Taiwan University Hospital. Results Ages of diagnosis were 12, 38 and 70 days, 5 and 9 months of age. Clinical presentations included macroglossia (5/5), hypertrophic cardiomyopathy (5/5), failure to thrive (5/5), facial weakness and hypotonia (3 patients diagnosed after 70 days of age), respiratory failure (1 patient diagnosed at 9 months of age). All patients had mildly elevated plasma CK (270–380 UI/L) and transaminase (60–260 UI/l). Ages at starting ERT were 28 and 58 days, 3, 6 and 10 months. The time intervals from diagnosis to starting ERT were between 14 days and 1 month. The durations of ERT were 4–22 months. The outcomes were good. All patients had improvement of cardiac functions shown on echocardiography, respiratory status, and motor development. The patient who first received ERT at 10 months of age was reportedly dead at home due to food obstruction at 18 months of age. Current ages of the survivors were 5–24 months. Conclusions Patients with classic infantile-onset PD will have good outcomes if ERT is started early. Newborn screening for this disease is necessary to yield an early diagnosis.

  19. Respiratory muscle training with enzyme replacement therapy improves muscle strength in late - onset Pompe disease.

    Science.gov (United States)

    Jevnikar, Mitja; Kodric, Metka; Cantarutti, Fabiana; Cifaldi, Rossella; Longo, Cinzia; Della Porta, Rossana; Bembi, Bruno; Confalonieri, Marco

    2015-12-01

    Pompe disease is an autosomal recessive metabolic disorder caused by the deficiency of the lysosomal enzyme acid α-glucosidase. This deficiency leads to glycogen accumulation in the lysosomes of muscle tissue causing progressive muscular weakness particularly of the respiratory system. Enzyme replacement therapy (ERT) has demonstrated efficacy in slowing down disease progression in infants. Despite the large number of studies describing the effects of physical training in juvenile and adult late onset Pompe disease (LOPD). There are very few reports that analyze the benefits of respiratory muscle rehabilitation or training. The effectiveness of respiratory muscle training was investigated using a specific appliance with adjustable resistance (Threshold). The primary endpoint was effect on respiratory muscular strength by measurements of MIP and MEP. Eight late-onset Pompe patients (aged 13 to 58 years; 4 female, 4 male) with respiratory muscle deficiency on functional respiratory tests were studied. All patients received ERT at the dosage of 20 mg/kg/every 2 weeks and underwent training with Threshold at specified pressures for 24 months. A significant increase in MIP was observed during the follow-up of 24 month: 39.6 cm H 2 O (+ 25.0%) at month 3; 39.5 cm H 2 O (+ 24.9%) at month 6; 39.1 cm H 2 O (+ 23.7%) at month 9; 37.3 cm H 2 O (+ 18.2%) at month 12; and 37.3 cm H 2 O (+ 17.8%) at month 24. Median MEP values also showed a significant increase during the first 9 months: 29.8 cm H 2 O, (+ 14.3%) at month 3; 31.0 cm H 2 O (+ 18.6) at month 6; and 29.5 cm H 2 O (+ 12.9) at month 9. MEP was then shown to be decreased at months 12 and 24; median MEP was 27.2 cm H 2 O (+ 4.3%) at 12 months and 26.6 cm H 2 O (+ 1.9%) at 24 months. The FVC remain stable throughout the study. An increase in respiratory muscular strength was demonstrated with Threshold training when used in combination with ERT.

  20. Pancreatic enzyme replacement therapy in cystic fibrosis: dose, variability and coefficient of fat absorption

    Directory of Open Access Journals (Sweden)

    Joaquim Calvo-Lerma

    Full Text Available Objectives: Pancreatic enzyme replacement therapy (PERT remains a backbone in the nutritional treatment of cystic fibrosis. Currently, there is a lack of an evidence-based tool that allows dose adjustment. To date, no studies have found an association between PERT dose and fat absorption. Therefore, the aim of the study was to assess the influence of both the PERT dose and the variability in this dose on the coefficient of fat absorption (CFA. Methods: This is a retrospective longitudinal study of 16 pediatric patients (192 food records with three consecutive visits to the hospital over a twelve-month period. Dietary fat intake and PERT were assessed via a four-day food record and fat content in stools was determined by means of a three-day stool sample collection. A beta regression model was built to explain the association between the CFA and the interaction between the PERT dose (lipase units [LU]/g dietary fat and the variability in the PERT dose (standard deviation [SD]. Results: The coefficient of fat absorption increased with the PERT dose when the variability in the dose was low. In contrast, even at the highest PERT dose values, the CFA decreased when the variability was high. The confidence interval suggested an association, although the analysis was not statistically significant. Conclusion: The variability in the PERT dose adjustment should be taken into consideration when performing studies on PERT efficiency. A clinical goal should be the maintenance of a constant PERT dose rather than trying to obtain an optimal value.

  1. Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

    Science.gov (United States)

    Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis

    2011-08-01

    Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network

    Directory of Open Access Journals (Sweden)

    Alícia Dorneles Dornelles

    2014-01-01

    Full Text Available Mucopolysaccharidosis type I (MPS I is a rare lysosomal disorder caused by deficiency of alph-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34 and at a median time of 2.5 years later (T2; n = 24/34. The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype; B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype. For all variables in which there was no between-group difference at baseline, a delta of ;±20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

  3. Enzyme oxidation of plant galactomannans yielding biomaterials with novel properties and applications, including as delivery systems.

    Science.gov (United States)

    Galante, Yves M; Merlini, Luca; Silvetti, Tiziana; Campia, Paola; Rossi, Bianca; Viani, Fiorenza; Brasca, Milena

    2018-06-01

    New biomaterials from renewable sources and the development of "functionalized biopolymers" are fields of growing industrial interest. Plant polysaccharides represent a valid alternative to traditional synthetic polymers, which are obtained from monomers of fossil, non-renewable origin. Several polysaccharides, either in their natural or chemically/biochemically modified forms, are currently employed in the biomedical, food and feed, and industrial fields, including packaging. Sustainable biochemical reactions, such as enzyme modifications of polysaccharides, open further possibilities for new product and process innovation. In the present review, we summarize the recent progress on enzyme oxidation of galactomannans (GM) from few leguminous plants (performed either with galactose oxidase or laccase) and we focus on the versatile and easily accessible laccase/TEMPO oxidative reaction. The latter causes a steep viscosity increase of GM water solutions and a transition of the gels from a viscous to an elastic form, due to formation of emiacetalic bonds and thus of internal cross-linking of the polymers. Following lyophilization of these hydrogels, stable aerogels can be obtained, which were shown to have good potential as delivery systems (DS) of actives. The active molecules tested and herewith described are polymyxin B, an antibiotic; nisin, an antimicrobial peptide; the enzymes lysozyme, protease and lipase; the mixture of the industrial microbiocides 5-chloro-2-methyl-4-isothiazolin-3-one (CIT) and 2-methyl-4-isothiazolin-3-one (MIT). The advantages of such aerogel systems and the possibilities they open for future developments, including as DS, are described.

  4. Intrathecal enzyme replacement therapy reduces lysosomal storage in the brain and meninges of the canine model of MPS I.

    Science.gov (United States)

    Kakkis, E; McEntee, M; Vogler, C; Le, S; Levy, B; Belichenko, P; Mobley, W; Dickson, P; Hanson, S; Passage, M

    2004-01-01

    Enzyme replacement therapy (ERT) has been developed for several lysosomal storage disorders, including mucopolysaccharidosis I (MPS I), and is effective at reducing lysosomal storage in many tissues and in ameliorating clinical disease. However, intravenous ERT does not adequately treat storage disease in the central nervous system (CNS), presumably due to effects of the blood-brain barrier on enzyme distribution. To circumvent this barrier, we studied whether intrathecal (IT) recombinant human alpha-L-iduronidase (rhIDU) could penetrate and treat the brain and meninges. An initial dose-response study showed that doses of 0.46-4.14 mg of IT rhIDU successfully penetrated the brain of normal dogs and reached tissue levels 5.6 to 18.9-fold normal overall and 2.7 to 5.9-fold normal in deep brain sections lacking CSF contact. To assess the efficacy and safety in treating lysosomal storage disease, four weekly doses of approximately 1 mg of IT rhIDU were administered to MPS I-affected dogs resulting in a mean 23- and 300-fold normal levels of iduronidase in total brain and meninges, respectively. Quantitative glycosaminoglycan (GAG) analysis showed that the IT treatment reduced mean total brain GAG to normal levels and achieved a 57% reduction in meningeal GAG levels accompanied by histologic improvement in lysosomal storage in all cell types. The dogs did develop a dose-dependent immune response against the recombinant human protein and a meningeal lymphocytic/plasmacytic infiltrate. The IT route of ERT administration may be an effective way to treat the CNS disease in MPS I and could be applicable to other lysosomal storage disorders.

  5. Renal function predicts long-term outcome on enzyme replacement therapy in patients with Fabry disease.

    Science.gov (United States)

    Lenders, Malte; Schmitz, Boris; Stypmann, Jörg; Duning, Thomas; Brand, Stefan-Martin; Kurschat, Christine; Brand, Eva

    2017-12-01

    Renal and cardiac involvement is responsible for substantial morbidity and mortality in Fabry disease (FD). We analysed the incidence of FD-related renal, cardiac and neurologic end points in patients with FD on long-term enzyme replacement therapy (ERT). A retrospective analysis of prospectively collected data from two German FD centres was performed. The impact of renal and cardiac function at ERT-naïve baseline on end point development despite ERT was analysed. Fifty-four patients (28 females) receiving ERT (mean 81 ± 21 months) were investigated. Forty per cent of patients were diagnosed with clinical end points before ERT initiation and 50% of patients on ERT developed new clinical end points. In patients initially diagnosed with an end point before ERT initiation, the risk for an additional end point on ERT was increased {hazard ratio [HR] 3.83 [95% confidence interval (CI) 1.61-9.08]; P = 0.0023}. A decreased glomerular filtration rate (eGFR) ≤75 mL/min/1.73 m2 in ERT-naïve patients at baseline was associated with an increased risk for cardiovascular end points [HR 3.59 (95% CI 1.15-11.18); P = 0.0273] as well as for combined renal, cardiac and neurologic end points on ERT [HR 4.77 (95% CI 1.93-11.81); P = 0.0007]. In patients with normal kidney function, left ventricular hypertrophy at baseline predicted a decreased end point-free survival [HR 6.90 (95% CI 2.04-23.27); P = 0.0018]. The risk to develop an end point was independent of sex. In addition to age, even moderately impaired renal function determines FD progression on ERT. In patients with FD, renal and cardiac protection is warranted to prevent patients from deleterious manifestations of the disease. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  6. A distinct urinary biomarker pattern characteristic of female Fabry patients that mirrors response to enzyme replacement therapy.

    Directory of Open Access Journals (Sweden)

    Andreas D Kistler

    Full Text Available Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naïve female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naïve Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy.

  7. Clinical response to long term enzyme replacement treatment in children, adolescent and adult patients with Hunter syndrome.

    Science.gov (United States)

    Dalmau Serra, Jaime; Vitoria Miñana, Isidro; Calderón Fernández, Rafael; Cortell Aznar, Isidoro

    2015-11-06

    Since enzyme replacement treatment (ERT) with idursulfase is available for Hunter syndrome (HS; mucopolysaccharidosis type II), for the first time, disease progression can be limited and organ damage reduced or prevented. We described retrospectively the clinical evolution of eight HS males, treated with ERT and followed in routine clinical practice in Hospital Infantil La Fe (Valencia, Spain). We studied three children, three adolescents and two adults. Time from diagnosis to ERT ranged from 13.7 to 0.2 years, and duration of ERT ranged from 24 to 77.1 months. From the start of ERT, weight and height increased in children and adolescents and remained stable in adults. Glycosaminoglycans (GAG) decreased in all patients; in patient 5 (aged 23 years), we observed the highest reduction (86%) with recovery of carpal tunnel syndrome, splenomegaly and a decrease in nocturnal oxygen dependence. Our results show that ERT improve respiratory impairment and organomegalies and decrease GAGs levels in all patients including children, adolescent and adults. While cardiac manifestations and facial features stabilized, responses in other parameters were heterogeneous. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  8. Timing of initiation of enzyme replacement therapy after diagnosis of type 1 Gaucher disease: effect on incidence of avascular necrosis

    Science.gov (United States)

    Mistry, Pramod K; Deegan, Patrick; Vellodi, Ashok; Cole, J Alexander; Yeh, Michael; Weinreb, Neal J

    2009-01-01

    Data from the International Collaborative Gaucher Group Gaucher Registry were analysed to assess the relationship between enzyme replacement therapy with imiglucerase (ERT) and incidence of avascular necrosis (AVN) in type 1 Gaucher disease (GD1), and to determine whether the time interval between diagnosis and initiation of ERT influences the incidence rate of AVN. All patients with GD1 enrolled in the Gaucher Registry who received ERT and did not report AVN prior to starting therapy (n = 2700) were included. The incidence rate of AVN following initiation of ERT was determined. An incidence rate of AVN of 13·8 per 1000 person-years was observed in patients receiving ERT. Patients who initiated ERT within 2 years of diagnosis had an incidence rate of 8·1 per 1000 person-years; patients who started ERT ≥2 years after diagnosis had an incidence rate of 16·6 per 1000 person-years. The adjusted incidence rate ratio was 0·59 [95% confidence interval (CI) 0·36–0·96, P = 0·0343]. Splenectomy was an independent risk factor for AVN (adjusted incidence rate ratio 2·23, 95% CI 1·61–3·08, P < 0·0001). In conclusion, the risk of AVN was reduced among patients who initiated ERT within 2 years of diagnosis, compared to initiating treatment ≥2 years after diagnosis. A higher risk of AVN was observed among patients who had previously undergone splenectomy. PMID:19732054

  9. Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1

    NARCIS (Netherlands)

    Grabowski, Gregory A.; Kacena, Katherine; Cole, J. Alexander; Hollak, Carla E. M.; Zhang, Lin; Yee, John; Mistry, Pramod K.; Zimran, Ari; Charrow, Joel; vom Dahl, Stephan

    2009-01-01

    Purpose: To determine whether enzyme therapy with imiglucerase/ alglucerase demonstrates dose-response relationships with doses and disease parameters used in routine clinical practice for Gaucher disease type 1 patients. Methods: Analyses included all patients with Gaucher disease type 1 on enzyme

  10. Biochemical Characterization of Porphobilinogen Deaminase–Deficient Mice During Phenobarbital Induction of Heme Synthesis and the Effect of Enzyme Replacement

    Science.gov (United States)

    Johansson, Annika; Möller, Christer; Fogh, Jens; Harper, Pauline

    2003-01-01

    Acute intermittent porphyria (AIP) is a genetic disorder caused by a deficiency of porphobilinogen deaminase (PBGD), the 3rd enzyme in heme synthesis. It is clinically characterized by acute attacks of neuropsychiatric symptoms and biochemically by increased urinary excretion of the porphyrin precursors porphobilinogen (PBG) and 5-aminolevulinic acid (ALA). A mouse model that is partially deficient in PBGD and biochemically mimics AIP after induction of the hepatic ALA synthase by phenobarbital was used in this study to identify the site of formation of the presumably toxic porphyrin precursors and study the effect of enzyme-replacement therapy by using recombinant human PBGD (rhPBGD). After 4 d of phenobarbital administration, high levels of PBG and ALA were found in liver, kidney, plasma, and urine of the PBGD-deficient mice. The administration of rhPBGD intravenously or subcutaneously after a 4-d phenobarbital induction was shown to lower the PBG level in plasma in a dose-dependent manner with maximal effect seen after 30 min and 2 h, respectively. Injection of rhPBGD subcutaneously twice daily during a 4-d phenobarbital induction reduced urinary PBG excretion to 25% of the levels found in PBGD-deficient mice administered with only phenobarbital. This study points to the liver as the main producer of PBG and ALA in the phenobarbital-induced PBGD-deficient mice and demonstrates efficient removal of accumulated PBG in plasma and urine by enzyme-replacement therapy. PMID:15208740

  11. Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet.

    Science.gov (United States)

    Basciani, Sabrina; Costantini, Daniela; Contini, Savina; Persichetti, Agnese; Watanabe, Mikiko; Mariani, Stefania; Lubrano, Carla; Spera, Giovanni; Lenzi, Andrea; Gnessi, Lucio

    2015-04-01

    To investigate safety, compliance, and efficacy, on weight loss and cardiovascular risk factors of a multiphasic dietary intervention based on meal replacements, including a period of very low calorie diet (VLCD) in a population of obese patients. Anthropometric parameters, blood tests (including insulin), dual-energy-X-ray absorptiometry (DXA), and questionnaires for the assessment of safety and compliance before and after (phase I) a 30-day VLCD, 700 kcal/day, normoproteic, 50 g/day carbohydrate, four meal replacements; (phase II) a 30-day low calorie diet (LCD), 820 kcal/day, three meal replacements plus a protein plate; (phase III) 60-day LCD, 1,100 kcal/day, two meal replacements plus two protein plates and reintroduction of small amounts of carbohydrates; (phase IV) 60-day hypocaloric balanced diet (HBD), 1,200 kcal/day, one meal replacement, two protein plates and the reintroduction of carbohydrates. 24 patients (17 females, 7 males, mean BMI 33.8±3.2 kg/m2, mean age 35.1±10.2 years) completed the study. The average weight loss was 15.4±6.7%, with a significant reduction of fat mass (from 32.8±4.7 to 26.1±6.3% p<0.05) and a relative increase of lean mass (from 61.9±4.8 to 67.1±5.9% p<0.05). An improvement of metabolic parameters and no variations of the liver and kidney functions were found. A high safety profile and an excellent dietary compliance were seen. The VLCD dietary program and the replacement dietary system described here is an effective, safe, and well-tolerated treatment for weight control.

  12. Enzyme

    Science.gov (United States)

    Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

  13. Survival, Quality of Life and Effects of Enzyme Replacement Therapy in Adults with Pompe Disease

    NARCIS (Netherlands)

    D. Güngör (Deniz)

    2013-01-01

    textabstractPompe disease, or glycogen storage disorder type II, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme acid α-glucosidase. This results in accumulation of glycogen in cells throughout the body, particularly muscle cells. The disease presents

  14. Replacing corn with pearl millet (raw and sprouted) with and without enzyme in chickens' diet.

    Science.gov (United States)

    Afsharmanesh, M; Ghorbani, N; Mehdipour, Z

    2016-04-01

    An experiment was conducted to compare a commercial corn-soya bean meal diet with a pearl millet (raw and sprouted) diet containing less soya bean meal, alone or in combination with exogenous enzyme, on growth performance and ileal villus development of chicks. Two-hundred-and-forty-one-day-old male broilers (10/pen) were randomly allocated to one of the following dietary treatments: (i) a standard corn-soya bean meal control diet (CTL); (ii) a raw pearl millet-soya bean meal diet (PM); (iii) a sprouted pearl millet-soya bean meal diet (SPM); (iv) CTL + exogenous enzymes (CE); (v) PM + exogenous enzymes (PE); and (vi) SPM + exogenous enzymes (SPE) with four replicate pens/treatment. Body weight of birds at day 21 did not differ between those fed the CTL, and SPM and PE diets. In comparison with feeding broilers the CTL diet, feeding the PE and SPM diets caused significant decrease in feed intake, but with equivalent growth and feed efficiency. However, at day 21, feed conversion ratio did not differ between birds fed the CTL diet and those fed the PM, PE and SPM diets. At day 21, broilers fed the PM and PE diets had longer villi (p diet. At day 21, villi width was reduced (p diet. It is concluded that, in comparison with corn, broiler diets formulated with sprouted pearl millet or pearl millet with enzyme require less soya bean meal and can be used to improve growth performance traits and villus development. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  15. Partial resolution of bone lesions. A child with severe combined immunodeficiency disease and adenosine deaminase deficiency after enzyme-replacement therapy

    International Nuclear Information System (INIS)

    Yulish, B.S.; Stern, R.C.; Polmar, S.H.

    1980-01-01

    A child with severe combined immunodeficiency disease and adenosine deaminase deficiency, with characteristic bone dysplasia, was treated with transfusions of frozen irradiated RBCs as a means of enzyme replacement. This therapy resulted in restoration of immunologic competence and partial resolution of the bone lesions. Although the natural history of these lesions without therapy is not known, enzyme-replacement therapy may have played a role in the resolution of this patient's bone lesions

  16. Survival, Quality of Life and Effects of Enzyme Replacement Therapy in Adults with Pompe Disease

    OpenAIRE

    Güngör, Deniz

    2013-01-01

    textabstractPompe disease, or glycogen storage disorder type II, is a rare inherited metabolic disorder caused by deficiency of the lysosomal enzyme acid α-glucosidase. This results in accumulation of glycogen in cells throughout the body, particularly muscle cells. The disease presents with (progressive) muscle weakness and can hence be categorized as a lysosomal storage disorder, a glycogen storage disorder and also a neuromuscular disorder. Pompe disease was the first neuromuscular disorde...

  17. The outcome of clinical parameters in adults with severe Type I Gaucher disease using very low dose enzyme replacement therapy.

    Science.gov (United States)

    Wilson, Callum; Spearing, Ruth; Teague, Lochie; Robertson, Patsy; Blacklock, Hilary

    2007-01-01

    Enzyme replacement therapy is now well established as the treatment of choice in Type I Gaucher disease. Historically higher dosage regimens have been used in preference to lower doses despite the little clinical evidence in the way of large controlled clinical trials to support this. Moreover, the extraordinary cost of therapy means that not all eligible patients are able to be treated at the higher dose. Twelve type I adult patients with relatively severe disease were commenced on a very low dose of 7.5U of alglucerase/imiglucerase per kg every two weeks (initially given thrice weekly and later weekly). Follow-up 5 year data reveal a good visceral and haematological response with outcomes consistent with recently published treatment guidelines. Satisfactory clinical and radiological skeletal improvement was also demonstrated in most patients. Three patients had an inadequate overall skeletal response to therapy. Biomarkers also steadily improved although perhaps not quite at the same rate as that seen in higher doses. Very low dose enzyme replacement therapy may be appropriate for adult type I Gaucher patients with mild-moderate skeletal disease.

  18. Effects of replacing groundnut cake with rumen content supplemented with or without enzyme in the diet of weaner rabbits.

    Science.gov (United States)

    Adeniji, A A; Rumak, S; Oluwafemi, R A

    2015-12-18

    Rabbits are also herbivores which efficiently convert fodder to food. They are prolific and converter of plant proteins of little or no use to people as food into high-value animal protein. Rabbit meat is high in protein, low in calories and low in fat and cholesterol contents, being considered as a delicacy and a healthy food product. Feeding rabbits with concentrates is expensive and therefore in order to reduce cost of production, hence the use of rumen content in this study as alternative feedstuff without competition. A total of thirty six (36) weaner rabbits (oryctalagus cuniculus) of different body weight and age where use in this experiment to determine the effects of replacing rumen content with or without enzyme supplementation for groundnut cake. This feeding trial which lasted for 8 weeks was carried out in order to determine the replacement value of groundnut cake with rumen content with or without enzyme in the diet of weaner rabbit. A 3x2 factorial experiment was adopted such that there where three (3) replacement level of rumen content (0, 25 and 50 %) for groundnut cake by two supplemental level (no enzyme and enzyme supplement). The results showed that increased inclusion level of rumen content has significant effects (p  0.05) with weight gained value of 7.62,7.44 and 7.36 g respectively. Similarly there was a significant (p  0.05) of the treatment on urinary nitrogen. Significant (p  0.05) of the supplementation on the nitrogen intake. The interaction between the varying levels of rumen content supplementation had significant effects (p < 0.05) on the feacal nitrogen, feed intake and feed to gain ratio but no significant (p < 0.05) effects on interaction of nitrogen intake. In conclusion, since the results from this study showed no negative effects on the performance of the experimental animals, the test ingredient can be used as alternative feedstuff at a lower inclusion level so as to reduce production cost and expand

  19. Case report of unexpected gastrointestinal involvement in type 1 Gaucher disease: comparison of eliglustat tartrate treatment and enzyme replacement therapy.

    Science.gov (United States)

    Kim, Yoo-Mi; Shin, Dong Hoon; Park, Su Bum; Cheon, Chong Kun; Yoo, Han-Wook

    2017-05-15

    Gastrointestinal involvement in Gaucher disease is very rare, and appears to be unresponsive to enzyme replacement therapy (ERT). Here, we describe identical twin, splenectomized, non-neuronopathic Gaucher patients on long-term ERT for 9 years, who complained of epigastric discomfort due to Gaucher cell infiltration of the gastroduodenal mucosa. Rare compound heterozygous mutations (p.Arg48Trp and p.Arg257Gln) of the GBA gene were found in both. Improvement in the gastroduodenal infiltration and reduced chitotriosidase levels were observed in one who switched to eliglustat tartrate for 1 year, whereas the other one who maintained ERT showed no improvement of chitotriosidase level and persistent duodenal lesions. This shows that eliglustat might be an effective treatment for Gaucher disease patients having lesions resistant to ERT.

  20. Comparative impact of AAV and enzyme replacement therapy on respiratory and cardiac function in adult Pompe mice

    Directory of Open Access Journals (Sweden)

    Darin J Falk

    Full Text Available Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA. Cardiac dysfunction and respiratory muscle weakness are primary features of this disorder. To attenuate the progressive and rapid accumulation of glycogen resulting in cardiorespiratory dysfunction, adult Gaa−/− mice were administered a single systemic injection of rAAV2/9-DES-hGAA (AAV9-DES or bimonthly injections of recombinant human GAA (enzyme replacement therapy (ERT. Assessment of cardiac function and morphology was measured 1 and 3 months after initiation of treatment while whole-body plethysmography and diaphragmatic contractile function was evaluated at 3 months post-treatment in all groups. Gaa−/− animals receiving either AAV9-DES or ERT demonstrated a significant improvement in cardiac function and diaphragmatic contractile function as compared to control animals. AAV9-DES treatment resulted in a significant reduction in cardiac dimension (end diastolic left ventricular mass/gram wet weight; EDMc at 3 months postinjection. Neither AAV nor ERT therapy altered minute ventilation during quiet breathing (eupnea. However, breathing frequency and expiratory time were significantly improved in AAV9-DES animals. These results indicate systemic delivery of either strategy improves cardiac function but AAV9-DES alone improves respiratory parameters at 3 months post-treatment in a murine model of Pompe disease.

  1. Echocardiographic and clinical findings in patients with Fabry disease during long-term enzyme replacement therapy

    DEFF Research Database (Denmark)

    Madsen, Christoffer Valdorff; Bundgaard, Henning; Rasmussen, Åse Krogh

    2017-01-01

    from baseline to follow-up; 30 mm [15-53] vs. 25 mm [3-44], p vs. 1520 mm·ms [550-5740], p within the non-ERT group. During follow-up, cardiac symptoms and use of cardiovascular procedures and -medication increased...... significantly in the ERT group, whereas no differences were observed within the non-ERT group. DISCUSSION: We raise concerns regarding the efficacy and benefit of ERT on cardiac involvement in Fabry disease and stress the need for further research....... and Holter-monitoring. RESULTS: We included 66 patients; 47 patients (27 women) received ERT (ERT group) and 19 patients (15 women) did not (non-ERT group). The groups were followed for a median of 8 [0-12] years and 6 [0-13] years, respectively. Comparison between ERT and non-ERT receiving patients by left...

  2. Pancreatic enzyme replacement therapy.

    Science.gov (United States)

    Layer, P; Keller, J; Lankisch, P G

    2001-04-01

    Malabsorption due to severe pancreatic exocrine insufficiency is one of the most important late features of chronic pancreatitis. Generally, steatorrhea is more severe and occurs several years prior to malabsorption of other nutrients because synthesis and secretion of lipase are impaired more rapidly, its intraluminal survival is shorter, and the lack of pancreatic lipase activity is not compensated for by nonpancreatic mechanisms. Patients suffer not only from nutritional deficiencies but also from increased nutrient delivery to distal intestinal sites, causing symptoms by profound alteration of upper gastrointestinal secretory and motor functions. Adequate nutrient absorption requires delivery of sufficient enzymatic activity into the duodenal lumen simultaneously with meal nutrients. The following recommendations are based on modern therapeutic concepts: 25,000 to 40,000 units of lipase per meal using pH-sensitive pancreatin microspheres, with dosage increases, compliance checks, and differential diagnosis in case of treatment failure. Still, in most patients, lipid digestion cannot be completely normalized by current standard therapy, and future developments are needed to optimize treatment.

  3. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction

    Science.gov (United States)

    Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L.; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R.; Kohn, Donald B.

    2012-01-01

    Gene therapy (GT) for adenosine deaminase–deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada−/−). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist. PMID:22833548

  4. Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

    International Nuclear Information System (INIS)

    Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis; Stirnemann, Jerome; Belmatoug, Nadia; Petrover, David

    2015-01-01

    To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

  5. Histological characterisation of visceral changes in a patient with type 2 Gaucher disease treated with enzyme replacement therapy.

    Science.gov (United States)

    Tezuka, Yuko; Fukuda, Mitsumasa; Watanabe, Shohei; Nakano, Takeshi; Okamoto, Kentaro; Kuzume, Kazuyo; Yano, Yoshiaki; Eguchi, Mariko; Ishimae, Minenori; Ishii, Eiichi; Miyazaki, Tatsuhiko

    2018-02-01

    Gaucher disease is a lysosomal storage disease caused by deficiency of glucocerebrosidase and accumulation of glucocerebroside. Three major sub-types have been described, type 2 is an acute neurological form that exhibits serious general symptoms and poor prognosis, compared with the other types. This case was a girl diagnosed with type 2 Gaucher disease at 12months of age who presented with poor weight gain from infancy, stridor, hypertonia, hepatosplenomegaly, trismus and an eye movement disorder. Enzyme replacement therapy (ERT) was administered, but she had frequent myoclonus and developmental regression. She needed artificial ventilation because of respiratory failure. She died at 11years of age. An autopsy demonstrated infiltrating CD68-positive large cells containing abundant lipids in alveoli, while in the liver, kidney and bone marrow CD68-positive cells were small and round. In the bone marrow, myelodysplastic changes were present without Gaucher cells. The infiltration of Gaucher cells in alveoli was marked, suggesting that ERT was relatively ineffective in pulmonary involvement, particularly intra-alveolar. Additional treatments are necessary to improve the neurological and pulmonary prognosis of type 2Gaucher disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders.

    Science.gov (United States)

    Broomfield, A; Jones, S A; Hughes, S M; Bigger, B W

    2016-07-01

    In the light of clinical experience in infantile onset Pompe patients, the immunological impact on the tolerability and long-term efficacy of enzyme replacement therapy (ERT) for lysosomal storage disorders has come under renewed scrutiny. This article details the currently proposed immunological mechanisms involved in the development of anti-drug antibodies and the current therapies used in their treatment. Given the current understanding of the adaptive immune response, it focuses particularly on T cell dependent mechanisms and the paradigm of using lymphocytic negative selection as a predictor of antibody formation. This concept originally postulated in the 1970s, stipulated that the genotypically determined lack of production or production of a variant protein determines an individual's lymphocytic repertoire. This in turn is the key factor in determining the potential severity of an individual's immunological response to ERT. It also highlights the need for immunological assay standardization particularly those looking at describing the degree of functional impact, robust biochemical or clinical endpoints and detailed patient subgroup identification if the true evaluations of impact are to be realised.

  7. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

    Science.gov (United States)

    Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

    2012-11-01

    Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

  8. Effects of Estrogen Replacement Therapy on Lipid Peroxidation and Antioxidant Enzyme Activities of Ovariectomized and Ovariectomized-Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Aslı F. Ceylan-Işık

    2007-01-01

    Full Text Available Menopause and diabetes are conditions producing free radicals independently from each other. Estrogen replacement therapy which widely used in postmenopausal period has beneficial effects because of its antioxidant property. The study groups were as follows: ovariectomy (n=8, ovariectomy+17-östradiol (n=8, ovariectomy+diabetes (n=10 and ovariectomy+diabetes+17-östradiol (n=8. Diabetes was induced by streptozotocin (45 mg/kg i.p. and the treatment with 17-östradiol (0.1 mg/kg/day was started a week after ovariectomy. After–week long experimental period aortic and uterine tissues were collected from the animals and the malondialdehyde concentration, glutathione peroxidase and catalase activities were quantified. The treatment did not effect blood glucose concentrations, but increased plasma estradiol concentrations. Increased malondialdehyde concentrations were reduced by the treatment in aorta from diabetics and nondiabetics, but the treatment increased malondialdehyde concentrations in nondiabetic uterine while were reducing in diabetic uterine. The treatment also reduced the increased activities of catalase and glutathione peroxidase in aorta from diabetics and nondiabetics, on the other hand the treatment increased the activities of those enzymes in uterine from diabetics and nondiabetics. Our results suggested that estrogen acts as an antioxidant or prooxidant depending on the tissues.

  9. Bone marrow involvement in Gaucher disease at MRI: what long-term evolution can we expect under enzyme replacement therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Fedida, Benjamin; Touraine, Sebastien; Laredo, Jean-Denis [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Stirnemann, Jerome [Universite Paris-Diderot Hopital Bichat, AP-HP, Department of Biostatistics and Medical Data Processing, INSERM UMR 738, Paris (France); Geneva University Hospital, Division of General Internal Medicine, Faculty of Medicine, Geneva (Switzerland); Belmatoug, Nadia [Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France); Hopital Beaujon, AP-HP, Department of Internal Medicine, Clichy (France); Petrover, David [Hopital Lariboisiere, AP-HP, Department of Musculoskeletal Imaging, Paris (France); Hopital Beaujon, AP-HP, Referral Center for Lysosomal Diseases (RCLD), Clichy (France)

    2015-10-15

    To study the long-term evolution of the bone marrow burden (BMB) score at MRI in patients with Gaucher disease (GD) under enzyme replacement therapy (ERT). Forty patients treated for GD were retrospectively studied in a referral centre. BMB scores were assessed on spine and femur MR examinations performed between January 2003 and June 2014. The long-term evolution of the BMB scores was analyzed using a linear mixed model. A total of 121 MRI examinations were performed during the study period with a mean follow-up of 7.1 years ± 5.6, an average rate of 3.1 MR examinations ± 1.7 per patient and an interval of 2.3 years ± 1.1 between examinations. Patients had received ERT during 12 years on average ± 6.7. The trend of BMB scores with time decreased significantly by 15 % (P = 0.008) during the total study period and 39 % (P = 0.01) during the first 5 years of treatment. No changes in BMB scores were observed after five years of treatment. In Gaucher patients, the trend of MRI BMB scores with time decreased significantly under ERT the first 5 years of treatment before a long-term stabilization. (orig.)

  10. Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

    International Nuclear Information System (INIS)

    Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U.; Dahl, S. vom; Niederau, C.; Haeussinger, D.; Willers, R.

    2001-01-01

    Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

  11. Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W.; Koch, J.A.; Scherer, A.; Boerner, D.; Moedder, U. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Niederau, C.; Haeussinger, D. [Duesseldorf Univ. (Germany). Medizinische Fakultaet; Willers, R. [Duesseldorf Univ. (Germany). Rechenzentrum

    2001-09-01

    Objective:. Since 1991, enzyme replacement therapy (ERT) has been available for patients with Gaucher disease in Germany. The aim of this study was to analyse the MR pattern of bone marrow involvement and response to ERT in Gaucher disease type I. Patients and design:. Thirty patients with Gaucher disease type I had MRI examinations prior to initiation of ERT with alglucerase/imiglucerase and during follow-up. Median MR follow-up and duration of ERT were 36 months. Coronal T1- and T2-weighted spin-echo images of the lower extremities were obtained to evaluate changes in the appearance of yellow marrow. MR images were categorized as having either a homogeneous (type A) or non-homogeneous patchy (type B) appearance of bone involvement and response to ERT was assessed by two radiologists. Results:. Overall, 19 of 30 patients (63%) showed an increased signal intensity on T1- and T2-weighted images after 36 months of ERT, consistent with partial reconversion of fatty marrow during treatment. Focal bone lesions surrounded by a low signal intensity (SI) rim did not respond to ERT, suggesting bone infarcts. Of the 11 patients with bone infarcts (low SI rim lesion), 82% had the non-homogeneous type B pattern (P=0.0021). In 86% of patients with splenectomy, bone infarcts were seen (P<0.05). Conclusions:. MRI using T1- and T2-weighted spin-echo sequences is a valuable, non-invasive method for monitoring bone marrow response in patients receiving ERT. A non- homogeneous patchy signal intensity of bone marrow involvement correlates with the presence of bone infarcts (P=0.0021). (orig.)

  12. The Effects of including a replacement questionnaire in the first follow-up to an industrial population

    DEFF Research Database (Denmark)

    Mortensen, Peter Stendahl

    2006-01-01

    was identical in all cases. The study compared the impact on response rates, costs, timeliness and quality. The response rate between the first and second reminders was significantly higher in the replacement group, but the second reminder evens out most of this difference. In addition, logistic......  This study reports on a field experiment in which the effects of manipulating the contents of the first reminder in an industrial survey were investigated. Every second non-responding company received a replacement questionnaire with the first mailed reminder, while the second reminder......-regression models revealed significant differences in the reaction from different industries and regions. For the replacement group, the cost/response rate was 20% higher and the marginal cost per extra response was four times that of the responses to the first mailing. However, the questionnaires were returned...

  13. Mucopolysaccharidosis type VI on enzyme replacement therapy since infancy: Six years follow-up of four children

    Directory of Open Access Journals (Sweden)

    Dafne D.G. Horovitz

    2015-12-01

    Full Text Available Clinical and biochemical improvements are reported on Mucopolysaccharidosis type VI (MPS VI patients on Enzyme Replacement Therapy (ERT with rhASB (galsulfase, Naglazyme®, and preclinical and clinical studies have shown clinical benefits of early initiation. We report four unrelated MPS VI children who began ERT as infants (ages 5 days–10 months. The three older patients showed the first clinical signs of MPS VI at baseline, also presenting different degrees of dysostosis multiplex, and two had mild heart disease. The two oldest also had mild facial coarseness, one had hearing conduction deficit and sleep disorder and the other corneal clouding at baseline. After six years on ERT, all four patients have normal urinary GAG values. Although they all showed normal motor and mental development, brain and cervical spine MRI images available from two of the older patients showed abnormalities, while the youngest child continues having normal images. The four patients presented slower progression of bone and joint disease when compared to their affected older siblings. It should be noticed that only two patients in this sample are currently below the 3rd percentile for height: the youngest who has a constitutional factor associated and the eldest who already presented frank dysostosis at 10 months of age. These findings confirm previous studies that report that skeletal features of the disease cannot be completely prevented despite early ERT. Heart disease already present in two of the four infants at baseline got worse over time and appeared in another patient, but the youngest child on ERT introduction still has a normal echocardiogram at six years of age; he also is the only one without corneal clouding after six years follow-up. Our results also suggest that early ERT prevented storage in spleen and liver and may also have improved or prevented progression of facial dysmorphic features, corroborating similar findings seen in previous studies

  14. Long term clinical history of an Italian cohort of infantile onset Pompe disease treated with enzyme replacement therapy.

    Science.gov (United States)

    Parini, Rossella; De Lorenzo, Paola; Dardis, Andrea; Burlina, Alberto; Cassio, Alessandra; Cavarzere, Paolo; Concolino, Daniela; Della Casa, Roberto; Deodato, Federica; Donati, Maria Alice; Fiumara, Agata; Gasperini, Serena; Menni, Francesca; Pagliardini, Veronica; Sacchini, Michele; Spada, Marco; Taurisano, Roberta; Valsecchi, Maria Grazia; Di Rocco, Maja; Bembi, Bruno

    2018-02-08

    Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). However, its long-term effectiveness is still not completely defined. Available data shows a close relationship between clinical outcome and patients' cross-reactive immunological status (CRIM), being CRIM-negative status a negative prognostic factor. At the same time limited data are available on the long-term treatment in CRIM-positive infants. A retrospective multicentre observational study was designed to analyse the long-term effectiveness of ERT in IOPD. Thirteen Italian centres spread throughout the country were involved and a cohort of 28 patients (15 females, 13 males, born in the period: February 2002-January 2013) was enrolled. IOPD diagnosis was based on clinical symptoms, enzymatic and molecular analysis. All patients received ERT within the first year of life. Clinical, laboratory, and functional data (motor, cardiac and respiratory) were collected and followed for a median period of 71 months (5 years 11 months). Median age at onset, diagnosis and start of ERT were 2, 3 and 4 months, respectively. CRIM status was available for 24/28 patients: 17/24 (71%) were CRIM-positive. Nineteen patients (67%) survived > 2 years: 4 were CRIM-negative, 14 CRIM-positive and one unknown. Six patients (5 CRIM-positive and one unknown) never needed ventilation support (21,4%) and seven (6 CRIM-positive and one unknown: 25%) developed independent ambulation although one subsequently lost this function. Brain imaging study was performed in 6 patients and showed peri-ventricular white matter abnormalities in all of them. Clinical follow-up confirmed the better prognosis for CRIM-positive patients, though a slow, progressive worsening of motor and/or respiratory functions was detected in 8 patients. These data are the result of the longest independent retrospective study on ERT in IOPD reported so far outside clinical trials. The data obtained

  15. Divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in two siblings with infantile-onset Pompe disease treated in the symptomatic or pre-symptomatic state

    OpenAIRE

    Matsuoka, Takashi; Miwa, Yoshiyuki; Tajika, Makiko; Sawada, Madoka; Fujimaki, Koichiro; Soga, Takashi; Tomita, Hideshi; Uemura, Shigeru; Nishino, Ichizo; Fukuda, Tokiko; Sugie, Hideo; Kosuga, Motomichi; Okuyama, Torayuki; Umeda, Yoh

    2016-01-01

    Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid ?-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectan...

  16. Intra-articular enzyme replacement therapy with rhIDUA is safe, well-tolerated, and reduces articular GAG storage in the canine model of mucopolysaccharidosis type I.

    Science.gov (United States)

    Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William C; Lawrence, Roger; Ellinwood, N Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

    2014-08-01

    Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for 6 months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and 1 month following the final injection. All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints were 8.62 ± 5.86 μg/mg dry weight and 21.6 ± 10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113 ± 39.5 ng/g wet weight) compared to saline-treated joints (142 ± 56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was

  17. The Effect of Replacing Fish Meal in the Diet with Enzyme-Treated Soybean Meal (HP310) on Growth and Body Composition of Rainbow Trout Fry.

    Science.gov (United States)

    Haghbayan, Samira; Shamsaie Mehrgan, Mehdi

    2015-11-26

    The potential of enzyme-treated soybean meal powder (HP310) as fish meal alternative in diets for rainbow trout weighing 1.17 ± 0.3 g was evaluated for 60 days. Fish meal was replaced with HP310 at 25%, 50%, 75% and 100% of experimental diets. A control group was also considered. The results showed that diets containing 75% and 100% HP310 had significantly higher feed conversion ratio and lower feed intake, weight gain and specific growth rate compared to fish feed diets containing higher levels of fish protein ingredients (p replacement levels of diet (p > 0.05). However increasing in level of HP310 in the diet caused a significant increase of the white blood cells (p replaced by HP310 showed the highest values of ash and moisture content among the diets and showed significantly different levels when compared with the control and other feeding treatments (p < 0.05).

  18. Digestibility, productive performance, and egg quality of laying hens as affected by dried cassava pulp replacement with corn and enzyme supplementation.

    Science.gov (United States)

    Khempaka, Sutisa; Maliwan, Prapot; Okrathok, Supattra; Molee, Wittawat

    2018-02-24

    Two experiments were conducted to investigate the potential use of dried cassava pulp (DCP) supplemented with enzymes as an alternative feed ingredient in laying hen diets. In experiment 1, 45 laying hens (Isa Brown) aged 45 weeks were placed in individual cages to measure nutrient digestibility for 10 days. Nine dietary treatments were control and DCP as a replacement for corn at 20, 25, 30, and 35% supplemented with mixed enzymes (cellulase, glucanase, and xylanase) at 0.10 and 0.15%. Results showed that the use of DCP at 20-35% added with mixed enzymes had no negative effects on dry matter digestibility, while organic matter digestibility and nitrogen retention decreased with increased DCP up to 30-35% in diets. Both enzyme levels (0.10 and 0.15%) showed similar results on nutrient digestibility and retention. In experiment 2, a total of 336 laying hens aged 32 weeks were randomly allocated to seven dietary treatments (control and DCP-substituted diets at 20, 25, and 30%) supplemented with mixed enzymes (0.10 and 0.15%). Diets incorporated with 20-30% of DCP and supplemented with mixed enzymes at both levels had no significant effects on egg production, egg weight, feed intake, egg mass, feed conversion ratio, protein efficiency ratio, or egg quality, except for egg yolk color being decreased with an increase of DCP in diets (P digestibility, productive performance, or egg quality.

  19. A two-stage algorithm for Clostridium difficile including PCR: can we replace the toxin EIA?

    Science.gov (United States)

    Orendi, J M; Monnery, D J; Manzoor, S; Hawkey, P M

    2012-01-01

    A two step, three-test algorithm for Clostridium difficile infection (CDI) was reviewed. Stool samples were tested by enzyme immunoassays for C. difficile common antigen glutamate dehydrogenase (G) and toxin A/B (T). Samples with discordant results were tested by polymerase chain reaction detecting the toxin B gene (P). The algorithm quickly identified patients with detectable toxin A/B, whereas a large group of patients excreting toxigenic C. difficile but with toxin A/B production below detection level (G(+)T(-)P(+)) was identified separately. The average white blood cell count in patients with a G(+)T(+) result was higher than in those with a G(+)T(-)P(+) result. Copyright © 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  20. Divergent clinical outcomes of alpha-glucosidase enzyme replacement therapy in two siblings with infantile-onset Pompe disease treated in the symptomatic or pre-symptomatic state.

    Science.gov (United States)

    Matsuoka, Takashi; Miwa, Yoshiyuki; Tajika, Makiko; Sawada, Madoka; Fujimaki, Koichiro; Soga, Takashi; Tomita, Hideshi; Uemura, Shigeru; Nishino, Ichizo; Fukuda, Tokiko; Sugie, Hideo; Kosuga, Motomichi; Okuyama, Torayuki; Umeda, Yoh

    2016-12-01

    Pompe disease is an autosomal recessive, lysosomal glycogen storage disease caused by acid α-glucosidase deficiency. Infantile-onset Pompe disease (IOPD) is the most severe form and is characterized by cardiomyopathy, respiratory distress, hepatomegaly, and skeletal muscle weakness. Untreated, IOPD generally results in death within the first year of life. Enzyme replacement therapy (ERT) with recombinant human acid alpha glucosidase (rhGAA) has been shown to markedly improve the life expectancy of patients with IOPD. However, the efficacy of ERT in patients with IOPD is affected by the presence of symptoms and cross-reactive immunologic material (CRIM) status. We have treated two siblings with IOPD with ERT at different ages: the first was symptomatic and the second was asymptomatic. The female proband (Patient 1) was diagnosed with IOPD and initiated ERT at 4 months of age. Her younger sister (Patient 2) was diagnosed with IOPD at 10 days of age and initiated ERT at Day 12. Patient 1, now 6 years old, is alive but bedridden, and requires 24-hour invasive ventilation due to gradually progressive muscle weakness. In Patient 2, typical symptoms of IOPD, including cardiac failure, respiratory distress, progressive muscle weakness, hepatomegaly and myopathic facial features were largely absent during the first 12 months of ERT. Her cardiac function and mobility were well-maintained for the first 3 years, and she had normal motor development. However, she developed progressive hearing impairment and muscle weakness after 3 years of ERT. Both siblings have had low anti-rhGAA immunoglobulin G (IgG) antibody titers during ERT and have tolerated the treatment well. These results suggest that initiation of ERT during the pre-symptomatic period can prevent and/or attenuate the progression of IOPD, including cardiomyopathy, respiratory distress, and muscle weakness for first several years of ERT. However, to improve the long-term efficacy of ERT for IOPD, new strategies

  1. 41 CFR 302-9.174 - What is the “authorized point of origin” when I transport a POV, including a replacement POV, to...

    Science.gov (United States)

    2010-07-01

    ... point of originâ when I transport a POV, including a replacement POV, to my post of duty subsequent to... Property Management Federal Travel Regulation System RELOCATION ALLOWANCES TRANSPORTATION AND STORAGE OF... Pov Transportation Subsequent to the Time of Assignment § 302-9.174 What is the “authorized point of...

  2. Effect of corn replacement with graded levels of wheat screening and enzyme supplementation on performance, blood lipids, viscosity and jejunal histomorphology of finisher broilers

    Energy Technology Data Exchange (ETDEWEB)

    Mazhari, M.; Golian, A.; Kermanshahi, H.

    2015-07-01

    An experiment was carried out to study the effect of corn replacement with five levels of wheat screening (0, 150, 300, 450 and 600 g/kg of diet) with (0.5 g/kg of diet) or without xylanase-glucanase enzyme on performance, blood lipids, viscosity and jejunal histomorphology of finisher broilers (25-42 days of age). Five hundred day-old Ross-308 male broiler chicks were fed by a standard commercial diet up to 24 days of age, then randomly assigned to 10 diets. Each diet was fed to five groups of ten chicks each. There was not significant differences in body weight gain (BWG), feed intake, and feed conversion ratio of birds fed with different levels of wheat screening (WS), whereas enzyme increased (p<0.05) BWG. Different levels of WS and enzyme did not have a significant effect on relative weights of carcass, breast, thigh, and abdominal fat of broilers. Relative weights of gizzard, pancreas, small and large intestine, and relative length of jejunum and jejunal and ileal viscosity were increased (p<0.05) by WS, while were decreased (p<0.05) by enzyme. The serum cholesterol level decreased (p<0.05) by increasing levels of WS. Jejunal histomorphological observations showed (p<0.05) shorter and thicker villus and lower crypt depth by increasing levels of WS, while addition of enzyme to the diets, affected (p<0.05) reversely to these parameters. The results showed that the addition of wheat screening up to an inclusion level of 600 g/kg of diet had no adverse effect on broiler performance in the finisher (25-42 d) phases whereas decreased serum cholesterol levels, increased viscosity and villus atrophy. The dietary administration of exogenous enzyme improved performance parameters and decreased viscosity and villus atrophy of broiler jejunum. (Author)

  3. Fermented soybean meal exhibits probiotic properties when included in Japanese quail diet in replacement of soybean meal.

    Science.gov (United States)

    Jazi, V; Ashayerizadeh, A; Toghyani, M; Shabani, A; Tellez, G; Toghyani, M

    2018-03-15

    This study was conducted to investigate and compare the effect of dietary probiotic mixture (PM) and organic acid (OA) mixture with fermented soybean meal (FSBM) on performance, crop, and ceca microbiota, small intestine morphology, and serum lipid profile in Japanese quails. A total of 800 day-old Japanese quails was randomly allotted to 5 treatments with 8 replicate pens of 20 birds each, for 35 days. The experimental diets consisted of a control corn-soybean meal diet and 4 test diets: 1) control diet + 0.1% PM; 2) control diet + 0.2% OA mixture; 3) control diet + the combination of both PM and OA; and 4) an additives-free diet in which the soybean meal in the control diet was replaced with FSBM. The results indicated that in starter and the entire rearing periods, FSBM, PM, and PM+OA diets had significantly lower FCR compared to control or OA diets (P < 0.05). Birds in the FSBM group gained higher weight than control and OA birds (P < 0.05; 1 to 35 d). At d 21 and 35, birds fed the control diet showed significantly lower numbers of lactic acid bacteria in the crop, while coliforms were higher in the cecal content compared to the other diets (P < 0.05). At d 21, the villus height and villus height to crypt depth ratio in the duodenum and jejunum of birds fed PM, PM+OA, and FSBM diets were greater than in other treatments (P < 0.05). The serum concentrations of cholesterol and low-density lipoprotein cholesterol of birds fed PM, PM+OA, and FSBM diets were significantly lower than birds in control and AO groups (P < 0.05). The results obtained herein suggest that FSBM exhibits probiotic properties and, when used in substitution of SBM in Japanese quail diet, can improve growth performance, balance of desirable gastrointestinal microbiota in crop and ceca, small intestinal morphology, and serum lipid profile-likewise, a probiotic supplement.

  4. Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with X-linked myotubular myopathy.

    Science.gov (United States)

    Lawlor, Michael W; Armstrong, Dustin; Viola, Marissa G; Widrick, Jeffrey J; Meng, Hui; Grange, Robert W; Childers, Martin K; Hsu, Cynthia P; O'Callaghan, Michael; Pierson, Christopher R; Buj-Bello, Anna; Beggs, Alan H

    2013-04-15

    No effective treatment exists for patients with X-linked myotubular myopathy (XLMTM), a fatal congenital muscle disease caused by deficiency of the lipid phosphatase, myotubularin. The Mtm1δ4 and Mtm1 p.R69C mice model severely and moderately symptomatic XLMTM, respectively, due to differences in the degree of myotubularin deficiency. Contractile function of intact extensor digitorum longus (EDL) and soleus muscles from Mtm1δ4 mice, which produce no myotubularin, is markedly impaired. Contractile forces generated by chemically skinned single fiber preparations from Mtm1δ4 muscle were largely preserved, indicating that weakness was largely due to impaired excitation contraction coupling. Mtm1 p.R69C mice, which produce small amounts of myotubularin, showed impaired contractile function only in EDL muscles. Short-term replacement of myotubularin with a prototypical targeted protein replacement agent (3E10Fv-MTM1) in Mtm1δ4 mice improved contractile function and muscle pathology. These promising findings suggest that even low levels of myotubularin protein replacement can improve the muscle weakness and reverse the pathology that characterizes XLMTM.

  5. Enzyme Replacement Therapy and/or Hematopoietic Stem Cell Transplantation at diagnosis in patients with Mucopolysaccharidosis type I: results of a European consensus procedure

    LENUS (Irish Health Repository)

    de Ru, Minke H

    2011-08-10

    Abstract Background Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder that results in the accumulation of glycosaminoglycans causing progressive multi-organ dysfunction. Its clinical spectrum is very broad and varies from the severe Hurler phenotype (MPS I-H) which is characterized by early and progressive central nervous system (CNS) involvement to the attenuated Scheie phenotype (MPS I-S) with no CNS involvement. Indication, optimal timing, safety and efficacy of the two available treatment options for MPS I, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), are subject to continuing debate. A European consensus procedure was organized to reach consensus about the use of these two treatment strategies. Methods A panel of specialists, including 8 specialists for metabolic disorders and 7 bone marrow transplant physicians, all with acknowledged expertise in MPS I, participated in a modified Delphi process to develop consensus-based statements on MPS I treatment. Fifteen MPS I case histories were used to initiate the discussion and to anchor decisions around either treatment mode. Before and at the meeting all experts gave their opinion on the cases (YES\\/NO transplantation) and reasons for their decisions were collected. A set of draft statements on MPS I treatment options composed by a planning committee were discussed and revised during the meeting until full consensus. Results Full consensus was reached on several important issues, including the following: 1) The preferred treatment for patients with MPS I-H diagnosed before age 2.5 yrs is HSCT; 2) In individual patients with an intermediate phenotype HSCT may be considered if there is a suitable donor. However, there are no data on efficacy of HSCT in patients with this phenotype; 3) All MPS I patients including those who have not been transplanted or whose graft has failed may benefit significantly from ERT; 4) ERT should be started at diagnosis and may be

  6. Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Birn, Henrik; Bibby, Bo M

    2014-01-01

    dysfunction in women with Fabry disease treated with ERT. METHODS: A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...... in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. CONCLUSIONS: The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestations....

  7. Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis.

    Science.gov (United States)

    Winny, Markus; Paroglou, Vagia; Bektas, Hüseyin; Kaltenborn, Alexander; Reichert, Benedikt; Zachau, Lea; Kleine, Moritz; Klempnauer, Jürgen; Schrem, Harald

    2014-02-01

    This retrospective, single-center, observational study on postoperative long-term results aims to define yet unknown factors for long-term outcome after operation for chronic pancreatitis. We analyzed 147 consecutive patients operated for chronic pancreatitis from 2000 to 2011. Mean follow-up was 5.3 years (range, 1 month to 12.7 years). Complete long-term survival data were provided by the German citizen registration authorities for all patients. A quality-of-life questionnaire was sent to surviving patients after a mean follow-up of 5.7 years. Surgical principles were resection (n = 86; 59%), decompression (n = 29; 20%), and hybrid procedures (n = 32; 21%). No significant influences of different surgical principles and operative procedures on survival, long-term quality of life and pain control could be detected. Overall 30-day mortality was 2.7%, 1-year survival 95.9%, and 3-year survival 90.8%. Multivariate Cox regression analysis revealed that only postoperative insulin dependence at the time of hospital discharge (P = .027; Exp(B) = 2.111; 95% confidence interval [CI], 1.089-4.090) and the absence of pancreas enzyme replacement therapy at the time of hospital discharge (P = .039; Exp(B) = 2.102; 95% CI, 1.037-4.262) were significant, independent risk factors for survival with significant hazard ratios for long-term survival. Long-term improvement in quality of life was reported by 55 of 76 long-term survivors (73%). Pancreatic enzyme replacement should be standard treatment after surgery for chronic pancreatitis at the time of hospital discharge, even when no clinical signs of exocrine pancreatic failure exist. This study underlines the potential importance of early operative intervention in chronic pancreatitis before irreversible endocrine dysfunction is present. Copyright © 2014 Mosby, Inc. All rights reserved.

  8. The use of port-a-caths in adult patients with Lysosomal Storage Disorders receiving Enzyme Replacement Therapy-one centre experience

    Directory of Open Access Journals (Sweden)

    Mairead McLoughlin

    2017-12-01

    Full Text Available Port-a-cath is a widely used device in patients with long-term venous access demand such as frequent or continuous administration of medications such as Enzyme Replacement Therapy (ERT, chemotherapy delivery, blood transfusions, blood products, and fluids. Patients with Lysosomal Storage Diseases (LSDs often require recurrent courses of ERT. We reviewed our experience of using port-a-caths in patients with LSDs with the focus on challenges and complications associated with these catheters. Among 245 adult patients who were treated with ERT, twenty patients (8.2% had a port-a-cath inserted due to poor venous access. Six patients were using their first port whereas five other patients had their port-a-caths replaced at least once. The remaining six patients had inactive port-a-caths. The majority of patients with active port-a-caths never missed more than one consecutive infusion, although one patient missed 2 consecutive infusions whilst on holiday. We identified significant gaps in patients' and their families' understanding of the management of port-a-caths and risks associated with them. It resulted in producing a leaflet and designing an educational program for our LSD patients.

  9. Cold and Heat Stress Diversely Alter Both Cauliflower Respiration and Distinct Mitochondrial Proteins Including OXPHOS Components and Matrix Enzymes

    Science.gov (United States)

    Rurek, Michał; Czołpińska, Magdalena; Pawłowski, Tomasz Andrzej; Krzesiński, Włodzimierz; Spiżewski, Tomasz

    2018-01-01

    Complex proteomic and physiological approaches for studying cold and heat stress responses in plant mitochondria are still limited. Variations in the mitochondrial proteome of cauliflower (Brassica oleracea var. botrytis) curds after cold and heat and after stress recovery were assayed by two-dimensional polyacrylamide gel electrophoresis (2D PAGE) in relation to mRNA abundance and respiratory parameters. Quantitative analysis of the mitochondrial proteome revealed numerous stress-affected protein spots. In cold, major downregulations in the level of photorespiratory enzymes, porine isoforms, oxidative phosphorylation (OXPHOS) and some low-abundant proteins were observed. In contrast, carbohydrate metabolism enzymes, heat-shock proteins, translation, protein import, and OXPHOS components were involved in heat response and recovery. Several transcriptomic and metabolic regulation mechanisms are also suggested. Cauliflower plants appeared less susceptible to heat; closed stomata in heat stress resulted in moderate photosynthetic, but only minor respiratory impairments, however, photosystem II performance was unaffected. Decreased photorespiration corresponded with proteomic alterations in cold. Our results show that cold and heat stress not only operate in diverse modes (exemplified by cold-specific accumulation of some heat shock proteins), but exert some associations at molecular and physiological levels. This implies a more complex model of action of investigated stresses on plant mitochondria. PMID:29547512

  10. Gaucher disease: MR evaluation of bone marrow features during treatment with enzyme replacement; Morbus Gaucher: Analyse der Knochenmarkveraenderungen in der MRT waehrend Enzymersatztherapie

    Energy Technology Data Exchange (ETDEWEB)

    Poll, L.W.; Koch, J.A.; Boerner, D.; Cohnen, M.; Jung, G.; Scherer, A.; Moedder, U. [Duesseldorf Univ. (DF). Inst. fuer Diagnostische Radiologie; Dahl, S. vom; Haeussinger, D. [Duesseldorf Univ. (Germany). Klinik fuer Gastroenterologie, Hepatologie und Infektiologie; Willers, R. [Rechenzentrum, Heinrich-Heine-Univ. Duesseldorf (Germany); Niederau, C. [Innere Abt., St. Josef-Hospital Oberhausen, Akademisches Lehrkrankenhaus der Univ. Essen (Germany)

    2001-10-01

    Purpose: Enzyme replacement therapy (ERT) arrests and reverses the hematological and visceral symptoms of adult Gaucher disease, the most frequent lysosomal storage disorder. There are only a few studies available evaluating bone disease during ERT. The aim of this study was to investigate the features of bone marrow (bm) by magnetic resonance imaging (MRI) in these patients during ERT. Materials and Methods: MRI was performed prospectively in thirty adult type I Gaucher patients before and during ERT with a mean follow-up of 3 years. Spin-echo sequences (T{sub 1}/T{sub 2}) of the lower extremities were obtained and the reconversion (response) or lack of reconversion (non-response) to fatty marrow during treatment was analyzed. The morphological features of bm involvement, a homogeneous or non-homogeneous distribution of bm changes and focal bone lesions surrounded by a rim of reduced signal intensity (SI), were analyzed. Results: Infiltration of bm by Gaucher cells is characterized by a reduction of Sl on both T{sub 1}- and T{sub 2}-weighted sequences. Bone marrow responses were seen in 19 patients (63%) during treatment. Focal bone lesions, surrounded by a rim of reduced Sl, did not respond to ERT and correlated with a non-homogenous distribution of bone involvement and splenectomy. (orig.) [German] Ziel: Unter Enzymersatztherapie (enzyme replacement therapy = ERT) zeigen Patienten mit adulter Form des Morbus Gaucher, der haeufigsten lysosomalen Speicherkrankheit, eine deutliche Besserung der haematologischen und visceralen Symptome. Bislang liegen nur wenige Untersuchungen zur Analyse der Knochenveraenderungen waehrend der ERT vor. Ziel war es, die Knochenmarkveraenderungen bei Gaucher-Patienten waehrend der Enzymersatztherapie mit Alglucerase/Imiglucerase in der Magnetresonanztomographie (MRT) zu evaluieren. Material und Methoden: In einer prospektiven Untersuchung wurden 30 adulte Patienten mit gesichertem Morbus Gaucher vor und waehrend der ERT in der MRT

  11. Biocatalyst including porous enzyme cluster composite immobilized by two-step crosslinking and its utilization as enzymatic biofuel cell

    Science.gov (United States)

    Chung, Yongjin; Christwardana, Marcelinus; Tannia, Daniel Chris; Kim, Ki Jae; Kwon, Yongchai

    2017-08-01

    An enzyme cluster composite (TPA/GOx) formed from glucose oxidase (GOx) and terephthalaldehyde (TPA) that is coated onto polyethyleneimine (PEI) and carbon nanotubes (CNTs) is suggested as a new catalyst ([(TPA/GOx)/PEI]/CNT). In this catalyst, TPA promotes inter-GOx links by crosslinking to form a large and porous structure, and the TPA/GOx composite is again crosslinked with PEI/CNT to increase the amount of immobilized GOx. Such a two-step crosslinking (i) increases electron transfer because of electron delocalization by π conjugation and (ii) reduces GOx denaturation because of the formation of strong chemical bonds while its porosity facilitates mass transfer. With these features, an enzymatic biofuel cell (EBC) employing the new catalyst is fabricated and induces an excellent maximum power density (1.62 ± 0.08 mW cm-2), while the catalytic activity of the [(TPA/GOx)/PEI]/CNT catalyst is outstanding. This is clear evidence that the two-step crosslinking and porous structure caused by adoption of the TPA/GOx composite affect the performance enhancement of EBC.

  12. Elosulfase alfa enzyme replacement therapy attenuates disease progression in a non-ambulatory Japanese patient with Morquio A syndrome (case report

    Directory of Open Access Journals (Sweden)

    Misako Hiramatsu

    2017-12-01

    Full Text Available Enzyme replacement therapy (ERT with elosulfase alfa is the only approved therapy in Japan for patients with Morquio A syndrome, a lysosomal storage disorder inherited in an autosomal recessive fashion. The experience with ERT in severely affected, non-ambulatory patients has not been reported in previous studies. This case report describes clinical evidence for the 1-year efficacy and safety of ERT with elosulfase alfa in a severely affected, non-ambulatory, 47-year-old patient with Morquio A syndrome who needs intensive respiratory management. ERT with elosulfase alfa was well tolerated in this patient. Because of the possibility of potential hypersensitivity adverse events, special attention is needed when using ERT in patients with respiratory disorders. However, under the appropriate management of specialists, the patient in this case report showed significant respiratory improvement after starting ERT, and abdominal bloating was improved by gas evacuation. In addition, the patient was able to lift up her arms, reach behind her back, and move her legs slightly, and she recovered her grip strength. Her hearing loss improved and she could hear without a hearing aid. This report shows that ERT with elosulfase alfa can be used with appropriate respiratory care in patients with severe respiratory dysfunction.

  13. [Shift of focus in the financing of Hungarian drugs. Reimbursement for orphan drugs for treating rare diseases: financing of enzyme replacement therapy in Hungary].

    Science.gov (United States)

    Szegedi, Márta; Molnár, Mária Judit; Boncz, Imre; Kosztolányi, György

    2014-11-02

    Focusing on the benefits of patients with rare disease the authors analysed the aspects of orphan medicines financed in the frame of the Hungarian social insurance system in 2012 in order to make the consumption more rational, transparent and predictable. Most of the orphan drugs were financed in the frame of compassionate use by the reimbursement system. Consequently, a great deal of crucial problems occurred in relation to the unconventional subsidized method, especially in the case of the highest cost enzyme replacement therapies. On the base of the findings, proposals of the authors are presented for access to orphan drugs, fitting to the specific professional, economical and ethical aspects of this unique field of the health care system. The primary goal is to provide a suitable subsidized method for the treatment of rare disease patients with unmet medical needs. The financial modification of orphans became indispensible in Hungary. Professionals from numerous fields dealing with rare disease patients' care expressed agreement on the issue. Transforming the orphan medicines' financial structure has been initiated according to internationally shared principles.

  14. Hunter syndrome in an 11-year old girl on enzyme replacement therapy with idursulfase: brain magnetic resonance imaging features and evolution.

    Science.gov (United States)

    Manara, Renzo; Rampazzo, Angelica; Cananzi, Mara; Salviati, Leonardo; Mardari, Rodica; Drigo, Paola; Tomanin, Rosella; Gasparotto, Nicoletta; Priante, Elena; Scarpa, Maurizio

    2010-12-01

    Mucopolysaccharidosis type II (MPS-II, Hunter disease) is a X-linked recessive disorder. Affected females are extremely rare, mostly due to skewed X chromosome inactivation. A few papers outline MPS-II brain magnetic resonance imaging (MRI) "gestalt" in males, but neuroradiological reports on females are still lacking. We present an 11-year-old girl affected by the severe form of MPS-II who was followed up over a time span of 8 years, focusing on clinical and brain MRI evolution. In the last 2.5 years, the patient has been treated with enzyme replacement therapy (ERT) with idursulfase (Elaprase™, Shire Human Genetic Therapies AB, Sweden). On brain and cervical MRI examination, abnormalities in our patient did not differ from those detected in male patients: J-shaped pituitary sella, enlargement of perivascular spaces, brain atrophy, mild T2-hyperintensity in the paratrigonal white matter, diffuse platyspondylia, and mild odontoid dysplasia with odontoid cup. Brain atrophy progressed despite ERT introduction, whereas perivascular space enlargement did not change significantly before and after ERT. Cognitive impairment worsened independently from the course of white matter abnormality. Despite a profound knowledge of genetic and biochemical aspects in MPS-II, neuroradiology is still poorly characterized, especially in female patients. Spinal and brain involvement and its natural course and evolution after ERT introduction still need to be clarified.

  15. Fabrication of Mediatorless/Membraneless Glucose/Oxygen Based Biofuel Cell using Biocatalysts Including Glucose Oxidase and Laccase Enzymes

    Science.gov (United States)

    Christwardana, Marcelinus; Kim, Ki Jae; Kwon, Yongchai

    2016-07-01

    Mediatorless and membraneless enzymatic biofuel cells (EBCs) employing new catalytic structure are fabricated. Regarding anodic catalyst, structure consisting of glucose oxidase (GOx), poly(ethylenimine) (PEI) and carbon nanotube (CNT) is considered, while three cathodic catalysts consist of glutaraldehyde (GA), laccase (Lac), PEI and CNT that are stacked together in different ways. Catalytic activities of the catalysts for glucose oxidation and oxygen reduction reactions (GOR and ORR) are evaluated. As a result, it is confirmed that the catalysts work well for promotion of GOR and ORR. In EBC tests, performances of EBCs including 150 μm-thick membrane are measured as references, while those of membraneless EBCs are measured depending on parameters like glucose flow rate, glucose concentration, distance between two electrodes and electrolyte pH. With the measurements, how the parameters affect EBC performance and their optimal conditions are determined. Based on that, best maximum power density (MPD) of membraneless EBC is 102 ± 5.1 μW · cm-2 with values of 0.5 cc · min-1 (glucose flow rate), 40 mM (glucose concentration), 1 mm (distance between electrodes) and pH 3. When membrane and membraneless EBCs are compared, MPD of the membraneless EBC that is run at the similar operating condition to EBC including membrane is speculated as about 134 μW · cm-2.

  16. Transformation in pretreatment manifestations of Gaucher disease type 1 during two decades of alglucerase/imiglucerase enzyme replacement therapy in the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

    Science.gov (United States)

    Mistry, Pramod K; Batista, Julie L; Andersson, Hans C; Balwani, Manisha; Burrow, Thomas Andrew; Charrow, Joel; Kaplan, Paige; Khan, Aneal; Kishnani, Priya S; Kolodny, Edwin H; Rosenbloom, Barry; Scott, C Ronald; Weinreb, Neal

    2017-09-01

    This study tests the hypothesis that the prevalence of severe clinical manifestations in Gaucher disease type 1 (GD1) patients at the time of treatment initiation has changed since alglucerase/imiglucerase enzyme replacement therapy (ERT) was approved in the United States (US) in 1991. US alglucerase/imiglucerase-treated GD1 patients from the International Collaborative Gaucher Group Gaucher Registry clinicaltrials.gov NCT00358943 were stratified by age at ERT initiation (<18, 18 to <50, ≥50 years), era of ERT initiation (1991-1995, 1996-2000, 2001-2005, 2006-2009), and splenectomy status pre-ERT. Prevalence of splenectomy decreased dramatically across the eras among all age groups. Bone manifestations were more prevalent in splenectomized patients than non-splenectomized patients in all age groups. Prevalence of bone manifestations differed across eras in certain age groups: non-splenectomized patients had a lower prevalence of ischemic bone events (pediatric patients) and bone crisis (pediatric patients and adults 18 to <50 years) in later eras; splenectomized adult (18 to <50 years) patients had a lower prevalence of ischemic bone events and bone crisis in later eras. Over two decades after the introduction of ERT, the prevalence of splenectomy and associated skeletal complications has declined dramatically. Concomitantly, the interval between diagnosis and initiation of ERT has decreased, most strikingly in pediatric patients who have the most severe disease. Together, these findings suggest that since the introduction of alglucerase/imiglucerase ERT, optimal standard of care has become established in the US to prevent destructive complications of GD1. © 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.

  17. Evaluation of treatment response to enzyme replacement therapy with Velaglucerase alfa in patients with Gaucher disease using whole-body magnetic resonance imaging.

    Science.gov (United States)

    Laudemann, K; Moos, L; Mengel, E; Lollert, A; Hoffmann, C; Brixius-Huth, M; Wagner, D; Düber, C; Staatz, G

    2016-03-01

    This was a retrospective data analysis to evaluate the treatment response to enzyme replacement therapy (ERT) with Velaglucerase alfa using whole-body magnetic resonance imaging (MRI). A baseline and follow-up MRI were performed on 18 Gaucher Type 1 patients at an interval of 11.6 months. The MRI score systems determined the Bone-Marrow-Burden (BMB) score, the Düsseldorf-Gaucher score (DGS), and the Vertebra-Disc-Ratio (VDR). The Severity Score Index Type 1 (GD-DS3) was also assessed. The baseline MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.70; while, the follow-up MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.73. The baseline GD-DS3 median was 2.40 (BMB excl.: 0.50) and the follow-up median was 2.00 (BMB excl.: 0.50). There was weak statistical significance with the Wilcoxon signed-rank test for the DGS (p=0.034) and GD-DS3 (p=0.047) between both MRIs. Velaglucerase alfa therapy is a effective long-term treatment for Gaucher Type 1 patients who are newly diagnosed or switching therapies. Measurements with whole-body MRI and an objective scoring system were reliable tools for detecting early stage bone marrow activity. Further research is needed to evaluate the "Booster-Effect" of Velaglucerase alfa therapy in Gaucher skeletal disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Effect of enzyme replacement therapy with alglucosidase alfa (Myozyme®) in 12 patients with advanced late-onset Pompe disease.

    Science.gov (United States)

    Papadopoulos, Constantinos; Orlikowski, David; Prigent, Hélène; Lacour, Arnaud; Tard, Céline; Furby, Alain; Praline, Julien; Solé, Guilhem; Hogrel, Jean-Yves; De Antonio, Marie; Semplicini, Claudio; Deibener-Kaminsky, Joelle; Kaminsky, Pierre; Eymard, Bruno; Taouagh, Nadjib; Perniconi, Barbara; Hamroun, Dalil; Laforêt, Pascal

    2017-09-01

    The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT in a cohort of patients with severe Pompe disease. We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared. Twelve patients (7 males) were identified. Median age at symptom onset was 24years [IQR=15.5; 36.0]. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24h [IQR=21.88; 24.00] (min 20; max 24). ERT was initiated at a median age of 52.5years [IQR=35.75; 66.50]. Median treatment duration was 55months [IQR=39.5; 81.0]. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90min and two increased their assisted walking distance, by 80 and 20m. Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Replacing Escherichia coli NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with a NADP-dependent enzyme from Clostridium acetobutylicum facilitates NADPH dependent pathways.

    Science.gov (United States)

    Martínez, Irene; Zhu, Jiangfeng; Lin, Henry; Bennett, George N; San, Ka-Yiu

    2008-11-01

    Reactions requiring reducing equivalents, NAD(P)H, are of enormous importance for the synthesis of industrially valuable compounds such as carotenoids, polymers, antibiotics and chiral alcohols among others. The use of whole-cell biocatalysis can reduce process cost by acting as catalyst and cofactor regenerator at the same time; however, product yields might be limited by cofactor availability within the cell. Thus, our study focussed on the genetic manipulation of a whole-cell system by modifying metabolic pathways and enzymes to improve the overall production process. In the present work, we genetically engineered an Escherichia coli strain to increase NADPH availability to improve the productivity of products that require NADPH in its biosynthesis. The approach involved an alteration of the glycolysis step where glyceraldehyde-3-phosphate (GAP) is oxidized to 1,3 bisphophoglycerate (1,3-BPG). This reaction is catalyzed by NAD-dependent endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) encoded by the gapA gene. We constructed a recombinant E. coli strain by replacing the native NAD-dependent gapA gene with a NADP-dependent GAPDH from Clostridium acetobutylicum, encoded by the gene gapC. The beauty of this approach is that the recombinant E. coli strain produces 2 mol of NADPH, instead of NADH, per mole of glucose consumed. Metabolic flux analysis showed that the flux through the pentose phosphate (PP) pathway, one of the main pathways that produce NADPH, was reduced significantly in the recombinant strain when compared to that of the parent strain. The effectiveness of the NADPH enhancing system was tested using the production of lycopene and epsilon-caprolactone as model systems using two different background strains. The recombinant strains, with increased NADPH availability, consistently showed significant higher productivity than the parent strains.

  20. Enzyme replacement therapy for Anderson-Fabry disease: A complementary overview of a Cochrane publication through a linear regression and a pooled analysis of proportions from cohort studies.

    Science.gov (United States)

    El Dib, Regina; Gomaa, Huda; Ortiz, Alberto; Politei, Juan; Kapoor, Anil; Barreto, Fellype

    2017-01-01

    Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. To evaluate the efficacy and safety of ERT for AFD. For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, plinear regression showed that Fabry patients receiving agalsidase alfa are more likely to have higher rates of composite endpoints compared to those receiving agalsidase beta. Agalsidase beta is associated to a significantly lower incidence of renal, cardiovascular and cerebrovascular events than no ERT, and to a significantly lower incidence of cerebrovascular events than agalsidase alfa. In view of these results, the use of agalsidase beta for preventing major organ complications related to AFD can be recommended.

  1. Use of cardiac magnetic resonance imaging to evaluate cardiac structure, function and fibrosis in children with infantile Pompe disease on enzyme replacement therapy.

    Science.gov (United States)

    Barker, Piers C A; Pasquali, Sara K; Darty, Stephen; Ing, Richard J; Li, Jennifer S; Kim, Raymond J; DeArmey, Stephanie; Kishnani, Priya S; Campbell, Michael J

    2010-12-01

    Pompe disease (acid α-glucosidase deficiency) is one of several lysosomal storage diseases amenable to treatment with enzyme replacement therapy (ERT). While echocardiography (echo) has been the standard method to evaluate the cardiac response to ERT, cardiac magnetic resonance imaging (CMR) has the advantage of a better tissue definition and characterization of myocardial fibrosis. However, CMR for Pompe disease is not frequently performed due to a high risk of sedation. We report the first use of CMR in a feasible protocol to quantify left ventricular (LV) mass, function, and the presence of myocardial fibrosis in the Pompe population. Children with Pompe disease on ERT were assessed with transthoracic echo and CMR over a 3 year period at a single institution. Echocardiography was performed using standard techniques without sedation. CMR was performed using retrospectively gated and real-time imaging, with and without sedation. LV mass indexed to body surface area (LVMI) and ejection fraction (EF) were measured by both echo and CMR, and evaluated for change over time. Myocardial fibrosis was assessed by CMR with delayed enhancement imaging 5-10 min after gadolinium contrast using single shot inversion recovery sequences with inversion time set to null the signal from normal myocardium. Seventeen CMR scans were successfully performed in 10 subjects with Pompe disease (median age at first CMR is 9 months, range 1-38 months, 80% male), with sedation only performed in 4 studies. There was a median interval of 5 months (range 0-34 months) from the start of ERT to first CMR (baseline). At baseline, the median indexed LVMI by CMR (140.0 g/m(2), range 43.8-334.0) tended to be lower than that assessed by echo (median 204.0 g/m(2), range 52.0-385.0), but did not reach statistical significance. At baseline, CMR EF was similar to that assessed by echo (55% vs. 55%). Overall, there was no significant decrease in CMR measured LVMI over time (CMR median LVMI at baseline 94 g

  2. Wakame and Nori in restructured meats included in cholesterol-enriched diets affect the antioxidant enzyme gene expressions and activities in Wistar rats.

    Science.gov (United States)

    Moreira, Adriana Schultz; González-Torres, Laura; Olivero-David, Raul; Bastida, Sara; Benedi, Juana; Sánchez-Muniz, Francisco J

    2010-09-01

    The effects of diets including restructured meats (RM) containing Wakame or Nori on total liver glutathione status, and several antioxidant enzyme gene expressions and activities were tested. Six groups of ten male growing Wistar rats each were fed a mix of 85% AIN-93 M diet and 15% freeze-dried RM for 35 days. The control group (C) consumed control RM, the Wakame (W) and the Nori (N) groups, RM with 5% Wakame and 5% Nori, respectively. Animals on added cholesterol diets (CC, CW, and CN) consumed their corresponding basal diets added with cholesterol (2%) and cholic acid (0.4%). Alga and dietary cholesterol significantly interact (P Nori-RM is a hypocholesterolemic food while Wakame-RM is an antioxidant food. This should be taken into account when including this kind of RM as potential functional foods in human.

  3. Construction and Characterization of a Chitosan-Immobilized-Enzyme and β-Cyclodextrin-Included-Ferrocene-Based Electrochemical Biosensor for H2O2 Detection

    Directory of Open Access Journals (Sweden)

    Wenbo Dong

    2017-07-01

    Full Text Available An electrochemical detection biosensor was prepared with the chitosan-immobilized-enzyme (CTS-CAT and β-cyclodextrin-included-ferrocene (β-CD-FE complex for the determination of H2O2. Ferrocene (FE was included in β-cyclodextrin (β-CD to increase its stability. The structure of the β-CD-FE was characterized. The inclusion amount, inclusion rate, and electrochemical properties of inclusion complexes were determined to optimize the reaction conditions for the inclusion. CTS-CAT was prepared by a step-by-step immobilization method, which overcame the disadvantages of the conventional preparation methods. The immobilization conditions were optimized to obtain the desired enzyme activity. CTS-CAT/β-CD-FE composite electrodes were prepared by compositing the CTS-CAT with the β-CD-FE complex on a glassy carbon electrode and used for the electrochemical detection of H2O2. It was found that the CTS-CAT could produce a strong reduction peak current in response to H2O2 and the β-CD-FE could amplify the current signal. The peak current exhibited a linear relationship with the H2O2 concentration in the range of 1.0 × 10−7–6.0 × 10−3 mol/L. Our work provided a novel method for the construction of electrochemical biosensors with a fast response, good stability, high sensitivity, and a wide linear response range based on the composite of chitosan and cyclodextrin.

  4. Residual glycosaminoglycan accumulation in mitral and aortic valves of a patient with attenuated MPS I (Scheie syndrome after 6 years of enzyme replacement therapy: Implications for early diagnosis and therapy

    Directory of Open Access Journals (Sweden)

    Yohei Sato

    2015-12-01

    Full Text Available Mucopolysaccharidosis (MPS is an inherited metabolic disease caused by deficiency of the enzymes needed for glycosaminoglycan (GAG degradation. MPS type I is caused by the deficiency of the lysosomal enzyme alpha-l-iduronidase and is classified into Hurler syndrome, Scheie syndrome, and Hurler–Scheie syndrome based on disease severity and onset. Cardiac complications such as left ventricular hypertrophy, cardiac valve disease, and coronary artery disease are often observed in MPS type I. Enzyme replacement therapy (ERT has been available for MPS type I, but the efficacy of this treatment for cardiac valve disease is unknown. We report on a 56-year-old female patient with attenuated MPS I (Scheie syndrome who developed aortic and mitral stenosis and coronary artery narrowing. The cardiac valve disease progressed despite ERT and she finally underwent double valve replacement and coronary artery bypass grafting. The pathology of the cardiac valves revealed GAG accumulation and lysosomal enlargement in both the mitral and aortic valves. Zebra body formation was also confirmed using electron microscopy. Our results suggest that ERT had limited efficacy in previously established cardiac valve disease. Early diagnosis and initiation of ERT is crucial to avoid further cardiac complications in MPS type I.

  5. Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype.

    Science.gov (United States)

    Moncada-Vélez, M; Vélez-Ortega, A; Orrego, J; Santisteban, I; Jagadeesh, J; Olivares, M; Olaya, N; Hershfield, M; Candotti, F; Franco, J

    2011-11-01

    Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B- SCID) due to ADA deficiency diagnosed at the age of 1 month, whose lymphocyte counts including CD4+ and CD8+ T and NK cells began to improve after several months with normalization of ADA activity in Peripheral blood lymphocytes (PBL), as a result of somatic mosaicism caused by monoallelic reversion of the causative mutation in the ADA gene. He was not eligible for haematopoietic stem cell transplantation (HSCT) or gene therapy (GT); therefore he was placed on enzyme replacement therapy (ERT) with bovine PEG-ADA. The follow-up of metabolic and immunologic responses to ERT included gradual improvement in ADA activity in erythrocytes and transient expansion of most lymphocyte subsets, followed by gradual stabilization of CD4+ and CD8+ T (with naïve phenotype) and NK cells, and sustained expansion of TCRγδ+ T cells. This was accompanied by the disappearance of the revertant T cells as shown by DNA sequencing from PBL. Although the patient's clinical condition improved marginally, he later developed a germinal cell tumour and eventually died at the age of 67 months from sepsis. This case adds to our current knowledge of spontaneous reversion of mutations in ADA deficiency and shows that the effects of the ERT may vary among these patients, suggesting that it could depend on the cell and type in which the somatic mosaicism is established upon reversion. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

  6. Analytical properties of some commercially available nitrate reductase enzymes evaluated as replacements for cadmium in automated, semiautomated, and manual colorimetric methods for determination of nitrate plus nitrite in water

    Science.gov (United States)

    Patton, Charles J.; Kryskalla, Jennifer R.

    2013-01-01

    A multiyear research effort at the U.S. Geological Survey (USGS) National Water Quality Laboratory (NWQL) evaluated several commercially available nitrate reductase (NaR) enzymes as replacements for toxic cadmium in longstanding automated colorimetric air-segmented continuous-flow analyzer (CFA) methods for determining nitrate plus nitrite (NOx) in water. This research culminated in USGS approved standard- and low-level enzymatic reduction, colorimetric automated discrete analyzer NOx methods that have been in routine operation at the NWQL since October 2011. The enzyme used in these methods (AtNaR2) is a product of recombinant expression of NaR from Arabidopsis thaliana (L.) Heynh. (mouseear cress) in the yeast Pichia pastoris. Because the scope of the validation report for these new automated discrete analyzer methods, published as U.S. Geological Survey Techniques and Methods 5–B8, was limited to performance benchmarks and operational details, extensive foundational research with different enzymes—primarily YNaR1, a product of recombinant expression of NaR from Pichia angusta in the yeast Pichia pastoris—remained unpublished until now. This report documents research and development at the NWQL that was foundational to development and validation of the discrete analyzer methods. It includes: (1) details of instrumentation used to acquire kinetics data for several NaR enzymes in the presence and absence of known or suspected inhibitors in relation to reaction temperature and reaction pH; and (2) validation results—method detection limits, precision and bias estimates, spike recoveries, and interference studies—for standard- and low-level automated colorimetric CFA-YNaR1 reduction NOx methods in relation to corresponding USGS approved CFA cadmium-reduction (CdR) NOx methods. The cornerstone of this validation is paired sample statistical and graphical analysis of NOx concentrations from more than 3,800 geographically and seasonally diverse surface

  7. Effects of brown fish meal replacement with fermented soybean meal on growth performance, feed efficiency and enzyme activities of Chinese soft-shelled turtle, Pelodiscus sinensis

    Science.gov (United States)

    Zou, Yurong; Ai, Qinghui; Mai, Kangsen; Zhang, Wenbing; Zhang, Yanjiao; Xu, Wei

    2012-06-01

    A 120-day feeding experiment was conducted to investigate the effects of partial replacement of brown fish meal (BFM) by fermented soybean meal (FSBM) in diets of Chinese soft-shelled turtle ( Pelodiscus sinensis). The turtles (initial mean body weight, (115.52 ± 1.05) g) were fed with three experimental diets, in which 0%, 4.72% and 9.44% BFM protein was replaced by 0%, 3% and 6% FSBM, respectively. Results showed that the feeding rate (FR), specific growth rate (SGR) and feed efficiency ratio (FER) of turtles fed with the diet containing 3% FSBM were not significantly different from the control group (0% FSBM) ( P > 0.05). However, FR, SGR and FER of turtles fed with the diet containing 6% FSBM were significantly lower than those of the control group ( P 0.05). However, the uric acid concentration in turtles fed with the diet containing 3% or 6% FSBM was significantly lower than that in the control group ( P 0.05). The results suggested that FSBM could replace 4.72% BFM protein in turtle diets without exerting adverse effects on turtle growth, feed utilization and measured immune parameters.

  8. Effects of dietary fish oil replacement by vegetable oil on the digestive enzymes activity and intestinal morphology in Meagre, Argyrosomus regius (Asso, 1801

    Directory of Open Access Journals (Sweden)

    Fernando Antunes Magalhães

    2014-07-01

    The results were analyzed by three way factorial. Amylase activity was bigger in FO when compared with VO (Table 1. The same result was observed in chymotrypsin activity. On the other hand, lipase activity was higher in VO. Regarding the levels of lipids, diets with 17% had higher amylase activity than diets with 12%. The inverse was observed in chymotrypsin activity. In relation to lipase activity, no differences were observed on the two levels of lipids studied. No differences in digestive enzymes activities were observed when diets were supplemented with selenium. Epithelium architecture of the posterior intestine was slightly affected by dietary treatments. Higher levels of lipids seem to induce enterocyte vacuolization, and vacuoles seem to be larger when a blend of vegetable oils was used instead of fish oil. No clear role can be attributed to selenium regarding intestinal morphology. In conclusion, our study showed that the source and levels of lipid in diets for meagre have influence in activity of digestible enzymes like amylase, lipase and chymotrypsin. Furthermore, levels of selenium do not cause an alteration in studied digestible enzymes.

  9. Ankle replacement

    Science.gov (United States)

    Ankle arthroplasty - total; Total ankle arthroplasty; Endoprosthetic ankle replacement; Ankle surgery ... Ankle replacement surgery is most often done while you are under general anesthesia. This means you will ...

  10. Enzyme Informatics

    Science.gov (United States)

    Alderson, Rosanna G.; Ferrari, Luna De; Mavridis, Lazaros; McDonagh, James L.; Mitchell, John B. O.; Nath, Neetika

    2012-01-01

    Over the last 50 years, sequencing, structural biology and bioinformatics have completely revolutionised biomolecular science, with millions of sequences and tens of thousands of three dimensional structures becoming available. The bioinformatics of enzymes is well served by, mostly free, online databases. BRENDA describes the chemistry, substrate specificity, kinetics, preparation and biological sources of enzymes, while KEGG is valuable for understanding enzymes and metabolic pathways. EzCatDB, SFLD and MACiE are key repositories for data on the chemical mechanisms by which enzymes operate. At the current rate of genome sequencing and manual annotation, human curation will never finish the functional annotation of the ever-expanding list of known enzymes. Hence there is an increasing need for automated annotation, though it is not yet widespread for enzyme data. In contrast, functional ontologies such as the Gene Ontology already profit from automation. Despite our growing understanding of enzyme structure and dynamics, we are only beginning to be able to design novel enzymes. One can now begin to trace the functional evolution of enzymes using phylogenetics. The ability of enzymes to perform secondary functions, albeit relatively inefficiently, gives clues as to how enzyme function evolves. Substrate promiscuity in enzymes is one example of imperfect specificity in protein-ligand interactions. Similarly, most drugs bind to more than one protein target. This may sometimes result in helpful polypharmacology as a drug modulates plural targets, but also often leads to adverse side-effects. Many cheminformatics approaches can be used to model the interactions between druglike molecules and proteins in silico. We can even use quantum chemical techniques like DFT and QM/MM to compute the structural and energetic course of enzyme catalysed chemical reaction mechanisms, including a full description of bond making and breaking. PMID:23116471

  11. Knee Replacement

    Science.gov (United States)

    Knee replacement is surgery for people with severe knee damage. Knee replacement can relieve pain and allow you to ... Your doctor may recommend it if you have knee pain and medicine and other treatments are not ...

  12. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  13. Familial LCAT deficiency: from renal replacement to enzyme replacement

    NARCIS (Netherlands)

    Stoekenbroek, R. M.; van den Bergh Weerman, M. A.; Hovingh, G. K.; Potter van Loon, B. J.; Siegert, C. E. H.; Holleboom, A. G.

    2013-01-01

    Familial LCAT deficiency (FLD) is a recessive lipid disorder ultimately leading to end-stage renal disease (ESRD). We present two brothers with considerable variation in the age at which they developed ESRD. Kidney biopsies revealed both tubular and glomerular pathology. To date, no causal therapy

  14. Evaluation of the efficacy and safety of three dosing regimens of agalsidase alfa enzyme replacement therapy in adults with Fabry disease

    Directory of Open Access Journals (Sweden)

    Goláň L

    2015-07-01

    Full Text Available Lubor Goláň,1 Ozlem Goker-Alpan,2 Myrl Holida,3 Ikka Kantola,4 Mariusz Klopotowski,5 Johanna Kuusisto,6 Aleš Linhart,1 Jacek Musial,7 Kathleen Nicholls,8 Derlis Gonzalez-Rodriguez,9 Reena Sharma,10 Bojan Vujkovac,11 Peter Chang,12 Anna Wijatyk12 1First Faculty of Medicine, Department of Cardiovascular Medicine, Charles University, Prague, Czech Republic; 2Lysosomal Research and Treatment Unit, Fairfax, VA, USA; 3Stead Family Department of Pediatrics, Division of Medical Genetics, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; 4Division of Medicine, Turku University Hospital, Turku, Finland; 5Institute of Cardiology, Warsaw, Poland; 6Department of Medicine, Center for Medicine and Clinical Research, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland; 7Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland; 8Department of Nephrology, Royal Melbourne Hospital and the University of Melbourne, VIC, Australia; 9Instituto Privado de Hematologia E Investigacion Clinica (IPHIC, Asuncion, Paraguay; 10Salford Royal NHS Foundation Trust, Salford, UK; 11General Hospital Slovenj Gradec, Slovenj Gradec, Slovenia; 12Shire, Lexington, MA, USA Purpose: Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW. Exploratory analyses were performed for 0.4 mg/kg weekly.Patients and methods: This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643 in treatment-naïve adults (≥18 years with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New

  15. Replacing penalties

    Directory of Open Access Journals (Sweden)

    Vitaly Stepashin

    2017-01-01

    Full Text Available УДК 343.24The subject. The article deals with the problem of the use of "substitute" penalties.The purpose of the article is to identify criminal and legal criteria for: selecting the replacement punishment; proportionality replacement leave punishment to others (the formalization of replacement; actually increasing the punishment (worsening of legal situation of the convicted.Methodology.The author uses the method of analysis and synthesis, formal legal method.Results. Replacing the punishment more severe as a result of malicious evasion from serving accused designated penalty requires the optimization of the following areas: 1 the selection of a substitute punishment; 2 replacement of proportionality is serving a sentence other (formalization of replacement; 3 ensuring the actual toughening penalties (deterioration of the legal status of the convict. It is important that the first two requirements pro-vide savings of repression in the implementation of the replacement of one form of punishment to others.Replacement of punishment on their own do not have any specifics. However, it is necessary to compare them with the contents of the punishment, which the convict from serving maliciously evaded. First, substitute the punishment should assume a more significant range of restrictions and deprivation of certain rights of the convict. Second, the perfor-mance characteristics of order substitute the punishment should assume guarantee imple-mentation of the new measures.With regard to replacing all forms of punishment are set significant limitations in the application that, in some cases, eliminates the possibility of replacement of the sentence, from serving where there has been willful evasion, a stricter measure of state coercion. It is important in the context of the topic and the possibility of a sentence of imprisonment as a substitute punishment in cases where the original purpose of the strict measures excluded. It is noteworthy that the

  16. Enzymes of industrial purpose - review of the market of enzyme preparations and prospects for its development

    Directory of Open Access Journals (Sweden)

    A. A. Tolkacheva

    2017-01-01

    Full Text Available Microbial enzyme preparations are increasingly replacing conventional chemical catalysts in a number of industrial processes. Such drugs, in addition to environmental friendliness and high activity, have a number of advantages over enzyme preparations of vegetable and animal origin, namely: the production of microbial enzymes in bioreactors is easily controlled and predictable; excreted microbiological enzymes are more stable than intracellular animals and plant enzymes; the genetic diversity of microorganisms makes it possible to produce enzyme preparations with a wide range of specificity; microbiological enzymes can be synthesized year-round, in contrast to the production of plant enzymes, which is often seasonal. The leaders of the world market of enzymes are proteases and amylases, which account for 25% and 15%, respectively. Over the past five years, the world market for carbohydrases, including mainly amylases, cellulases and xylanases, has been the fastest growing segment of the enzyme market with an aggregate annual growth rate of more than 7.0%. Another major product of the industrial enzyme market, which has a great potential for growth, is lipases. From the point of view of designation, the main part is represented by food and food enzymes. The Russian market continues to be unsaturated - the current supply is not able to meet the needs of the Russian feed and food industry in enzyme preparations. Enzyme preparations of domestic producers are in demand in forage production, while food industrial enterprises prefer imported products. The most significant enterprises in the enzymatic industry in Russia at the moment are Sibbiofarm, AgroSistema, Agroferment. In the light of the Russian policy of increasing food security, the development of the domestic enzyme industry is an extremely topical task.

  17. Atom-replaced pins in a Y-based superconductor—single-crystalline perovskite structure including both PrBa2Cu3O7‑x and YBa2Cu3O7‑y

    Science.gov (United States)

    Hayashi, Mariko; Araki, Takeshi; Ishii, Hirotaka; Nishijima, Gen; Matsumoto, Akiyoshi

    2018-05-01

    Metal organic deposition using trifluoroacetates (TFA-MOD) provides many uniform superconductors on long metal tapes. The large numbers of long wires have been applied for power grids or superconducting fault current limiters. The related applications worked for a long time without fatal trouble. The quasi-liquid produced during the firing process assisted the perfectly uniform structure in TFA-MOD. On the other hand, when it was desired to introduce artificial pinning centers, the quasi-liquid also enlarged the diameter of the artificial pinning centers to several tens of nanometers. In other words, due to the nature of TFA-MOD, there is very little chance of using TFA-MOD to prepare several nm-sized artificial pinning centers. By proposing atom-replaced pins (ARPs), we aim to overcome the impasse. ARPs are realized by replacing yttrium (Y) with praseodymium (Pr) whose valence number changes from 3+ to approximately 4+. Analytical results suggested that Pr makes pinning centers on a PrBa2Cu3O7‑x (PrBCO) unit cell, and the weak-linked superconductivity derived from PrBCO extends to the adjacent unit cells in the a/b-plane. J c decrease by Pr is five times as large as the volume fraction of Pr in the Y-site of the perovskite structure. On the other hand, T c does not show large degradation in YBCO including 10% PrBCO. These results suggest that PrBCO unit cells are fully dispersed in YBa2Cu3O7‑y matrix. With regard to J c in the magnetic field, (Y0.98, Pr0.02)BCO has been slightly improved compared with pure YBCO only in the region of high temperature and low magnetic field of less than 1 T.

  18. Replacement of Ser108 in Plasmodium falciparum enolase results in weak Mg(II) binding: role of a parasite-specific pentapeptide insert in stabilizing the active conformation of the enzyme.

    Science.gov (United States)

    Dutta, Sneha; Mukherjee, Debanjan; Jarori, Gotam K

    2015-06-01

    A distinct structural feature of Plasmodium falciparum enolase (Pfeno) is the presence of a five amino acid insert -104EWGWS108- that is not found in host enolases. Its conservation among apicomplexan enolases has raised the possibility of its involvement in some important physiological function(s). Deletion of this sequence is known to lower k(cat)/K(m), increase K(a) for Mg(II) and convert dimer into monomers (Vora HK, Shaik FR, Pal-Bhowmick I, Mout R & Jarori GK (2009) Arch Biochem Biophys 485, 128-138). These authors also raised the possibility of the formation of an H-bond between Ser108 and Leu49 that could stabilize the apo-Pfeno in an active closed conformation that has high affinity for Mg(II). Here, we examined the effect of replacement of Ser108 with Gly/Ala/Thr on enzyme activity, Mg(II) binding affinity, conformational states and oligomeric structure and compared it with native recombinant Pfeno. The results obtained support the view that Ser108 is likely to be involved in the formation of certain crucial H-bonds with Leu49. The presence of these interactions can stabilize apo-Pfeno in an active closed conformation similar to that of Mg(II) bound yeast enolase. As predicted, S108G/A-Pfeno variants (where Ser108-Leu49 H-bonds are likely to be disrupted) were found to exist in an open conformation and had low affinity for Mg(II). They also required Mg(II) induced conformational changes to acquire the active closed conformational state essential for catalysis. The possible physiological relevance of apo-Pfeno being in such an active state is discussed. © 2015 FEBS.

  19. Knee Replacement

    Science.gov (United States)

    ... days. Medications prescribed by your doctor should help control pain. During the hospital stay, you'll be encouraged to move your ... exercise your new knee. After you leave the hospital, you'll continue physical ... mobility and a better quality of life. And most knee replacements can be ...

  20. The replacement research reactor

    International Nuclear Information System (INIS)

    Cameron, R.

    1999-01-01

    As a consequences of the government decision in September 1997. ANSTO established a replacement research reactor project to manage the procurement of the replacement reactor through the necessary approval, tendering and contract management stages This paper provides an update of the status of the project including the completion of the Environmental Impact Statement. Prequalification and Public Works Committee processes. The aims of the project, management organisation, reactor type and expected capabilities are also described

  1. Pancreatic Enzymes

    Science.gov (United States)

    ... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  2. Replacement rod

    International Nuclear Information System (INIS)

    Hatfield, S.C.

    1989-01-01

    This patent describes in an elongated replacement rod for use with fuel assemblies of the type having two end fittings connected by guide tubes with a plurality of rod and guide tube cell defining spacer grids containing rod support features and mixing vanes. The grids secured to the guide tubes in register between the end fittings at spaced intervals. The fuel rod comprising: an asymmetrically beveled tip; a shank portion having a straight centerline; and a permanently diverging portion between the tip and the shank portion

  3. Carbohydrates as Fat Replacers.

    Science.gov (United States)

    Peng, Xingyun; Yao, Yuan

    2017-02-28

    The overconsumption of dietary fat contributes to various chronic diseases, which encourages attempts to develop and consume low-fat foods. Simple fat reduction causes quality losses that impede the acceptance of foods. Fat replacers are utilized to minimize the quality deterioration after fat reduction or removal to achieve low-calorie, low-fat claims. In this review, the forms of fats and their functions in contributing to food textural and sensory qualities are discussed in various food systems. The connections between fat reduction and quality loss are described in order to clarify the rationales of fat replacement. Carbohydrate fat replacers usually have low calorie density and provide gelling, thickening, stabilizing, and other texture-modifying properties. In this review, carbohydrates, including starches, maltodextrins, polydextrose, gums, and fibers, are discussed with regard to their interactions with other components in foods as well as their performances as fat replacers in various systems.

  4. Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy.

    Science.gov (United States)

    Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

    2017-06-02

    Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11-1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants, and the investigators will explain the study to the

  5. Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy

    Science.gov (United States)

    Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

    2017-01-01

    Introduction Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. Methods and analysis The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. Ethics and dissemination This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11–1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants

  6. Shoulder replacement - discharge

    Science.gov (United States)

    Total shoulder arthroplasty - discharge; Endoprosthetic shoulder replacement - discharge; Partial shoulder replacement - discharge; Partial shoulder arthroplasty - discharge; Replacement - shoulder - discharge; Arthroplasty - shoulder - discharge

  7. Engineering Cellulase Enzymes for Bioenergy

    Science.gov (United States)

    Atreya, Meera Elizabeth

    Sustainable energy sources, such as biofuels, offer increasingly important alternatives to fossil fuels that contribute less to global climate change. The energy contained within cellulosic biofuels derives from sunlight energy stored in the form of carbon-carbon bonds comprising sugars such as glucose. Second-generation biofuels are produced from lignocellulosic biomass feedstocks, including agricultural waste products and non-food crops like Miscanthus, that contain lignin and the polysaccharides hemicellulose and cellulose. Cellulose is the most abundant biological material on Earth; it is a polymer of glucose and a structural component of plant cell walls. Accessing the sugar is challenging, as the crystalline structure of cellulose resists degradation; biochemical and thermochemical means can be used to depolymerize cellulose. Cellulase enzymes catalyze the biochemical depolymerization of cellulose into glucose. Glucose can be used as a carbon source for growth of a biofuel-producing microorganism. When it converts glucose to a hydrocarbon fuel, this microbe completes the biofuels process of transforming sunlight energy into accessible, chemical energy capable of replacing non-renewable transportation fuels. Due to strong intermolecular interactions between polymer chains, cellulose is significantly more challenging to depolymerize than starch, a more accessible polymer of glucose utilized in first-generation biofuels processes (often derived from corn). While most mammals cannot digest cellulose (dietary fiber), certain fungi and bacteria produce cellulase enzymes capable of hydrolyzing it. These organisms secrete a wide variety of glycoside hydrolase and other classes of enzymes that work in concert. Because cellulase enzymes are slow-acting and expensive to produce, my aim has been to improve the properties of these enzymes as a means to make a cellulosic biofuels process possible that is more efficient and, consequently, more economical than current

  8. Immobilized enzymes and cells

    Energy Technology Data Exchange (ETDEWEB)

    Bucke, C; Wiseman, A

    1981-04-04

    This article reviews the current state of the art of enzyme and cell immobilization and suggests advances which might be made during the 1980's. Current uses of immobilized enzymes include the use of glucoamylase in the production of glucose syrups from starch and glucose isomerase in the production of high fructose corn syrup. Possibilities for future uses of immobilized enzymes and cells include the utilization of whey and the production of ethanol.

  9. Hip joint replacement

    Science.gov (United States)

    Hip arthroplasty; Total hip replacement; Hip hemiarthroplasty; Arthritis - hip replacement; Osteoarthritis - hip replacement ... Your hip joint is made up of 2 major parts. One or both parts may be replaced during surgery: ...

  10. Transcatheter aortic valve replacement

    Science.gov (United States)

    ... gov/ency/article/007684.htm Transcatheter aortic valve replacement To use the sharing features on this page, please enable JavaScript. Transcatheter aortic valve replacement (TAVR) is surgery to replace the aortic valve. ...

  11. Hip Replacement Surgery

    Science.gov (United States)

    ... Outreach Initiative Breadcrumb Home Health Topics English Español Hip Replacement Surgery Basics In-Depth Download Download EPUB ... PDF What is it? Points To Remember About Hip Replacement Surgery Hip replacement surgery removes damaged or ...

  12. Nicotine replacement therapy

    Science.gov (United States)

    Smoking cessation - nicotine replacement; Tobacco - nicotine replacement therapy ... Before you start using a nicotine replacement product, here are some things to know: The more cigarettes you smoke, the higher the dose you may need to ...

  13. Agreement between the results of meta-analyses from case reports and from clinical studies regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult age: An example of case reports meta-analyses as an useful tool for evidence-based medicine in rare diseases.

    Science.gov (United States)

    Sampayo-Cordero, Miguel; Miguel-Huguet, Bernat; Pardo-Mateos, Almudena; Moltó-Abad, Marc; Muñoz-Delgado, Cecilia; Pérez-López, Jordi

    2018-02-01

    Case reports might have a prominent role in the rare diseases field, due to the small number of patients affected by one such disease. A previous systematic review regarding the efficacy of laronidase therapy in patients with mucopolysaccharidosis type I (MPS-I) who initiated enzyme replacement therapy (ERT) in adult age has been published. The review included a meta-analysis of 19 clinical studies and the description of eleven case reports. It was of interest to perform a meta-analysis of those case reports to explore the role of such meta-analyses as a tool for evidence-based medicine in rare diseases. The study included all case reports with standard treatment regimen. Primary analysis was the percentage of case reports showing an improvement in a specific outcome. Only when that percentage was statistically higher than 5%, the improvement was confirmed as such. The outcomes that accomplished this criterion were ranked and compared to the GRADE criteria obtained by those same outcomes in the previous meta-analysis of clinical studies. There were three outcomes that had a significant improvement: Urine glycosaminoglycans, liver volume and 6-minute walking test. Positive and negative predictive values, sensitivity and specificity for the results of the meta-analysis of case reports as compared to that of clinical studies were 100%, 88.9%, 75% and 100%, respectively. Accordingly, absolute (Rho=0.82, 95%CI: 0.47 to 0.95) and relative agreement (Kappa=0.79, 95%CI: 0.593 to 0.99) between the number of case reports with improvement in a specific outcome and the GRADE evidence score for that outcome were good. Sensitivity analysis showed that agreement between the meta-analysis of case reports and that of the clinical studies were good only when using a strong confirmatory strategy for outcome improvement in case reports. We found an agreement between the results of meta-analyses from case reports and from clinical studies in the efficacy of laronidase therapy in

  14. CLINICAL USE OF ENZYMES IN PEDIATRIC GASTROENTEROLOGY

    Directory of Open Access Journals (Sweden)

    А.N. Surkov

    2011-01-01

    Full Text Available High incidence of various pediatric gastroenterologic diseases including congenital still remains an important issue for a Russian healthcare. The latter may be attended by relative or total excretory pancreatic failure with the following symptoms: stool abnormalities, abdominal pain, meteorism, weakness, low appetite and physical exercise, weight reduction and growth retardation. Pancreatic enzymes that contribute to protein, lipids and carbohydrates digestion are often used as a replacement therapy in pediatric care. Nowadays there is a plenty of choice among enzymatic medications. However, not all aforesaid medications can ensure adequate replacement treatment especially in children with chronic pancreatic failure. That is why among agents of choice are modern and highly effective microgranulated encapsulated pancreatines. For example Micrazim.Key words: children, pancreas, pancreatic failure, enzymotherapy.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2011; 10 (3: 114–118

  15. Defining line replaceable units

    NARCIS (Netherlands)

    Parada Puig, J. E.; Basten, R. J I

    2015-01-01

    Defective capital assets may be quickly restored to their operational condition by replacing the item that has failed. The item that is replaced is called the Line Replaceable Unit (LRU), and the so-called LRU definition problem is the problem of deciding on which item to replace upon each type of

  16. Overproduction of ligninolytic enzymes

    Science.gov (United States)

    Elisashvili, Vladimir; Kachlishvili, Eva; Torok, Tamas

    2014-06-17

    Methods, compositions, and systems for overproducing ligninolytic enzymes from the basidiomycetous fungus are described herein. As described, the method can include incubating a fungal strain of Cerrena unicolor IBB 303 in a fermentation system having growth medium which includes lignocellulosic material and then cultivating the fungal strain in the fermentation system under conditions wherein the fungus expresses the ligninolytic enzymes. In some cases, the lignocellulosic material is mandarin peel, ethanol production residue, walnut pericarp, wheat bran, wheat straw, or banana peel.

  17. Targeted enzyme prodrug therapies.

    Science.gov (United States)

    Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

    2010-09-01

    The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

  18. Terapia de reposição enzimática para as mucopolissacaridoses I, II e VI: recomendações de um grupo de especialistas brasileiros Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts

    Directory of Open Access Journals (Sweden)

    Roberto Giugliani

    2010-01-01

    já está em desenvolvimento clínico, com perspectivas para o tratamento da MPS III A e do déficit cognitivo na MPS II através de administração da enzima diretamente no sistema nervoso central (SNC. Um grande número de centros brasileiros, incluindo serviços de todas as regiões do país, já têm experiência com TRE para MPS I, II e VI. Essa experiência foi adquirida não só com o tratamento de pacientes como também com a participação de alguns grupos em ensaios clínicos envolvendo TRE para essas condições. Somados os três tipos de MPS, mais de 250 pacientes já foram tratados com TRE em nosso país. A experiência dos profissionais brasileiros, somada aos dados disponíveis na literatura internacional, permitiu elaborar este documento, produzido com o objetivo de reunir e harmonizar as informações disponíveis sobre o tratamento destas doenças graves e progressivas, mas que, felizmente, são hoje tratáveis, uma realidade que traz novas perspectivas para os pacientes brasileiros afetados por essas condições.Mucopolysaccharidoses (MPS are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG. Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified. Before introduction of therapies to restore deficient enzyme activity, treatment of MPS focused primnarily on prevention and care of complications, still a very important aspect in the management of these patients. In the 80's treatment of MPS with bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT was proposed and in the 90's, enzyme replacement therapy (ERT,began to be

  19. New protein involved in the replacement of cell molecules

    DEFF Research Database (Denmark)

    Poulsen, Jesper Buchhave

    2011-01-01

    In collaboration with colleagues from La Trobe University, Australia, scientists at Aarhus University have discovered and defined a novel enzyme involved in the replacement and renewal of cell molecules. The enzyme exerts its function within the so-called mitochondria - small “enclosed” compartme......In collaboration with colleagues from La Trobe University, Australia, scientists at Aarhus University have discovered and defined a novel enzyme involved in the replacement and renewal of cell molecules. The enzyme exerts its function within the so-called mitochondria - small “enclosed...

  20. Power Plant Replacement Study

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University's aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  1. Power Plant Replacement Study

    Energy Technology Data Exchange (ETDEWEB)

    Reed, Gary

    2010-09-30

    This report represents the final report for the Eastern Illinois University power plant replacement study. It contains all related documentation from consideration of possible solutions to the final recommended option. Included are the economic justifications associated with the chosen solution along with application for environmental permitting for the selected project for construction. This final report will summarize the results of execution of an EPC (energy performance contract) investment grade audit (IGA) which lead to an energy services agreement (ESA). The project includes scope of work to design and install energy conservation measures which are guaranteed by the contractor to be self-funding over its twenty year contract duration. The cost recovery is derived from systems performance improvements leading to energy savings. The prime focus of this EPC effort is to provide a replacement solution for Eastern Illinois University’s aging and failing circa 1925 central steam production plant. Twenty-three ECMs were considered viable whose net impact will provide sufficient savings to successfully support the overall project objectives.

  2. Ankle replacement - discharge

    Science.gov (United States)

    ... total - discharge; Total ankle arthroplasty - discharge; Endoprosthetic ankle replacement - discharge; Osteoarthritis - ankle ... You had an ankle replacement. Your surgeon removed and reshaped ... an artificial ankle joint. You received pain medicine and were ...

  3. Artificial Disc Replacement

    Science.gov (United States)

    ... Spondylolisthesis BLOG FIND A SPECIALIST Treatments Artificial Disc Replacement (ADR) Patient Education Committee Jamie Baisden The disc ... Disc An artificial disc (also called a disc replacement, disc prosthesis or spine arthroplasty device) is a ...

  4. Partial knee replacement - slideshow

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/presentations/100225.htm Partial knee replacement - series—Normal anatomy To use the sharing ... A.M. Editorial team. Related MedlinePlus Health Topics Knee Replacement A.D.A.M., Inc. is accredited ...

  5. Flued head replacement alternatives

    International Nuclear Information System (INIS)

    Smetters, J.L.

    1987-01-01

    This paper discusses flued head replacement options. Section 2 discusses complete flued head replacement with a design that eliminates the inaccessible welds. Section 3 discusses alternate flued head support designs that can drastically reduce flued head installation costs. Section 4 describes partial flued head replacement designs. Finally, Section 5 discusses flued head analysis methods. (orig./GL)

  6. Capital Equipment Replacement Decisions

    OpenAIRE

    Batterham, Robert L.; Fraser, K.I.

    1995-01-01

    This paper reviews the literature on the optimal replacement of capital equipment, especially farm machinery. It also considers the influence of taxation and capital rationing on replacement decisions. It concludes that special taxation provisions such as accelerated depreciation and investment allowances are unlikely to greatly influence farmers' capital equipment replacement decisions in Australia.

  7. Implementing Replacement Cost Accounting

    Science.gov (United States)

    1976-12-01

    cost accounting Clickener, John Ross Monterey, California. Naval Postgraduate School http://hdl.handle.net/10945/17810 Downloaded from NPS Archive...Calhoun IMPLEMENTING REPLACEMENT COST ACCOUNTING John Ross CHckener NAVAL POSTGRADUATE SCHOOL Monterey, California THESIS IMPLEMENTING REPLACEMENT COST ...Implementing Replacement Cost Accounting 7. AUTHORS John Ross Clickener READ INSTRUCTIONS BEFORE COMPLETING FORM 3. RECIPIENT’S CATALOG NUMBER 9. TYRE OF

  8. Epigenetic-based combinatorial resveratrol and pterostilbene alters DNA damage response by affecting SIRT1 and DNMT enzyme expression, including SIRT1-dependent γ-H2AX and telomerase regulation in triple-negative breast cancer

    International Nuclear Information System (INIS)

    Kala, Rishabh; Shah, Harsh N.; Martin, Samantha L.; Tollefsbol, Trygve O.

    2015-01-01

    , the effects of this combination treatment was also explored on DNA methyltransferases (DNMTs) expression. Interestingly, the compounds resulted in a significant down-regulation of DNMT enzymes with no significant effects on DNMT enzyme expression in MCF10A control cells. Collectively, these results provide new insights into the epigenetic mechanisms of a novel combinatorial nutrient control strategy that exhibits synergy and may contribute to future recalcitrant TNBC prevention and/or therapy. The online version of this article (doi:10.1186/s12885-015-1693-z) contains supplementary material, which is available to authorized users

  9. Computer simulation of replacement sequences in copper

    International Nuclear Information System (INIS)

    Schiffgens, J.O.; Schwartz, D.W.; Ariyasu, R.G.; Cascadden, S.E.

    1978-01-01

    Results of computer simulations of , , and replacement sequences in copper are presented, including displacement thresholds, focusing energies, energy losses per replacement, and replacement sequence lengths. These parameters are tabulated for six interatomic potentials and shown to vary in a systematic way with potential stiffness and range. Comparisons of results from calculations made with ADDES, a quasi-dynamical code, and COMENT, a dynamical code, show excellent agreement, demonstrating that the former can be calibrated and used satisfactorily in the analysis of low energy displacement cascades. Upper limits on , , and replacement sequences were found to be approximately 10, approximately 30, and approximately 14 replacements, respectively. (author)

  10. Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, H.E.; Ott, Peter

    2007-01-01

    Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

  11. Iron replacement therapy

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Coskun, Mehmet; Weiss, Günter

    2016-01-01

    PURPOSE OF REVIEW: Approximately, one-third of the world's population suffers from anemia, and at least half of these cases are because of iron deficiency. With the introduction of new intravenous iron preparations over the last decade, uncertainty has arisen when these compounds should...... be administered and under which circumstances oral therapy is still an appropriate and effective treatment. RECENT FINDINGS: Numerous guidelines are available, but none go into detail about therapeutic start and end points or how iron-deficiency anemia should be best treated depending on the underlying cause...... of iron deficiency or in regard to concomitant underlying or additional diseases. SUMMARY: The study points to major issues to be considered in revisions of future guidelines for the true optimal iron replacement therapy, including how to assess the need for treatment, when to start and when to stop...

  12. Total ankle joint replacement.

    Science.gov (United States)

    2016-02-01

    Ankle arthritis results in a stiff and painful ankle and can be a major cause of disability. For people with end-stage ankle arthritis, arthrodesis (ankle fusion) is effective at reducing pain in the shorter term, but results in a fixed joint, and over time the loss of mobility places stress on other joints in the foot that may lead to arthritis, pain and dysfunction. Another option is to perform a total ankle joint replacement, with the aim of giving the patient a mobile and pain-free ankle. In this article we review the efficacy of this procedure, including how it compares to ankle arthrodesis, and consider the indications and complications. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  13. Avaliação de dois anos de tratamento da doença de Gaucher tipo 1 com terapia de reposição enzimática em pacientes do estado de São Paulo, Brasil Evaluation of two years of treatment with enzyme replacement therapy in type 1 Gaucher disease patients of São Paulo State, Brazil

    Directory of Open Access Journals (Sweden)

    Elisa A. P. Sobreira

    2008-01-01

    marrow. The symptoms are heterogeneous and include hepatosplenomegaly, anemia, thrombocytopenia, bone marrow infiltration, and skeletal lesions. We evaluated the effects of enzyme replacement therapy (ERT on anemia, thrombocytopenia, hepatosplenomegaly, growth retardation (children and adolescents and bone pain among 90 patients with type 1 Gaucher's disease treated during 24 months in Sao Paulo State. Baseline signs and symptoms were anemia (50%, thrombocytopenia (59%, hepatomegaly (97%, splenomegaly (96%, growth retardation (46% and bone pain (62%. The mean dose of ERT was 35 U/kg every two weeks. Reduction in anemia, thrombocytopenia and bone pain was greatest during the first six months of ERT and of hepatosplenomegaly and growth retardation within 18 months. Improvements were sustained by most of the patients during the follow-up. Within 24 months of ERT, therapeutic goals were achieved in at least 88% of patients with anemia, 80% with thrombocytopenia, 34% with hepatosplenomegaly, 77% with growth retardation and 76% with bone pain. Other studies are needed to evaluate the treatment efficacy over a longer period, mainly for skeletal lesions and growth retardation, which may present a slower recovery due to low penetration of imiglucerase in bones.

  14. Aeronautical Information System Replacement -

    Data.gov (United States)

    Department of Transportation — Aeronautical Information System Replacement is a web-enabled, automation means for the collection and distribution of Service B messages, weather information, flight...

  15. Optimization of station battery replacement

    International Nuclear Information System (INIS)

    Jancauskas, J.R.; Shook, D.A.

    1994-01-01

    During a loss of ac power at a nuclear generating station (including diesel generators), batteries provide the source of power which is required to operate safety-related components. Because traditional lead-acid batteries have a qualified life of 20 years, the batteries must be replaced a minimum of once during a station's lifetime, twice if license extension is pursued, and more often depending on actual in-service dates and the results of surveillance tests. Replacement of batteries often occurs prior to 20 years as a result of systems changes caused by factors such as Station Blackout Regulations, control system upgrades, incremental load growth, and changes in the operating times of existing equipment. Many of these replacement decisions are based on the predictive capabilities of manual design basis calculations. The inherent conservatism of manual calculations may result in battery replacements occurring before actually required. Computerized analysis of batteries can aid in optimizing the timing of replacements as well as in interpreting service test data. Computerized analysis also provides large benefits in maintaining the as-configured load profile and corresponding design margins, while also providing the capability of quickly analyze proposed modifications and response to internal and external audits

  16. DGAT enzymes and triacylglycerol biosynthesis

    Science.gov (United States)

    Yen, Chi-Liang Eric; Stone, Scot J.; Koliwad, Suneil; Harris, Charles; Farese, Robert V.

    2008-01-01

    Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, and the use of molecular tools, including mice deficient in either enzyme, has shed light on their functions. Although DGAT enzymes are involved in TG synthesis, they have distinct protein sequences and differ in their biochemical, cellular, and physiological functions. Both enzymes may be useful as therapeutic targets for diseases. Here we review the current knowledge of DGAT enzymes, focusing on new advances since the cloning of their genes, including possible roles in human health and diseases. PMID:18757836

  17. Radiation Source Replacement Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, Jeffrey W.; Moran, Traci L.; Bond, Leonard J.

    2010-12-01

    This report summarizes a Radiation Source Replacement Workshop in Houston Texas on October 27-28, 2010, which provided a forum for industry and researchers to exchange information and to discuss the issues relating to replacement of AmBe, and potentially other isotope sources used in well logging.

  18. Could wind replace nuclear?

    International Nuclear Information System (INIS)

    2017-01-01

    This article aims at assessing the situation produced by a total replacement of nuclear energy by wind energy, while facing consumption demand at any moment, notably in December. The authors indicate the evolution of the French energy mix during December 2016, and the evolution of the rate between wind energy production and the sum of nuclear and wind energy production during the same month, and then give briefly some elements regarding necessary investments in wind energy to wholly replace nuclear energy. According to them, such a replacement would be ruinous

  19. EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific O pinion Flavouring Group Evaluation 23, Revision 4 (FGE.23Rev4): Aliphatic, alicyclic and aromatic ethers including anisole derivatives from chemical groups 15, 16, 22, 26 and 30

    DEFF Research Database (Denmark)

    Beltoft, Vibe Meister; Binderup, Mona-Lise; Frandsen, Henrik Lauritz

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 21 flavouring substances in the Flavouring Group Evaluation 23, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision i...... also been considered. Specifications including complete purity criteria and identity for the materials of commerce have been provided for all 21 candidate substances. © European Food Safety Authority, 2013......The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 21 flavouring substances in the Flavouring Group Evaluation 23, Revision 4, using the Procedure in Commission Regulation (EC) No 1565/2000. This revision...

  20. A useful framework for optimal replacement models

    International Nuclear Information System (INIS)

    Aven, Terje; Dekker, Rommert

    1997-01-01

    In this note we present a general framework for optimization of replacement times. It covers a number of models, including various age and block replacement models, and allows a uniform analysis for all these models. A relation to the marginal cost concept is described

  1. Slab replacement maturity guidelines.

    Science.gov (United States)

    2014-04-01

    This study investigated the use of maturity method to determine early age strength of concrete in slab : replacement application. Specific objectives were (1) to evaluate effects of various factors on the compressive : maturity-strength relationship ...

  2. Partial knee replacement

    Science.gov (United States)

    ... good range of motion in your knee. The ligaments in your knee are stable. However, most people with knee arthritis have a surgery called a total knee arthroplasty (TKA). Knee replacement is most often done in people age 60 ...

  3. Hip joint replacement - slideshow

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/presentations/100006.htm Hip joint replacement - series—Normal anatomy To use the ... to slide 5 out of 5 Overview The hip joint is made up of two major parts: ...

  4. Tool Inventory and Replacement

    Science.gov (United States)

    Bear, W. Forrest

    1976-01-01

    Vocational agriculture teachers are encouraged to evaluate curriculum offerings, the new trends in business and industry, and develop a master tool purchase and replacement plan over a 3- to 5-year period. (HD)

  5. Knee joint replacement

    Science.gov (United States)

    ... to make everyday tasks easier. Practice using a cane, walker , crutches , or a wheelchair correctly. On the ... ask your doctor Knee joint replacement - discharge Preventing falls Preventing falls - what to ask your doctor Surgical ...

  6. Product Platform Replacements

    DEFF Research Database (Denmark)

    Sköld, Martin; Karlsson, Christer

    2012-01-01

    . To shed light on this unexplored and growing managerial concern, the purpose of this explorative study is to identify operational challenges to management when product platforms are replaced. Design/methodology/approach – The study uses a longitudinal field-study approach. Two companies, Gamma and Omega...... replacement was chosen in each company. Findings – The study shows that platform replacements primarily challenge managers' existing knowledge about platform architectures. A distinction can be made between “width” and “height” in platform replacements, and it is crucial that managers observe this in order...... to challenge their existing knowledge about platform architectures. Issues on technologies, architectures, components and processes as well as on segments, applications and functions are identified. Practical implications – Practical implications are summarized and discussed in relation to a framework...

  7. A stochastic model of enzyme kinetics

    Science.gov (United States)

    Stefanini, Marianne; Newman, Timothy; McKane, Alan

    2003-10-01

    Enzyme kinetics is generally modeled by deterministic rate equations, and in the simplest case leads to the well-known Michaelis-Menten equation. It is plausible that stochastic effects will play an important role at low enzyme concentrations. We have addressed this by constructing a simple stochastic model which can be exactly solved in the steady-state. Throughout a wide range of parameter values Michaelis-Menten dynamics is replaced by a new and simple theoretical result.

  8. The Enzyme Function Initiative†

    Science.gov (United States)

    Gerlt, John A.; Allen, Karen N.; Almo, Steven C.; Armstrong, Richard N.; Babbitt, Patricia C.; Cronan, John E.; Dunaway-Mariano, Debra; Imker, Heidi J.; Jacobson, Matthew P.; Minor, Wladek; Poulter, C. Dale; Raushel, Frank M.; Sali, Andrej; Shoichet, Brian K.; Sweedler, Jonathan V.

    2011-01-01

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily-specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include: 1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation); 2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia; 3) computational and bioinformatic tools for using the strategy; 4) provision of experimental protocols and/or reagents for enzyme production and characterization; and 5) dissemination of data via the EFI’s website, enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal and pharmaceutical efforts. PMID

  9. The Enzyme Function Initiative.

    Science.gov (United States)

    Gerlt, John A; Allen, Karen N; Almo, Steven C; Armstrong, Richard N; Babbitt, Patricia C; Cronan, John E; Dunaway-Mariano, Debra; Imker, Heidi J; Jacobson, Matthew P; Minor, Wladek; Poulter, C Dale; Raushel, Frank M; Sali, Andrej; Shoichet, Brian K; Sweedler, Jonathan V

    2011-11-22

    The Enzyme Function Initiative (EFI) was recently established to address the challenge of assigning reliable functions to enzymes discovered in bacterial genome projects; in this Current Topic, we review the structure and operations of the EFI. The EFI includes the Superfamily/Genome, Protein, Structure, Computation, and Data/Dissemination Cores that provide the infrastructure for reliably predicting the in vitro functions of unknown enzymes. The initial targets for functional assignment are selected from five functionally diverse superfamilies (amidohydrolase, enolase, glutathione transferase, haloalkanoic acid dehalogenase, and isoprenoid synthase), with five superfamily specific Bridging Projects experimentally testing the predicted in vitro enzymatic activities. The EFI also includes the Microbiology Core that evaluates the in vivo context of in vitro enzymatic functions and confirms the functional predictions of the EFI. The deliverables of the EFI to the scientific community include (1) development of a large-scale, multidisciplinary sequence/structure-based strategy for functional assignment of unknown enzymes discovered in genome projects (target selection, protein production, structure determination, computation, experimental enzymology, microbiology, and structure-based annotation), (2) dissemination of the strategy to the community via publications, collaborations, workshops, and symposia, (3) computational and bioinformatic tools for using the strategy, (4) provision of experimental protocols and/or reagents for enzyme production and characterization, and (5) dissemination of data via the EFI's Website, http://enzymefunction.org. The realization of multidisciplinary strategies for functional assignment will begin to define the full metabolic diversity that exists in nature and will impact basic biochemical and evolutionary understanding, as well as a wide range of applications of central importance to industrial, medicinal, and pharmaceutical efforts.

  10. Electrocatalysts Prepared by Galvanic Replacement

    Directory of Open Access Journals (Sweden)

    Athanasios Papaderakis

    2017-03-01

    Full Text Available Galvanic replacement is the spontaneous replacement of surface layers of a metal, M, by a more noble metal, Mnoble, when the former is treated with a solution containing the latter in ionic form, according to the general replacement reaction: nM + mMnoblen+ → nMm+ + mMnoble. The reaction is driven by the difference in the equilibrium potential of the two metal/metal ion redox couples and, to avoid parasitic cathodic processes such as oxygen reduction and (in some cases hydrogen evolution too, both oxygen levels and the pH must be optimized. The resulting bimetallic material can in principle have a Mnoble-rich shell and M-rich core (denoted as Mnoble(M leading to a possible decrease in noble metal loading and the modification of its properties by the underlying metal M. This paper reviews a number of bimetallic or ternary electrocatalytic materials prepared by galvanic replacement for fuel cell, electrolysis and electrosynthesis reactions. These include oxygen reduction, methanol, formic acid and ethanol oxidation, hydrogen evolution and oxidation, oxygen evolution, borohydride oxidation, and halide reduction. Methods for depositing the precursor metal M on the support material (electrodeposition, electroless deposition, photodeposition as well as the various options for the support are also reviewed.

  11. Phage lytic enzymes: a history.

    Science.gov (United States)

    Trudil, David

    2015-02-01

    There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of 'bacteria-eaters' or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well (Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specific disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay (Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes-from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

  12. EFSA Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (CEF); Scientific Opinion on Flavouring Group Evaluation 23, Revision 3 (FGE.23Rev3): Aliphatic, alicyclic and aromatic ethers including anisole derivatives from chemical groups 15, 16, 22, 26 and 30

    DEFF Research Database (Denmark)

    Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

    The Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids of the European Food Safety Authority was requested to evaluate 20 flavouring substances in the Flavouring Group Evaluation 23, Revision 3, using the Procedure in Commission Regulation (EC) No 1565/2000. None...... of the MSDI approach. Besides the safety assessment of these flavouring substances, the specifications for the materials of commerce have also been considered. Specifications including complete purity criteria and identity for the materials of commerce have been provided for all 20 candidate substances....

  13. Enzyme detection by microfluidics

    DEFF Research Database (Denmark)

    2013-01-01

    Microfluidic-implemented methods of detecting an enzyme, in particular a DNA-modifying enzyme, are provided, as well as methods for detecting a cell, or a microorganism expressing said enzyme. The enzyme is detected by providing a nucleic acid substrate, which is specifically targeted...... by that enzyme...

  14. Type II dehydroquinase: molecular replacement with many copies

    International Nuclear Information System (INIS)

    Stewart, Kirsty Anne; Robinson, David Alexander; Lapthorn, Adrian Jonathan

    2007-01-01

    The type II dehydroquinase enzyme is a symmetrical dodecameric protein which crystallizes in either high-symmetry cubic space groups or low-symmetry crystal systems with multiple copies in the asymmetric unit. Both systems have provided challenging examples for molecular replacement; for example, a triclinic crystal form has 16 dodecamers (192 monomers) in the unit cell. Three difficult examples are discussed and two are used as test cases to compare the performance of four commonly used molecular-replacement packages. Type II dehydroquinase is a small (150-amino-acid) protein which in solution packs together to form a dodecamer with 23 cubic symmetry. In crystals of this protein the symmetry of the biological unit can be coincident with the crystallographic symmetry, giving rise to cubic crystal forms with a single monomer in the asymmetric unit. In crystals where this is not the case, multiple copies of the monomer are present, giving rise to significant and often confusing noncrystallographic symmetry in low-symmetry crystal systems. These different crystal forms pose a variety of challenges for solution by molecular replacement. Three examples of structure solutions, including a highly unusual triclinic crystal form with 16 dodecamers (192 monomers) in the unit cell, are described. Four commonly used molecular-replacement packages are assessed against two of these examples, one of high symmetry and the other of low symmetry; this study highlights how program performance can vary significantly depending on the given problem. In addition, the final refined structure of the 16-dodecamer triclinic crystal form is analysed and shown not to be a superlattice structure, but rather an F-centred cubic crystal with frustrated crystallographic symmetry

  15. Allosteric regulation of epigenetic modifying enzymes.

    Science.gov (United States)

    Zucconi, Beth E; Cole, Philip A

    2017-08-01

    Epigenetic enzymes including histone modifying enzymes are key regulators of gene expression in normal and disease processes. Many drug development strategies to target histone modifying enzymes have focused on ligands that bind to enzyme active sites, but allosteric pockets offer potentially attractive opportunities for therapeutic development. Recent biochemical studies have revealed roles for small molecule and peptide ligands binding outside of the active sites in modulating the catalytic activities of histone modifying enzymes. Here we highlight several examples of allosteric regulation of epigenetic enzymes and discuss the biological significance of these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Enzymes - important players in green chemistry

    Directory of Open Access Journals (Sweden)

    Agata Tarczykowska

    2017-09-01

    Full Text Available Green chemistry has become a worldwide approach that leads to sustainable growth through application and development of its principles. A lot of work has to be put into designing new processes comprising of materials which do not emit pollutants to the atmosphere. Inventing new safer methods and finding less harmful products can be challenging. Enzymes are a great hope of scientists in the field of green chemistry. Enzymes as catalysts require mild conditions therefore it is a great way of saving resources such as energy or water. Processes with the use of enzymes have become more feasible by being more cost effective and eco friendly. Taking into account the benefits of green chemistry, enzyme biocatalysis has quickly replaced traditional chemical processes in several fields, and this substitution is going to reach even more areas because of new emerging technologies in enzyme engineering.

  17. Prioritizing equipment for replacement.

    Science.gov (United States)

    Capuano, Mike

    2010-01-01

    It is suggested that clinical engineers take the lead in formulating evaluation processes to recommend equipment replacement. Their skill, knowledge, and experience, combined with access to equipment databases, make them a logical choice. Based on ideas from Fennigkoh's scheme, elements such as age, vendor support, accumulated maintenance cost, and function/risk were used.6 Other more subjective criteria such as cost benefits and efficacy of newer technology were not used. The element of downtime was also omitted due to the data element not being available. The resulting Periop Master Equipment List and its rationale was presented to the Perioperative Services Program Council. They deemed the criteria to be robust and provided overwhelming acceptance of the list. It was quickly put to use to estimate required capital funding, justify items already thought to need replacement, and identify high-priority ranked items for replacement. Incorporating prioritization criteria into an existing equipment database would be ideal. Some commercially available systems do have the basic elements of this. Maintaining replacement data can be labor-intensive regardless of the method used. There is usually little time to perform the tasks necessary for prioritizing equipment. However, where appropriate, a clinical engineering department might be able to conduct such an exercise as shown in the following case study.

  18. Thyroid hormone replacement therapy

    NARCIS (Netherlands)

    Wiersinga, W. M.

    2001-01-01

    Thyroid hormone replacement has been used for more than 100 years in the treatment of hypothyroidism, and there is no doubt about its overall efficacy. Desiccated thyroid contains both thyroxine (T(4)) and triiodothyronine (T(3)); serum T(3) frequently rises to supranormal values in the absorption

  19. Can photovoltaic replace nuclear?

    International Nuclear Information System (INIS)

    2017-01-01

    As the French law on energy transition for a green growth predicts that one third of nuclear energy production is to be replaced by renewable energies (wind and solar) by 2025, and while the ADEME proposes a 100 per cent renewable scenario for 2050, this paper proposes a brief analysis of the replacement of nuclear energy by solar photovoltaic energy. It presents and discusses some characteristics of photovoltaic production: production level during a typical day for each month (a noticeable lower production in December), evolution of monthly production during a year, evolution of the rate between nuclear and photovoltaic production. A cost assessment is then proposed for energy storage and for energy production, and a minimum cost of replacement of nuclear by photovoltaic is assessed. The seasonal effect is outlined, as well as the latitude effect. Finally, the authors outline the huge cost of such a replacement, and consider that public support to new photovoltaic installations without an at least daily storage mean should be cancelled

  20. Fluorescent Lamp Replacement Study

    Science.gov (United States)

    2017-07-01

    not be cited for purposes of advertisement. DISPOSITION INSTRUCTIONS: Destroy this document when no longer needed. Do not return to the... recycling , and can be disposed safely in a landfill. (2) LEDs offer reduced maintenance costs and fewer bulb replacements, significantly reducing... recycling . Several fixtures, ballasts and energy efficient fluorescent bulbs that were determined to be in pristine condition were returned to ATC

  1. Replacing Recipe Realism

    OpenAIRE

    Saatsi, J

    2017-01-01

    Many realist writings exemplify the spirit of ‘recipe realism’. Here I characterise recipe realism, challenge it, and propose replacing it with ‘exemplar realism’. This alternative understanding of realism is more piecemeal, robust, and better in tune with scientists’ own attitude towards their best theories, and thus to be preferred.

  2. The caudal septum replacement graft.

    Science.gov (United States)

    Foda, Hossam M T

    2008-01-01

    To describe a technique for reconstructing the lost tip support in cases involving caudal septal and premaxillary deficiencies. The study included 120 patients with aesthetic and functional nasal problems resulting from the loss of caudal septal and premaxillary support. An external rhinoplasty approach was performed to reconstruct the lost support using a cartilaginous caudal septum replacement graft and premaxillary augmentation with Mersilene mesh. The majority of cases (75%) involved revisions in patients who had previously undergone 1 or more nasal surgical procedures. A caudal septum replacement graft was combined with premaxillary augmentation in 93 patients (77.5%). The mean follow-up period was 3 years (range, 1-12 years). The technique succeeded in correcting the external nasal deformities in all patients and resulted in a significant improvement in breathing in 74 patients (86%) with preoperative nasal obstruction. There were no cases of infection, displacement, or extrusion. The caudal septum replacement graft proved to be very effective in restoring the lost tip support in patients with caudal septal deficiency. Combining the graft with premaxillary augmentation using Mersilene mesh helped increase support and stability over long-term follow-up.

  3. Curious Cases of the Enzymes.

    Science.gov (United States)

    Ulusu, Nuriye Nuray

    2015-07-01

    Life as we know it heavily relies on biological catalysis, in fact, in a very nonromantic version of it, life could be considered as a series of chemical reactions, regulated by the guarding principles of thermodynamics. In ancient times, a beating heart was a good sign of vitality, however, to me, it is actually the presence of active enzymes that counts… Though we do not usually pay attention, the history of enzymology is as old as humanity itself, and dates back to the ancient times. This paper is dedicated to these early moments of this remarkable science that touched our lives in the past and will make life a lot more efficient for humanity in the future. There was almost always a delicate, fundamentally essential relationship between mankind and the enzymes. Challenged by a very alien and hostile Nature full of predators, prehistoric men soon discovered the medicinal properties of the plants, through trial and error. In fact, they accidently discovered the enzyme inhibitors and thus, in crude terms, kindled a sparkling area of research. These plant-derivatives that acted as enzyme inhibitors helped prehistoric men in their pursuit of survival and protection from predators; in hunting and fishing… Later in history, while the underlying purposes of survival and increasing the quality of life stayed intact, the ways and means of enzymology experienced a massive transformation, as the 'trial and error' methodology of the ancients is now replaced with rational scientific theories.

  4. Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

    Science.gov (United States)

    Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

    2017-01-01

    Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Conceptual Design Plan SM-43 Replacement Project

    Energy Technology Data Exchange (ETDEWEB)

    University of California, Los Alamos National Laboratory, SCC Project Office

    2000-11-01

    The Los Alamos National Laboratory Conceptual Design Plan for the SM-43 Replacement Project outlines plans for replacing the SM-43 Administration Building. Topics include the reasons that replacement is considered a necessity; the roles of the various project sponsors; and descriptions of the proposed site and facilities. Also covered in this proposal is preliminary information on the project schedule, cost estimates, acquisition strategy, risk assessment, NEPA strategy, safety strategy, and safeguards and security. Spreadsheets provide further detail on space requirements, project schedules, and cost estimates.

  6. Glaucoma after corneal replacement.

    Science.gov (United States)

    Baltaziak, Monika; Chew, Hall F; Podbielski, Dominik W; Ahmed, Iqbal Ike K

    Glaucoma is a well-known complication after corneal transplantation surgery. Traditional corneal transplantation surgery, specifically penetrating keratoplasty, has been slowly replaced by the advent of new corneal transplantation procedures: primarily lamellar keratoplasties. There has also been an emergence of keratoprosthesis implants for eyes that are high risk of failure with penetrating keratoplasty. Consequently, there are different rates of glaucoma, pathogenesis, and potential treatment in the form of medical, laser, or surgical therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The replacement research reactor

    International Nuclear Information System (INIS)

    Cameron, R.; Horlock, K.

    2001-01-01

    The contract for the design, construction and commissioning of the Replacement Research Reactor was signed in July 2000. This was followed by the completion of the detailed design and an application for a construction licence was made in May 2001. This paper will describe the main elements of the design and their relation to the proposed applications of the reactor. The future stages in the project leading to full operation are also described

  8. Replacement Saltwell Pumping System Document Bibliography

    International Nuclear Information System (INIS)

    BELLOMY, J.R.

    2000-01-01

    This document bibliography is prepared to identify engineering documentation developed during the design of the Replacement Saltwell Pumping System. The bibliography includes all engineering supporting documents and correspondence prepared prior to the deployment of the system in the field. All documents referenced are available electronically through the Records Management Information System (RMIS). Major components of the Replacement Saltwell Pumping System include the Sundyne Canned Motor Pump, the Water Filter Skid, the Injection Water Skid and the Backflow Preventer Assembly. Drawing H-14-104498 provides an index of drawings (fabrication details, PandIDs, etc.) prepared to support development of the Replacement Saltwell Pumping System. Specific information pertaining to new equipment can be found in Certified Vendor Information (CVI) File 50124. This CVI file has been established specifically for new equipment associated with the Replacement Saltwell Pumping System

  9. Apparatus for fuel replacement

    International Nuclear Information System (INIS)

    Imada, Takahiko.

    1974-01-01

    Object: To support a telescope mast such that no deforming load is applied to it even during massive vibration, it is held fixed at the time of fuel replacement to permit satisfactory remote control operation by automatic operation. Structure: The body of the fuel replacement apparatus is provided with telescope mast fixing means comprising a slide base supported for reciprocal movement with respect to a telescope mast, an operating arm pivoted at the slide base, a wrist member mounted on the free end of the operating arm and an engagement member for restricting the slide base and operating arm at the time of loading and unloading the fuel. When loading and unloading the fuel, the slide base and operating arm are restrained by the engagement member to reliably restrict the vibration of the telescope mast. When the fuel replacement apparatus is moved, the means provided on the operating arm is smoothly displaced to follow the swing (vibration) of the telescope mast to prevent the deforming load from being applied to the support portion or other areas. The wrist member supports the telescope mast such that it can be rotated while restraining movement in the axial direction, and it is provided with revolution drive means for rotating the telescope mast under remote control. (Kamimura, M.)

  10. Optimal composition of fluid-replacement beverages.

    Science.gov (United States)

    Baker, Lindsay B; Jeukendrup, Asker E

    2014-04-01

    The objective of this article is to provide a review of the fundamental aspects of body fluid balance and the physiological consequences of water imbalances, as well as discuss considerations for the optimal composition of a fluid replacement beverage across a broad range of applications. Early pioneering research involving fluid replacement in persons suffering from diarrheal disease and in military, occupational, and athlete populations incurring exercise- and/or heat-induced sweat losses has provided much of the insight regarding basic principles on beverage palatability, voluntary fluid intake, fluid absorption, and fluid retention. We review this work and also discuss more recent advances in the understanding of fluid replacement as it applies to various populations (military, athletes, occupational, men, women, children, and older adults) and situations (pathophysiological factors, spaceflight, bed rest, long plane flights, heat stress, altitude/cold exposure, and recreational exercise). We discuss how beverage carbohydrate and electrolytes impact fluid replacement. We also discuss nutrients and compounds that are often included in fluid-replacement beverages to augment physiological functions unrelated to hydration, such as the provision of energy. The optimal composition of a fluid-replacement beverage depends upon the source of the fluid loss, whether from sweat, urine, respiration, or diarrhea/vomiting. It is also apparent that the optimal fluid-replacement beverage is one that is customized according to specific physiological needs, environmental conditions, desired benefits, and individual characteristics and taste preferences.

  11. Design verification for reactor head replacement

    International Nuclear Information System (INIS)

    Dwivedy, K.K.; Whitt, M.S.; Lee, R.

    2005-01-01

    must be negotiated. This paper does not describe the massive efforts required by the NSSS and manufacturer's engineering groups nor does it include the challenges of construction in development of mechanical handling of heavy and large components, or the effort for providing adequate access for the head replacement and restoring the containment structure. The paper outlines the analysis and design efforts needed to support reactor head replacement. The paper concludes that the verification efforts performed by the utility design group not only provide increased assurance of design adequacy, but also serves as an important player on the strong team that is required for a successful head replacement. (authors)

  12. 78 FR 26383 - Environmental Assessment of the Proposed Increase in Operation, Maintenance and Replacement...

    Science.gov (United States)

    2013-05-06

    ... Proposed Increase in Operation, Maintenance and Replacement Activities Associated With the Wasatch County... of potential impacts associated with a proposed change in Operation, Maintenance and Replacement..., Maintenance, and Replacement Proposed Action includes: stabilizing canal banks; lining, piping, or enclosing...

  13. PIXE analysis of Zn enzymes

    International Nuclear Information System (INIS)

    Solis, C.; Oliver, A.; Andrade, E.; Ruvalcaba-Sil, J.L.; Romero, I.; Celis, H.

    1999-01-01

    Zinc is a necessary component in the action and structural stability of many enzymes. Some of them are well characterized, but in others, Zn stoichiometry and its association is not known. PIXE has been proven to be a suitable technique for analyzing metallic proteins embedded in electrophoresis gels. In this study, PIXE has been used to investigate the Zn content of enzymes that are known to carry Zn atoms. These include the carbonic anhydrase, an enzyme well characterized by other methods and the cytoplasmic pyrophosphatase of Rhodospirillum rubrum that is known to require Zn to be stable but not how many metal ions are involved or how they are bound to the enzyme. Native proteins have been purified by polyacrylamide gel electrophoresis and direct identification and quantification of Zn in the gel bands was performed with an external proton beam of 3.7 MeV energy

  14. Enzymes: The possibility of production and applications

    Directory of Open Access Journals (Sweden)

    Petronijević Živomir B.

    2003-01-01

    Full Text Available Enzymes are biological catalysts with increasing application in the food pharmaceutical, cosmetic, textile and chemical industry. They are also important as reagents in chemical analysis, leather fabrications and as targets for the design of new drugs. Keeping in mind the growing need to replace classical chemical processes by alternative ones, because of ever growing environmental pollution, it is important that enzyme and other biotechnological processes are economical. Therefore, price decrease and stability and enzyme preparation efficiency increase are required more and more. This paper presents a short review of methods for yield increase and the improvement of the quality of enzyme products as commercial products, as well as a review of the possibilities of their application.

  15. Toleration, Synthesis or Replacement?

    DEFF Research Database (Denmark)

    Holtermann, Jakob v. H.; Madsen, Mikael Rask

    2016-01-01

    , in order to answer is not yet another partisan suggestion, but rather an attempt at making intelligible both the oppositions and the possibilities of synthesis between normative and empirical approaches to law. Based on our assessment and rational reconstruction of current arguments and positions, we...... therefore outline a taxonomy consisting of the following three basic, ideal-types in terms of the epistemological understanding of the interface of law and empirical studies: toleration, synthesis and replacement. This tripartite model proves useful with a view to teasing out and better articulating...

  16. Upgrade, rebuild or replace?

    International Nuclear Information System (INIS)

    Forbes, C.A.

    1990-01-01

    Ageing reactor simulators present some tough decisions for utility managers. Although most utilities have chosen the cheaper, upgrading solution as the best compromise between costs and outage length, some US utilities have found that for them, replacement represents the best option. Simulators may be less than ten years old, but they have limited instructor systems, older low fidelity models that cannot reproduce important training scenarios, and out of date, difficult to maintain computers that do not permit much expansion of the models anyway. Perhaps worse than this is the possibility that the simulator may no longer be a faithful reproduction of the referenced plant, or have poor (or non-existent) documentation. (author)

  17. Steam-generator replacement sets new marks

    International Nuclear Information System (INIS)

    Beck, R.L.

    1995-01-01

    This article describes how, in one of the most successful steam-generator replacement experiences at PWRs worldwide, the V C Summer retrofit exceeded plant goals for critical-path duration, radiation, exposure, and radwaste generation. Intensive planning and teamwork, combined with the firm support of station management and the use of mockups to prepare the work crews for activity in a radiological environment, were key factors in the record performance achieved by South Carolina Electric and Gas Co (SCE and G) in replacing three steam generators at V C Summer nuclear station. The 97-day, two-hour breaker-to-breaker replacement outage -- including an eight-day delay for repair of leak in a small-bore seal-injection line of a reactor coolant pump (unrelated to the replacement activities) -- surpassed the project goal by over one day. Moreover, the outage was only 13 hours shy of the world record held by Virginia Power Co's North Anna Unit 1

  18. Cadmium plating replacements

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, M.J.; Groshart, E.C.

    1995-03-01

    The Boeing Company has been searching for replacements to cadmium plate. Two alloy plating systems seem close to meeting the needs of a cadmium replacement. The two alloys, zinc-nickel and tin-zinc are from alloy plating baths; both baths are neutral pH. The alloys meet the requirements for salt fog corrosion resistance, and both alloys excel as a paint base. Currently, tests are being performed on standard fasteners to compare zinc-nickel and tin-zinc on threaded hardware where cadmium is heavily used. The Hydrogen embrittlement propensity of the zinc-nickel bath has been tested, and just beginning for the tin-zinc bath. Another area of interest is the electrical properties on aluminum for tin-zinc and will be discussed. The zinc-nickel alloy plating bath is in production in Boeing Commercial Airplane Group for non-critical low strength steels. The outlook is promising that these two coatings will help The Boeing Company significantly reduce its dependence on cadmium plating.

  19. REPLACEMENT OF FRENCH CARDS

    CERN Multimedia

    Human Resources Division

    2001-01-01

    The French Ministry of Foreign Affairs has informed the Organization that it is shortly to replace all diplomatic cards, special cards and employment permits ('attestations de fonctions') now held by members of the personnel and their families. Between 2 July and 31 December 2001, these cards are to be replaced by secure, computerized equivalents. A 'personnel office' stamped photocopy of the old cards may continue to be used until 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015), between 8:30 and 12:30, in order to fill a 'fiche individuelle' form (in black ink only), which has to be personally signed by themselves and another separately signed by members of their family, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format (signed on the back) The French card in their possession an A4 photocopy of the same Fre...

  20. Volume of Requests for Internet Medicare Replacement Cards

    Data.gov (United States)

    Social Security Administration — This dataset provides monthly volumes at the national level from federal fiscal year 2008 onwards for Internet Medicare Replacement Card. The dataset includes only...

  1. Effect of Barley and Enzyme on Performance, Carcass, Enzyme Activity and Digestion Parameters of Broilers

    Directory of Open Access Journals (Sweden)

    majid kalantar

    2016-04-01

    Full Text Available Introduction Corn has been recently used for producing ethanol fuel in the major corn-producing countries such as the US and Brazil. Recent diversion of corn for biofuel production along with the increased world's demand for this feedstuff has resulted in unprecedented rise in feed cost for poultry worldwide. Alternative grains such as wheat and barley can be successfully replaced for corn in poultry diets. These cereal grains can locally grow in many parts of the world as they have remarkably lower water requirement than corn. Wheat and barley are generally used as major sources of energy in poultry diets. Though the major components of these grains are starch and proteins, they have considerable content of non-starch polysaccharides (NSPs, derived from the cell walls (Olukosi et al. 2007; Mirzaie et al. 2012. NSPs are generally considered as anti-nutritional factors (Jamroz et al. 2002. The content and structure of NSP polymers vary between different grains, which consequently affect their nutritive value (Olukosi et al. 2007.Wheat and barley are generally used as major sources of energy in poultry diets. The major components of these grains are starch and proteins, they have considerable content of non-starch polysaccharides (NSPs, derived from the cell walls. NSPs are generally considered as anti-nutritional factors. The content and structure of NSP polymers vary between different grains, which consequently affect their nutritive value. The major part of NSPs in barley comprises polymers of (1→3 (1→4-β- glucans which could impede growth factors and consequently carcass quality through lowering the rate and amount of available nutrients in the mucosal surface of the intestinal. Materials and Methods This experiment was conducted to evaluate the effect of corn and barley based diets supplemented with multi-enzyme on growth, carcass, pancreas enzyme activity and physiological characteristics of broilers. A total number of 375 one day old

  2. Replace with abstract title

    Science.gov (United States)

    Coho, Aleksander; Kioussis, Nicholas

    2003-03-01

    We use the semidiscrete variational generelized Peierls-Nabarro model to study the effect of Cu alloying on the dislocation properties of Al. First-principles density functional theory (DFT) is used to calculate the generalized-stacking-fault (GSF) energy surface when a plane, on which one in four Al atoms has been replaced with a Cu atom, slips over a pure Al plane. Various dislocation core properties (core width, energy, Peierls stress, dissociation tendency) are investigated and compared with the pure Al case. Cu alloying lowers the intrinsic stacking fault (ISF) energy, which makes dislocations more likely to dissociate into partials. We also try to understand the lowering of ISF energy in terms of Al-Cu and Al-Al bond formation and braking during shearing along the direction. From the above we draw conclusions about the effects of Cu alloying on the mechanical properties of Al.

  3. The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

    Science.gov (United States)

    Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

    2017-05-01

    Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

  4. Strategic vehicle fleet management - the replacement problem

    Directory of Open Access Journals (Sweden)

    Adam Redmer

    2016-03-01

    Full Text Available Background: Fleets constitute the most important production means in transportation. Their appropriate management is crucial for all companies having transportation duties. The paper is the third one of a series of three papers that the author dedicates to the strategic vehicle fleet management topic. Material and methods: The paper discusses ways of building replacement strategies for companies' fleets of vehicles. It means deciding for how long to exploit particular vehicles in a fleet (the fleet replacement problem - FR. The essence of this problem lies in the minimization of vehicle / fleet exploitation costs by balancing ownership and utilization costs and taking into account budget limitations. In the paper an original mathematical model (an optimization method allowing for the FR analysis is proposed. Results: An application of the proposed optimization method in a real-life decision situation (the case study within the Polish environment and the obtained solution are presented. The solution shows that there exist optimal exploitation periods of particular vehicles in a fleet. However, combination of them gives a replacement plan for an entire fleet violating budget constraints. But it is possible to adjust individual age to replacement of particular vehicles to fulfill budget constraints without losing economical optimality of a developed replacement plan for an entire fleet. Conclusions: The paper is the last one of a series of three papers that the author dedicated to the strategic vehicle fleet management topic including the following managerial decision problems: MAKE-or-BUY, sizing / composition and replacement.

  5. A Theoretical Approach to Engineering a New Enzyme

    International Nuclear Information System (INIS)

    Anderson, Greg; Gomatam, Ravi; Behera, Raghu N.

    2016-01-01

    Density function theory, a subfield of quantum mechanics (QM), in combination with molecular mechanics (MM) has opened the way to engineer new artificial enzymes. Herein, we report theoretical calculations done using QM/MM to examine whether the regioselectivity and rate of chlorination of the enzyme chloroperoxidase can be improved by replacing the vanadium of this enzyme with niobium through dialysis. Our calculations show that a niobium substituted chloroperoxidase will be able to enter the initial steps of the catalytic cycle for chlorination. Although the protonation state of the niobium substituted enzyme is calculated to be different from than that of the natural vanadium substituted enzyme, our calculations show that the catalytic cycle can still proceed forward. Using natural bond orbitals, we analyse the electronic differences between the niobium substituted enzyme and the natural enzyme. We conclude by briefly examining how good of a model QM/MM provides for understanding the mechanism of catalysis of chloroperoxidase. (paper)

  6. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  7. 21 CFR 864.9400 - Stabilized enzyme solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Stabilized enzyme solution. 864.9400 Section 864... and Blood Products § 864.9400 Stabilized enzyme solution. (a) Identification. A stabilized enzyme... enzyme solutions include papain, bromelin, ficin, and trypsin. (b) Classification. Class II (performance...

  8. Fish condensate as effective replacer of fish meal protein in diet for striped snakehead, Channa striata (Bloch).

    Science.gov (United States)

    Wattanakul, Wattana; Wattanakul, Uraiwan; Thongprajukaew, Karun; Muenpo, Chutchawan

    2017-02-01

    The optimal protein replacement of fish meal (FM) by fish condensate (FC) was investigated in striped snakehead, Channa striata (Bloch) (1.78 ± 0.02 g initial weight). The FM-based diet (0FC) was replaced by substituting protein from FC for 100 (100FC), 200 (200FC), 300 (300FC), 400 (400FC), 500 (500FC) or 600 (600FC) g kg -1 of the FM, and a commercial diet (CD) for carnivorous fish was included for comparison. The experiment was conducted indoors under completely randomized design (8 treatments × 3 replications × 60 fish per pond) over a 6-month trial. There were no significant differences in water quality during the experiment. The fish fed with 500FC had superior growth performance and feed utilization. This dietary treatment gave similar levels to all observed specific activities of digestive enzymes as did baseline 0FC. Survival, carcass composition, hematological parameters and liver histopathology were not negatively impacted by this protein replacement level. Economic analysis also supports the use of this by-product as a potent protein replacer in striped snakehead diet. Findings from the current study indicate that a 500 g kg -1 protein replacement of FM by FC is near optimal for striped snakehead, and similar use of it in the aquafeed of other species appears worth further studies.

  9. Molecular replacement then and now

    International Nuclear Information System (INIS)

    Scapin, Giovanna

    2013-01-01

    A brief overview, with examples, of the evolution of molecular-replacement methods and models over the past few years is presented. The ‘phase problem’ in crystallography results from the inability to directly measure the phases of individual diffracted X-ray waves. While intensities are directly measured during data collection, phases must be obtained by other means. Several phasing methods are available (MIR, SAR, MAD, SAD and MR) and they all rely on the premise that phase information can be obtained if the positions of marker atoms in the unknown crystal structure are known. This paper is dedicated to the most popular phasing method, molecular replacement (MR), and represents a personal overview of the development, use and requirements of the methodology. The first description of noncrystallographic symmetry as a tool for structure determination was explained by Rossmann and Blow [Rossmann & Blow (1962 ▶), Acta Cryst.15, 24–31]. The term ‘molecular replacement’ was introduced as the name of a book in which the early papers were collected and briefly reviewed [Rossmann (1972 ▶), The Molecular Replacement Method. New York: Gordon & Breach]. Several programs have evolved from the original concept to allow faster and more sophisticated searches, including six-dimensional searches and brute-force approaches. While careful selection of the resolution range for the search and the quality of the data will greatly influence the outcome, the correct choice of the search model is probably still the main criterion to guarantee success in solving a structure using MR. Two of the main parameters used to define the ‘best’ search model are sequence identity (25% or more) and structural similarity. Another parameter that may often be undervalued is the quality of the probe: there is clearly a relationship between the quality and the correctness of the chosen probe and its usefulness as a search model. Efforts should be made by all structural biologists to

  10. Antenna Controller Replacement Software

    Science.gov (United States)

    Chao, Roger Y.; Morgan, Scott C.; Strain, Martha M.; Rockwell, Stephen T.; Shimizu, Kenneth J.; Tehrani, Barzia J.; Kwok, Jaclyn H.; Tuazon-Wong, Michelle; Valtier, Henry; Nalbandi, Reza; hide

    2010-01-01

    The Antenna Controller Replacement (ACR) software accurately points and monitors the Deep Space Network (DSN) 70-m and 34-m high-efficiency (HEF) ground-based antennas that are used to track primarily spacecraft and, periodically, celestial targets. To track a spacecraft, or other targets, the antenna must be accurately pointed at the spacecraft, which can be very far away with very weak signals. ACR s conical scanning capability collects the signal in a circular pattern around the target, calculates the location of the strongest signal, and adjusts the antenna pointing to point directly at the spacecraft. A real-time, closed-loop servo control algorithm performed every 0.02 second allows accurate positioning of the antenna in order to track these distant spacecraft. Additionally, this advanced servo control algorithm provides better antenna pointing performance in windy conditions. The ACR software provides high-level commands that provide a very easy user interface for the DSN operator. The operator only needs to enter two commands to start the antenna and subreflector, and Master Equatorial tracking. The most accurate antenna pointing is accomplished by aligning the antenna to the Master Equatorial, which because of its small size and sheltered location, has the most stable pointing. The antenna has hundreds of digital and analog monitor points. The ACR software provides compact displays to summarize the status of the antenna, subreflector, and the Master Equatorial. The ACR software has two major functions. First, it performs all of the steps required to accurately point the antenna (and subreflector and Master Equatorial) at the spacecraft (or celestial target). This involves controlling the antenna/ subreflector/Master-Equatorial hardware, initiating and monitoring the correct sequence of operations, calculating the position of the spacecraft relative to the antenna, executing the real-time servo control algorithm to maintain the correct position, and

  11. Enzymes for improved biomass conversion

    Science.gov (United States)

    Brunecky, Roman; Himmel, Michael E.

    2016-02-02

    Disclosed herein are enzymes and combinations of the enzymes useful for the hydrolysis of cellulose and the conversion of biomass. Methods of degrading cellulose and biomass using enzymes and cocktails of enzymes are also disclosed.

  12. Radiological evaluation of failed total hip replacement

    International Nuclear Information System (INIS)

    Raspa, V.; Aldrovandi, S.; Pompei, G.

    1988-01-01

    The retrospective study of 50 operated cases of cemented total hip replacement and a review of the literature enabled the authors to define the radiological features of the above-mentioned condition. These features include one or more of the following signs: calcar reabsorption, lacunar erosions, modified relatioships between the prosthesis components, sepsis and loosening, periarticular calcifications dislocation and fracture of prosthesis components. Careful evaluation of these radiological features is extremely important for both an early diagnosis of failed total hip replacement and the choice of an adequate surgical treatment

  13. Testosterone Replacement, Muscle Strength, and Physical Function

    Directory of Open Access Journals (Sweden)

    You-Seon Nam

    2018-05-01

    Full Text Available Muscle strength and physical function decrease in older men, as do testosterone levels. Nonetheless, the effects of testosterone replacement therapy on muscle strength and physical function remain inconclusive and equivocal. We conducted a rapid systematic review, the results of which showed that testosterone replacement does not affect muscle strength (measured by hand grip strength and leg muscle strength, although it may increase physical function (measured by the 6-minute walk test, Physical Activity Scale for the Elderly score, and other physical performance tests. However, most of the studies were conducted in the United States or Europe and did not include participants from Asian or other ethnic backgrounds; therefore, further studies are needed to evaluate the effects of testosterone replacement in a broader population.

  14. Severe Heterotopic Ossification following Total Knee Replacement

    Directory of Open Access Journals (Sweden)

    Alexander L. Dodds

    2014-01-01

    Full Text Available Although the incidence of minor heterotopic ossification is probably higher than what is usually expected, severe heterotopic ossification (HO is an extremely rare event following total knee replacement surgery. We present the case of a 66-year-old woman who initially had achieved an excellent range of motion following bilateral uncemented rotating platform total knee replacement, before presenting with pain and loss of range of motion at 2 months after surgery. Severe HO was diagnosed on X-rays. Treatment consisted of nonoperative measures only, including physiotherapy with hydrotherapy and anti-inflammatories. She eventually regained her range of motion when seen at 8 months after operation. This case illustrates that nonoperative treatment without the use of radiotherapy or surgery can be used to safely resolve stiffness caused by HO after total knee replacement.

  15. Hip Replacement: MedlinePlus Health Topic

    Science.gov (United States)

    ... invasive hip replacement (Medical Encyclopedia) Also in Spanish Topic Image MedlinePlus Email Updates Get Hip Replacement updates ... replacement - precautions Minimally invasive hip replacement Related Health Topics Hip Injuries and Disorders National Institutes of Health ...

  16. Profiling the orphan enzymes

    Science.gov (United States)

    2014-01-01

    The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called “orphan enzymes”. The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to “local orphan enzymes” that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new

  17. Prediction of Wild-type Enzyme Characteristics

    DEFF Research Database (Denmark)

    Geertz-Hansen, Henrik Marcus

    of biotechnology, including enzyme discovery and characterization. This work presents two articles on sequence-based discovery and functional annotation of enzymes in environmental samples, and two articles on analysis and prediction of enzyme thermostability and cofactor requirements. The first article presents...... a sequence-based approach to discovery of proteolytic enzymes in metagenomes obtained from the Polar oceans. We show that microorganisms living in these extreme environments of constant low temperature harbour genes encoding novel proteolytic enzymes with potential industrial relevance. The second article...... presents a web server for the processing and annotation of functional metagenomics sequencing data, tailored to meet the requirements of non-bioinformaticians. The third article presents analyses of the molecular determinants of enzyme thermostability, and a feature-based prediction method of the melting...

  18. Production of Enzymes from Marine Actinobacteria.

    Science.gov (United States)

    Zhao, X Q; Xu, X N; Chen, L Y

    Marine actinobacteria are well recognized for their capabilities to produce valuable natural products, which have great potential for applications in medical, agricultural, and fine chemical industries. In addition to producing unique enzymes responsible for biosynthesis of natural products, many marine actinobacteria also produce hydrolytic enzymes which are able to degrade various biopolymers, such as cellulose, xylan, and chitin. These enzymes are important to produce biofuels and biochemicals of interest from renewable biomass. In this chapter, the recent reports of novel enzymes produced by marine actinobacteria are reviewed, and advanced technologies that can be applied to search for novel marine enzymes as well as for improved enzyme production by marine actinobacteria are summarized, which include ribosome engineering, genome mining, as well as synthetic biology studies. © 2016 Elsevier Inc. All rights reserved.

  19. Educating My Replacement

    Science.gov (United States)

    Tarter, Jill

    , in partnership with the dedicated teachers out there, I think I can help promote the critical thinking skills and scientific literacy of the next generation of voters. Hopefully, I can also help train my replacement to be a better scientist, capable of seizing all the opportunities generated by advances in technology and our improved understanding of the universe to craft search strategies with greater probability of success than those I have initiated.

  20. Transforming Normal Programs by Replacement

    NARCIS (Netherlands)

    Bossi, Annalisa; Pettorossi, A.; Cocco, Nicoletta; Etalle, Sandro

    1992-01-01

    The replacement transformation operation, already defined in [28], is studied wrt normal programs. We give applicability conditions able to ensure the correctness of the operation wrt Fitting's and Kunen's semantics. We show how replacement can mimic other transformation operations such as thinning,

  1. Optimal timing for intravascular administration set replacement.

    Science.gov (United States)

    Ullman, Amanda J; Cooke, Marie L; Gillies, Donna; Marsh, Nicole M; Daud, Azlina; McGrail, Matthew R; O'Riordan, Elizabeth; Rickard, Claire M

    2013-09-15

    The tubing (administration set) attached to both venous and arterial catheters may contribute to bacteraemia and other infections. The rate of infection may be increased or decreased by routine replacement of administration sets. This review was originally published in 2005 and was updated in 2012. The objective of this review was to identify any relationship between the frequency with which administration sets are replaced and rates of microbial colonization, infection and death. We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6), MEDLINE (1950 to June 2012), CINAHL (1982 to June 2012), EMBASE (1980 to June 2012), reference lists of identified trials and bibliographies of published reviews. The original search was performed in February 2004. We also contacted researchers in the field. We applied no language restriction. We included all randomized or controlled clinical trials on the frequency of venous or arterial catheter administration set replacement in hospitalized participants. Two review authors assessed all potentially relevant studies. We resolved disagreements between the two review authors by discussion with a third review author. We collected data for seven outcomes: catheter-related infection; infusate-related infection; infusate microbial colonization; catheter microbial colonization; all-cause bloodstream infection; mortality; and cost. We pooled results from studies that compared different frequencies of administration set replacement, for instance, we pooled studies that compared replacement ≥ every 96 hours versus every 72 hours with studies that compared replacement ≥ every 48 hours versus every 24 hours. We identified 26 studies for this updated review, 10 of which we excluded; six did not fulfil the inclusion criteria and four did not report usable data. We extracted data from the remaining 18 references (16 studies) with 5001 participants: study designs included neonate and adult

  2. Minimally invasive aortic valve replacement

    DEFF Research Database (Denmark)

    Foghsgaard, Signe; Schmidt, Thomas Andersen; Kjaergard, Henrik K

    2009-01-01

    In this descriptive prospective study, we evaluate the outcomes of surgery in 98 patients who were scheduled to undergo minimally invasive aortic valve replacement. These patients were compared with a group of 50 patients who underwent scheduled aortic valve replacement through a full sternotomy...... operations were completed as mini-sternotomies, 4 died later of noncardiac causes. The aortic cross-clamp and perfusion times were significantly different across all groups (P replacement...... is an excellent operation in selected patients, but its true advantages over conventional aortic valve replacement (other than a smaller scar) await evaluation by means of randomized clinical trial. The "extended mini-aortic valve replacement" operation, on the other hand, is a risky procedure that should...

  3. The composition of accessory enzymes of Penicillium chrysogenum P33 revealed by secretome and synergistic effects with commercial cellulase on lignocellulose hydrolysis.

    Science.gov (United States)

    Yang, Yi; Yang, Jinshui; Liu, Jiawen; Wang, Ruonan; Liu, Liang; Wang, Fengqin; Yuan, Hongli

    2018-06-01

    Herein, we report the secretome of Penicillium chrysogenum P33 under induction of lignocellulose for the first time. A total of 356 proteins were identified, including complete cellulases and numerous hemicellulases. Supplementing a commercial cellulase with increasing dosage of P33 enzyme cocktail from 1 to 5 mg/g substrate increased the release of reducing sugars from delignified corn stover by 21.4% to 106.8%. When 50% cellulase was replaced by P33 enzyme cocktail, release of reducing sugars was 78.6% higher than with cellulase alone. Meanwhile, glucan and xylan conversion was increased by 37% and 106%, respectively. P33 enzyme cocktail also enhanced commercial cellulase hydrolysis against four different delignified lignocellulosic biomass. These findings demonstrate that mixing appropriate amount of P33 cocktail with cellulase improves polysaccharide hydrolysis, suggesting P33 enzymes have great potential for industrial applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Metagenomics as a Tool for Enzyme Discovery: Hydrolytic Enzymes from Marine-Related Metagenomes.

    Science.gov (United States)

    Popovic, Ana; Tchigvintsev, Anatoly; Tran, Hai; Chernikova, Tatyana N; Golyshina, Olga V; Yakimov, Michail M; Golyshin, Peter N; Yakunin, Alexander F

    2015-01-01

    This chapter discusses metagenomics and its application for enzyme discovery, with a focus on hydrolytic enzymes from marine metagenomic libraries. With less than one percent of culturable microorganisms in the environment, metagenomics, or the collective study of community genetics, has opened up a rich pool of uncharacterized metabolic pathways, enzymes, and adaptations. This great untapped pool of genes provides the particularly exciting potential to mine for new biochemical activities or novel enzymes with activities tailored to peculiar sets of environmental conditions. Metagenomes also represent a huge reservoir of novel enzymes for applications in biocatalysis, biofuels, and bioremediation. Here we present the results of enzyme discovery for four enzyme activities, of particular industrial or environmental interest, including esterase/lipase, glycosyl hydrolase, protease and dehalogenase.

  5. Artificial Enzymes, "Chemzymes"

    DEFF Research Database (Denmark)

    Bjerre, Jeannette; Rousseau, Cyril Andre Raphaël; Pedersen, Lavinia Georgeta M

    2008-01-01

    Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models that successf......Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models...... that successfully perform Michaelis-Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called...... "Chemzymes", based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well...

  6. Magnetically responsive enzyme powders

    Energy Technology Data Exchange (ETDEWEB)

    Pospiskova, Kristyna, E-mail: kristyna.pospiskova@upol.cz [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Safarik, Ivo, E-mail: ivosaf@yahoo.com [Regional Centre of Advanced Technologies and Materials, Palacky University, Slechtitelu 11, 783 71 Olomouc (Czech Republic); Department of Nanobiotechnology, Institute of Nanobiology and Structural Biology of GCRC, Na Sadkach 7, 370 05 Ceske Budejovice (Czech Republic)

    2015-04-15

    Powdered enzymes were transformed into their insoluble magnetic derivatives retaining their catalytic activity. Enzyme powders (e.g., trypsin and lipase) were suspended in various liquid media not allowing their solubilization (e.g., saturated ammonium sulfate and highly concentrated polyethylene glycol solutions, ethanol, methanol, 2-propanol) and subsequently cross-linked with glutaraldehyde. Magnetic modification was successfully performed at low temperature in a freezer (−20 °C) using magnetic iron oxides nano- and microparticles prepared by microwave-assisted synthesis from ferrous sulfate. Magnetized cross-linked enzyme powders were stable at least for two months in water suspension without leakage of fixed magnetic particles. Operational stability of magnetically responsive enzymes during eight repeated reaction cycles was generally without loss of enzyme activity. Separation of magnetically modified cross-linked powdered enzymes from reaction mixtures was significantly simplified due to their magnetic properties. - Highlights: • Cross-linked enzyme powders were prepared in various liquid media. • Insoluble enzymes were magnetized using iron oxides particles. • Magnetic iron oxides particles were prepared by microwave-assisted synthesis. • Magnetic modification was performed under low (freezing) temperature. • Cross-linked powdered trypsin and lipase can be used repeatedly for reaction.

  7. Enzymes in Fermented Fish.

    Science.gov (United States)

    Giyatmi; Irianto, H E

    Fermented fish products are very popular particularly in Southeast Asian countries. These products have unique characteristics, especially in terms of aroma, flavor, and texture developing during fermentation process. Proteolytic enzymes have a main role in hydrolyzing protein into simpler compounds. Fermentation process of fish relies both on naturally occurring enzymes (in the muscle or the intestinal tract) as well as bacteria. Fermented fish products processed using the whole fish show a different characteristic compared to those prepared from headed and gutted fish. Endogenous enzymes like trypsin, chymotrypsin, elastase, and aminopeptidase are the most involved in the fermentation process. Muscle tissue enzymes like cathepsins, peptidases, transaminases, amidases, amino acid decarboxylases, glutamic dehydrogenases, and related enzymes may also play a role in fish fermentation. Due to the decreased bacterial number during fermentation, contribution of microbial enzymes to proteolysis may be expected prior to salting of fish. Commercial enzymes are supplemented during processing for specific purposes, such as quality improvement and process acceleration. In the case of fish sauce, efforts to accelerate fermentation process and to improve product quality have been studied by addition of enzymes such as papain, bromelain, trypsin, pepsin, and chymotrypsin. © 2017 Elsevier Inc. All rights reserved.

  8. Patients Unicondylar Knee Replacement vs. Total Knee Replacement

    OpenAIRE

    Hedra Eskander

    2017-01-01

    The aim of this review article is to analyse the clinical effectiveness of total knee replacement (TKR) compared to unicondylar knee replacement (UKR) on patients. In terms of survival rates, revision rates and postoperative complications. The keywords used were: knee arthroplasty. Nearly three thousand articles were found on 25 August 2016. Of those, only twenty-five were selected and reviewed because they were strictly focused on the topic of this article. Compared with those who have TKR, ...

  9. An overview of technologies for immobilization of enzymes and surface analysis techniques for immobilized enzymes

    Science.gov (United States)

    Mohamad, Nur Royhaila; Marzuki, Nur Haziqah Che; Buang, Nor Aziah; Huyop, Fahrul; Wahab, Roswanira Abdul

    2015-01-01

    The current demands of sustainable green methodologies have increased the use of enzymatic technology in industrial processes. Employment of enzyme as biocatalysts offers the benefits of mild reaction conditions, biodegradability and catalytic efficiency. The harsh conditions of industrial processes, however, increase propensity of enzyme destabilization, shortening their industrial lifespan. Consequently, the technology of enzyme immobilization provides an effective means to circumvent these concerns by enhancing enzyme catalytic properties and also simplify downstream processing and improve operational stability. There are several techniques used to immobilize the enzymes onto supports which range from reversible physical adsorption and ionic linkages, to the irreversible stable covalent bonds. Such techniques produce immobilized enzymes of varying stability due to changes in the surface microenvironment and degree of multipoint attachment. Hence, it is mandatory to obtain information about the structure of the enzyme protein following interaction with the support surface as well as interactions of the enzymes with other proteins. Characterization technologies at the nanoscale level to study enzymes immobilized on surfaces are crucial to obtain valuable qualitative and quantitative information, including morphological visualization of the immobilized enzymes. These technologies are pertinent to assess efficacy of an immobilization technique and development of future enzyme immobilization strategies. PMID:26019635

  10. Filter replacement lifetime prediction

    Science.gov (United States)

    Hamann, Hendrik F.; Klein, Levente I.; Manzer, Dennis G.; Marianno, Fernando J.

    2017-10-25

    Methods and systems for predicting a filter lifetime include building a filter effectiveness history based on contaminant sensor information associated with a filter; determining a rate of filter consumption with a processor based on the filter effectiveness history; and determining a remaining filter lifetime based on the determined rate of filter consumption. Methods and systems for increasing filter economy include measuring contaminants in an internal and an external environment; determining a cost of a corrosion rate increase if unfiltered external air intake is increased for cooling; determining a cost of increased air pressure to filter external air; and if the cost of filtering external air exceeds the cost of the corrosion rate increase, increasing an intake of unfiltered external air.

  11. Enzyme based soil stabilization for unpaved road construction

    Directory of Open Access Journals (Sweden)

    Renjith Rintu

    2017-01-01

    Full Text Available Enzymes as soil stabilizers have been successfully used in road construction in several countries for the past 30 years. However, research has shown that the successful application of these enzymes is case specific, emphasizing that enzyme performance is dependent on subgrade soil type, condition and the type of enzyme used as the stabilizer. A universal standard or a tool for road engineers to assess the performance of stabilized unbound pavements using well-established enzymes is not available to date. The research aims to produce a validated assessment tool which can be used to predict strength enhancement within a generalized statistical framework. The objective of the present study is to identify new materials for developing the assessment tool which supports enzyme based stabilization, as well as to identify the correct construction sequence for such new materials. A series of characterization tests were conducted on several soil types obtained from proposed construction sites. Having identified the suitable soil type to mix with the enzyme, a trial road construction has been performed to investigate the efficiency of the enzyme stabilization along with the correct construction sequence. The enzyme stabilization has showed significant improvement of the road performance as was evidenced from the test results which were based on site soil obtained before and after stabilization. The research will substantially benefit the road construction industry by not only replacing traditional construction methods with economical/reliable approaches, but also eliminating site specific tests required in current practice of enzyme based road construction.

  12. 9 CFR 82.15 - Replacement birds and poultry.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Replacement birds and poultry. 82.15... AGRICULTURE INTERSTATE TRANSPORTATION OF ANIMALS (INCLUDING POULTRY) AND ANIMAL PRODUCTS EXOTIC NEWCASTLE DIS- EASE (END) AND CHLAMYDIOSIS Exotic Newcastle Disease (END) § 82.15 Replacement birds and poultry. Birds...

  13. Turbine Replacement Issue

    Science.gov (United States)

    This document may be of assistance in applying the New Source Review (NSR) air permitting regulations including the Prevention of Significant Deterioration (PSD) requirements. This document is part of the NSR Policy and Guidance Database. Some documents in the database are a scanned or retyped version of a paper photocopy of the original. Although we have taken considerable effort to quality assure the documents, some may contain typographical errors. Contact the office that issued the document if you need a copy of the original.

  14. Nuclear reactor fuel replacement system

    International Nuclear Information System (INIS)

    Kayano, Hiroyuki; Joge, Toshio.

    1976-01-01

    Object: To permit the direction in which a fuel replacement unit is moving to be monitored by the operator. Structure: When a fuel replacement unit approaches an intermediate goal position preset in the path of movement, renewal of data display on a goal position indicator is made every time the goal position is changed. With this renewal, the prevailing direction of movement of the fuel replacement unit can be monitored by the operator. When the control of movement is initiated, the co-ordinates of the intermediate goal point A are displayed on a goal position indicator. When the replacement unit reaches point A, the co-ordinates of the next intermediate point B are displayed, and upon reaching point B the co-ordinates of the (last) goal point C are displayed. (Nakamura, S.)

  15. Slab replacement maturity guidelines : [summary].

    Science.gov (United States)

    2014-04-01

    Concrete sets in hours at moderate temperatures, : but the bonds that make concrete strong continue : to mature over days to years. However, for : replacement concrete slabs on highways, it is : crucial that concrete develop enough strength : within ...

  16. Prolonged Intermittent Renal Replacement Therapy.

    Science.gov (United States)

    Edrees, Fahad; Li, Tingting; Vijayan, Anitha

    2016-05-01

    Prolonged intermittent renal replacement therapy (PIRRT) is becoming an increasingly popular alternative to continuous renal replacement therapy in critically ill patients with acute kidney injury. There are significant practice variations in the provision of PIRRT across institutions, with respect to prescription, technology, and delivery of therapy. Clinical trials have generally demonstrated that PIRRT is non-inferior to continuous renal replacement therapy regarding patient outcomes. PIRRT offers cost-effective renal replacement therapy along with other advantages such as early patient mobilization and decreased nursing time. However, due to lack of standardization of the procedure, PIRRT still poses significant challenges, especially pertaining to appropriate drug dosing. Future guidelines and clinical trials should work toward developing consensus definitions for PIRRT and ensure optimal delivery of therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  17. Replacement of sub-systems

    International Nuclear Information System (INIS)

    Rosen, S.E.

    1992-01-01

    This paper describes a number of quality aspects related to replacement of important systems or components in a nuclear power station. Reference is given to the steam generator replacement and power uprating performed at Ringhals 2 in Sweden in 1989. Since quality is a wide concept there has been put special emphasis in this paper to the important aspects that traditionally are not connected to quality. (author) 1 fig

  18. Feeder replacement tooling and processes

    International Nuclear Information System (INIS)

    Mallozzi, R.; Goslin, R.; Pink, D.; Askari, A.

    2008-01-01

    Primary heat transport system feeder integrity has become a concern at some CANDU nuclear plants as a result of thinning caused by flow accelerated corrosion (FAC). Feeder inspections are indicating that life-limiting wall thinning can occur in the region between the Grayloc hub weld and second elbow of some outlet feeders. In some cases it has become necessary to replace thinned sections of affected feeders to restore feeder integrity to planned end of life. Atomic Energy of Canada Limited (AECL) and Babcock and Wilcox Canada Ltd. (B and W) have developed a new capability for replacement of single feeders at any location on the reactor face without impacting or interrupting operation of neighbouring feeders. This new capability consists of deploying trained crews with specialized tools and procedures for feeder replacements during planned outages. As may be expected, performing single feeder replacement in the congested working environment of an operational CANDU reactor face involves overcoming many challenges with respect to access to feeders, available clearances for tooling, and tooling operation and performance. This paper describes some of the challenges encountered during single feeder replacements and actions being taken by AECL and B and W to promote continuous improvement of feeder replacement tooling and processes and ensure well-executed outages. (author)

  19. Enzymes in Human Milk.

    Science.gov (United States)

    Dallas, David C; German, J Bruce

    2017-01-01

    Milk proteins are a complex and diverse source of biological activities. Beyond their function, intact milk proteins also act as carriers of encrypted functional sequences that, when released as peptides, exert biological functions, including antimicrobial and immunomodulatory activity, which could contribute to the infant's competitive success. Research has now revealed that the release of these functional peptides begins within the mammary gland itself. A complex array of proteases produced in mother's milk has been shown to be active in the milk, releasing these peptides. Moreover, our recent research demonstrates that these milk proteases continue to digest milk proteins within the infant's stomach, possibly even to a larger extent than the infant's own proteases. As the neonate has relatively low digestive capacity, the activity of milk proteases in the infant may provide important assistance to digesting milk proteins. The coordinated release of these encrypted sequences is accomplished by selective proteolytic action provided by an array of native milk proteases and infant-produced enzymes. The task for scientists is now to discover the selective advantages of this protein-protease-based peptide release system. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  20. CANDU-PHW fuel channel replacement experience

    International Nuclear Information System (INIS)

    Dunn, J.T.; Kakaria, B.K.

    1982-09-01

    One of the main characteristics of the CANDU pressurized heavy water reactor is the use of pressure tubes rather than one large pressure vessel to contain the fuel and coolant. This provides an inherent design capability to permit their replacement in an expeditious manner, without seriously affecting the high capacity factors of the reactor units. Of th eight Ontario Hydro commercial nuclear generating units, the lifetime performance places seven of them (including two that have had some of their fuel channels replaced), in the top ten positions in the world's large nuclear-electric unit performance ranking. Pressure tube cracks in the rolled joint region have resulted in 70 fuel channels being replaced in three reactor units, the latest being at the Bruce Nuclear Generating Station 'A', Unit 2 in February 1982. The rolled joint design and rolling procedures have been modified to eliminate this problem on CANDU units subsequent to Bruce 'A'. This paper describes the CANDU pressure tube performance history and expectations, and the tooling and procedures used to carry out the fuel channel replacement

  1. Replacing Fortran Namelists with JSON

    Science.gov (United States)

    Robinson, T. E., Jr.

    2017-12-01

    Maintaining a log of input parameters for a climate model is very important to understanding potential causes for answer changes during the development stages. Additionally, since modern Fortran is now interoperable with C, a more modern approach to software infrastructure to include code written in C is necessary. Merging these two separate facets of climate modeling requires a quality control for monitoring changes to input parameters and model defaults that can work with both Fortran and C. JSON will soon replace namelists as the preferred key/value pair input in the GFDL model. By adding a JSON parser written in C into the model, the input can be used by all functions and subroutines in the model, errors can be handled by the model instead of by the internal namelist parser, and the values can be output into a single file that is easily parsable by readily available tools. Input JSON files can handle all of the functionality of a namelist while being portable between C and Fortran. Fortran wrappers using unlimited polymorphism are crucial to allow for simple and compact code which avoids the need for many subroutines contained in an interface. Errors can be handled with more detail by providing information about location of syntax errors or typos. The output JSON provides a ground truth for values that the model actually uses by providing not only the values loaded through the input JSON, but also any default values that were not included. This kind of quality control on model input is crucial for maintaining reproducibility and understanding any answer changes resulting from changes in the input.

  2. Replacement Power Facility site selection report

    Energy Technology Data Exchange (ETDEWEB)

    Wike, L.D.; Toole, G.L.; Specht, W.L.

    1992-06-01

    The Department of Energy (DOE) has proposed the construction and operation of a Replacement Power Facility (RPF) for supplementing and replacing existing sources of steam and possibly electricity at the Savannah River Site (SRS). DOE is preparing an Environmental Impact Statement (EIS) for this project As part of the impact analysis of the proposed action, the EIS will include a detailed description of the environment where the RPF will be constructed. This description must be specific to the recommended site at SRS, which contains more than 300 square miles of land including streams, lakes, impoundments, wetlands, and upland areas. A formal site-selection process was designed and implemented to identify the preferred RPF site.

  3. Enzymic lactose hydrolysis

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J J; Brand, J C

    1980-01-01

    Acid or enzymic hydrolysis can be used to hydrolyze lactose. Advantages of both are compared and details of enzymic hydrolysis using yeast or fungal enzymes given. The new scheme outlined involves recycling lactase. Because lactose and lactase react to ultrafiltration (UF) membranes differently separation is possible. Milk or milk products are ultrafiltered to separate a concentrate from a lactose-rich permeate which is treated with lactase in a reactor until hydrolysis reaches a required level. The lactase can be removed by UF as it does not permeate the membrane, and it is recycled back to the reactor. Permeate from the second UF stage may or may not be recombined with the concentrate from the first stage to produce a low lactose product (analysis of a typical low-lactose dried whole milk is given). Batch or continuous processes are explained and a batch process without enzyme recovery is discussed. (Refs. 4).

  4. Indicators: Sediment Enzymes

    Science.gov (United States)

    Sediment enzymes are proteins that are produced by microorganisms living in the sediment or soil. They are indicators of key ecosystem processes and can help determine which nutrients are affecting the biological community of a waterbody.

  5. Enzyme Vs. Extremozyme -32 ...

    Indian Academy of Sciences (India)

    Enzymes are biocatalytic protein molecules that enhance the rates of ... to physical forces (hydrogen bonds, hydrophobic 1, electrostatic and Van der ... conformation. In 1995 ... surface against 14.7% in Klenow poll (some of the hydrophobic.

  6. Practical steady-state enzyme kinetics.

    Science.gov (United States)

    Lorsch, Jon R

    2014-01-01

    Enzymes are key components of most biological processes. Characterization of enzymes is therefore frequently required during the study of biological systems. Steady-state kinetics provides a simple and rapid means of assessing the substrate specificity of an enzyme. When combined with site-directed mutagenesis (see Site-Directed Mutagenesis), it can be used to probe the roles of particular amino acids in the enzyme in substrate recognition and catalysis. Effects of interaction partners and posttranslational modifications can also be assessed using steady-state kinetics. This overview explains the general principles of steady-state enzyme kinetics experiments in a practical, rather than theoretical, way. Any biochemistry textbook will have a section on the theory of Michaelis-Menten kinetics, including derivations of the relevant equations. No specific enzymatic assay is described here, although a method for monitoring product formation or substrate consumption over time (an assay) is required to perform the experiments described. © 2014 Elsevier Inc. All rights reserved.

  7. Replacement team of mining drilling rigs

    OpenAIRE

    Hamodi, Hussan; Lundberg, Jan

    2014-01-01

    This paper presents a practical model to calculate the optimal replacement time (ORT) of drilling rigs used in underground mining. As a case study, cost data for drilling rig were collected over four years from a Swedish mine. The cost data include acquisition, operating, maintenance and downtime costs when using a redundant rig. A discount rate is used to determine the value of these costs over time. The study develops an optimisation model to identify the ORT of a mining drilling rig which ...

  8. Maintenance and replacement policies under technological obsolescence

    International Nuclear Information System (INIS)

    Clavareau, Julien; Labeau, Pierre-Etienne

    2009-01-01

    The technological obsolescence of a unit is characterized by the existence of challenger units displaying identical functionalities, but with higher performances. This paper aims to define and model in a realistic way, possible maintenance policies of a system including replacement strategies when one type of challenger unit is available. The comparison of these possible strategies is performed based on a Monte Carlo estimation of the costs they incur

  9. Maintenance and replacement policies under technological obsolescence

    Energy Technology Data Exchange (ETDEWEB)

    Clavareau, Julien [Service de Metrologie Nucleaire, Universite Libre de Bruxelles, Av. Franklin Roosevelt 50, CP165/84 Bruxelles B-1050 (Belgium)], E-mail: jclavare@ulb.ac.be; Labeau, Pierre-Etienne [Service de Metrologie Nucleaire, Universite Libre de Bruxelles, Av. Franklin Roosevelt 50, CP165/84 Bruxelles B-1050 (Belgium)], E-mail: pelabeau@ulb.ac.be

    2009-02-15

    The technological obsolescence of a unit is characterized by the existence of challenger units displaying identical functionalities, but with higher performances. This paper aims to define and model in a realistic way, possible maintenance policies of a system including replacement strategies when one type of challenger unit is available. The comparison of these possible strategies is performed based on a Monte Carlo estimation of the costs they incur.

  10. Measurement of enzyme activity.

    Science.gov (United States)

    Harris, T K; Keshwani, M M

    2009-01-01

    To study and understand the nature of living cells, scientists have continually employed traditional biochemical techniques aimed to fractionate and characterize a designated network of macromolecular components required to carry out a particular cellular function. At the most rudimentary level, cellular functions ultimately entail rapid chemical transformations that otherwise would not occur in the physiological environment of the cell. The term enzyme is used to singularly designate a macromolecular gene product that specifically and greatly enhances the rate of a chemical transformation. Purification and characterization of individual and collective groups of enzymes has been and will remain essential toward advancement of the molecular biological sciences; and developing and utilizing enzyme reaction assays is central to this mission. First, basic kinetic principles are described for understanding chemical reaction rates and the catalytic effects of enzymes on such rates. Then, a number of methods are described for measuring enzyme-catalyzed reaction rates, which mainly differ with regard to techniques used to detect and quantify concentration changes of given reactants or products. Finally, short commentary is given toward formulation of reaction mixtures used to measure enzyme activity. Whereas a comprehensive treatment of enzymatic reaction assays is not within the scope of this chapter, the very core principles that are presented should enable new researchers to better understand the logic and utility of any given enzymatic assay that becomes of interest.

  11. Enzyme Engineering for In Situ Immobilization.

    Science.gov (United States)

    Rehm, Fabian B H; Chen, Shuxiong; Rehm, Bernd H A

    2016-10-14

    Enzymes are used as biocatalysts in a vast range of industrial applications. Immobilization of enzymes to solid supports or their self-assembly into insoluble particles enhances their applicability by strongly improving properties such as stability in changing environments, re-usability and applicability in continuous biocatalytic processes. The possibility of co-immobilizing various functionally related enzymes involved in multistep synthesis, conversion or degradation reactions enables the design of multifunctional biocatalyst with enhanced performance compared to their soluble counterparts. This review provides a brief overview of up-to-date in vitro immobilization strategies while focusing on recent advances in enzyme engineering towards in situ self-assembly into insoluble particles. In situ self-assembly approaches include the bioengineering of bacteria to abundantly form enzymatically active inclusion bodies such as enzyme inclusions or enzyme-coated polyhydroxyalkanoate granules. These one-step production strategies for immobilized enzymes avoid prefabrication of the carrier as well as chemical cross-linking or attachment to a support material while the controlled oriented display strongly enhances the fraction of accessible catalytic sites and hence functional enzymes.

  12. Prioritization methodology for chemical replacement

    Science.gov (United States)

    Cruit, Wendy; Goldberg, Ben; Schutzenhofer, Scott

    1995-01-01

    Since United States of America federal legislation has required ozone depleting chemicals (class 1 & 2) to be banned from production, The National Aeronautics and Space Administration (NASA) and industry have been required to find other chemicals and methods to replace these target chemicals. This project was initiated as a development of a prioritization methodology suitable for assessing and ranking existing processes for replacement 'urgency.' The methodology was produced in the form of a workbook (NASA Technical Paper 3421). The final workbook contains two tools, one for evaluation and one for prioritization. The two tools are interconnected in that they were developed from one central theme - chemical replacement due to imposed laws and regulations. This workbook provides matrices, detailed explanations of how to use them, and a detailed methodology for prioritization of replacement technology. The main objective is to provide a GUIDELINE to help direct the research for replacement technology. The approach for prioritization called for a system which would result in a numerical rating for the chemicals and processes being assessed. A Quality Function Deployment (QFD) technique was used in order to determine numerical values which would correspond to the concerns raised and their respective importance to the process. This workbook defines the approach and the application of the QFD matrix. This technique: (1) provides a standard database for technology that can be easily reviewed, and (2) provides a standard format for information when requesting resources for further research for chemical replacement technology. Originally, this workbook was to be used for Class 1 and Class 2 chemicals, but it was specifically designed to be flexible enough to be used for any chemical used in a process (if the chemical and/or process needs to be replaced). The methodology consists of comparison matrices (and the smaller comparison components) which allow replacement technology

  13. Replacement research reactor for Australia

    International Nuclear Information System (INIS)

    Miller, Ross

    1998-01-01

    In 1992, the Australian Government commissioned a review into the need for a replacement research reactor. That review concluded that in about years, if certain conditions were met, the Government could make a decision in favour of a replacement reactor. A major milestone was achieved when, on 3 September 1997, the Australian Government announced the construction of a replacement research reactor at the site of Australia's existing research reactor HIFAR, subject to the satisfactory outcome of an environmental assessment process. The reactor will be have the dual purpose of providing a first class facility for neutron beam research as well as providing irradiation facilities for both medical isotope production and commercial irradiations. The project is scheduled for completion before the end of 2005. (author)

  14. Joint replacement in Zambia: A review of Hip & Knee Replacement ...

    African Journals Online (AJOL)

    Methods: Data captured by the different variables entered into the Joint Register covering the pre-op, intra-op and post-op period of all total hip and knee replacement surgery done at the ZIOH from 1998 to 2010 was entered into a spreadsheet after verification with individual patient medical records. This was then imported ...

  15. Comprehensive Care For Joint Replacement Model - Provider Data

    Data.gov (United States)

    U.S. Department of Health & Human Services — Comprehensive Care for Joint Replacement Model - provider data. This data set includes provider data for two quality measures tracked during an episode of care:...

  16. Software-based annunciator replacement: a tale of two projects

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, G.T., E-mail: simmongt@westinghouse.com [Westinghouse Electric Company LLC, Cranberry Township, PA (United States)

    2015-07-01

    Annunciator upgrade projects are often included as parts of operating plant life extension projects as the systems are old and replacement parts are difficult to source. This paper contains case studies of the software-based annunciator replacement projects at the Westinghouse SNUPPS training simulator in Pennsylvania and the Axpo Beznau nuclear power plant in Switzerland. Software-based annunciator systems can offer a number of feature enhancements including improved readability and operator awareness, easy configuration, alarm suppression features, and alarm management at operator workstations. This paper provides an overview of each project and discusses advantages, challenges, and lessons learned from both annunciator-replacement projects. (author)

  17. Software-based annunciator replacement: a tale of two projects

    International Nuclear Information System (INIS)

    Simmons, G.T.

    2015-01-01

    Annunciator upgrade projects are often included as parts of operating plant life extension projects as the systems are old and replacement parts are difficult to source. This paper contains case studies of the software-based annunciator replacement projects at the Westinghouse SNUPPS training simulator in Pennsylvania and the Axpo Beznau nuclear power plant in Switzerland. Software-based annunciator systems can offer a number of feature enhancements including improved readability and operator awareness, easy configuration, alarm suppression features, and alarm management at operator workstations. This paper provides an overview of each project and discusses advantages, challenges, and lessons learned from both annunciator-replacement projects. (author)

  18. Random-walk enzymes

    Science.gov (United States)

    Mak, Chi H.; Pham, Phuong; Afif, Samir A.; Goodman, Myron F.

    2015-09-01

    Enzymes that rely on random walk to search for substrate targets in a heterogeneously dispersed medium can leave behind complex spatial profiles of their catalyzed conversions. The catalytic signatures of these random-walk enzymes are the result of two coupled stochastic processes: scanning and catalysis. Here we develop analytical models to understand the conversion profiles produced by these enzymes, comparing an intrusive model, in which scanning and catalysis are tightly coupled, against a loosely coupled passive model. Diagrammatic theory and path-integral solutions of these models revealed clearly distinct predictions. Comparison to experimental data from catalyzed deaminations deposited on single-stranded DNA by the enzyme activation-induced deoxycytidine deaminase (AID) demonstrates that catalysis and diffusion are strongly intertwined, where the chemical conversions give rise to new stochastic trajectories that were absent if the substrate DNA was homogeneous. The C →U deamination profiles in both analytical predictions and experiments exhibit a strong contextual dependence, where the conversion rate of each target site is strongly contingent on the identities of other surrounding targets, with the intrusive model showing an excellent fit to the data. These methods can be applied to deduce sequence-dependent catalytic signatures of other DNA modification enzymes, with potential applications to cancer, gene regulation, and epigenetics.

  19. HST Replacement Battery Initial Performance

    Science.gov (United States)

    Krol, Stan; Waldo, Greg; Hollandsworth, Roger

    2009-01-01

    The Hubble Space Telescope (HST) original Nickel-Hydrogen (NiH2) batteries were replaced during the Servicing Mission 4 (SM4) after 19 years and one month on orbit.The purpose of this presentation is to highlight the findings from the assessment of the initial sm4 replacement battery performance. The batteries are described, the 0 C capacity is reviewed, descriptions, charts and tables reviewing the State Of Charge (SOC) Performance, the Battery Voltage Performance, the battery impedance, the minimum voltage performance, the thermal performance, the battery current, and the battery system recharge ratio,

  20. Insurance for replacement power costs

    International Nuclear Information System (INIS)

    Cleaver, A.

    1980-01-01

    Although careful consideration is given to insurance against physical damage to plant and equipment, little thought is given to the costs that will be incurred in replacing the power that is lost while a relatively efficient system is out of action. The results of an investigation carried out for a generating authority with an installed capacity of about 3000 MW is given. Replacement power costs for different cases of severity of damage range from Pound1.17m per month for damage to central services taking out all four units. (author)

  1. Replacing fuel alignment in Germany

    International Nuclear Information System (INIS)

    Poetz, F.; Kalthoff, W.

    1991-01-01

    Up to the end of 1989 varying numbers of broken fuel alignment pins were detected in several German PWRs (80 broken pins in all). The distribution of these broken pins over the core cross-section was more or less random. The problem was due to the stress corrosion cracking of the pin material and was restricted to individual pins. It was concluded that all fuel alignment pins made of Inconel X-750 should be replaced. The development of a new pin, more resistant to intergranular stress corrosion, and the replacement technique are outlined. (author)

  2. Optimal glucocorticoid replacement in adrenal insufficiency.

    Science.gov (United States)

    Øksnes, Marianne; Ross, Richard; Løvås, Kristian

    2015-01-01

    Adrenal insufficiency (glucocorticoid deficiency) comprises a group of rare diseases, including primary adrenal insufficiency, secondary adrenal insufficiency and congenital adrenal hyperplasia. Lifesaving glucocorticoid therapy was introduced over 60 years ago, but since then a number of advances in treatment have taken place. Specifically, little is known about short- and long-term treatment effects, and morbidity and mortality. Over the past decade, systematic cohort and registry studies have described reduced health-related quality of life, an unfavourable metabolic profile and increased mortality in patients with adrenal insufficiency, which may relate to unphysiological glucocorticoid replacement. This has led to the development of new modes of replacement that aim to mimic normal glucocorticoid physiology. Here, evidence for the inadequacy of conventional glucocorticoid therapy and recent developments in treatment are reviewed, with an emphasis on primary adrenal insufficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. The efficacy of using exogenous enzymes cocktail on production, egg quality, egg nutrients and blood metabolites of laying hens fed distiller's dried grains with solubles.

    Science.gov (United States)

    Abd El-Hack, M E; Chaudhry, M T; Mahrose, K M; Noreldin, A; Emam, M; Alagawany, M

    2018-04-01

    An experiment was performed using 120 Hisex Brown laying hens for evaluating the effects of different inclusion levels of corn distiller's dried grains with solubles (DDGS) as a replacement of soybean meal (SBM) with or without enzyme cocktail on performance, egg quality, egg nutrients and blood metabolites in laying hens through 22-42 weeks of age. A 4 × 2 factorial design experiment was performed including four substitution levels of DDGS (0, 250, 500 and 750 g/kg respectively) and two enzyme cocktail levels (0 and 250 mg/kg diet). The used enzyme in this study "Gallazyme" composed of xylanase, Trichoderma longibrachiatum (600 units/g), protease, Bacillus subtilis (8,000 units/g) and amylase and Bacillus amyloliquofaciens (800 units/g). The control diet showed the best feed efficiency followed by the intermediate levels of DDGS. The lowest value of feed efficiency was found in the group fed the highest level of DDGS. Enzyme addition improved feed efficiency and decreased laying rate. Increasing DDGS levels was associated with albumin and shell thickness increases. Dietary DDGS depressed all egg components except the organic matter which maximised in enzyme-treated groups. Increasing DDGS level was accompanied by increase in yolk cholesterol and total lipids. No significant impacts were detected with enzymes supplementation on yolk lipids profile. Excepting serum calcium and phosphorous, all serum constituents increased with increasing level of DDGS. Using enzyme markedly depressed serum ammonia by 15.02% and increased calcium by 6.44% compared with enzyme-free diets. Interaction between DDGS and enzyme was significant on most of studied parameters. It could be concluded that using enzyme cocktail in DDGS-based diets may improve feed efficiency and egg quality, in addition to lowering blood ammonia and increasing blood calcium. It is recommended to substitute SBM by DDGS up to 500 g/kg diet. © 2017 Blackwell Verlag GmbH.

  4. Psychosocial determinants of outcomes in knee replacement.

    Science.gov (United States)

    Lopez-Olivo, Maria A; Landon, Glenn C; Siff, Sherwin J; Edelstein, David; Pak, Chong; Kallen, Michael A; Stanley, Melinda; Zhang, Hong; Robinson, Kausha C; Suarez-Almazor, Maria E

    2011-10-01

    To identify potential psychosocial and educational barriers to clinical success following knee replacement. The authors evaluated 241 patients undergoing total knee replacement, preoperatively and 6 months after surgery. Outcomes included the Western Ontario McMaster (WOMAC) scale and the Knee Society rating system (KSRS). Independent variables included: the medical outcome study-social support scale; depression, anxiety and stress scale; brief COPE inventory; health locus of control; arthritis self-efficacy scale and the life orientation test-revised. Multiple regression models evaluated associations of baseline demographic and psychosocial variables with outcomes at 6 months, controlling for body mass index, comorbidities and baseline outcome scores. Patients' mean age was 65 ± 9 years; 65% were women. Most patients improved outcomes after surgery. Several psychosocial variables were associated with outcomes. Regression analyses indicated lower education, less tangible support, depression, less problem-solving coping, more dysfunctional coping, lower internal locus of control were associated with worse WOMAC scores (R(2) contribution of psychosocial variables for pain 0.07; for function, 0.14). Older age, lower education, depression and less problem-solving coping were associated with poorer total KSRS scores (R(2) contribution of psychosocial variables to total KSRS model 0.09). Psychosocial variables as a set contributed from 25% to 74% of total explained variance across the models tested. Patients' level of education, tangible support, depression, problem-solving coping, dysfunctional coping and internal locus of control were associated with pain and functional outcomes after knee replacement. The findings suggest that, in addition to medical management, perioperative psychosocial evaluation and intervention are crucial in enhancing knee replacement outcomes.

  5. Reactor vessel closure head replacements in 1997

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    The Framatome-Jeumont Industrie consortium have completed in 1997 28 reactor vessel (RV) closure head replacements, including five on 1300 MWe class PWR units. Framatome manages the operations and handles removal and reinstallation of equipment (not including the control rod drive mechanisms (CRDM)) and the requalification tests, while JI, which manufactures the CRDMs, is involved in the CRDM cutting, re-machining and welding operations, using tools of original design, in order to optimize the RV closure head operation in terms of costs, schedule and dosage

  6. Matrix Metalloproteinase Enzyme Family

    Directory of Open Access Journals (Sweden)

    Ozlem Goruroglu Ozturk

    2013-04-01

    Full Text Available Matrix metalloproteinases play an important role in many biological processes such as embriogenesis, tissue remodeling, wound healing, and angiogenesis, and in some pathological conditions such as atherosclerosis, arthritis and cancer. Currently, 24 genes have been identified in humans that encode different groups of matrix metalloproteinase enzymes. This review discuss the members of the matrix metalloproteinase family and their substrate specificity, structure, function and the regulation of their enzyme activity by tissue inhibitors. [Archives Medical Review Journal 2013; 22(2.000: 209-220

  7. Self-powered enzyme micropumps

    Science.gov (United States)

    Sengupta, Samudra; Patra, Debabrata; Ortiz-Rivera, Isamar; Agrawal, Arjun; Shklyaev, Sergey; Dey, Krishna K.; Córdova-Figueroa, Ubaldo; Mallouk, Thomas E.; Sen, Ayusman

    2014-05-01

    Non-mechanical nano- and microscale pumps that function without the aid of an external power source and provide precise control over the flow rate in response to specific signals are needed for the development of new autonomous nano- and microscale systems. Here we show that surface-immobilized enzymes that are independent of adenosine triphosphate function as self-powered micropumps in the presence of their respective substrates. In the four cases studied (catalase, lipase, urease and glucose oxidase), the flow is driven by a gradient in fluid density generated by the enzymatic reaction. The pumping velocity increases with increasing substrate concentration and reaction rate. These rechargeable pumps can be triggered by the presence of specific analytes, which enables the design of enzyme-based devices that act both as sensor and pump. Finally, we show proof-of-concept enzyme-powered devices that autonomously deliver small molecules and proteins in response to specific chemical stimuli, including the release of insulin in response to glucose.

  8. The Effect of Hypotensive Anesthesia on Hepatic Function in Hip Replacement

    OpenAIRE

    Zagrekov V.I.; Zhirova T.A.; Ezhov I.Y.; Taranyuk А.V.

    2011-01-01

    The objective of the work is to assess the influence of spinal and epidural anesthesia with controlled hypotensive effect on hepatic function in patients in total hip replacement. Materials and Methods. There has been studied the dynamics of hepatic enzymes and bilirubin indexes in 80 patients in hip replacement. Depending on the anesthesia method, three groups were considered: with spinal and epidural anesthesia with controlled hypotensive effect and normotensive spinal anesthesia using ...

  9. Testing of Replacement Bag Material

    International Nuclear Information System (INIS)

    Laurinat, J.E.

    1998-01-01

    Recently, the FB-Line bagout material was changed to simplify the processing of sand, slag, and crucible.The results of the strength tests and the outgassing measurements and calculations demonstrate that the proposed replacement nylon bag materials (HRMP and orange anti-static material) are acceptable substitutes for LDPE and the original nylon with respect to mechanical properties

  10. Testosterone replacement in male hypogonadism

    OpenAIRE

    Kalra, Sanjay; Agrawal, Navneet; Kumar, Satish; Sharma, Amit

    2010-01-01

    Sanjay Kalra1, Navneet Agrawal2, Satish Kumar3, Amit Sharma11Department of Endocrinology, Bharti Hospital, Karnal, India; 2Dept of Medicine, GR Medical College, Gwalior, India; 3Clinical Research, EXCEL Life Sciences, NOIDA, IndiaAbstract: This article contains a review of the clinical aspects of testosterone replacement in androgen deficiency of the aging male.Keywords: testosterone, supplementation, hypogonadism, ADAM

  11. The surface science of enzymes

    DEFF Research Database (Denmark)

    Rod, Thomas Holm; Nørskov, Jens Kehlet

    2002-01-01

    One of the largest challenges to science in the coming years is to find the relation between enzyme structure and function. Can we predict which reactions an enzyme catalyzes from knowledge of its structure-or from its amino acid sequence? Can we use that knowledge to modify enzyme function......? To solve these problems we must understand in some detail how enzymes interact with reactants from its surroundings. These interactions take place at the surface of the enzyme and the question of enzyme function can be viewed as the surface science of enzymes. In this article we discuss how to describe...... catalysis by enzymes, and in particular the analogies between enzyme catalyzed reactions and surface catalyzed reactions. We do this by discussing two concrete examples of reactions catalyzed both in nature (by enzymes) and in industrial reactors (by inorganic materials), and show that although analogies...

  12. Structure and function of α-glucan debranching enzymes

    DEFF Research Database (Denmark)

    Møller, Marie Sofie; Henriksen, Anette; Svensson, Birte

    2016-01-01

    α-Glucan debranching enzymes hydrolyse α-1,6-linkages in starch/glycogen, thereby, playing a central role in energy metabolism in all living organisms. They belong to glycoside hydrolase families GH13 and GH57 and several of these enzymes are industrially important. Nine GH13 subfamilies include α......-glucan debranching enzymes; isoamylase and glycogen debranching enzymes (GH13_11); pullulanase type I/limit dextrinase (GH13_12–14); pullulan hydrolase (GH13_20); bifunctional glycogen debranching enzyme (GH13_25); oligo-1 and glucan-1,6-α-glucosidases (GH13_31); pullulanase type II (GH13_39); and α-amylase domains......_39 enzymes could represent a “missing link” between the strictly α-1,6-specific debranching enzymes and the enzymes with dual specificity and α-1,4-linkage preference....

  13. Expression of lignocellulolytic enzymes in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Mellitzer Andrea

    2012-05-01

    Full Text Available Abstract Background Sustainable utilization of plant biomass as renewable source for fuels and chemical building blocks requires a complex mixture of diverse enzymes, including hydrolases which comprise the largest class of lignocellulolytic enzymes. These enzymes need to be available in large amounts at a low price to allow sustainable and economic biotechnological processes. Over the past years Pichia pastoris has become an attractive host for the cost-efficient production and engineering of heterologous (eukaryotic proteins due to several advantages. Results In this paper codon optimized genes and synthetic alcohol oxidase 1 promoter variants were used to generate Pichia pastoris strains which individually expressed cellobiohydrolase 1, cellobiohydrolase 2 and beta-mannanase from Trichoderma reesei and xylanase A from Thermomyces lanuginosus. For three of these enzymes we could develop strains capable of secreting gram quantities of enzyme per liter in fed-batch cultivations. Additionally, we compared our achieved yields of secreted enzymes and the corresponding activities to literature data. Conclusion In our experiments we could clearly show the importance of gene optimization and strain characterization for successfully improving secretion levels. We also present a basic guideline how to correctly interpret the interplay of promoter strength and gene dosage for a successful improvement of the secretory production of lignocellulolytic enzymes in Pichia pastoris.

  14. Magnetically responsive enzyme powders

    Czech Academy of Sciences Publication Activity Database

    Pospišková, K.; Šafařík, Ivo

    2015-01-01

    Roč. 380, APR 2015 (2015), s. 197-200 ISSN 0304-8853 R&D Projects: GA MŠk(CZ) LD13021 Institutional support: RVO:67179843 Keywords : enzyme powders * cross-linking * magnetic modification * magnetic separation * magnetic iron oxides particles * microwave-assisted synthesis Subject RIV: CE - Biochemistry Impact factor: 2.357, year: 2015

  15. Enzyme with rhamnogalacturonase activity.

    NARCIS (Netherlands)

    Kofod, L.V.; Andersen, L.N.; Dalboge, H.; Kauppinen, M.S.; Christgau, S.; Heldt-Hansen, H.P.; Christophersen, C.; Nielsen, P.M.; Voragen, A.G.J.; Schols, H.A.

    1998-01-01

    An enzyme exhibiting rhamnogalacturonase activity, capable of cleaving a rhamnogalacturonan backbone in such a manner that galacturonic acids are left as the non-reducing ends, and which exhibits activity on hairy regions from a soy bean material and/or on saponified hairy regions from a sugar beet

  16. Implantable enzyme amperometric biosensors.

    Science.gov (United States)

    Kotanen, Christian N; Moussy, Francis Gabriel; Carrara, Sandro; Guiseppi-Elie, Anthony

    2012-05-15

    The implantable enzyme amperometric biosensor continues as the dominant in vivo format for the detection, monitoring and reporting of biochemical analytes related to a wide range of pathologies. Widely used in animal studies, there is increasing emphasis on their use in diabetes care and management, the management of trauma-associated hemorrhage and in critical care monitoring by intensivists in the ICU. These frontier opportunities demand continuous indwelling performance for up to several years, well in excess of the currently approved seven days. This review outlines the many challenges to successful deployment of chronically implantable amperometric enzyme biosensors and emphasizes the emerging technological approaches in their continued development. The foreign body response plays a prominent role in implantable biotransducer failure. Topics considering the approaches to mitigate the inflammatory response, use of biomimetic chemistries, nanostructured topographies, drug eluting constructs, and tissue-to-device interface modulus matching are reviewed. Similarly, factors that influence biotransducer performance such as enzyme stability, substrate interference, mediator selection and calibration are reviewed. For the biosensor system, the opportunities and challenges of integration, guided by footprint requirements, the limitations of mixed signal electronics, and power requirements, has produced three systems approaches. The potential is great. However, integration along the multiple length scales needed to address fundamental issues and integration across the diverse disciplines needed to achieve success of these highly integrated systems, continues to be a challenge in the development and deployment of implantable amperometric enzyme biosensor systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Advances in enzyme bioelectrochemistry

    Directory of Open Access Journals (Sweden)

    ANDRESSA R. PEREIRA

    Full Text Available ABSTRACT Bioelectrochemistry can be defined as a branch of Chemical Science concerned with electron-proton transfer and transport involving biomolecules, as well as electrode reactions of redox enzymes. The bioelectrochemical reactions and system have direct impact in biotechnological development, in medical devices designing, in the behavior of DNA-protein complexes, in green-energy and bioenergy concepts, and make it possible an understanding of metabolism of all living organisms (e.g. humans where biomolecules are integral to health and proper functioning. In the last years, many researchers have dedicated itself to study different redox enzymes by using electrochemistry, aiming to understand their mechanisms and to develop promising bioanodes and biocathodes for biofuel cells as well as to develop biosensors and implantable bioelectronics devices. Inside this scope, this review try to introduce and contemplate some relevant topics for enzyme bioelectrochemistry, such as the immobilization of the enzymes at electrode surfaces, the electron transfer, the bioelectrocatalysis, and new techniques conjugated with electrochemistry vising understand the kinetics and thermodynamics of redox proteins. Furthermore, examples of recent approaches in designing biosensors and biofuel developed are presented.

  18. Cold-Adapted Enzymes

    Science.gov (United States)

    Georlette, D.; Bentahir, M.; Claverie, P.; Collins, T.; D'amico, S.; Delille, D.; Feller, G.; Gratia, E.; Hoyoux, A.; Lonhienne, T.; Meuwis, M.-a.; Zecchinon, L.; Gerday, Ch.

    In the last few years, increased attention has been focused on enzymes produced by cold-adapted micro-organisms. It has emerged that psychrophilic enzymes represent an extremely powerful tool in both protein folding investigations and for biotechnological purposes. Such enzymes are characterised by an increased thermosensitivity and, most of them, by a higher catalytic efficiency at low and moderate temperatures, when compared to their mesophilic counterparts. The high thermosensitivity probably originates from an increased flexibility of either a selected area of the molecular edifice or the overall protein structure, providing enhanced abilities to undergo conformational changes during catalysis at low temperatures. Structure modelling and recent crystallographic data have allowed to elucidate the structural parameters that could be involved in this higher resilience. It was demonstrated that each psychrophilic enzyme adopts its own adaptive strategy. It appears, moreover, that there is a continuum in the strategy of protein adaptation to temperature, as the previously mentioned structural parameters are implicated in the stability of thermophilic proteins. Additional 3D crystal structures, site-directed and random mutagenesis experiments should now be undertaken to further investigate the stability-flexibility-activity relationship.

  19. Embedded enzymes catalyse capture

    Science.gov (United States)

    Kentish, Sandra

    2018-05-01

    Membrane technologies for carbon capture can offer economic and environmental advantages over conventional amine-based absorption, but can suffer from limited gas flux and selectivity to CO2. Now, a membrane based on enzymes embedded in hydrophilic pores is shown to exhibit combined flux and selectivity that challenges the state of the art.

  20. Photoperiodism and Enzyme Activity

    Science.gov (United States)

    Queiroz, Orlando; Morel, Claudine

    1974-01-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system. PMID:16658749

  1. ISFET based enzyme sensors

    NARCIS (Netherlands)

    van der Schoot, Bart H.; Bergveld, Piet

    1987-01-01

    This paper reviews the results that have been reported on ISFET based enzyme sensors. The most important improvement that results from the application of ISFETs instead of glass membrane electrodes is in the method of fabrication. Problems with regard to the pH dependence of the response and the

  2. Transdermal testosterone replacement therapy in men

    Directory of Open Access Journals (Sweden)

    Ullah MI

    2014-01-01

    Full Text Available M Iftekhar Ullah,1 Daniel M Riche,1,2 Christian A Koch1,31Department of Medicine, University of Mississippi Medical Center, 2Department of Pharmacy Practice, The University of Mississippi, 3GV (Sonny Montgomery VA Medical Center, Jackson, MS, USAAbstract: Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule.Keywords: hypogonadism, transdermal, testosterone, sexual function, testosterone replacement therapy, estradiol

  3. 25 CFR 700.53 - Dwelling, replacement.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Dwelling, replacement. 700.53 Section 700.53 Indians THE... Policies and Instructions Definitions § 700.53 Dwelling, replacement. The term replacement dwelling means a dwelling selected by the head of a household as a replacement dwelling that meets the criteria of this...

  4. 24 CFR 880.602 - Replacement reserve.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 880.602... Replacement reserve. (a) A replacement reserve must be established and maintained in an interest-bearing account to aid in funding extraordinary maintenance and repair and replacement of capital items. (1) Part...

  5. 24 CFR 891.405 - Replacement reserve.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 891.405....405 Replacement reserve. (a) Establishment of reserve. The Owner shall establish and maintain a replacement reserve to aid in funding extraordinary maintenance and repair and replacement of capital items...

  6. 24 CFR 891.855 - Replacement reserves.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserves. 891.855... § 891.855 Replacement reserves. (a) The mixed-finance owner shall establish and maintain a replacement... the funds will be used to pay for capital replacement costs for the Section 202 or 811 supportive...

  7. A Bayesian perspective on some replacement strategies

    International Nuclear Information System (INIS)

    Mazzuchi, Thomas A.; Soyer, Refik

    1996-01-01

    In this paper we present a Bayesian decision theoretic approach for determining optimal replacement strategies. This approach enables us to formally incorporate, express, and update our uncertainty when determining optimal replacement strategies. We develop relevant expressions for both the block replacement protocol with minimal repair and the age replacement protocol and illustrate the use of our approach with real data

  8. Production of fructose-containing syrup with enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Helwiig-Nielsen, B

    1981-01-01

    A review on enzymic processes used for production of fructose- high syrup from starch including liquefaction by alpha-amylase, saccharification by amyloglucosidase, and isomerization with glucose isomerase.

  9. Steam generator replacement: a story of continuous improvement

    International Nuclear Information System (INIS)

    Sills, M.S.; Wilkerson, R.

    2009-01-01

    This paper provides a review of the history of steam generator replacement in the US focusing on the last five years. From the early replacements in the 1980s, there have been major technology improvements resulting in dramatically shorter outages and reduced radiological exposure for workers. Even though the changes for the last five years have been less dramatic, the improvement trend continues. No two steam generator replacement (SGR) projects are the same and there are some major differences including; the access path for the components to containment (is a construction opening in containment required), type of containment, number of steam generators, one piece or two piece replacement, plant type (Westinghouse, CE or B and W) and plant layout. These differences along with other variables such as delays due to plant operations and other activities not related to the steam generator replacement make analysis of performance data difficult. However, trends in outage performance and owner expectations can be identified. How far this trend will go is also discussed. Along with the trend of improved performance, there is also a significant variation in performance. Some of the contributors to this variation are identified. This paper addresses what is required for a successful outage, meeting the increasing expectations and setting new records. The authors will discuss various factors that contribute to the success of a steam generator replacement. These factors include technical issues and, equally important, organizational interface and the role the customer plays. Recommendations are provided for planning a successful steam generator replacement outage. (author)

  10. EFSA Panel on food contact materials, enzymes, flavourings and processing aids (CEF); Scientific Opinion on Flavouring Group Evaluation 23, Revision 2 (FGE.23Rev2): Aliphatic, alicyclic and aromatic ethers including anisole derivatives from chemical groups 15, 16, 22, 26 and 30

    DEFF Research Database (Denmark)

    Larsen, John Christian; Nørby, Karin Kristiane; Beltoft, Vibe Meister

    The European Food Safety Authority (EFSA) asked the Panel on Food Contact Materials, Enzymes, Flavourings and Processing Aids (the Panel) to provide scientific advice to the Commission on the implications for human health of chemically defined flavouring substances used in or on foodstuffs...... in the Member States. In particular, the Panel was requested to evaluate 19 flavouring substances in the Flavouring Group Evaluation 23, Revision 2 (FGE.23Rev2), using the Procedure as referred to in the Commission Regulation (EC) No 1565/2000. These 19 flavouring substances belong to chemical groups 15, 16, 22......-no: 03.022] Industry has informed that it occurs as a mixture of E- & Z-isomers, however, the composition of the mixture has to be specified. Two of the flavouring substances are classified into structural class I, seven are classified into structural class II and 10 are classified into structural class...

  11. Binding affinity and adhesion force of organophosphate hydrolase enzyme with soil particles related to the isoelectric point of the enzyme.

    Science.gov (United States)

    Islam, Shah Md Asraful; Yeasmin, Shabina; Islam, Md Saiful; Islam, Md Shariful

    2017-07-01

    The binding affinity of organophosphate hydrolase enzyme (OphB) with soil particles in relation to the isoelectric point (pI) was studied. Immobilization of OphB with soil particles was observed by confocal microscopy, Fourier transform infrared spectroscopy (FT-IR), and Atomic force microscopy (AFM). The calculated pI of OphB enzyme was increased from 8.69 to 8.89, 9.04 and 9.16 by the single, double and triple mutant of OphB enzyme, respectively through the replacement of negatively charged aspartate with positively charged histidine. Practically, the binding affinity was increased to 5.30%, 11.50%, and 16.80% for single, double and triple mutants, respectively. In contrast, enzyme activity of OphB did not change by the mutation of the enzyme. On the other hand, adhesion forces were gradually increased for wild type OphB enzyme (90 pN) to 96, 100 and 104 pN for single, double and triple mutants of OphB enzyme, respectively. There was an increasing trend of binding affinity and adhesion force by the increase of isoelectric point (pI) of OphB enzyme. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. New seismograph includes filters

    Energy Technology Data Exchange (ETDEWEB)

    1979-11-02

    The new Nimbus ES-1210 multichannel signal enhancement seismograph from EG and G geometrics has recently been redesigned to include multimode signal fillers on each amplifier. The ES-1210F is a shallow exploration seismograph for near subsurface exploration such as in depth-to-bedrock, geological hazard location, mineral exploration, and landslide investigations.

  13. Impact of Bee Venom Enzymes on Diseases and Immune Responses.

    Science.gov (United States)

    Hossen, Md Sakib; Shapla, Ummay Mahfuza; Gan, Siew Hua; Khalil, Md Ibrahim

    2016-12-27

    Bee venom (BV) is used to treat many diseases and exhibits anti-inflammatory, anti-bacterial, antimutagenic, radioprotective, anti-nociceptive immunity promoting, hepatocyte protective and anti-cancer activity. According to the literature, BV contains several enzymes, including phospholipase A2 (PLA2), phospholipase B, hyaluronidase, acid phosphatase and α-glucosidase. Recent studies have also reported the detection of different classes of enzymes in BV, including esterases, proteases and peptidases, protease inhibitors and other important enzymes involved in carbohydrate metabolism. Nevertheless, the physiochemical properties and functions of each enzyme class and their mechanisms remain unclear. Various pharmacotherapeutic effects of some of the BV enzymes have been reported in several studies. At present, ongoing research aims to characterize each enzyme and elucidate their specific biological roles. This review gathers all the current knowledge on BV enzymes and their specific mechanisms in regulating various immune responses and physiological changes to provide a basis for future therapies for various diseases.

  14. Impact of Bee Venom Enzymes on Diseases and Immune Responses

    Directory of Open Access Journals (Sweden)

    Md. Sakib Hossen

    2016-12-01

    Full Text Available Bee venom (BV is used to treat many diseases and exhibits anti-inflammatory, anti-bacterial, antimutagenic, radioprotective, anti-nociceptive immunity promoting, hepatocyte protective and anti-cancer activity. According to the literature, BV contains several enzymes, including phospholipase A2 (PLA2, phospholipase B, hyaluronidase, acid phosphatase and α-glucosidase. Recent studies have also reported the detection of different classes of enzymes in BV, including esterases, proteases and peptidases, protease inhibitors and other important enzymes involved in carbohydrate metabolism. Nevertheless, the physiochemical properties and functions of each enzyme class and their mechanisms remain unclear. Various pharmacotherapeutic effects of some of the BV enzymes have been reported in several studies. At present, ongoing research aims to characterize each enzyme and elucidate their specific biological roles. This review gathers all the current knowledge on BV enzymes and their specific mechanisms in regulating various immune responses and physiological changes to provide a basis for future therapies for various diseases.

  15. Modifications to Replacement Costs System

    International Nuclear Information System (INIS)

    Godec, M.

    1989-01-01

    The purpose of this memorandum is to document the improvements and modifications made to the Replacement Costs of Crude Oil (REPCO) Supply Analysis System. While some of this work was performed under our previous support contract to DOE/ASFE, we are presenting all modifications and improvements are presented here for completeness. The memo primarily documents revisions made to the Lower-48 Onshore Model. Revisions and modifications made to other components and models in the REPCO system which are documented elsewhere are only highlighted in this memo. Generally, the modifications made to the Lower-48 Onshore Model reflect changes that have occurred in domestic drilling, oil field costs, and reserves since 1982, the date of the most recent available data used for the original Replacement Costs report, published in 1985

  16. Results of Austin Moore replacement.

    Directory of Open Access Journals (Sweden)

    Jadhav A

    1996-04-01

    Full Text Available Forty cases of Austin Moore Replacement done for transcervical fractures of the femur in patients were reviewed after a period of 12 to 48 months postoperatively (mean 26 mth. 30 cases (75% had mild to severe pain of non-infective origin, starting as early as 6 months postoperatively. This was irrespective of the make, size or position (varus/valgus of the prosthesis. Though the Aufranc and Sweet clinical scoring was satisfactory in 65% cases, radiological evidence of complications like sinking, protrusion, etc. were seen in majority of the cases. Calcar resorption was seen in 34 cases (85% as early as 4 months postoperatively. Results of THR and bipolar replacement done for transcervical fractures in recent literature show 85% pain-free cases at 5 years. We feel that Austin Moore Replacement should be reserved for patients more than 65 years of age and those who are less active or debilitated because of other factors, because of increased acetabular wear with time in the younger individual. This is corroborated by unsatisfactory results in patients less than 65 years of age (p < 0.05.

  17. BWR control blade replacement strategies

    Energy Technology Data Exchange (ETDEWEB)

    Kennard, M W [Stoller Nuclear Fuel, NAC International, Pleasantville, NY (United States); Harbottle, J E [Stoller Nuclear Fuel, NAC International, Thornbury, Bristol (United Kingdom)

    2000-02-01

    The reactivity control elements in a BWR, the control blades, perform three significant functions: provide shutdown margin during normal and accident operating conditions; provide overall core reactivity control; and provide axial power shaping control. As such, the blades are exposed to the core's neutron flux, resulting in irradiation of blade structural and absorber materials. Since the absorber depletes with time (if B{sub 4}C is used, it also swells) and the structural components undergo various degradation mechanisms (e.g., embrittlement, corrosion), the blades have limits on their operational lifetimes. Consequently, BWR utilities have implemented strategies that aim to maximize blade lifetimes while balancing operational costs, such as extending a refuelling outage to shuffle high exposure blades. This paper examines the blade replacement strategies used by BWR utilities operating in US, Europe and Asia by assembling information related to: the utility's specific blade replacement strategy; the impact the newer blade designs and changes in core operating mode were having on those strategies; the mechanical and nuclear limits that determined those strategies; the methods employed to ensure that lifetime limits were not exceeded during operation; and blade designs used (current and replacement blades). (author)

  18. BWR control blade replacement strategies

    International Nuclear Information System (INIS)

    Kennard, M.W.; Harbottle, J.E.

    2000-01-01

    The reactivity control elements in a BWR, the control blades, perform three significant functions: provide shutdown margin during normal and accident operating conditions; provide overall core reactivity control; and provide axial power shaping control. As such, the blades are exposed to the core's neutron flux, resulting in irradiation of blade structural and absorber materials. Since the absorber depletes with time (if B 4 C is used, it also swells) and the structural components undergo various degradation mechanisms (e.g., embrittlement, corrosion), the blades have limits on their operational lifetimes. Consequently, BWR utilities have implemented strategies that aim to maximize blade lifetimes while balancing operational costs, such as extending a refuelling outage to shuffle high exposure blades. This paper examines the blade replacement strategies used by BWR utilities operating in US, Europe and Asia by assembling information related to: the utility's specific blade replacement strategy; the impact the newer blade designs and changes in core operating mode were having on those strategies; the mechanical and nuclear limits that determined those strategies; the methods employed to ensure that lifetime limits were not exceeded during operation; and blade designs used (current and replacement blades). (author)

  19. Analytic device including nanostructures

    KAUST Repository

    Di Fabrizio, Enzo M.; Fratalocchi, Andrea; Totero Gongora, Juan Sebastian; Coluccio, Maria Laura; Candeloro, Patrizio; Cuda, Gianni

    2015-01-01

    A device for detecting an analyte in a sample comprising: an array including a plurality of pixels, each pixel including a nanochain comprising: a first nanostructure, a second nanostructure, and a third nanostructure, wherein size of the first nanostructure is larger than that of the second nanostructure, and size of the second nanostructure is larger than that of the third nanostructure, and wherein the first nanostructure, the second nanostructure, and the third nanostructure are positioned on a substrate such that when the nanochain is excited by an energy, an optical field between the second nanostructure and the third nanostructure is stronger than an optical field between the first nanostructure and the second nanostructure, wherein the array is configured to receive a sample; and a detector arranged to collect spectral data from a plurality of pixels of the array.

  20. Saskatchewan resources. [including uranium

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    The production of chemicals and minerals for the chemical industry in Saskatchewan are featured, with some discussion of resource taxation. The commodities mentioned include potash, fatty amines, uranium, heavy oil, sodium sulfate, chlorine, sodium hydroxide, sodium chlorate and bentonite. Following the successful outcome of the Cluff Lake inquiry, the uranium industry is booming. Some developments and production figures for Gulf Minerals, Amok, Cenex and Eldorado are mentioned.

  1. Reoperative aortic root replacement: Outcome in a contemporary series.

    Science.gov (United States)

    Esaki, Jiro; Leshnower, Bradley G; Binongo, Jose N; Lasanajak, Yi; McPherson, LaRonica; Thourani, Vinod H; Chen, Edward P

    2017-09-01

    Reoperative aortic root replacement is a challenging procedure associated with significant mortality and morbidity. The purpose of this study was to investigate the outcomes of reoperative aortic root replacement when performed in a number of complex clinical settings and to identify risk factors for operative mortality and long-term survival. From 2006 to 2015, 280 consecutive patients at an academic center underwent reoperative aortic root replacement after a variety of previous aortic or cardiac operations. Logistic regression and extended Cox proportional hazards regression analyses were used to determine risk factors for operative mortality and long-term survival, respectively. The mean age of patients was 52.5 ± 14.1 years. Prior operations included proximal aortic replacement in 113 patients, valve surgery in 162 patients, and coronary artery bypass grafting in 46 patients. Concomitant procedures included arch replacement in 135 patients, coronary artery bypass grafting in 68 patients, and mitral valve repair/replacement in 18 patients. Operative mortality was 14.3%. Five-year survival was 74.0%. Univariable analysis did not find previous root replacement, prior proximal aortic surgery, and concomitant arch replacement to be risk factors for operative mortality. In the multivariable analysis, chronic lung disease, prior myocardial infarction, and concomitant mitral valve surgery were risk factors for operative mortality. Age, peripheral artery disease, emergency, and concomitant mitral valve surgery were risk factors for mortality in the late phase. Reoperative aortic root replacement represents complex procedures carrying significant morbidity and mortality. Chronic lung disease, prior myocardial infarction, and concomitant mitral valve surgery were risk factors for operative mortality. Age, peripheral artery disease, emergency, and concomitant mitral valve surgery were risk factors for long-term mortality. Copyright © 2017 The American Association for

  2. Replacement of Antibodies in Pseudo-ELISAs: Molecularly Imprinted Nanoparticles for Vancomycin Detection.

    Science.gov (United States)

    Canfarotta, Francesco; Smolinska-Kempisty, Katarzyna; Piletsky, Sergey

    2017-01-01

    The enzyme-linked immunosorbent assay (ELISA) is a widely employed analytical test used to quantify a given molecule. It relies on the use of specific antibodies, linked to an enzyme, to target the desired molecule. The reaction between the enzyme and its substrate gives rise to the analytical signal that can be quantified. Thanks to their robustness and low cost, molecularly imprinted polymer nanoparticles (nanoMIPs) are a viable alternative to antibodies. Herein, we describe the synthesis of nanoMIPs imprinted for vancomycin and their subsequent application in an ELISA-like format for direct replacement of antibodies.

  3. Meniscus tear surgery and meniscus replacement

    Science.gov (United States)

    Vaquero, Javier; Forriol, Francisco

    2016-01-01

    Summary Objective the menisci are easily injured and difficult to repair. The aim of this study was to analyze the current state of meniscal surgery aimed at preserving morphology and conserving the biomechanics of the knee to prevent joint degeneration. Methodology a search of the electronic medical literature database Medline was conducted, from http://www.ncbi.nlm.nih.gov/pubmed. The search was not limited by language. Candidate articles were identified by searching for those that included the keywords meniscus, surgery, suture, implant, allograft. The limits were included for clinical research and clinical trials. Basic research was not included. The studies selected were evaluated and classified in three different categories: basic science, reconstruction (suture and meniscectomy) and implants (scaffolds and allograft). Results the consequences of meniscectomy performed at a young age can lead to a joint cartilage degeneration twenty years later. There are few surgical options for the repair of meniscal injuries in order both to preserve the meniscus and to ensure the long term survival of the knee joint, meniscectomy, repair, suturing the tear, or reconstruction, when a meniscal allograft or synthetic substitute is used to replace the meniscus, but the biomechanical properties of the native meniscus are not reproduced entirely by the scaffolds that exist today. Conclusion therapies that successfully repair or replace the meniscus are therefore likely to prevent or delay osteoarthritis progression. PMID:27331034

  4. Extended replacement of the thoracic aorta.

    Science.gov (United States)

    Hino, Yutaka; Okada, Kenji; Oka, Takanori; Inoue, Takeshi; Tanaka, Akiko; Omura, Atsushi; Kano, Hiroya; Okita, Yutaka

    2013-01-01

    We present our experience of total aortic arch replacement. Twenty-nine patients (21 males and 8 females; mean age 63.3 ± 13.3 years) with extended thoracic aortic aneurysms underwent graft replacement. The pathology of the diseased aorta was non-dissecting aneurysm in 11 patients, including one aortitis and aortic dissection in 18 patients (acute type A: one, chronic type A: 11, chronic type B: six). Five patients had Marfan syndrome. In their previous operation, two patients had undergone the Bentall procedure, three had endovascular stenting, one had aortic root replacement with valve sparing and 12 had hemi-arch replacement for acute type A dissection. Approaches to the aneurysm were as follows: posterolateral thoracotomy with rib-cross incision in 16, posterolateral thoracotomy extended to the retroperitoneal abdominal aorta in seven, mid-sternotomy and left pleurotomy in three, anterolateral thoracotomy with partial lower sternotomy in two and clam-shell incision in one patient. Extension of aortic replacement was performed from the aortic root to the descending aorta in 4, from the ascending aorta to the descending aorta in 17 and from the ascending to the abdominal aorta in eight patients. Arterial inflow for cardiopulmonary bypass consisted of the femoral artery in 15 patients, ascending aorta and femoral artery in seven, descending or abdominal aorta in five and ascending aorta in two. Venous drainage site was the femoral vein in 10, pulmonary artery in eight, right atrium in five, femoral artery with right atrium/pulmonary artery in four and pulmonary artery with right atrium in two patients. The operative mortality, 30-day mortality and hospital mortality was one (cardiac arrest due to aneurysm rupture), one (rupture of infected aneurysm) and one (brain contusion), respectively. Late mortality occurred in three patients due to pneumonia, ruptured residual aneurysm and intracranial bleeding. Actuarial survival at 5 years after the operations was 80.6

  5. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes.

    Science.gov (United States)

    Wei, Hui; Wang, Erkang

    2013-07-21

    Over the past few decades, researchers have established artificial enzymes as highly stable and low-cost alternatives to natural enzymes in a wide range of applications. A variety of materials including cyclodextrins, metal complexes, porphyrins, polymers, dendrimers and biomolecules have been extensively explored to mimic the structures and functions of naturally occurring enzymes. Recently, some nanomaterials have been found to exhibit unexpected enzyme-like activities, and great advances have been made in this area due to the tremendous progress in nano-research and the unique characteristics of nanomaterials. To highlight the progress in the field of nanomaterial-based artificial enzymes (nanozymes), this review discusses various nanomaterials that have been explored to mimic different kinds of enzymes. We cover their kinetics, mechanisms and applications in numerous fields, from biosensing and immunoassays, to stem cell growth and pollutant removal. We also summarize several approaches to tune the activities of nanozymes. Finally, we make comparisons between nanozymes and other catalytic materials (other artificial enzymes, natural enzymes, organic catalysts and nanomaterial-based catalysts) and address the current challenges and future directions (302 references).

  6. Being Included and Excluded

    DEFF Research Database (Denmark)

    Korzenevica, Marina

    2016-01-01

    Following the civil war of 1996–2006, there was a dramatic increase in the labor mobility of young men and the inclusion of young women in formal education, which led to the transformation of the political landscape of rural Nepal. Mobility and schooling represent a level of prestige that rural...... politics. It analyzes how formal education and mobility either challenge or reinforce traditional gendered norms which dictate a lowly position for young married women in the household and their absence from community politics. The article concludes that women are simultaneously excluded and included from...... community politics. On the one hand, their mobility and decision-making powers decrease with the increase in the labor mobility of men and their newly gained education is politically devalued when compared to the informal education that men gain through mobility, but on the other hand, schooling strengthens...

  7. NRSA enzyme decomposition model data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microbial enzyme activities measured at more than 2000 US streams and rivers. These enzyme data were then used to predict organic matter decomposition and microbial...

  8. Cellulase enzyme and biomass utilization

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... human population grows and economic development. However, the current .... conditions and the production cost of the related enzyme system. Therefore ... Given the importance of this enzyme to these so many industries,.

  9. Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis.

    Science.gov (United States)

    Muro, Silvia; Schuchman, Edward H; Muzykantov, Vladimir R

    2006-01-01

    Enzyme replacement therapy, a state-of-the-art treatment for many lysosomal storage disorders, relies on carbohydrate-mediated binding of recombinant enzymes to receptors that mediate lysosomal delivery via clathrin-dependent endocytosis. Suboptimal glycosylation of recombinant enzymes and deficiency of clathrin-mediated endocytosis in some lysosomal enzyme-deficient cells limit delivery and efficacy of enzyme replacement therapy for lysosomal disorders. We explored a novel delivery strategy utilizing nanocarriers targeted to a glycosylation- and clathrin-independent receptor, intercellular adhesion molecule (ICAM)-1, a glycoprotein expressed on diverse cell types, up-regulated and functionally involved in inflammation, a hallmark of many lysosomal disorders. We targeted recombinant human acid sphingomyelinase (ASM), deficient in types A and B Niemann-Pick disease, to ICAM-1 by loading this enzyme to nanocarriers coated with anti-ICAM. Anti-ICAM/ASM nanocarriers, but not control ASM or ASM nanocarriers, bound to ICAM-1-positive cells (activated endothelial cells and Niemann-Pick disease patient fibroblasts) via ICAM-1, in a glycosylation-independent manner. Anti-ICAM/ASM nanocarriers entered cells via CAM-mediated endocytosis, bypassing the clathrin-dependent pathway, and trafficked to lysosomes, where delivered ASM displayed stable activity and alleviated lysosomal lipid accumulation. Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease.

  10. Gentilly 2 divider plate replacement

    International Nuclear Information System (INIS)

    Forest, J.; Klisel, E.; McClellan, G.; Schnelder, W.

    1995-01-01

    The steam generators at the Gentilly 2 Nuclear Plant in operation since 1983 were built with primary divider plates of a bolted panel configuration. During a routine outage inspection, it was noted that two bolts had dislodged from the divider and were located lying in the primary head. Subsequent inspections revealed erosion damage to a substantial number of divider plate bolts and to a lesser extent, to the divider plate itself. After further inspection and repair the units were returned to operation, however, it was determined that a permanent replacement of the primary divider plates was going to be necessary. After evaluation of various options, it was decided that the panel type dividers would be replaced with a single piece floating design. The divider itself was to be of a one piece all-welded arrangement to be constructed from individual panels to be brought in through the manways. In view of the strength limitations of the bolted attachment of the upper seat bar to the tubesheet, a new welded seat bar was provided. To counteract erosion concerns, the new divider is fitted with erosion resistant inserts or weld buildup and with improved sealing features in order to minimize leakage and erosion. At an advanced stage in the design and manufacture of the components, the issue of divider strength during LOCA conditions came into focus. Analysis was performed to determine the strength and/or failure characteristics of the divider to a variety of small and large LOCA conditions. The paper describes the diagnosis of the original divider plates and the design, manufacture, field mobilization, installation and subsequent operation of the replacement divider plates. (author)

  11. In Defense of Artificial Replacement.

    Science.gov (United States)

    Shiller, Derek

    2017-06-01

    If it is within our power to provide a significantly better world for future generations at a comparatively small cost to ourselves, we have a strong moral reason to do so. One way of providing a significantly better world may involve replacing our species with something better. It is plausible that in the not-too-distant future, we will be able to create artificially intelligent creatures with whatever physical and psychological traits we choose. Granted this assumption, it is argued that we should engineer our extinction so that our planet's resources can be devoted to making artificial creatures with better lives. © 2017 John Wiley & Sons Ltd.

  12. Enzymes for Enhanced Oil Recovery (EOR)

    Energy Technology Data Exchange (ETDEWEB)

    Nasiri, Hamidreza

    2011-04-15

    Primary oil recovery by reservoir pressure depletion and secondary oil recovery by waterflooding usually result in poor displacement efficiency. As a consequence there is always some trapped oil remaining in oil reservoirs. Oil entrapment is a result of complex interactions between viscous, gravity and capillary forces. Improving recovery from hydrocarbon fields typically involves altering the relative importance of the viscous and capillary forces. The potential of many EOR methods depends on their influence on fluid/rock interactions related to wettability and fluid/fluid interactions reflected in IFT. If the method has the potential to change the interactions favorably, it may be considered for further investigation, i.e. core flooding experiment, pilot and reservoir implementation. Enzyme-proteins can be introduced as an enhanced oil recovery method to improve waterflood performance by affecting interactions at the oil-water-rock interfaces. An important part of this thesis was to investigate how selected enzymes may influence wettability and capillary forces in a crude oil-brine-rock system, and thus possibly contribute to enhanced oil recovery. To investigate further by which mechanisms selected enzyme-proteins may contribute to enhance oil recovery, groups of enzymes with different properties and catalytic functions, known to be interfacially active, were chosen to cover a wide range of possible effects. These groups include (1) Greenzyme (GZ) which is a commercial EOR enzyme and consists of enzymes and stabilizers (surfactants), (2) The Zonase group consists of two types of pure enzyme, Zonase1 and Zonase2 which are protease enzymes and whose catalytic functions are to hydrolyze (breakdown) peptide bonds, (3) The Novozyme (NZ) group consists of three types of pure enzyme, NZ2, NZ3 and NZ6 which are esterase enzymes and whose catalytic functions are to hydrolyze ester bonds, and (4) Alpha-Lactalbumin ( -La) which is an important whey protein. The effect of

  13. Replacement and inspection policies for products with random life cycle

    International Nuclear Information System (INIS)

    Yun, Won Young; Nakagawa, Toshio

    2010-01-01

    In this paper, we consider maintenance policies for products in which the economical life cycle of products is a random variable. First, we study a periodic replacement policy with minimal repair. The system is minimally repaired at failure and is replaced by new one at age T (periodic replacement policy with minimal repair of Barlow and Hunter). The expected present value of total maintenance cost of products with random life cycle is obtained and the optimal replacement interval minimizing the cost is found. Second, we consider an inspection policy for products with random life cycle to detect the system failure. The expected total cost is obtained and the optimal inspection interval is found. Numerical examples are also included.

  14. Optimization on replacement and inspection period of plant equipment

    International Nuclear Information System (INIS)

    Takase, Kentaro; Kasai, Masao

    2004-01-01

    Rationalization of the plant maintenance is one of the main topics being investigated in Japanese nuclear power industries. Optimization of the inspection and replacement period of equipments is effective for the maintenance cost reduction. The more realistic model of the replacement policy is proposed in this study. It is based on the classical replacement policy model and its cost is estimated. Then, to consider the inspection for the maintenance, the formulation that includes the risk concept is discussed. Based on it, two variations of the combination of the inspection and the replacement are discussed and the costs are estimated. In this study the effect of the degradation of the equipment is important. The optimized maintenance policy depends on the existence of significant degradation. (author)

  15. Service water system repair/replacement guidelines: Planning and implementation

    International Nuclear Information System (INIS)

    Frederick, G.J.; Gandy, D.W.; Peterson, A.G. Jr.; Findlan, S.J.

    1993-11-01

    Service water system failures have prompted concerns related to extended power plant operating life and plant availability. Selection and procurement of materials for repair or replacement of piping and components may be the most important factors in improving service water system reliability. The authors examined factors that contribute to reduced SWS reliability. The factors include material selection inadequacies, water treatment problems, operational/maintenance practices, fabrication procedures, environmental degradation mechanisms, and coating problems. The authors investigated material selection for replacement and repair, taking into account fabrication practices, environmental concerns, and cost comparisons of materials. They examined specific components such as piping, pumps, valves, and heat exchangers with regard to material selection and fabrication practice. Although proper material selection is essential in upgrading and maintaining the designed functions of a SWS, it is critical to address SWS repair/replacement activities with a systemwide approach. Degradation of materials in SWS applications are plant specific, depending on factors unique to each site such as geographic location, existing materials, operating procedures, and environment. All these characteristics must be addressed in making repair/replacement decisions. Criteria that must be integrated for successful long-term operation of SWS include the following: Materials selection (upgrade or in-kind replacement), Evaluation of root cause or nature of the failure mechanism, Scope of the repair/replacement activities, Material compatibility of the existing materials, Operational and maintenance procedures, Code or jurisdictional requirements, Economic considerations, Water treatment programs, System design improvements or modifications

  16. Hormone Replacement Therapy and Your Heart

    Science.gov (United States)

    Hormone replacement therapy and your heart Are you taking — or considering — hormone therapy to treat bothersome menopausal symptoms? Understand ... you. By Mayo Clinic Staff Long-term hormone replacement therapy used to be routinely prescribed for postmenopausal ...

  17. Skilled nursing facilities after joint replacement

    Science.gov (United States)

    ... care providers in the weeks before your joint replacement. They can advise you about whether going directly ... of many people who have had a joint replacement? Can they tell you how many? A good ...

  18. Risks of hip and knee replacement

    Science.gov (United States)

    ... is normal to lose blood during and after hip or knee replacement surgery. Some people need a ... clot form are higher during and soon after hip or knee replacement surgery. Sitting or lying down ...

  19. Fleet replacement modeling : final report, July 2009.

    Science.gov (United States)

    2009-07-01

    This project focused on two interrelated areas in equipment replacement modeling for fleets. The first area was research-oriented and addressed a fundamental assumption in engineering economic replacement modeling that all assets providing a similar ...

  20. Long-life slab replacement concrete : [summary].

    Science.gov (United States)

    2015-04-01

    Concrete slab replacement projects in Florida have demonstrated a high incidence of : replacement slab cracking. Causes of cracking have not been reliably determined. University of South Florida researchers : sought to identify the factors or : param...

  1. Long-life slab replacement concrete.

    Science.gov (United States)

    2015-03-01

    This research was initiated following reports of high incidence of cracking on FDOT concrete pavement replacement : slab projects. Field slabs were instrumented for data acquisition from high-early-strength concrete pavement : replacement slabs place...

  2. Digestive enzymes in the alimentary canal of Clarias anguillaris ...

    African Journals Online (AJOL)

    Three groups of digestive enzymes were observed in the alimentary canals of the fingerlings and adults of Clarias anguillaris. The enzymes were carbohydrases including amylase, sucrase, lactase and maltase, proteases including peptase, tryptase and peptidase, and lipase. The activities of the protease were found to be ...

  3. Alpha Adrenergic Induction of Transport of Lysosomal Enzyme across the Blood-Brain Barrier.

    Directory of Open Access Journals (Sweden)

    Akihiko Urayama

    Full Text Available The impermeability of the adult blood-brain barrier (BBB to lysosomal enzymes impedes the ability to treat the central nervous system manifestations of lysosomal storage diseases. Here, we found that simultaneous stimulation of the alpha1 and alpha2 adrenoreceptor restores in adult mice the high rate of transport for the lysosomal enzyme P-GUS that is seen in neonates but lost with development. Beta adrenergics, other monoamines, and acetylcholine did not restore this transport. A high dose (500 microg/mouse of clonidine, a strong alpha2 and weak alpha1 agonist, was able to act as monotherapy in the stimulation of P-GUS transport. Neither use of alpha1 plus alpha2 agonists nor the high dose clonidine disrupted the BBB to albumin. In situ brain perfusion and immunohistochemistry studies indicated that adrengerics act on transporters already at the luminal surface of brain endothelial cells. These results show that adrenergic stimulation, including monotherapy with clonidine, could be key for CNS enzyme replacement therapy.

  4. Ethanol from wood. Cellulase enzyme production

    Energy Technology Data Exchange (ETDEWEB)

    Szengyel, Zsolt

    2000-03-01

    Conversion of biomass to liquid fuels, such as ethanol, has been investigated during the past decades. First due to the oil crisis of the 1970s and lately because of concerns about greenhouse effect, ethanol has been found to be a suitable substitute for gasoline in transportation. Although ethanol is produced in large quantities from corn starch, the conversion of lignocellulosic biomass to ethanol is rather problematic. However, cellulosic raw materials are important as they are available in large quantities from agriculture and forestry. One of the most extensively investigated processes is the enzymatic process, in which fungal cellulolytic enzymes are used to convert the cellulose content of the biomass to glucose, which is then fermented to ethanol. In order to make the raw material accessible to biological attack, it has to be pretreated first. The most successful method, which has been evaluated for various lignocellulosic materials, is the steam pretreatment. In this thesis the utilization of steam pretreated willow (hardwood) and spruce (softwood) was examined for enzyme production using a filamentous fungus T. reesei RUT C30. Various carbon sources originating from the steam pretreated materials have been investigated. The replacement of the solid carbon source with a liquid carbon source, as well as the effect of pH, was studied. The effect of toxic compounds generated during pretreatment was also examined. Comparative study of softwood and hardwood showed that steam pretreated hardwood is a better carbon source than softwood. The hydrolytic potential of enzyme solutions produced on wood derived carbon sources was better compared to commercial cellulases. Also enzyme solutions produced on steam pretreated spruce showed less sensitivity towards toxic compounds formed during steam pretreatment.

  5. Rehabilitation after total joint replacement: a scoping study.

    Science.gov (United States)

    L Snell, Deborah; Hipango, Julia; Sinnott, K Anne; Dunn, Jennifer A; Rothwell, Alastair; Hsieh, C Jean; DeJong, Gerben; Hooper, Gary

    2018-07-01

    The evidence supporting rehabilitation after joint replacement, while vast, is of variable quality making it difficult for clinicians to apply the best evidence to their practice. We aimed to map key issues for rehabilitation following joint replacement, highlighting potential avenues for new research. We conducted a scoping study including research published between January 2013 and December 2016, evaluating effectiveness of rehabilitation following hip and knee total joint replacement. We reviewed this work in the context of outcomes described from previously published research. Thirty individual studies and seven systematic reviews were included, with most research examining the effectiveness of physiotherapy-based exercise rehabilitation after total knee replacement using randomized control trial methods. Rehabilitation after hip and knee replacement whether carried out at the clinic or monitored at home, appears beneficial but type, intensity and duration of interventions were not consistently associated with outcomes. The burden of comorbidities rather than specific rehabilitation approach may better predict rehabilitation outcome. Monitoring of recovery and therapeutic attention appear important but little is known about optimal levels and methods required to maximize outcomes. More work exploring the role of comorbidities and key components of therapeutic attention and the therapy relationship, using a wider range of study methods may help to advance the field. Implications for Rehabilitation Physiotherapy-based exercise rehabilitation after total hip replacement and total knee replacement, whether carried out at the clinic or monitored at home, appears beneficial. Type, intensity, and duration of interventions do not appear consistently associated with outcomes. Monitoring a patient's recovery appears to be an important component. The available research provides limited guidance regarding optimal levels of monitoring needed to achieve gains following hip

  6. 21 CFR 184.1027 - Mixed carbohydrase and protease enzyme product.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Mixed carbohydrase and protease enzyme product. 184... RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1027 Mixed carbohydrase and protease enzyme product. (a) Mixed carbohydrase and protease enzyme product is an enzyme preparation that includes...

  7. B Plant process piping replacement feasibility study

    International Nuclear Information System (INIS)

    Howden, G.F.

    1996-01-01

    Reports on the feasibility of replacing existing embedded process piping with new more corrosion resistant piping between cells and between cells and a hot pipe trench of a Hanford Site style canyon facility. Provides concepts for replacement piping installation, and use of robotics to replace the use of the canyon crane as the primary means of performing/supporting facility modifications (eg, cell lining, pipe replacement, equipment reinstallation) and operational maintenenace

  8. Permanent Quadriplegia Following Replacement of Voice Prosthesis.

    Science.gov (United States)

    Ozturk, Kayhan; Erdur, Omer; Kibar, Ertugrul

    2016-11-01

    The authors presented a patient with quadriplegia caused by cervical spine abscess following voice prosthesis replacement. The authors present the first reported permanent quadriplegia patient caused by voice prosthesis replacement. The authors wanted to emphasize that life-threatening complications may be faced during the replacement of voice prosthesis. Care should be taken during the replacement of voice prosthesis and if some problems have been faced during the procedure patients must be followed closely.

  9. Non-homologous isofunctional enzymes: a systematic analysis of alternative solutions in enzyme evolution.

    Science.gov (United States)

    Omelchenko, Marina V; Galperin, Michael Y; Wolf, Yuri I; Koonin, Eugene V

    2010-04-30

    Evolutionarily unrelated proteins that catalyze the same biochemical reactions are often referred to as analogous - as opposed to homologous - enzymes. The existence of numerous alternative, non-homologous enzyme isoforms presents an interesting evolutionary problem; it also complicates genome-based reconstruction of the metabolic pathways in a variety of organisms. In 1998, a systematic search for analogous enzymes resulted in the identification of 105 Enzyme Commission (EC) numbers that included two or more proteins without detectable sequence similarity to each other, including 34 EC nodes where proteins were known (or predicted) to have distinct structural folds, indicating independent evolutionary origins. In the past 12 years, many putative non-homologous isofunctional enzymes were identified in newly sequenced genomes. In addition, efforts in structural genomics resulted in a vastly improved structural coverage of proteomes, providing for definitive assessment of (non)homologous relationships between proteins. We report the results of a comprehensive search for non-homologous isofunctional enzymes (NISE) that yielded 185 EC nodes with two or more experimentally characterized - or predicted - structurally unrelated proteins. Of these NISE sets, only 74 were from the original 1998 list. Structural assignments of the NISE show over-representation of proteins with the TIM barrel fold and the nucleotide-binding Rossmann fold. From the functional perspective, the set of NISE is enriched in hydrolases, particularly carbohydrate hydrolases, and in enzymes involved in defense against oxidative stress. These results indicate that at least some of the non-homologous isofunctional enzymes were recruited relatively recently from enzyme families that are active against related substrates and are sufficiently flexible to accommodate changes in substrate specificity.

  10. Enzymes- An Existing and Promising Tool of Food Processing Industry.

    Science.gov (United States)

    Ray, Lalitagauri; Pramanik, Sunita; Bera, Debabrata

    2016-01-01

    The enzyme catalyzed process technology has enormous potential in the food sectors as indicated by the recent patents studies. It is very well realized that the adaptation of the enzyme catalyzed process depends on the availability of enzyme in affordable prices. Enzymes may be used in different food sectors like dairy, fruits & vegetable processing, meat tenderization, fish processing, brewery and wine making, starch processing and many other. Commercially only a small number of enzymes are used because of several factors including instability of enzymes during processing and high cost. More and more enzymes for food technology are now derived from specially selected or genetically modified microorganisms grown in industrial scale fermenters. Enzymes with microbial source have commercial advantages of using microbial fermentation rather than animal and plant extraction to produce food enzymes. At present only a relatively small number of enzymes are used commercially in food processing. But the number is increasing day by day and field of application will be expanded more and more in near future. The purpose of this review is to describe the practical applications of enzymes in the field of food processing.

  11. 24 CFR 970.31 - Replacement units.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement units. 970.31 Section... PUBLIC HOUSING PROGRAM-DEMOLITION OR DISPOSITION OF PUBLIC HOUSING PROJECTS § 970.31 Replacement units. Notwithstanding any other provision of law, replacement public housing units may be built on the original public...

  12. Diagenetic replacement of Micas by Carbonates

    NARCIS (Netherlands)

    Oele, E.

    1961-01-01

    In the Ordovician sandstones of the Cantabrian Mountains a replacement of the micas by carbonate minerals could be observed. The absence of metamorphic minerals suggests a diagenetic replacement. This is supported by the finding of the same type of replacement in some undisturbed Pliocene sediments

  13. 47 CFR 13.17 - Replacement license.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Replacement license. 13.17 Section 13.17 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL COMMERCIAL RADIO OPERATORS General § 13.17 Replacement... request a replacement. The application must be accompanied by the required fee and submitted to the...

  14. 24 CFR 891.605 - Replacement reserve.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 891.605... 8 Assistance § 891.605 Replacement reserve. (a) Establishment of reserve. The Borrower shall establish and maintain a replacement reserve to aid in funding extraordinary maintenance, and repair and...

  15. 24 CFR 891.745 - Replacement reserve.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Replacement reserve. 891.745... and Individuals-Section 162 Assistance § 891.745 Replacement reserve. The general requirements for the replacement reserve are provided in § 891.605. For projects funded under §§ 891.655 through 891.790, the...

  16. 24 CFR 572.125 - Replacement reserves.

    Science.gov (United States)

    2010-04-01

    ...) Homeownership Program Requirements-Implementation Grants § 572.125 Replacement reserves. (a) Purpose. A single replacement reserve may be established for the homeownership program only if HUD determines it is necessary to... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Replacement reserves. 572.125...

  17. Material Science in Cervical Total Disc Replacement

    Science.gov (United States)

    Pham, Martin H.; Mehta, Vivek A.; Tuchman, Alexander; Hsieh, Patrick C.

    2015-01-01

    Current cervical total disc replacement (TDR) designs incorporate a variety of different biomaterials including polyethylene, stainless steel, titanium (Ti), and cobalt-chrome (CoCr). These materials are most important in their utilization as bearing surfaces which allow for articular motion at the disc space. Long-term biological effects of implanted materials include wear debris, host inflammatory immune reactions, and osteolysis resulting in implant failure. We review here the most common materials used in cervical TDR prosthetic devices, examine their bearing surfaces, describe the construction of the seven current cervical TDR devices that are approved for use in the United States, and discuss known adverse biological effects associated with long-term implantation of these materials. It is important to appreciate and understand the variety of biomaterials available in the design and construction of these prosthetics and the considerations which guide their implementation. PMID:26523281

  18. Material Science in Cervical Total Disc Replacement

    Directory of Open Access Journals (Sweden)

    Martin H. Pham

    2015-01-01

    Full Text Available Current cervical total disc replacement (TDR designs incorporate a variety of different biomaterials including polyethylene, stainless steel, titanium (Ti, and cobalt-chrome (CoCr. These materials are most important in their utilization as bearing surfaces which allow for articular motion at the disc space. Long-term biological effects of implanted materials include wear debris, host inflammatory immune reactions, and osteolysis resulting in implant failure. We review here the most common materials used in cervical TDR prosthetic devices, examine their bearing surfaces, describe the construction of the seven current cervical TDR devices that are approved for use in the United States, and discuss known adverse biological effects associated with long-term implantation of these materials. It is important to appreciate and understand the variety of biomaterials available in the design and construction of these prosthetics and the considerations which guide their implementation.

  19. Material Science in Cervical Total Disc Replacement.

    Science.gov (United States)

    Pham, Martin H; Mehta, Vivek A; Tuchman, Alexander; Hsieh, Patrick C

    2015-01-01

    Current cervical total disc replacement (TDR) designs incorporate a variety of different biomaterials including polyethylene, stainless steel, titanium (Ti), and cobalt-chrome (CoCr). These materials are most important in their utilization as bearing surfaces which allow for articular motion at the disc space. Long-term biological effects of implanted materials include wear debris, host inflammatory immune reactions, and osteolysis resulting in implant failure. We review here the most common materials used in cervical TDR prosthetic devices, examine their bearing surfaces, describe the construction of the seven current cervical TDR devices that are approved for use in the United States, and discuss known adverse biological effects associated with long-term implantation of these materials. It is important to appreciate and understand the variety of biomaterials available in the design and construction of these prosthetics and the considerations which guide their implementation.

  20. Performance of broilers fed enzyme-supplemented tigernut ...

    African Journals Online (AJOL)

    A feeding trial was set up to study the effects of replacing maize with tigernut meal (TGN) at 0, 33.33, 66.67 and 100 per cent levels, with 0.10 per cent enzyme supplementation of all levels, on performance characteristics and carcass yield in broiler chicken for 8 weeks (56 days). A total of 200 Anak-2000 breed of broilers ...

  1. Enzyme recycling in lignocellulosic biorefineries

    DEFF Research Database (Denmark)

    Jørgensen, Henning; Pinelo, Manuel

    2017-01-01

    platform. Cellulases are the most important enzymes required in this process, but the complex nature of lignocellulose requires several other enzymes (hemicellulases and auxiliary enzymes) for efficient hydrolysis. Enzyme recycling increases the catalytic productivity of the enzymes by reusing them...... for several batches of hydrolysis, and thereby reduces the overall cost associated with the hydrolysis. Research on this subject has been ongoing for many years and several promising technologies and methods have been developed and demonstrated. But only in a very few cases have these technologies been...... upscaled and tested in industrial settings, mainly because of many difficulties with recycling of enzymes from the complex lignocellulose hydrolyzate at industrially relevant conditions, i.e., high solids loadings. The challenges are associated with the large number of different enzymes required...

  2. Characterising Complex Enzyme Reaction Data.

    Directory of Open Access Journals (Sweden)

    Handan Melike Dönertaş

    Full Text Available The relationship between enzyme-catalysed reactions and the Enzyme Commission (EC number, the widely accepted classification scheme used to characterise enzyme activity, is complex and with the rapid increase in our knowledge of the reactions catalysed by enzymes needs revisiting. We present a manual and computational analysis to investigate this complexity and found that almost one-third of all known EC numbers are linked to more than one reaction in the secondary reaction databases (e.g., KEGG. Although this complexity is often resolved by defining generic, alternative and partial reactions, we have also found individual EC numbers with more than one reaction catalysing different types of bond changes. This analysis adds a new dimension to our understanding of enzyme function and might be useful for the accurate annotation of the function of enzymes and to study the changes in enzyme function during evolution.

  3. Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis.

    Science.gov (United States)

    Yen, Chi-Liang Eric; Stone, Scot J; Koliwad, Suneil; Harris, Charles; Farese, Robert V

    2008-11-01

    Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, and the use of molecular tools, including mice deficient in either enzyme, has shed light on their functions. Although DGAT enzymes are involved in TG synthesis, they have distinct protein sequences and differ in their biochemical, cellular, and physiological functions. Both enzymes may be useful as therapeutic targets for diseases. Here we review the current knowledge of DGAT enzymes, focusing on new advances since the cloning of their genes, including possible roles in human health and diseases.

  4. An improved financial tool to replace BHT

    CERN Multimedia

    2002-01-01

    In November, the BHT tool used to control financial data will be replaced by an improved and more powerful system, called CET for CERN Expenditure Tracking. The team in charge of CET. From left to right, sitting, Martyn Rankin, David McGlashan, standing, Per Gunnar Jonsson, James Purvis and Mikael Angberg. After 10 years of BHT at CERN, in order to face the challenges of the LHC era, and following the recommendations of the External Review Committee, the BHT application will be replaced by an improved and more powerful expenditure tracking tool called CET for CERN Expenditure Tracking. For those who are not familiar with it, the BHT, Budget Holders Toolkit, is a utility that provides a way to view CERN financial data. It is available for users who have access to at least one budget code. The new CET represents a tool that not only allows powerful analysis of the past, but also assists in forecasting the future. CET will offer significantly more functionality than BHT, including extended contract analysis, ...

  5. Transdermal testosterone replacement therapy in men

    Science.gov (United States)

    Ullah, M Iftekhar; Riche, Daniel M; Koch, Christian A

    2014-01-01

    Androgen deficiency syndrome in men is a frequently diagnosed condition associated with clinical symptoms including fatigue, decreased libido, erectile dysfunction, and metabolic syndrome. Serum testosterone concentrations decline steadily with age. The prevalence of androgen deficiency syndrome in men varies depending on the age group, known and unknown comorbidities, and the respective study group. Reported prevalence rates may be underestimated, as not every man with symptoms of androgen deficiency seeks treatment. Additionally, men reporting symptoms of androgen deficiency may not be correctly diagnosed due to the vagueness of the symptom quality. The treatment of androgen deficiency syndrome or male hypogonadism may sometimes be difficult due to various reasons. There is no consensus as to when to start treating a respective man or with regards to the best treatment option for an individual patient. There is also lack of familiarity with treatment options among general practitioners. The formulations currently available on the market are generally expensive and dose adjustment protocols for each differ. All these factors add to the complexity of testosterone replacement therapy. In this article we will discuss the general indications of transdermal testosterone replacement therapy, available formulations, dosage, application sites, and recommended titration schedule. PMID:24470750

  6. Controversies in hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    A. Baziad

    2001-09-01

    Full Text Available Deficiency of estrogen hormone will result in either long-term or short-term health problems which may reduce the quality of life. There are numerous methods by which the quality of female life can be achieved. Since the problems occuring are due to the deficiency of estrogen hormone, the appropriate method to tackle the problem is by administration of estrogen hormone. The administration of hormone replacement therapy (HRT with estrogen may eliminate climacteric complaints, prevent osteoporosis, coronary heart disease, dementia, and colon cancer. Although HRT has a great deal of advantage, its use is still low and may result in controversies. These controversies are due to fact that both doctor and patient still hold on to the old, outmoded views which are not supported by numerous studies. Currently, the use of HRT is not only based on experience, or temporary observation, but more on evidence based medicine. (Med J Indones 2001; 10: 182-6Keywords: controversies, HRT

  7. Tracheal replacement by autogenous aorta

    Directory of Open Access Journals (Sweden)

    Anoosh Farhad

    2009-06-01

    Full Text Available Abstract Background Tracheal defects may occur after trauma or prolonged intubation. Resection of tracheal tumors also poses a major challenge for substitution. In an effort to solve this problem, different techniques have been tried with little success. We report on a new animal model which showed acceptable results with fewer complications. Methods We replaced 5 cm of cervical trachea in 10 dogs with harvested infra-renal aorta and repaired the aortic defect with Dacron graft. Results Necropsy of the grafted aorta and anastomotic site revealed well healed anastomosis in all animals together with ciliated columnar epithelium coverage of grafted aorta and neovascularization of aortic wall. Conclusion Aortic graft is preferable to other substitutes because of less antigenicity, less vascularity, and no mucous secretions or peristalsis

  8. Tracheal replacement by autogenous aorta.

    Science.gov (United States)

    Anoosh, Farhad; Hodjati, Hossain; Dehghani, Seifollah; Tanideh, Nader; Kumar, Perikala V

    2009-06-09

    Tracheal defects may occur after trauma or prolonged intubation. Resection of tracheal tumors also poses a major challenge for substitution. In an effort to solve this problem, different techniques have been tried with little success. We report on a new animal model which showed acceptable results with fewer complications. We replaced 5 cm of cervical trachea in 10 dogs with harvested infra-renal aorta and repaired the aortic defect with Dacron graft. Necropsy of the grafted aorta and anastomotic site revealed well healed anastomosis in all animals together with ciliated columnar epithelium coverage of grafted aorta and neovascularization of aortic wall. Aortic graft is preferable to other substitutes because of less antigenicity, less vascularity, and no mucous secretions or peristalsis.

  9. Renal replacement therapy in Europe

    DEFF Research Database (Denmark)

    Pippias, Maria; Stel, Vianda S; Abad Diez, José Maria

    2015-01-01

    BACKGROUND: This article summarizes the 2012 European Renal Association-European Dialysis and Transplant Association Registry Annual Report (available at www.era-edta-reg.org) with a specific focus on older patients (defined as ≥65 years). METHODS: Data provided by 45 national or regional renal...... disease (ESRD) receiving renal replacement therapy (RRT) and renal transplantation rates for 2012 are presented. RESULTS: In 2012, the overall unadjusted incidence rate of patients with ESRD receiving RRT was 109.6 per million population (pmp) (n = 69 035), ranging from 219.9 pmp in Portugal to 24.2 pmp...... to 32% between countries. The overall renal transplantation rate in 2012 was 28.3 pmp (n = 15 673), with the highest rate seen in the Spanish region of Catalonia. The proportion of patients ≥65 years receiving a transplant ranged from 0 to 35%. Five-year adjusted survival for all RRT patients was 59...

  10. Cost justification of chiller replacement

    International Nuclear Information System (INIS)

    Baker, T.J.; Baumer, R.A.

    1993-01-01

    We often hear of products with paybacks that are too good to be true. Just a few weeks ago,a client received a recommendation from a national service company's local office. In the letter the company recommended that open-quotes due to the age and condition of the boiler ... that the school consider replacing the boiler... The cost for the new boiler can usually be recovered by lower fuel bills in 2 to 3 yearsclose quotes. This was for an installation in Southeast Texas where the boiler is only used 4 to 5 months per year. Analysis show the above claims to be nonsense. A new boiler would cost about $47,000 installed. Current total gas bills for the facility are $15,630 per year. They would have to shutoff the gas to the facility to have a three year payback. In fact, only two-thirds of the gas is used to heat the facility so we have only $10, 000 to write off against the new boiler. How much will the greater efficiency save? A 30% savings due to greater efficiency produces $3,000 per year in gas savings to offset the $47,000 cost, a 16 year payback. And much of the efficiency savings can be realized by adjusting the existing boiler. In another care a client wanted to investigate replacement of a twenty year old chiller plant with more efficient equipment. We investigated the project and determined that the payback would be greater than ten years. They did not operate the equipment during the summer and at less than 50% of capacity the balance of the year

  11. Detection of Extracellular Enzyme Activities in Ganoderma neo-japonicum

    OpenAIRE

    Jo, Woo-Sik; Park, Ha-Na; Cho, Doo-Hyun; Yoo, Young-Bok; Park, Seung-Chun

    2011-01-01

    The ability of Ganoderma to produce extracellular enzymes, including β-glucosidase, cellulase, avicelase, pectinase, xylanase, protease, amylase, and ligninase was tested in chromogenic media. β-glucosidase showed the highest activity, among the eight tested enzymes. In particular, Ganoderma neo-japonicum showed significantly stronger activity for β-glucosidase than that of the other enzymes. Two Ganoderma lucidum isolates showed moderate activity for avicelase; however, Ganoderma neo-japonic...

  12. Protein engineering of enzymes for process applications

    DEFF Research Database (Denmark)

    Woodley, John M

    2013-01-01

    opportunities will be targeted on modification to enable process application. This article discusses the challenges involved in enzyme modification focused on process requirements, such as the need to fulfill reaction thermodynamics, specific activity under the required conditions, kinetics at required...... concentrations, and stability. Finally, future research directions are discussed, including the integration of biocatalysis with neighboring chemical steps....

  13. Transition state theory for enzyme kinetics

    Science.gov (United States)

    Truhlar, Donald G.

    2015-01-01

    This article is an essay that discusses the concepts underlying the application of modern transition state theory to reactions in enzymes. Issues covered include the potential of mean force, the quantization of vibrations, the free energy of activation, and transmission coefficients to account for nonequilibrium effect, recrossing, and tunneling. PMID:26008760

  14. CELLULOSE DEGRADATION BY OXIDATIVE ENZYMES

    Directory of Open Access Journals (Sweden)

    Maria Dimarogona

    2012-09-01

    Full Text Available Enzymatic degradation of plant biomass has attracted intensive research interest for the production of economically viable biofuels. Here we present an overview of the recent findings on biocatalysts implicated in the oxidative cleavage of cellulose, including polysaccharide monooxygenases (PMOs or LPMOs which stands for lytic PMOs, cellobiose dehydrogenases (CDHs and members of carbohydrate-binding module family 33 (CBM33. PMOs, a novel class of enzymes previously termed GH61s, boost the efficiency of common cellulases resulting in increased hydrolysis yields while lowering the protein loading needed. They act on the crystalline part of cellulose by generating oxidized and non-oxidized chain ends. An external electron donor is required for boosting the activity of PMOs. We discuss recent findings concerning their mechanism of action and identify issues and questions to be addressed in the future.

  15. Biochemical characterization of enzyme fidelity of influenza A virus RNA polymerase complex.

    Directory of Open Access Journals (Sweden)

    Shilpa Aggarwal

    2010-04-01

    Full Text Available It is widely accepted that the highly error prone replication process of influenza A virus (IAV, together with viral genome assortment, facilitates the efficient evolutionary capacity of IAV. Therefore, it has been logically assumed that the enzyme responsible for viral RNA replication process, influenza virus type A RNA polymerase (IAV Pol, is a highly error-prone polymerase which provides the genomic mutations necessary for viral evolution and host adaptation. Importantly, however, the actual enzyme fidelity of IAV RNA polymerase has never been characterized.Here we established new biochemical assay conditions that enabled us to assess both polymerase activity with physiological NTP pools and enzyme fidelity of IAV Pol. We report that IAV Pol displays highly active RNA-dependent RNA polymerase activity at unbiased physiological NTP substrate concentrations. With this robust enzyme activity, for the first time, we were able to compare the enzyme fidelity of IAV Pol complex with that of bacterial phage T7 RNA polymerase and the reverse transcriptases (RT of human immunodeficiency virus (HIV-1 and murine leukemia virus (MuLV, which are known to be low and high fidelity enzymes, respectively. We observed that IAV Pol displayed significantly higher fidelity than HIV-1 RT and T7 RNA polymerase and equivalent or higher fidelity than MuLV RT. In addition, the IAV Pol complex showed increased fidelity at lower temperatures. Moreover, upon replacement of Mg(++ with Mn(++, IAV Pol displayed increased polymerase activity, but with significantly reduced processivity, and misincorporation was slightly elevated in the presence of Mn(++. Finally, when the IAV nucleoprotein (NP was included in the reactions, the IAV Pol complex exhibited enhanced polymerase activity with increased fidelity.Our study indicates that IAV Pol is a high fidelity enzyme. We envision that the high fidelity nature of IAV Pol may be important to counter-balance the multiple rounds of

  16. Optimization on replacement period of plant equipment

    International Nuclear Information System (INIS)

    Kasai, Masao; Asano, Hiromi

    2002-01-01

    Optimization of the replacement period of plant equipment is one of the main items to rationalize the activities on plant maintenance. There are several models to replace the equipment and the formulations for optimizing the replacement period are different among these models. In this study, we calculated the optimum replacement periods for some equipment parts based on the replacement models and found that the optimum solutions are not so largely differ from the replacement models as far as the replacement period is not so large. So we will be able to use the most usable model especially in the early phase of rationalization on plant maintenance, since there are large uncertainties in data for optimization. (author)

  17. Measuring the Enzyme Activity of Arabidopsis Deubiquitylating Enzymes.

    Science.gov (United States)

    Kalinowska, Kamila; Nagel, Marie-Kristin; Isono, Erika

    2016-01-01

    Deubiquitylating enzymes, or DUBs, are important regulators of ubiquitin homeostasis and substrate stability, though the molecular mechanisms of most of the DUBs in plants are not yet understood. As different ubiquitin chain types are implicated in different biological pathways, it is important to analyze the enzyme characteristic for studying a DUB. Quantitative analysis of DUB activity is also important to determine enzyme kinetics and the influence of DUB binding proteins on the enzyme activity. Here, we show methods to analyze DUB activity using immunodetection, Coomassie Brilliant Blue staining, and fluorescence measurement that can be useful for understanding the basic characteristic of DUBs.

  18. Ultrasound in Enzyme Activation and Inactivation

    Science.gov (United States)

    Mawson, Raymond; Gamage, Mala; Terefe, Netsanet Shiferaw; Knoerzer, Kai

    As discussed in previous chapters, most effects due to ultrasound arise from cavitation events, in particular, collapsing cavitation bubbles. These collapsing bubbles generate very high localized temperatures and pressure shockwaves along with micro-streaming that is associated with high shear forces. These effects can be used to accelerate the transport of substrates and reaction products to and from enzymes, and to enhance mass transfer in enzyme reactor systems, and thus improve efficiency. However, the high velocity streaming, together with the formation of hydroxy radicals and heat generation during collapsing of bubbles, may also potentially affect the biocatalyst stability, and this can be a limiting factor in combined ultrasound/enzymatic applications. Typically, enzymes can be readily denatured by slight changes in environmental conditions, including temperature, pressure, shear stress, pH and ionic strength.

  19. Enzyme Histochemistry for Functional Histology in Invertebrates.

    Science.gov (United States)

    Cima, Francesca

    2017-01-01

    In invertebrates, enzyme histochemistry has recently found a renaissance regarding its applications in morphology and ecology. Many enzyme activities are useful for the morphofunctional characterization of cells, as biomarkers of biological and pathologic processes, and as markers of the response to environmental stressors. Here, the adjustments to classic techniques, including the most common enzymes used for digestion, absorption, transport, and oxidation, as well as techniques for azo-coupling, metal salt substitution and oxidative coupling polymerization, are presented in detail for various terrestrial and aquatic invertebrates. This chapter also provides strategies to solve the problems regarding anesthesia, small body size, the presence of an exo- or endoskeleton and the search for the best fixative in relation to the internal fluid osmolarity. These techniques have the aim of obtaining good results for both the pre- and post-embedding labeling of specimens, tissue blocks, sections, and hemolymph smears using both light and transmission electron microscopy.

  20. Microbial Enzyme Activity and Carbon Cycling in Grassland Soil Fractions

    Science.gov (United States)

    Allison, S. D.; Jastrow, J. D.

    2004-12-01

    Extracellular enzymes are necessary to degrade complex organic compounds present in soils. Using physical fractionation procedures, we tested whether old soil carbon is spatially isolated from degradative enzymes across a prairie restoration chronosequence in Illinois, USA. We found that carbon-degrading enzymes were abundant in all soil fractions, including macroaggregates, microaggregates, and the clay fraction, which contains carbon with a mean residence time of ~200 years. The activities of two cellulose-degrading enzymes and a chitin-degrading enzyme were 2-10 times greater in organic matter fractions than in bulk soil, consistent with the rapid turnover of these fractions. Polyphenol oxidase activity was 3 times greater in the clay fraction than in the bulk soil, despite very slow carbon turnover in this fraction. Changes in enzyme activity across the restoration chronosequence were small once adjusted for increases in soil carbon concentration, although polyphenol oxidase activity per unit carbon declined by 50% in native prairie versus cultivated soil. These results are consistent with a `two-pool' model of enzyme and carbon turnover in grassland soils. In light organic matter fractions, enzyme production and carbon turnover both occur rapidly. However, in mineral-dominated fractions, both enzymes and their carbon substrates are immobilized on mineral surfaces, leading to slow turnover. Soil carbon accumulation in the clay fraction and across the prairie restoration chronosequence probably reflects increasing physical isolation of enzymes and substrates on the molecular scale, rather than the micron to millimeter scale.

  1. Enzyme Molecules in Solitary Confinement

    Directory of Open Access Journals (Sweden)

    Raphaela B. Liebherr

    2014-09-01

    Full Text Available Large arrays of homogeneous microwells each defining a femtoliter volume are a versatile platform for monitoring the substrate turnover of many individual enzyme molecules in parallel. The high degree of parallelization enables the analysis of a statistically representative enzyme population. Enclosing individual enzyme molecules in microwells does not require any surface immobilization step and enables the kinetic investigation of enzymes free in solution. This review describes various microwell array formats and explores their applications for the detection and investigation of single enzyme molecules. The development of new fabrication techniques and sensitive detection methods drives the field of single molecule enzymology. Here, we introduce recent progress in single enzyme molecule analysis in microwell arrays and discuss the challenges and opportunities.

  2. Enzyme stabilization for pesticide degradation

    Energy Technology Data Exchange (ETDEWEB)

    Rivers, D.B.; Frazer, F.R. III; Mason, D.W.; Tice, T.R.

    1988-01-01

    Enzymes offer inherent advantages and limitations as active components of formulations used to decontaminate soil and equipment contaminated with toxic materials such as pesticides. Because of the catalytic nature of enzymes, each molecule of enzyme has the potential to destroy countless molecules of a contaminating toxic compound. This degradation takes place under mild environmental conditions of pH, temperature, pressure, and solvent. The basic limitation of enzymes is their degree of stability during storage and application conditions. Stabilizing methods such as the use of additives, covalent crosslinking, covalent attachment, gel entrapment, and microencapsulation have been directed developing an enzyme preparation that is stable under extremes of pH, temperature, and exposure to organic solvents. Initial studies were conducted using the model enzymes subtilisin and horseradish peroxidase.

  3. In this issue: Time to replace doctors’ judgement with computers

    Directory of Open Access Journals (Sweden)

    Simon de Lusignan

    2015-11-01

    Full Text Available Informaticians continue to rise to the challenge, set by the English Health Minister, of trying to replace doctors’ judgement with computers. This issue describes successes and where there are barriers. However, whilst there is progress this tends to be incremental and there are grand challenges to be overcome before computers can replace clinician. These grand challenges include: (1 improving usability so it is possible to more readily incorporate technology into clinical workflow; (2 rigorous new analytic methods that make use of the mass of available data, ‘Big data’, to create real-world evidence; (3 faster ways of meeting regulatory and legal requirements including ensuring privacy; (4 provision of reimbursement models to fund innovative technology that can substitute for clinical time and (5 recognition that innovations that improve quality also often increase cost. Informatics more is likely to support and augment clinical decision making rather than replace clinicians.

  4. NIF Laser Line Replaceable Units (LRUs)

    International Nuclear Information System (INIS)

    Larson, D W

    2003-01-01

    The National Ignition Facility (NIF) is designed with its high value optical systems in cassettes called Line Replaceable Units (LRUs). Virtually all of the NIF's active components are assembled in one of the ∼4000 electrical and optical LRUs that serve between two and eight of NIF's 192 laser beam lines. Many of these LRUs are optomechanical assemblies that are roughly the size of a telephone booth. The primary design challenges for this hardware include meeting stringent mechanical precision, stability and cleanliness requirements. Pre-production units of each LRU type have been fielded on the first bundle of NIF and used to demonstrate that NIF meets its performance objectives. This presentation provides an overview of the NIF LRUs, their design and production plans for building out the remaining NIF bundles

  5. Australia's replacement research reactor project

    International Nuclear Information System (INIS)

    Harris, K.J.

    1999-01-01

    HIFAR, a 10 MW tank type DIDO Class reactor has operated at the Lucas Heights Science and Technology Centre for 43 years. HIFAR and the 10 kW Argonaut reactor 'Moata' which is in the Care and Maintenance phase of decommissioning are Australia's only nuclear reactors. The initial purpose for HIFAR was for materials testing to support a nuclear power program. Changing community attitude through the 1970's and a Government decision not to proceed with a planned nuclear power reactor resulted in a reduction of materials testing activities and a greater emphasis being placed on neutron beam research and the production of radioisotopes, particularly for medical purposes. HIFAR is not fully capable of satisfying the expected increase in demand for medical radiopharmaceuticals beyond the next 5 years and the radial configuration of the beam tubes severely restricts the scope and efficiency of neutron beam research. In 1997 the Australian Government decided that a replacement research reactor should be built by the Australian Nuclear Science and Technology Organisation at Lucas Heights subject to favourable results of an Environmental Impact Study. The Ei identified no reasons on the grounds of safety, health, hazard or risk to prevent construction on the preferred site and it was decided in May 1999 that there were no environmental reasons why construction of the facility should not proceed. In recent years ANSTO has been reviewing the operation of HIFAR and observing international developments in reactor technology. Limitations in the flexibility and efficiency achievable in operation of a tank type reactor and the higher intrinsic safety sought in fundamental design resulted in an early decision that the replacement reactor must be a pool type having cleaner and higher intensity tangential neutron beams of wider energy range than those available from HIFAR. ANSTO has chosen to use it's own resources supported by specialised external knowledge and experience to identify

  6. Kinetic alteration of a human dihydrodiol/3alpha-hydroxysteroid dehydrogenase isoenzyme, AKR1C4, by replacement of histidine-216 with tyrosine or phenylalanine.

    Science.gov (United States)

    Ohta, T; Ishikura, S; Shintani, S; Usami, N; Hara, A

    2000-01-01

    Human dihydrodiol dehydrogenase with 3alpha-hydroxysteroid dehydrogenase activity exists in four forms (AKR1C1-1C4) that belong to the aldo-keto reductase (AKR) family. Recent crystallographic studies on the other proteins in this family have indicated a role for a tyrosine residue (corresponding to position 216 in these isoenzymes) in stacking the nicotinamide ring of the coenzyme. This tyrosine residue is conserved in most AKR family members including AKR1C1-1C3, but is replaced with histidine in AKR1C4 and phenylalanine in some AKR members. In the present study we prepared mutant enzymes of AKR1C4 in which His-216 was replaced with tyrosine or phenylalanine. The two mutations decreased 3-fold the K(m) for NADP(+) and differently influenced the K(m) and k(cat) for substrates depending on their structures. The kinetic constants for bile acids with a 12alpha-hydroxy group were decreased 1.5-7-fold and those for the other substrates were increased 1.3-9-fold. The mutation also yielded different changes in sensitivity to competitive inhibitors such as hexoestrol analogues, 17beta-oestradiol, phenolphthalein and flufenamic acid and 3,5,3', 5'-tetraiodothyropropionic acid analogues. Furthermore, the mutation decreased the stimulatory effects of the enzyme activity by sulphobromophthalein, clofibric acid and thyroxine, which increased the K(m) for the coenzyme and substrate of the mutant enzymes more highly than those of the wild-type enzyme. These results indicate the importance of this histidine residue in creating the cavity of the substrate-binding site of AKR1C4 through the orientation of the nicotinamide ring of the coenzyme, as well as its involvement in the conformational change by binding non-essential activators. PMID:11104674

  7. Direct comparison of enzyme histochemical and immunohistochemical methods to localize an enzyme

    NARCIS (Netherlands)

    van Noorden, Cornelis J. F.

    2002-01-01

    Immunohistochemical localization of enzymes is compared directly with localization of enzyme activity with (catalytic) enzyme histochemical methods. The two approaches demonstrate principally different aspects of an enzyme. The immunohistochemical method localizes the enzyme protein whether it is

  8. Halophiles and their enzymes: Negativity put to good use

    Science.gov (United States)

    DasSarma, Shiladitya; DasSarma, Priya

    2015-01-01

    Halophilic microorganisms possess stable enzymes that function in very high salinity, an extreme condition that leads to denaturation, aggregation, and precipitation of most other proteins. Genomic and structural analyses have established that the enzymes of halophilic Archaea and many halophilic Bacteria are negatively charged due to an excess of acidic over basic residues, and altered hydrophobicity, which enhance solubility and promote function in low water activity conditions. Here, we provide an update on recent bioinformatic analysis of predicted halophilic proteomes as well as experimental molecular studies on individual halophilic enzymes. On-going efforts on discovery and utilization of halophiles and their enzymes for biotechnology, including biofuel applications are also considered. PMID:26066288

  9. Enzymes are a sweet way to do business

    Energy Technology Data Exchange (ETDEWEB)

    1980-01-04

    The use of enzymes in industry is growing steadily. This artic discusses some areas of enzyme research: included are enzyme treatments for the production of high-fructose corn syrup and ethanol for gasohol blends, enzyme research focusing on cellulose breakdown, especially from municipal waste and pulp and paper waste to produce ethanol and the conversion of soybeans into a protein-rich powder. The enzymatic process for nitrogen fixation in the nodules of certain leguminous plants and in medical diagnostics are also mentioned.

  10. Assimilation of wheat starch in patients with chronic pancreatitis. Positive effect of enzyme replacement

    DEFF Research Database (Denmark)

    Nordgaard, I; Rumessen, J J; Gudmand-Høyer, E

    1992-01-01

    Pancreatic insufficiency due to chronic pancreatitis may lead to symptomatic malabsorption of both starch and fat. The absorption capacity of wheat starch has not been studied previously in patients with chronic pancreatitis, although this carbohydrate is a quantitatively important component of t...

  11. Enzyme replacement therapy in late-onset Pompe's disease : A three-year follow-up

    NARCIS (Netherlands)

    Winkel, LPF; Van den Hout, JMP; Kamphoven, JHJ; Disseldorp, JAM; Remmerswaal, M; Arts, WFM; Loonen, MCB; Vulto, AG; Van Doorn, PA; De Jong, G; Hop, W; Smit, GPA; Shapira, SK; Boer, MA; van Diggelen, OP; Reuser, AJJ; Van der Ploeg, AT

    Pompe's disease is an autosomal recessive myopathy. The characteristic lysosomal storage of glycogen is caused by acid et-glucosidase deficiency. Patients with late-onset Pompe's disease present with progressive muscle weakness also affecting pulmonary function. In search of a treatment, we

  12. Fabry disease under enzyme replacement therapy-new insights in efficacy of different dosages.

    Science.gov (United States)

    Krämer, Johannes; Lenders, Malte; Canaan-Kühl, Sima; Nordbeck, Peter; Üçeyler, Nurcan; Blaschke, Daniela; Duning, Thomas; Reiermann, Stefanie; Stypmann, Jörg; Brand, Stefan-Martin; Gottschling, Timo; Störk, Stefan; Wanner, Christoph; Sommer, Claudia; Brand, Eva; Weidemann, Frank

    2017-11-23

    Fabry patients on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and an increase of the Mainz Severity Score Index. In this prospective observational study, we assessed end-organ damage and clinical symptoms in 112 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i) non-randomly assigned to continue this treatment regime (regular-dose group, n = 37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n = 38); or (iii) were re-switched to agalsidase-beta after receiving agalsidase-alfa for at least 12 months (re-switch group, n = 37) with a median follow-up of 53 (38-57) months. eGFR of patients in the regular-dose group remained stable. Patients in the switch group showed an annual eGFR loss of - 4.6  ±  9.1 mL/min/1.73 m2 (P risk 0.42; 95% confidence interval 0.19-0.93; P = 0.02). Lyso-Gb3 remained stable in the switch (P = 0.97) and the regular-dose (P = 0.48) groups, but decreased in the re-switch group after change of the therapy regimen (P < 0.05). After switch to agalsidase-alfa, Fabry patients experienced a continuous decline in eGFR, while this decline was attenuated in patients who were re-switched to agalsidase-beta. Decreasing lyso-Gb3 levels may indicate a better treatment response in the latter group. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  13. Near universal support for covalent immobilisation of enzymes for biotechnology

    International Nuclear Information System (INIS)

    Elnashar, M.M.; Millner, P.A.; Gibson, T.D.

    2005-01-01

    Carrageenan [1], natural polymer, has been modified to be used as a universal/near universal support to immobilise enzymes, where the gel remained stable at 70 degree C for 24 h at a wide range of buffers and ph s and its mechanical strength was 400% greater than the unmodified gel. The new matrix successfully immobilised covalently eight commercially used enzymes including hydrolases, Upases, oxidoreductases, proteases and dehydrogenases. It also acted as a self buffering system in case of hydrolases and stopped enzyme's product inhibition. The apparent Km values of immobilised enzymes were found in many cases to be much less than those of the free enzymes. Another interesting correlation was observed where the great lowering of the apparent Km with immobilised enzymes was directly proportional to the substrate molecular weight. In economic terms, the new matrix is at least two orders of magnitude cheaper than supports such as Eupergit C

  14. Enzymes as Biocatalysts for Lipid-based Bioproducts Processing

    DEFF Research Database (Denmark)

    Cheong, Ling-Zhi; Guo, Zheng; Fedosov, Sergey

    2012-01-01

    Bioproducts are materials, chemicals and energy derived from renewable biological resources such as agriculture, forestry, and biologically-derived wastes. To date, the use of enzymes as biocatalysts for lipid-based bioproducts processing has shown marked increase. This is mainly due to the fact...... that cost benefit derived from enzymatic processing such as enzyme specificity, higher product purity and lesser or none toxic waste disposal has surpassed the cost of biocatalysts itself. This chapter provided insights into distinct enzymes characteristics essential in industrial processing especially...... enzymes kinetics. Understanding of enzyme kinetics is important especially in designing efficient reaction set-ups including type of bioreactors, reaction conditions and reusability of biocatalysts to ensure efficient running cost. A brief review of state-of-the-art in industrial applications of enzymes...

  15. Structural Evaluation of the RSRM Nozzle Replacement Adhesive

    Science.gov (United States)

    Batista-Rodriguez, A.; McLennan, M. L.; Palumbos, A. V.; Richardson, D. E.

    1999-01-01

    This paper describes the structural performance evaluation of a replacement adhesive for the Reusable Solid Rocket Motor (RSRM) nozzle utilizing finite element analysis. Due to material obsolescence and industrial safety issues, the two current structural adhesives, EA 913 and EA 946 are to be replaced with a new adhesive. TIGA 321. The structural evaluation in support of the adhesive replacement effort includes residual stress, transportation, and flight analyses. Factors of safety are calculated using the stress response from each analysis. The factors of safety are used as the limiting criteria to compare the replacement adhesive against the current adhesives. Included in this paper are the analytical approach, assumptions and modeling techniques as well as the results of the evaluation. An important factor to the evaluation is the similarity in constitutive material properties (elastic modulus and Poisson's ratio) between TIGA 321 and EA 913. This similarity leads to equivalent material response from the two adhesives. However, TIGA 321 surpasses EA 913's performance due to higher material capabilities. Conversely, the change in stress response from EA 946 to TIGA 321 is more apparent: this is primarily attributed to the difference in the modulii of the two adhesives, which differ by two orders of magnitude. The results of the bondline evaluation indicate that the replacement adhesive provides superior performance than the current adhesives with only minor exceptions. Furthermore, TIGA 321 causes only a minor chance in the response of the phenolic and metal components.

  16. Enzyme Mimics: Advances and Applications.

    Science.gov (United States)

    Kuah, Evelyn; Toh, Seraphina; Yee, Jessica; Ma, Qian; Gao, Zhiqiang

    2016-06-13

    Enzyme mimics or artificial enzymes are a class of catalysts that have been actively pursued for decades and have heralded much interest as potentially viable alternatives to natural enzymes. Aside from having catalytic activities similar to their natural counterparts, enzyme mimics have the desired advantages of tunable structures and catalytic efficiencies, excellent tolerance to experimental conditions, lower cost, and purely synthetic routes to their preparation. Although still in the midst of development, impressive advances have already been made. Enzyme mimics have shown immense potential in the catalysis of a wide range of chemical and biological reactions, the development of chemical and biological sensing and anti-biofouling systems, and the production of pharmaceuticals and clean fuels. This Review concerns the development of various types of enzyme mimics, namely polymeric and dendrimeric, supramolecular, nanoparticulate and proteinic enzyme mimics, with an emphasis on their synthesis, catalytic properties and technical applications. It provides an introduction to enzyme mimics and a comprehensive summary of the advances and current standings of their applications, and seeks to inspire researchers to perfect the design and synthesis of enzyme mimics and to tailor their functionality for a much wider range of applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. [The rise of enzyme engineering in China].

    Science.gov (United States)

    Li, Gaoxiang

    2015-06-01

    Enzyme engineering is an important part of the modern biotechnology. Industrial biocatalysis is considered the third wave of biotechnology following pharmaceutical and agricultural waves. In 25 years, China has made a mighty advances in enzyme engineering research. This review focuses on enzyme genomics, enzyme proteomics, biosynthesis, microbial conversion and biosensors in the Chinese enzyme engineering symposiums and advances in enzyme preparation industry in China.

  18. On the Temperature Dependence of Enzyme-Catalyzed Rates.

    Science.gov (United States)

    Arcus, Vickery L; Prentice, Erica J; Hobbs, Joanne K; Mulholland, Adrian J; Van der Kamp, Marc W; Pudney, Christopher R; Parker, Emily J; Schipper, Louis A

    2016-03-29

    One of the critical variables that determine the rate of any reaction is temperature. For biological systems, the effects of temperature are convoluted with myriad (and often opposing) contributions from enzyme catalysis, protein stability, and temperature-dependent regulation, for example. We have coined the phrase "macromolecular rate theory (MMRT)" to describe the temperature dependence of enzyme-catalyzed rates independent of stability or regulatory processes. Central to MMRT is the observation that enzyme-catalyzed reactions occur with significant values of ΔCp(‡) that are in general negative. That is, the heat capacity (Cp) for the enzyme-substrate complex is generally larger than the Cp for the enzyme-transition state complex. Consistent with a classical description of enzyme catalysis, a negative value for ΔCp(‡) is the result of the enzyme binding relatively weakly to the substrate and very tightly to the transition state. This observation of negative ΔCp(‡) has important implications for the temperature dependence of enzyme-catalyzed rates. Here, we lay out the fundamentals of MMRT. We present a number of hypotheses that arise directly from MMRT including a theoretical justification for the large size of enzymes and the basis for their optimum temperatures. We rationalize the behavior of psychrophilic enzymes and describe a "psychrophilic trap" which places limits on the evolution of enzymes in low temperature environments. One of the defining characteristics of biology is catalysis of chemical reactions by enzymes, and enzymes drive much of metabolism. Therefore, we also expect to see characteristics of MMRT at the level of cells, whole organisms, and even ecosystems.

  19. Visual Image Sensor Organ Replacement

    Science.gov (United States)

    Maluf, David A.

    2014-01-01

    This innovation is a system that augments human vision through a technique called "Sensing Super-position" using a Visual Instrument Sensory Organ Replacement (VISOR) device. The VISOR device translates visual and other sensors (i.e., thermal) into sounds to enable very difficult sensing tasks. Three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. Because the human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns, the translation of images into sounds reduces the risk of accidentally filtering out important clues. The VISOR device was developed to augment the current state-of-the-art head-mounted (helmet) display systems. It provides the ability to sense beyond the human visible light range, to increase human sensing resolution, to use wider angle visual perception, and to improve the ability to sense distances. It also allows compensation for movement by the human or changes in the scene being viewed.

  20. Gene replacement in Penicillium roqueforti.

    Science.gov (United States)

    Goarin, Anne; Silar, Philippe; Malagnac, Fabienne

    2015-05-01

    Most cheese-making filamentous fungi lack suitable molecular tools to improve their biotechnology potential. Penicillium roqueforti, a species of high industrial importance, would benefit from functional data yielded by molecular genetic approaches. This work provides the first example of gene replacement by homologous recombination in P. roqueforti, demonstrating that knockout experiments can be performed in this fungus. To do so, we improved the existing transformation method to integrate transgenes into P. roqueforti genome. In the meantime, we cloned the PrNiaD gene, which encodes a NADPH-dependent nitrate reductase that reduces nitrate to nitrite. Then, we performed a deletion of the PrNiaD gene from P. roqueforti strain AGO. The ΔPrNiaD mutant strain is more resistant to chlorate-containing medium than the wild-type strain, but did not grow on nitrate-containing medium. Because genomic data are now available, we believe that generating selective deletions of candidate genes will be a key step to open the way for a comprehensive exploration of gene function in P. roqueforti.

  1. Aβ-degrading enzymes: potential for treatment of Alzheimer disease.

    Science.gov (United States)

    Miners, James Scott; Barua, Neil; Kehoe, Patrick Gavin; Gill, Steven; Love, Seth

    2011-11-01

    There is increasing evidence that deficient clearance of β-amyloid (Aβ) contributes to its accumulation in late-onset Alzheimer disease (AD). Several Aβ-degrading enzymes, including neprilysin (NEP), insulin-degrading enzyme, and endothelin-converting enzyme reduce Aβ levels and protect against cognitive impairment in mouse models of AD. The activity of several Aβ-degrading enzymes rises with age and increases still further in AD, perhaps as a physiological response to minimize the buildup of Aβ. The age- and disease-related changes in expression of more recently recognized Aβ-degrading enzymes (e.g. NEP-2 and cathepsin B) remain to be investigated, and there is strong evidence that reduced NEP activity contributes to the development of cerebral amyloid angiopathy. Regardless of the role of Aβ-degrading enzymes in the development of AD, experimental data indicate that increasing the activity of these enzymes (NEP in particular) has therapeutic potential in AD, although targeting their delivery to the brain remains a major challenge. The most promising current approaches include the peripheral administration of agents that enhance the activity of Aβ-degrading enzymes and the direct intracerebral delivery of NEP by convection-enhanced delivery. In the longer term, genetic approaches to increasing the intracerebral expression of NEP or other Aβ-degrading enzymes may offer advantages.

  2. Enzyme structure, enzyme function and allozyme diversity in ...

    African Journals Online (AJOL)

    In estimates of population genetic diversity based on allozyme heterozygosity, some enzymes are regularly more variable than others. Evolutionary theory suggests that functionally less important molecules, or parts of molecules, evolve more rapidly than more important ones; the latter enzymes should then theoretically be ...

  3. Fluorometric Assessment Of Lysosomal Enzymes In Garlic Oil ...

    African Journals Online (AJOL)

    The effect of Garlic oil on Lysosomal enzymes in streptozotocin-induced diabetic rats were investigated fluorometrically. The serum lysosomal enzymes assayed include β-glucuronidase, N-acetylglucosaminidase (NAG) β-D-galactosidase and α-D-galactosidase. The results of the study in nMole-4Mu/hr/ml show that ...

  4. Angiotensin I-converting enzyme inhibitor derived from cottonseed ...

    African Journals Online (AJOL)

    Six proteolytic enzymes, including alcalase, flavourzyme, trypsin, neutrase, papain and pepsin, were employed to hydrolyze cottonseed protein to produce the hydrolysates of Angiotensin I-converting enzyme (ACE) inhibitory activity. The result indicated that the cottonseed protein hydrolysate (CPH) produced by papain had ...

  5. Licensing of ANSTO's Replacement Research Reactor

    International Nuclear Information System (INIS)

    Summerfield, M.W.; Garea, V.

    2003-01-01

    This paper presents a general description of the licensing of the 20 MW Pool-type Replacement Research Reactor (RRR) currently being built by the Australian Nuclear Science and Technology Organisation (ANSTO) at their Lucas Heights site. The following aspects will be addressed: 1) The influence of ARPANSA's (the Australian regulator) Regulatory Assessment Principles and Design Criteria on the design of the RRR. 2) The Site Licence Application, including the EIS and the supporting siting documentation. 3) The Construction Licence Application, including the PSAR and associated documentation. 4) The review process, including the IAEA Peer Review and the Public Submissions as well as ARPANSA's own review. 5) The interface between ANSTO, INVAP and ARPANSA in relation to the ongoing compliance with ARPANS Regulation 51 and 54. 6) The future Operating Licence Application, including the draft FSAR and associated documentation. These aspects are all addressed from the point of view of the licensee ANSTO and the RRR Project. Particular emphasis will be given to the way in which the licensing process is integrated into the overall project program and how the licensing and regulatory regime within Australia influenced the design of the RRR. In particular, the safety design features that have been incorporated as a result of the specific requirements of ANSTO and the Australian regulator will be briefly described. The paper will close with a description of how the RRR meets, and in many aspects exceeds the requirements of ANSTO and the Australian regulator. (author)

  6. Computational enzyme design: transitioning from catalytic proteins to enzymes.

    Science.gov (United States)

    Mak, Wai Shun; Siegel, Justin B

    2014-08-01

    The widespread interest in enzymes stem from their ability to catalyze chemical reactions under mild and ecologically friendly conditions with unparalleled catalytic proficiencies. While thousands of naturally occurring enzymes have been identified and characterized, there are still numerous important applications for which there are no biological catalysts capable of performing the desired chemical transformation. In order to engineer enzymes for which there is no natural starting point, efforts using a combination of quantum chemistry and force-field based protein molecular modeling have led to the design of novel proteins capable of catalyzing chemical reactions not catalyzed by naturally occurring enzymes. Here we discuss the current status and potential avenues to pursue as the field of computational enzyme design moves forward. Published by Elsevier Ltd.

  7. Immobilized enzymes: understanding enzyme - surface interactions at the molecular level.

    Science.gov (United States)

    Hoarau, Marie; Badieyan, Somayesadat; Marsh, E Neil G

    2017-11-22

    Enzymes immobilized on solid supports have important and industrial and medical applications. However, their uses are limited by the significant reductions in activity and stability that often accompany the immobilization process. Here we review recent advances in our understanding of the molecular level interactions between proteins and supporting surfaces that contribute to changes in stability and activity. This understanding has been facilitated by the application of various surface-sensitive spectroscopic techniques that allow the structure and orientation of enzymes at the solid/liquid interface to be probed, often with monolayer sensitivity. An appreciation of the molecular interactions between enzyme and surface support has allowed the surface chemistry and method of enzyme attachement to be fine-tuned such that activity and stability can be greatly enhanced. These advances suggest that a much wider variety of enzymes may eventually be amenable to immobilization as green catalysts.

  8. Stability of Enzymes in Granular Enzyme Products for Laundry Detergents

    DEFF Research Database (Denmark)

    Biran, Suzan; Bach, Poul; Simonsen, Ole

    Enzymes have long been of interest to the detergent industry due to their ability to improve the cleaning efficiency of synthetic detergents, contribute to shortening washing times, and reduce energy and water consumption, provision of environmentally friendlier wash water effluents and fabric care....... However, incorporating enzymes in detergent formulations gives rise to numerous practical problems due to their incompatibility with and stability against various detergent components. In powdered detergent formulations, these issues can be partly overcome by physically isolating the enzymes in separate...... particles. However, enzymes may loose a significant part of their activity over a time period of several weeks. Possible causes of inactivation of enzymes in a granule may be related to the release of hydrogen peroxide from the bleaching chemicals in a moisture-containing atmosphere, humidity, autolysis...

  9. Enzyme Immobilization: An Overview on Methods, Support Material, and Applications of Immobilized Enzymes.

    Science.gov (United States)

    Sirisha, V L; Jain, Ankita; Jain, Amita

    Immobilized enzymes can be used in a wide range of processes. In recent years, a variety of new approaches have emerged for the immobilization of enzymes that have greater efficiency and wider usage. During the course of the last two decades, this area has rapidly expanded into a multidisciplinary field. This current study is a comprehensive review of a variety of literature produced on the different enzymes that have been immobilized on various supporting materials. These immobilized enzymes have a wide range of applications. These include applications in the sugar, fish, and wine industries, where they are used for removing organic compounds from waste water. This study also reviews their use in sophisticated biosensors for metabolite control and in situ measurements of environmental pollutants. Immobilized enzymes also find significant application in drug metabolism, biodiesel and antibiotic production, bioremediation, and the food industry. The widespread usage of immobilized enzymes is largely due to the fact that they are cheaper, environment friendly, and much easier to use when compared to equivalent technologies. © 2016 Elsevier Inc. All rights reserved.

  10. Optimal timing for intravenous administration set replacement.

    Science.gov (United States)

    Gillies, D; O'Riordan, L; Wallen, M; Morrison, A; Rankin, K; Nagy, S

    2005-10-19

    Administration of intravenous therapy is a common occurrence within the hospital setting. Routine replacement of administration sets has been advocated to reduce intravenous infusion contamination. If decreasing the frequency of changing intravenous administration sets does not increase infection rates, a change in practice could result in considerable cost savings. The objective of this review was to identify the optimal interval for the routine replacement of intravenous administration sets when infusate or parenteral nutrition (lipid and non-lipid) solutions are administered to people in hospital via central or peripheral venous catheters. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, CINAHL, EMBASE: all from inception to February 2004; reference lists of identified trials, and bibliographies of published reviews. We also contacted researchers in the field. We did not have a language restriction. We included all randomized or quasi-randomized controlled trials addressing the frequency of replacing intravenous administration sets when parenteral nutrition (lipid and non-lipid containing solutions) or infusions (excluding blood) were administered to people in hospital via a central or peripheral catheter. Two authors assessed all potentially relevant studies. We resolved disagreements between the two authors by discussion with a third author. We collected data for the outcomes; infusate contamination; infusate-related bloodstream infection; catheter contamination; catheter-related bloodstream infection; all-cause bloodstream infection and all-cause mortality. We identified 23 references for review. We excluded eight of these studies; five because they did not fit the inclusion criteria and three because of inadequate data. We extracted data from the remaining 15 references (13 studies) with 4783 participants. We conclude that there is no evidence that changing intravenous administration sets more often than every 96 hours

  11. Media and Australia's replacement reactor project

    International Nuclear Information System (INIS)

    Keenan, Pamela

    2001-01-01

    In September 1997, the Commonwealth Government of Australia announced a proposal to build a replacement nuclear research reactor at Lucas Heights in Sydney. Extensive public consultation, parliamentary debate and independent reports were prepared to ensure that the new facility would meet strict international requirements, national safety and environmental standards, and performance specifications servicing the needs of Australia - for decades to come. On 6 June 2000, Argentine company INVAP SE was announced as the preferred tenderer. In July 2000 contracts were signed between INVAP and the Australian Nuclear Science and Technology Organisation for the construction the replacement reactor, due to be completed in 2005. In order to retain a strong local presence, INVAP undertook a joint venture with two of Australia's foremost heavy construction businesses. Briefly the new research reactor will be a replacement for the ageing Australian Reactor (HIFAR). Nuclear science and technology, in Australia, is no stranger to media controversy and misinformation. Understandably the announcement of a preferred tenderer followed by the signing of contracts, attracted significant national and international media attention. However in the minds of the media, the issue is far from resolved and is now a constant 'news story' in the Australian media. Baseless media stories have made claims that the project will cost double the original estimates; question the credibility of the contractors; and raise issues of international security. The project is currently linked with Australia's requirements for long term nuclear waste management and there has been an attempt to bring national Indigenous People's issues into play. Some of these issues have been profiled in the press internationally. So, just to set the record straight and give you an appropriate impression of what's 'really happening' I would like to highlight a few issues, how ANSTO dealt with these, and what was finally reported

  12. Opportunistic replacement of fusion power system parts

    International Nuclear Information System (INIS)

    Day, J.A.; George, L.L.

    1981-01-01

    This paper describes a maintenance problem in a fusion power plant. The problem is to specify which life limited parts should be replaced when there is an opportunity. The objective is to minimize the cost rate of replacement parts and of maintenance actions while satisfying a power plant availability constraint. The maintenance policy is to look ahead and replace all parts that will reach their life limits within a time called a screen. Longer screens yield greater system availabilities because more parts are replaced prior to their life limits

  13. Aortic valve replacement in octogenarians

    Directory of Open Access Journals (Sweden)

    Dark John H

    2007-07-01

    Full Text Available Abstract Background and Aims As our population ages and life expectancy increases the number of people aged over 80 and more referred for cardiac surgery is growing. This study sought to identify the outcome of aortic valve replacement (AVR in octogenarians. Methods 68 patients aged 80 years or more underwent AVR at the Freeman Hospital, between April 2001 and April 2004. A retrospective review of the notes and outcomes from the patients' GP and the NHS strategic tracking service was performed. 54% (37 underwent isolated AVR whilst 46% (31 underwent combined AVR and CABG. Results Follow up was 100% complete. The mean age was 83.1 ± s.d. 2.9 years, a mean gradient of 83 ± s.d. 31 mmHg and mean AVA of 0.56 cm2. The mean additive EuroSCORE was 8.6 ± s.d. 1.2, the logistic EuroSCORE mean 12.0 ± s.d. 5.9. In hospital 30 day mortality was 13 %. Survival was 80% at 1 year and 78% at 2 years. Median follow up was for 712 days. Stepwise logistic regression identified chronic obstructive airways disease as an independent predictor of mortality (p Conclusion Our study demonstrates that the operative mortality for AVR in the over eighties is good, whilst the mid to long term outcome is excellent There is a very low attrition rate with those undergoing the procedure living as long than their age matched population. This study confirms AVR is a safe, acceptable treatment for octogenarians with excellent mid term outcomes.

  14. Menopause and hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    Ali Baziad

    2001-12-01

    Full Text Available The global population in the 21st century has reached 6.2 billion people, by the year 2025 it is to be around 8.3-8.5 billion, and will increase further. Elderly people are expected to grow rapidly than other groups. The fastest increase in the elderly population will take place in Asia. Life expectancy is increasing steadily throughout developed and developing countries. For many  menopausal women, increased life expectancy will accompanied by many health problems. The consequences of estrogen deficiency are the menopausal symptoms. The treatment of menopause related complaints and diseases became an  important socioeconomic and medical issue. Long term symptoms, such as the increase in osteoporosis fractures, cardio and cerebrovascular disesses and dementia, created a large financial burden on individuals and society. All these health problems can be lreated or prevented by hormone replacement therapy (HRT. Natural HRT is usually prefened. Synthetic  estrogen in oral contraceptives (oc are not recommended for HRT. Many contra-indications for oc, but now it is widely usedfor HRT. The main reasons for discontinuing HRT are unwanted bleeding, fear of cancer, and negative side effects. Until now there are sill debates about the rebrtonship between HRT and the incidence of breast cancer. Many data showed that there were no clear relationship between the use of HRT and breast cancer. ThereÎore, nwny experts advocate the use of HRTfrom the first sign of climacteric complaints until death. (Med J Indones 2001;10: 242-51Keywords: estrogen deficiency, climacteric phases, tibolone.

  15. Tissue engineered devices for ligament repair, replacement and ...

    African Journals Online (AJOL)

    potential, severe damage warrants surgical intervention including complete replacement. Ligaments are longitudinally arranged, complex tissues; the mechanical properties of ligaments are a direct result of their components and the arrangement of these components in the tissue. It is these mechanics that have made ...

  16. Aortic valve replacement for aortic stenosis caused by alkaptonuria.

    Science.gov (United States)

    Hiroyoshi, Junko; Saito, Aya; Panthee, Nirmal; Imai, Yasushi; Kawashima, Dai; Motomura, Noboru; Ono, Minoru

    2013-03-01

    We report a case of aortic stenosis associated with ochronosis in a 70-year-old man who underwent biologic aortic valve replacement. Intraoperative findings included ochronosis of a severely calcified pigmented aortic valve along with pigmentation of the intima of the aorta. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Digestive enzymes of some earthworms.

    Science.gov (United States)

    Mishra, P C; Dash, M C

    1980-10-15

    4 species of tropical earthworms differed with regard to enzyme activity. The maximum activity of protease and of cellulase occurred in the posterior region of the gut of the earthworms. On the average Octochaetona surensis shows maximum activity and Drawida calebi shows minimum activity for all the enzymes studied.

  18. Trenchless Replacement of Buried Cable Lines

    Directory of Open Access Journals (Sweden)

    Hans-Joachim Bayer

    2007-01-01

    Full Text Available An enormous amount of underground electricity and telecommunication cables have been worn over the time with technical defects or need capacity increases. Thus, new lines need to be installed. In urban areas, even in smaller communities and in natural reserves, open trenching is difficult and often not permitted.In response, new patented methods of trenchless cable replacement using the HDD equipment have been developed by the TT Group. The new technology is called “Wash-over-cable-replacement” and applies specially designed drill heads, cutting around the old cable string in various configurations (completely closed, U-shape or S-shape embracing, depending to the coating type of the old cable. This special cable replacement drill head separates the cable from the surrounding adhesive soil or the sand bedding by creating a very small annular space around the cable thus enabling the pulling or dragging out of the old cable section between the start and the exit pit. After the old cable has been loosened from the surrounding soil by means of the wash over process and pulled out, the new cable can be smoothly pulled into the void using the drill rods and embedding the new cable in a rich bed of Bentonite.The wash-over drill heads are slim and have inner and outer nozzles for Bentonite and bits to handle roots, pebbles, gravel and the like. These drill heads perform very quickly (up to 3 meters per minute to effectively wash over existing cables without damaging the cable coating and prepare the ground for a fast new laying of a new cable in the existing line. Network owners also benefit from the fact that new geodetic or topographic surveys and documentations of the new cable are not necessary. Only the documents, remarks, technical codes and existing geodetic data need to be updated.The paper will outline the technological background and include several practical job examples.

  19. Neonatal varicella pneumonia, surfactant replacement therapy

    Directory of Open Access Journals (Sweden)

    Mousa Ahmadpour-kacho

    2015-12-01

    Full Text Available Background: Chickenpox is a very contagious viral disease that caused by varicella-zoster virus, which appears in the first week of life secondary to transplacental transmission of infection from the affected mother. When mother catches the disease five days before and up to two days after the delivery, the chance of varicella in neonate in first week of life is 17%. A generalized papulovesicular lesion is the most common clinical feature. Respiratory involvement may lead to giant cell pneumonia and respiratory failure. The mortality rate is up to 30% in the case of no treatment, often due to pneumonia. Treatment includes hospitalization, isolation and administration of intravenous acyclovir. The aim of this case report is to introduce the exogenous surfactant replacement therapy after intubation and mechanical ventilation for respiratory failure in neonatal chickenpox pneumonia and respiratory distress. Case Presentation: A seven-day-old neonate boy was admitted to the Neonatal Intensive Care Unit at Amirkola Children’s Hospital, Babol, north of Iran, with generalized papulovesicular lesions and respiratory distress. His mother has had a history of Varicella 4 days before delivery. He was isolated and given supportive care, intravenous acyclovir and antibiotics. On the second day, he was intubated and connected to mechanical ventilator due to severe pneumonia and respiratory failure. Because of sever pulmonary involvement evidenced by Chest X-Ray and high ventilators set-up requirement, intratracheal surfactant was administered in two doses separated by 12 hours. He was discharged after 14 days without any complication with good general condition. Conclusion: Exogenous surfactant replacement therapy can be useful as an adjunctive therapy for the treatment of respiratory failure due to neonatal chickenpox.

  20. Steam generator replacement at Kansai Electric Power Co., Inc

    International Nuclear Information System (INIS)

    Kimura, S.; Dodo, Takashi; Negishi, Kazuo

    1995-01-01

    Eleven nuclear units are in operation at the Kansai Electric Power Co., Inc.. In seven of them, Mihama-1·2·3, Takahama-1·2, and Ohi-1·2, comparatively long duration for tube inspection and repair have been required during late annual outages. KEPCO decided to replace all steam generators in these 7 units with the latest model which was improved upon the past degradation experiences, as a result of comprehensive considerations including public confidence in nuclear power generation, maintenability, and economic efficiency. This report presents the design improvements in new steam generators, replacement techniques, and so on. (author)

  1. Primary extra-cranial meningioma following total hip replacement

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, T.J.; Beggs, I. [Royal Infirmary, Department of Radiology, Edinburgh (United Kingdom); Patton, J.T.; Porter, D. [Royal Infirmary, Department of Orthopaedics, Edinburgh (United Kingdom); Salter, D.M.; Al-Nafussi, A. [Royal Infirmary, Department of Pathology, Edinburgh (United Kingdom)

    2009-01-15

    A 61-year-old man presented with pain at the left hip and decreased mobility 10 years after total hip replacement. Imaging demonstrated a large destructive expansile mass adjacent to the prosthesis. Histological analysis confirmed the presence of an extra-cranial meningioma. Primary tumours after total hip replacement are rare and include soft tissue sarcomas, bone sarcomas and lymphomas. To our knowledge, no previous cases of primary extracranial meningioma have been identified. The imaging features, histology, pathogenesis and differential diagnosis are discussed. (orig.)

  2. Status of the beryllium replacement project

    Energy Technology Data Exchange (ETDEWEB)

    Dimayuga, I. [Atomic Energy of Canada, Chalk River, Ontario (Canada); Corcoran, E. [Royal Military College of Canada, Kingston, Ontario (Canada); Daniels, T. [Ontario Power Generation, Pickering, Ontario (Canada); Harmsen, J. [Cameco Fuel Manufacturing Inc., Port Hope, Ontario (Canada); Lu, E. [Bruce Power, Tiverton, Ontario (Canada); Onderwater, T.; Palleck, S. [General Electric- Hitachi, Wilmington, North Carolina (United States); Pant, A. [Cameco Fuel Manufacturing Inc., Port Hope, Ontario (Canada)

    2013-07-01

    Currently, beryllium (Be) is used as the filler metal for brazing appendages on the sheaths of CANDU® fuel elements. Because of its toxicity, occupational exposure limits for Be are being reduced to very low levels, resulting in significant challenges to CANDU® fuel fabricators. The CANDU® Owners Group (COG) initiated a test program to identify a filler material to replace Be and confirm that the brazed joints meet the established technical requirements for CANDU® fuel. Together with eliminating health risks associated with the use of Be, the industry needs to be assured that continuation of fuel supply remains unaffected and that fuel fabrication processes continue to comply with health and safety standards. A literature survey of studies on brazing and joining of Zircaloy identified potential filler materials that can meet or exceed existing design requirements of the brazed joint, including the required mechanical, microstructural, corrosion resistance, and irradiation properties equivalent to those obtained with Be as braze material. Candidate materials were evaluated against several criteria, including manufacturability, melting point, wettability, mechanical properties, corrosion resistance, effect on neutron economy, potential activation products, and interaction with fuel channels and other related disciplines. This exercise resulted in a list of promising candidate materials that were recommended for the first phase of testing. These materials include stainless steel (304 or 316), Al-Si, Ni-P, and Zr-Mn alloys. To allow a CANDU® utility have sufficient confidence in considering implementation of a different braze filler material, a Be Replacement Test Program, involving out-reactor and in-reactor tests, is being undertaken as a collaborative endeavour by the Canadian nuclear industry. The out-reactor tests consist of: a constructability assessment to determine the material’s suitability with current fuel manufacturing methods; evaluation of

  3. Photoreactivating enzyme from Escherichia coli

    International Nuclear Information System (INIS)

    Snapka, R.M.; Fuselier, C.O.

    1977-01-01

    Escherichia coli photoreactivating enzyme (PRE) has been purified in large amounts from an E.coli strain lysogenic for a defective lambda bacteriophage carrying the phr gene. The resulting enzyme had a pH optimum of 7.2 and an ionic strength optimum of 0.18. It consisted of an apoprotein and cofactor, both of which were necessary for catalytic activity. The apoprotein had a monomer molecular weight of 35,200 and showed stable aggregates under denaturing conditions. The amino acid analysis of the E.coli enzyme was very similar to that of the photoreactivating enzyme from orchid seedlings (Cattelya aurantiaca). Both had arginine at the amino terminus. The cofactor, like the holoenzyme, showed absorption, magnetic circular dichroism, and emission properties indicative of an adenine moiety. Although the isolated enzyme had an action spectrum which peaked at about 360 nm, neither the cofactor, apoenzyme nor holoenzyme showed any detectable absorption between 300 and 400 nm. (author)

  4. Positron emitter labeled enzyme inhibitors

    International Nuclear Information System (INIS)

    Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.; Langstrom, B.

    1990-01-01

    This invention involves a new strategy for imagining and mapping enzyme activity in the living human and animal body using positron emitter-labeled suicide enzyme inactivators or inhibitors which become covalently bound to the enzyme as a result of enzymatic catalysis. Two such suicide inactivators for monoamine oxidase have been labeled with carbon-11 and used to map the enzyme subtypes in the living human and animal body using PET. By using positron emission tomography to image the distribution of radioactivity produced by the body penetrating radiation emitted by carbon-11, a map of functionally active monoamine oxidase activity is obtained. Clorgyline and L-deprenyl are suicide enzyme inhibitors and irreversibly inhibit monoamine oxidase. When these inhibitors are labeled with carbon-11 they provide selective probes for monoamine oxidase localization and reactivity in vivo using positron emission tomography

  5. Photoreactivating enzyme from Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Snapka, R M; Fuselier, C O [California Univ., Irvine (USA)

    1977-05-01

    Escherichia coli photoreactivating enzyme (PRE) has been purified in large amounts from an E.coli strain lysogenic for a defective lambda bacteriophage carrying the phr gene. The resulting enzyme had a pH optimum of 7.2 and an ionic strength optimum of 0.18. It consisted of an apoprotein and cofactor, both of which were necessary for catalytic activity. The apoprotein had a monomer molecular weight of 35,200 and showed stable aggregates under denaturing conditions. The amino acid analysis of the E.coli enzyme was very similar to that of the photoreactivating enzyme from orchid seedlings (Cattelya aurantiaca). Both had arginine at the amino terminus. The cofactor, like the holoenzyme, showed absorption, magnetic circular dichroism, and emission properties indicative of an adenine moiety. Although the isolated enzyme had an action spectrum which peaked at about 360 nm, neither the cofactor, apoenzyme nor holoenzyme showed any detectable absorption between 300 and 400 nm.

  6. A general approach to total repair cost limit replacement policies

    Directory of Open Access Journals (Sweden)

    F. Beichelt

    2014-01-01

    Full Text Available A common replacement policy for technical systems consists in replacing a system by a new one after its economic lifetime, i.e. at that moment when its long-run maintenance cost rate is minimal. However, the strict application of the economic lifetime does not take into account the individual deviations of maintenance cost rates of single systems from the average cost development. Hence, Beichet proposed the total repair cost limit replacement policy: the system is replaced by a new one as soon as its total repair cost reaches or exceeds a given level. He modelled the repair cost development by functions of the Wiener process with drift. Here the same policy is considered under the assumption that the one-dimensional probability distribution of the process describing the repair cost development is given. In the examples analysed, applying the total repair cost limit replacement policy instead of the economic life-time leads to cost savings of between 4% and 30%. Finally, it is illustrated how to include the reliability aspect into the policy.

  7. Radiation sterilization of enzyme hybrids with biodegradable polymers

    International Nuclear Information System (INIS)

    Furuta, Masakazu; Oka, Masahito; Hayashi, Toshio

    2002-01-01

    Ionizing radiations, which have already been utilized for the sterilization of medical supplies as well as gas fumigation, should be the final candidate to decontaminate 'hybrid' biomaterials containing bio-active materials including enzymes because irradiation induces neither heat nor substances affecting the quality of the materials and our health. In order to check the feasibility of 60 Co-gamma rays on these materials, we selected commercial proteases including papain and bromelain hybridized with commercial activated chitosan beads and demonstrated that these enzyme-hybrids suspended in water showed the significant radiation durability of more than twice as much as free enzyme solution at 25-kGy irradiation. Enhanced thermal and storage stability of the enzyme hybrids were not affected by the same dose level of irradiation, either, indicating that commercial irradiation sterilization method is applicable to enzyme hybrids without modification

  8. Structural analysis of enzymes used for bioindustry and bioremediation.

    Science.gov (United States)

    Tanokura, Masaru; Miyakawa, Takuya; Guan, Lijun; Hou, Feng

    2015-01-01

    Microbial enzymes have been widely applied in the large-scale, bioindustrial manufacture of food products and pharmaceuticals due to their high substrate specificity and stereoselectivity, and their effectiveness under mild conditions with low environmental burden. At the same time, bioremedial techniques using microbial enzymes have been developed to solve the problem of industrial waste, particularly with respect to persistent chemicals and toxic substances. And finally, structural studies of these enzymes have revealed the mechanistic basis of enzymatic reactions, including the stereoselectivity and binding specificity of substrates and cofactors. The obtained structural insights are useful not only to deepen our understanding of enzymes with potential bioindustrial and/or bioremedial application, but also for the functional improvement of enzymes through rational protein engineering. This review shows the structural bases for various types of enzymatic reactions, including the substrate specificity accompanying cofactor-controlled and kinetic mechanisms.

  9. Moderator inlet line hanger replacement for Pickering nuclear power station

    International Nuclear Information System (INIS)

    Kirkpatrick, R.A.; Bowman, J.M.; Symmons, W.R.; El-Nesr, S.

    1988-01-01

    Ontario Hydro's Pickering Nuclear Generating Station (PNGS), Units 1 and 2 were shutdown for large scale fuel channel replacement. Other nonroutine inspection and maintenance activities were performed to determine the overall condition of the units and it was seen that a moderator inlet line hanger (identified as HR-29) had failed in both units. Subsequent inspections during planned maintenance outages of Pickering NGS Units 3 and 4 revealed that hanger HR-29 had failed and required replacement. A research program was conducted to find a suitable technique. These problems included accessing tooling through small inspection ports, manipulating tooling from a significant distance and the high radiation fields within the vault. This paper describes the program undertaken to replace hanger HR-29. (author)

  10. Aortic Root Replacement for Children With Loeys-Dietz Syndrome.

    Science.gov (United States)

    Patel, Nishant D; Alejo, Diane; Crawford, Todd; Hibino, Narutoshi; Dietz, Harry C; Cameron, Duke E; Vricella, Luca A

    2017-05-01

    Loeys-Dietz syndrome (LDS) is an aggressive aortopathy with a proclivity for aortic aneurysm rupture and dissection at smaller diameters than other connective tissue disorders. We reviewed our surgical experience of children with LDS to validate our guidelines for prophylactic aortic root replacement (ARR). We reviewed all children (younger than 18 years) with a diagnosis of LDS who underwent ARR at our institution. The primary endpoint was mortality, and secondary endpoints included complications and the need for further interventions. Thirty-four children with LDS underwent ARR. Mean age at operation was 10 years, and 15 (44%) were female. Mean preoperative root diameter was 4 cm. Three children (9%) had composite ARR with a mechanical prosthesis, and 31 (91%) underwent valve-sparing ARR. Concomitant procedures included arch replacement in 2 (6%), aortic valve repair in 1 (3%), and patent foramen ovale closure in 16 (47%). There was no operative mortality. Two children (6%) required late replacement of the ascending aorta, 5 (15%) required arch replacement, 1 (3%) required mitral valve replacement, and 2 (6%) had coronary button aneurysms/pseudoaneurysms requiring repair. Three children required redo valve-sparing ARR after a Florida sleeve procedure, and 2 had progressive aortic insufficiency requiring aortic valve replacement after a valve-sparing procedure. There were 2 late deaths (6%). These data confirm the aggressive aortopathy of LDS. Valve-sparing ARR should be performed when feasible to avoid the risks of prostheses. Serial imaging of the arterial tree is critical, given the rate of subsequent intervention. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  11. 30 CFR 57.19122 - Replacement parts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Replacement parts. 57.19122 Section 57.19122 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Inspection and Maintenance § 57.19122 Replacement parts. Parts used to repair hoists shall have properties...

  12. Transcatheter Aortic Valve Replacement in Europe

    DEFF Research Database (Denmark)

    Mylotte, Darren; Osnabrugge, Ruben L J; Windecker, Stephan

    2013-01-01

    The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy.......The authors sought to examine the adoption of transcatheter aortic valve replacement (TAVR) in Western Europe and investigate factors that may influence the heterogeneous use of this therapy....

  13. 30 CFR 56.19122 - Replacement parts.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Replacement parts. 56.19122 Section 56.19122 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE... Inspection and Maintenance § 56.19122 Replacement parts. Parts used to repair hoists shall have properties...

  14. An abstract machine for module replacement

    OpenAIRE

    Walton, Chris; Krl, Dilsun; Gilmore, Stephen

    1998-01-01

    In this paper we define an abstract machine model for the mλ typed intermediate language. This abstract machine is used to give a formal description of the operation of run-time module replacement from the programming language Dynamic ML. The essential technical device which we employ for module replacement is a modification of two-space copying garbage collection.

  15. Temelin NPP - IandC replacement

    International Nuclear Information System (INIS)

    Spalenka, I.

    1997-01-01

    The original instrumentation and control system of the Temelin nuclear power plant is being upgraded and replaced by a modern Westinghouse-supplied system which meets the requirements imposed on current nuclear power plant designs. The history and purpose of the IandC system replacement is given, and the design of the new system is described in some detail. (A.K.)

  16. Replacement Value of fermented millet ( Pennisetum americanum ...

    African Journals Online (AJOL)

    The replacement value of fermented millet for maize in the diets of Clarias gariepinus fingerlings reared in a recirculation system was determined. Five isonitrogenous diets were formulated to contain graded levels of fermented millet meal replacing 0, 20, 40, 60 and 80% of maize and fed to triplicate groups of fingerlings ...

  17. 30 CFR 823.14 - Soil replacement.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Soil replacement. 823.14 Section 823.14 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR PERMANENT PROGRAM PERFORMANCE STANDARDS SPECIAL PERMANENT PROGRAM PERFORMANCE STANDARDS-OPERATIONS ON PRIME FARMLAND § 823.14 Soil replacement. (a) Soil...

  18. 7 CFR 1944.659 - Replacement housing.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Replacement housing. 1944.659 Section 1944.659 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) PROGRAM REGULATIONS (CONTINUED) HOUSING Housing Preservation Grants § 1944.659 Replacement housing...

  19. the influence of replacing maize with chrysophyllum albidum seed

    African Journals Online (AJOL)

    AGROSEARCH UIL

    Starch. 17.22. 17.66. 18.09. 18.53. 18.97. Total. 100. 100. 100. 100. 100 ... Water temperature and dissolved oxygen were measured using a combined digital .... Aderolu and Oyedokun (2009) reported that high fibre in diets limits the rate of digestion ... the activity of various enzymes system including amylase and possibly.

  20. Microbial nitrilases: versatile, spiral forming, industrial enzymes.

    Science.gov (United States)

    Thuku, R N; Brady, D; Benedik, M J; Sewell, B T

    2009-03-01

    The nitrilases are enzymes that convert nitriles to the corresponding acid and ammonia. They are members of a superfamily, which includes amidases and occur in both prokaryotes and eukaryotes. The superfamily is characterized by having a homodimeric building block with a alpha beta beta alpha-alpha beta beta alpha sandwich fold and an active site containing four positionally conserved residues: cys, glu, glu and lys. Their high chemical specificity and frequent enantioselectivity makes them attractive biocatalysts for the production of fine chemicals and pharmaceutical intermediates. Nitrilases are also used in the treatment of toxic industrial effluent and cyanide remediation. The superfamily enzymes have been visualized as dimers, tetramers, hexamers, octamers, tetradecamers, octadecamers and variable length helices, but all nitrilase oligomers have the same basic dimer interface. Moreover, in the case of the octamers, tetradecamers, octadecamers and the helices, common principles of subunit association apply. While the range of industrially interesting reactions catalysed by this enzyme class continues to increase, research efforts are still hampered by the lack of a high resolution microbial nitrilase structure which can provide insights into their specificity, enantioselectivity and the mechanism of catalysis. This review provides an overview of the current progress in elucidation of structure and function in this enzyme class and emphasizes insights that may lead to further biotechnological applications.

  1. BAKERY ENZYMES IN CEREAL TECHNOLOGIES

    Directory of Open Access Journals (Sweden)

    Václav Koman

    2012-10-01

    Full Text Available Normal 0 21 false false false SK X-NONE X-NONE Bread is the most common and traditional food in the world. For years, enzymes such as malt and fungal alpha-amylase have been used in bread making. Due to the changes in the baking industry and the ever-increasing demand for more natural products, enzymes have gained real importance in bread-making. If an enzyme is added, it is often destroyed by the heat during the baking process. For generations, enzymes have been used for the improvement of texture and appearance, enhancement of nutritional values and generation of appealing flavours and aromas. Enzymes used in bakery industry constitute nearly one third of the market. The bakery products have undergone radical improvements in quality over the past years in terms of flavour, texture and shelf-life. The the biggest contributor for these improvementsis the usage of enzymes. Present work seeks to systematically describe bakery enzymes, their classification, benefits, usage and chemical reactions in the bread making process.doi:10.5219/193

  2. Enzymes involved in organellar DNA replication in photosynthetic eukaryotes.

    Science.gov (United States)

    Moriyama, Takashi; Sato, Naoki

    2014-01-01

    Plastids and mitochondria possess their own genomes. Although the replication mechanisms of these organellar genomes remain unclear in photosynthetic eukaryotes, several organelle-localized enzymes related to genome replication, including DNA polymerase, DNA primase, DNA helicase, DNA topoisomerase, single-stranded DNA maintenance protein, DNA ligase, primer removal enzyme, and several DNA recombination-related enzymes, have been identified. In the reference Eudicot plant Arabidopsis thaliana, the replication-related enzymes of plastids and mitochondria are similar because many of them are dual targeted to both organelles, whereas in the red alga Cyanidioschyzon merolae, plastids and mitochondria contain different replication machinery components. The enzymes involved in organellar genome replication in green plants and red algae were derived from different origins, including proteobacterial, cyanobacterial, and eukaryotic lineages. In the present review, we summarize the available data for enzymes related to organellar genome replication in green plants and red algae. In addition, based on the type and distribution of replication enzymes in photosynthetic eukaryotes, we discuss the transitional history of replication enzymes in the organelles of plants.

  3. Hydrolytic enzyme activity enhanced by Barium supplementation

    Directory of Open Access Journals (Sweden)

    Camilo Muñoz

    2016-10-01

    Full Text Available Hydrolysis of polymers is a first and often limiting step during the degradation of plant residues. Plant biomass is generally a major component of waste residues and a major renewable resource to obtain a variety of secondary products including biofuels. Improving the performance of enzymatic hydrolysis of plant material with minimum costs and limiting the use of additional microbial biomass or hydrolytic enzymes directly influences competitiveness of these green biotechnological processes. In this study, we cloned and expressed a cellulase and two esterases recovered from environmental thermophilic soil bacterial communities and characterize their optimum activity conditions including the effect of several metal ions. Results showed that supplementing these hydrolytic reactions with Barium increases the activity of these extracellular hydrolytic enzymes. This observation represents a simple but major improvement to enhance the efficiency and competitiveness of this process within an increasingly important biotechnological sector.

  4. [Automated analyzer of enzyme immunoassay].

    Science.gov (United States)

    Osawa, S

    1995-09-01

    Automated analyzers for enzyme immunoassay can be classified by several points of view: the kind of labeled antibodies or enzymes, detection methods, the number of tests per unit time, analytical time and speed per run. In practice, it is important for us consider the several points such as detection limits, the number of tests per unit time, analytical range, and precision. Most of the automated analyzers on the market can randomly access and measure samples. I will describe the recent advance of automated analyzers reviewing their labeling antibodies and enzymes, the detection methods, the number of test per unit time and analytical time and speed per test.

  5. Replacing lactose from calf milk replacers : effects on digestion and post-absorptive metabolism

    NARCIS (Netherlands)

    Gilbert, M.S.

    2015-01-01

    Summary PhD thesis Myrthe S. Gilbert

    Replacing lactose from calf milk replacers – Effects on digestion and post-absorptive metabolism

    Veal calves are fed milk replacer (MR) and solid feed. The largest part of the energy provided to veal calves

  6. Pipe replacement in a water supply network: coordinated versus uncoordinated replacement and budget effects

    NARCIS (Netherlands)

    Dijk, van D.; Hendrix, E.M.T.

    2016-01-01

    Operators of underground water supply networks are challenged with pipe replacement
    decisions, because pipes are subject to increased failure rates as they age and financial resources
    are often limited.We study the optimal replacement time and optimal number of pipe replacements
    such

  7. Microbial keratinases: industrial enzymes with waste management potential.

    Science.gov (United States)

    Verma, Amit; Singh, Hukum; Anwar, Shahbaz; Chattopadhyay, Anirudha; Tiwari, Kapil K; Kaur, Surinder; Dhilon, Gurpreet Singh

    2017-06-01

    Proteases are ubiquitous enzymes that occur in various biological systems ranging from microorganisms to higher organisms. Microbial proteases are largely utilized in various established industrial processes. Despite their numerous industrial applications, they are not efficient in hydrolysis of recalcitrant, protein-rich keratinous wastes which result in environmental pollution and health hazards. This paved the way for the search of keratinolytic microorganisms having the ability to hydrolyze "hard to degrade" keratinous wastes. This new class of proteases is known as "keratinases". Due to their specificity, keratinases have an advantage over normal proteases and have replaced them in many industrial applications, such as nematicidal agents, nitrogenous fertilizer production from keratinous waste, animal feed and biofuel production. Keratinases have also replaced the normal proteases in the leather industry and detergent additive application due to their better performance. They have also been proved efficient in prion protein degradation. Above all, one of the major hurdles of enzyme industrial applications (cost effective production) can be achieved by using keratinous waste biomass, such as chicken feathers and hairs as fermentation substrate. Use of these low cost waste materials serves dual purposes: to reduce the fermentation cost for enzyme production as well as reducing the environmental waste load. The advent of keratinases has given new direction for waste management with industrial applications giving rise to green technology for sustainable development.

  8. Substrates and method for determining enzymes

    Science.gov (United States)

    Smith, R.E.; Bissell, E.R.

    1981-10-13

    A method is disclosed for determining the presence of an enzyme in a biological fluid, which includes the steps of contacting the fluid with a synthetic chromogenic substrate, which is an amino acid derivative of 7-amino-4-trifluoromethylcoumarin; incubating the substrate-containing fluid to effect enzymatic hydrolysis; and fluorometrically determining the presence of the free 7-amino-4-trifluoromethylcoumarin chromophore in the hydrolyzate. No Drawings

  9. Nedd8 processing enzymes in Schizosaccharomyces pombe

    DEFF Research Database (Denmark)

    O'Donoghue, Jean; Bech-Otschir, Dawadschargal; Larsen, Ida

    2013-01-01

    Conjugation of the ubiquitin-like modifier Nedd8 to cullins is critical for the function of SCF-type ubiquitin ligases and thus facilitates ubiquitin conjugation and ultimately degradation of SCF substrates, including several cell cycle regulators. Like ubiquitin, Nedd8 is produced as a precursor...... that must first be processed before it becomes active. In Saccharomyces cerevisiae this is carried out exclusively by the enzyme Yuh1....

  10. Spectroscopic studies of copper enzymes

    International Nuclear Information System (INIS)

    Dooley, D.M.; Moog, R.; Zumft, W.; Koenig, S.H.; Scott, R.A.; Cote, C.E.; McGuirl, M.

    1986-01-01

    Several spectroscopic methods, including absorption, circular dichroism (CD), magnetic CD (MCD), X-ray absorption, resonance Raman, EPR, NMR, and quasi-elastic light-scattering spectroscopy, have been used to probe the structures of copper-containing amine oxidases, nitrite reductase, and nitrous oxide reductase. The basic goals are to determine the copper site structure, electronic properties, and to generate structure-reactivity correlations. Collectively, the results on the amine oxidases permit a detailed model for the Cu(II) sites in these enzymes to be constructed that, in turn, rationalizes the ligand-binding chemistry. Resonance Raman spectra of the phenylhydrazine and 2,4-dinitrophenyl-hydrazine derivatives of bovine plasma amine oxidase and models for its organic cofactor, e.g. pyridoxal, methoxatin, are most consistent with methoxatin being the intrinsic cofactor. The structure of the Cu(I) forms of the amine oxidases have been investigated by X-ray absorption spectroscopy (XAS); the copper coordination geometry is significantly different in the oxidized and reduced forms. Some anomalous properties of the amine oxidases in solution are explicable in terms of their reversible aggregation, which the authors have characterized via light scattering. Nitrite and nitrous oxide reductases display several novel spectral properties. The data suggest that new types of copper sites are present

  11. Nitrilase enzymes and their role in plant–microbe interactions

    OpenAIRE

    Howden, Andrew J. M.; Preston, Gail M.

    2009-01-01

    Summary Nitrilase enzymes (nitrilases) catalyse the hydrolysis of nitrile compounds to the corresponding carboxylic acid and ammonia, and have a wide range of industrial and biotechnological applications, including the synthesis of industrially important carboxylic acids and bioremediation of cyanide and toxic nitriles. Nitrilases are produced by a wide range of organisms, including plants, bacteria and fungi, but despite their biotechnological importance, the role of these enzymes in living ...

  12. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis

    OpenAIRE

    Elahi, Maqsood M.; Choi, Charles H.; Konda, Subbareddy; Shake, Jay G.

    2015-01-01

    This report describes a patient's self-substitution of nattokinase for the vitamin K antagonist warfarin after aortic valve replacement with a mechanical prosthesis. Nattokinase is an enzyme derived from a popular fermented soybean preparation in Japan (natto), which has fibrinolytic properties and is gaining popularity in nontraditional health journals and nonmedical health websites as an over-the-counter thrombolytic. After nearly a year of use of nattokinase without warfarin, the patient d...

  13. A review on seashells ash as partial cement replacement

    Science.gov (United States)

    Mohammad, Wan Ahmad Soffian Bin Wan; Hazurina Othman, Nor; Ibrahim, Mohd Haziman Wan; Rahim, Masazurah A.; Shahidan, Shahiron; Rahman, Raha Abd

    2017-11-01

    This review paper emphasis on various sea shells ash such as cockle, clam, oyster, mollusc, periwinkle, snail, and green mussel shell ash as partial cement replacement and its objective is to create sustainable environment and reduce problems of global warming. Cement production give huge impact to environment in every stage of its production. These include air pollution in form of dust and, gases, sound and vibration during quarry crushing and milling. One of the solutions to solve this problem is by using modified cement. The modified cement is a cementitious material that meets or exceeds the Portland cement performance by combining and optimizes the recycle and wasted materials. This will indirectly reduce the use of raw materials and then, become a sustain construction materials. Therefore, the replacement of cement in concrete by various sea shell ash may create tremendous saving of energy and also leads to important environmental benefits. This study includes previous investigation done on the properties of chemical and mechanical such as specific gravity, chemical composition, compressive strength, tensile strength and flexural strength of concrete produced using partial replacement of cement by seashells ash. Results show that the optimum percentage of seashells as cement replacement is between 4 - 5%.

  14. Multi-enzyme Process Modeling

    DEFF Research Database (Denmark)

    Andrade Santacoloma, Paloma de Gracia

    are affected (in a positive or negative way) by the presence of the other enzymes and compounds in the media. In this thesis the concept of multi-enzyme in-pot term is adopted for processes that are carried out by the combination of enzymes in a single reactor and implemented at pilot or industrial scale...... features of the process and provides the information required to structure the process model by using a step-by-step procedure with the required tools and methods. In this way, this framework increases efficiency of the model development process with respect to time and resources needed (fast and effective....... In this way the model parameters that drives the main dynamic behavior can be identified and thus a better understanding of this type of processes. In order to develop, test and verify the methodology, three case studies were selected, specifically the bi-enzyme process for the production of lactobionic acid...

  15. GRE Enzymes for Vector Analysis

    Data.gov (United States)

    U.S. Environmental Protection Agency — Microbial enzyme data that were collected during the 2004-2006 EMAP-GRE program. These data were then used by Moorhead et al (2016) in their ecoenzyme vector...

  16. Watching Individual Enzymes at Work

    Science.gov (United States)

    Blank, Kerstin; Rocha, Susana; De Cremer, Gert; Roeffaers, Maarten B. J.; Uji-i, Hiroshi; Hofkens, Johan

    Single-molecule fluorescence experiments are a powerful tool to analyze reaction mechanisms of enzymes. Because of their unique potential to detect heterogeneities in space and time, they have provided unprecedented insights into the nature and mechanisms of conformational changes related to the catalytic reaction. The most important finding from experiments with single enzymes is the generally observed phenomenon that the catalytic rate constants fluctuate over time (dynamic disorder). These fluctuations originate from conformational changes occurring on time scales, which are similar to or slower than that of the catalytic reaction. Here, we summarize experiments with enzymes that show dynamic disorder and introduce new experimental strategies showing how single-molecule fluorescence experiments can be applied to address other open questions in medical and industrial enzymology, such as enzyme inactivation processes, reactant transfer in cascade reactions, and the mechanisms of interfacial catalysis.

  17. Photosynthetic fuel for heterologous enzymes

    DEFF Research Database (Denmark)

    Mellor, Silas Busck; Vavitsas, Konstantinos; Nielsen, Agnieszka Janina Zygadlo

    2017-01-01

    of reducing power. Recent work on the metabolic engineering of photosynthetic organisms has shown that the electron carriers such as ferredoxin and flavodoxin can be used to couple heterologous enzymes to photosynthetic reducing power. Because these proteins have a plethora of interaction partners and rely...... on electrostatically steered complex formation, they form productive electron transfer complexes with non-native enzymes. A handful of examples demonstrate channeling of photosynthetic electrons to drive the activity of heterologous enzymes, and these focus mainly on hydrogenases and cytochrome P450s. However......, competition from native pathways and inefficient electron transfer rates present major obstacles, which limit the productivity of heterologous reactions coupled to photosynthesis. We discuss specific approaches to address these bottlenecks and ensure high productivity of such enzymes in a photosynthetic...

  18. Delirium After Transcatheter Aortic Valve Replacement.

    Science.gov (United States)

    Giuseffi, Jennifer L; Borges, Nyal E; Boehm, Leanne M; Wang, Li; McPherson, John A; Fredi, Joseph L; Ahmad, Rashid M; Ely, E Wesley; Pandharipande, Pratik P

    2017-07-01

    Postoperative delirium is associated with increased mortality. Patients undergoing transcatheter aortic valve replacement are at risk for delirium because of comorbid conditions. To compare the incidence, odds, and mortality implications of delirium between patients undergoing transcatheter replacement and patients undergoing surgical replacement. The Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the Intensive Care Unit were used to assess arousal level and delirium prospectively in all patients with severe aortic stenosis who had transcatheter or surgical aortic valve replacement at an academic medical center. Multivariable logistic regression was used to determine the relationship between procedure type and occurrence of delirium. Cox regression was used to assess the association between postoperative delirium and 6-month mortality. A total of 105 patients had transcatheter replacement and 121 had surgical replacement. Patients in the transcatheter group were older (median age, 81 vs 68 years; P replacement. Delirium is less likely to develop in the transcatheter group but is associated with higher mortality in both groups. ©2017 American Association of Critical-Care Nurses.

  19. Optimum body size of Holstein replacement heifers.

    Science.gov (United States)

    Hoffman, P C

    1997-03-01

    Criteria that define optimum body size of replacement heifers are required by commercial dairy producers to evaluate replacement heifer management programs. Historically recommended body size criteria have been based on live BW measurements. Numerous research studies have observed a positive relationship between BW at first calving and first lactation milk yield, which has served as the impetus for using live BW to define body size of replacement heifers. Live BW is, however, not the only available measurement to define body size. Skeletal measurements such as wither height, length, and pelvic area have been demonstrated to be related to first lactation performance and (or) dystocia. Live BW measurements also do not define differences in body composition. Differences in body composition of replacement heifers at first calving are also related to key performance variables. An updated research data base is available for the modern Holstein genotype to incorporate measures of skeletal growth and body composition with BW when defining body size. These research projects also lend insight into the relative importance of measurements that define body size of replacement heifers. Incorporation of these measurements from current research into present BW recommendations should aid commercial dairy producers to better define replacement heifer growth and management practices. This article proposes enhancements in defining optimum body size and growth characteristics of Holstein replacement heifers.

  20. Comparing replacement rates under private and federal retirement systems.

    Science.gov (United States)

    Martin, Patricia P

    One measure of the adequacy of retirement income is replacement rate - the percentage of pre-retirement salary that is available to a worker in retirement. This article compares salary replacement rates for private-sector employees of medium and large private establishments with those for federal employees under the Civil Service Retirement System and the Federal Employees Retirement System. Because there is no standard benefit formula to represent the variety of formulas available in the private sector, a composite defined benefit formula was developed using the characteristics of plans summarized in the Bureau of Labor Statistics Medium and Large Employer Plan Survey. The resulting "typical" private-sector defined benefit plan, with an accompanying defined contribution plan, was then compared with the two federal systems. The Civil Service Retirement System (CSRS) is a stand-alone defined benefit plan whose participants are not covered by Social Security. Until passage of the 1983 Amendments to Social Security Act, it was the only retirement plan for most federal civilian employees. Provisions of the 1983 Amendments were designed to restore long-term financial stability to the Social Security trust funds. One provision created the Federal Employees Retirement System (FERS), which covers federal employees hired after 1983. It was one of the provisions designed to restore long-term financial stability to the Social Security trust funds. FERS employees contribute to and are covered by Social Security. FERS, which is a defined benefit plan, also includes a basic benefit and a 401(k)-type plan known as the Thrift Savings Plan (TSP). To compare how retirees would fare under the three different retirement systems, benefits of employees retiring at age 65 with 35 years of service were calculated using hypothetical workers with steady earnings. Workers were classified according to a percentage of the average wage in the economy: low earners (45 percent), average earners

  1. DGAT enzymes and triacylglycerol biosynthesis

    OpenAIRE

    Yen, Chi-Liang Eric; Stone, Scot J.; Koliwad, Suneil; Harris, Charles; Farese, Robert V.

    2008-01-01

    Triacylglycerols (triglycerides) (TGs) are the major storage molecules of metabolic energy and FAs in most living organisms. Excessive accumulation of TGs, however, is associated with human diseases, such as obesity, diabetes mellitus, and steatohepatitis. The final and the only committed step in the biosynthesis of TGs is catalyzed by acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes. The genes encoding two DGAT enzymes, DGAT1 and DGAT2, were identified in the past decade, ...

  2. Enzymes: principles and biotechnological applications

    Science.gov (United States)

    Robinson, Peter K.

    2015-01-01

    Enzymes are biological catalysts (also known as biocatalysts) that speed up biochemical reactions in living organisms, and which can be extracted from cells and then used to catalyse a wide range of commercially important processes. This chapter covers the basic principles of enzymology, such as classification, structure, kinetics and inhibition, and also provides an overview of industrial applications. In addition, techniques for the purification of enzymes are discussed. PMID:26504249

  3. de novo computational enzyme design.

    Science.gov (United States)

    Zanghellini, Alexandre

    2014-10-01

    Recent advances in systems and synthetic biology as well as metabolic engineering are poised to transform industrial biotechnology by allowing us to design cell factories for the sustainable production of valuable fuels and chemicals. To deliver on their promises, such cell factories, as much as their brick-and-mortar counterparts, will require appropriate catalysts, especially for classes of reactions that are not known to be catalyzed by enzymes in natural organisms. A recently developed methodology, de novo computational enzyme design can be used to create enzymes catalyzing novel reactions. Here we review the different classes of chemical reactions for which active protein catalysts have been designed as well as the results of detailed biochemical and structural characterization studies. We also discuss how combining de novo computational enzyme design with more traditional protein engineering techniques can alleviate the shortcomings of state-of-the-art computational design techniques and create novel enzymes with catalytic proficiencies on par with natural enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. How to replace a reactor pressure vessel

    International Nuclear Information System (INIS)

    Huber, R.

    1996-01-01

    A potential life extending procedure for a nuclear reactor after, say, 40 years of service life, might in some circumstances be the replacement of the reactor pressure vessel. Neutron induced degradation of the vessel might make replacement by one of a different material composition desirable, for example. Although the replacement of heavy components, such as steam generators, has been possible for many years, the pressure vessel presents a much more demanding task if only because it is highly irradiated. Some preliminary feasibility studies by Siemens are reported for the two removal strategies that might be considered. These are removal of the entire pressure vessel in one piece and dismantling it into sections. (UK)

  5. The influence of NSAIDs on coumarin sensitivity in patients with CYP2C9 polymorphism after total hip replacement surgery.

    NARCIS (Netherlands)

    Beinema, M.J.; Jong, P.H. de; Salden, H.J.; Wijnen, M.H.W.A.; Meer, J.W.M. van der; Brouwers, J.R.B.J.

    2007-01-01

    OBJECTIVE: To determine the influence of NSAIDs on the international normalized ratio (INR) in patients with cytochrome P450 (CYP)-2C9 enzyme variants starting acenocoumarol (an oral coumarin) therapy during the first 7 days after total hip replacement surgery. METHODS: In this prospective study, an

  6. The influence of NSAIDs on coumarin sensitivity in patients with CYP2C9 polymorphism after total hip replacement surgery

    NARCIS (Netherlands)

    Beinema, Maarten J.; de Jong, Petra H.; Salden, Har J. M.; van Wijnen, Merel; van der Meer, Jan; Brouwers, Jacobus R. B. J.

    2007-01-01

    Objective: To determine the influence of NSAIDs on the international normalized ratio (INR) in patients with cytochrome P450 (CYP)-2C9 enzyme variants starting acenocoumarol (an oral coumarin) therapy during the first 7 days after total hip replacement surgery. Methods: In this prospective study, an

  7. Replacement energy, capacity, and reliability costs for permanent nuclear reactor shutdowns

    International Nuclear Information System (INIS)

    VanKuiken, J.C., Buehring, W.A.; Hamilton, S.; Kavicky, J.A.; Cavallo, J.D.; Veselka, T.D.; Willing, D.L.

    1993-10-01

    Average replacement power costs are estimated for potential permanent shutdowns of nuclear electricity-generating units. Replacement power costs are considered to include replacement energy, capacity, and reliability cost components. These estimates were developed to assist the US Nuclear Regulatory Commission in evaluating regulatory issues that potentially affect changes in serious reactor accident frequencies. Cost estimates were derived from long-term production-cost and capacity expansion simulations of pooled utility-system operations. Factors that affect replacement power cost, such as load growth, replacement sources of generation, and capital costs for replacement capacity, were treated in the analysis. Costs are presented for a representative reactor and for selected subcategories of reactors, based on estimates for 112 individual reactors

  8. Study of wettability of calcite surfaces using oil-brine-enzyme systems for enhanced oil recovery applications

    DEFF Research Database (Denmark)

    Khusainova, Alsu; Nielsen, Sidsel Marie; Pedersen, Hanne Høst

    2015-01-01

    and adhesion behaviour tests. Comparative studies with a surfactant, protein, purified enzyme, enzyme stabiliser using n-decane (as a model for the oil) have also been carried out in order to verify experimental results. The enzymes that have the highest effect on the wettability have been identified. Those...... action has been found to be replacement of oil at the solid surface by the enzyme. Other mechanisms (modification of the surface tension or catalytic modification of hydrocarbons resulting in reducing the oil viscosity) have shown to be much less pronounced from the measurements reported here....

  9. Evaluation of biochemical parameters and productive performance of japanese quail in response to the replacement of soybean meal with canola meal

    Directory of Open Access Journals (Sweden)

    Ali Asghar Saki

    2017-02-01

    Full Text Available The present study was conducted to evaluation the different levels canola meal (CM replacement by soybean meal (SBM in Japanese quails diets on productive performance, egg quality trails and blood parameters including blood protein, minerals concentration, liver enzymes and thyroid hormones. In this study, 160 of Japanese quails in second laying phase from 46 to 56 weeks of age were divided in four treatments with four replicates and 10 quail in each per replicate, on a completely randomized design (CRD.Treatments consisted:T1 control (without CM, T2, T3 and T4 replacing 30, 60 and 90% of SBM with CM respectively. The results were shown no significant variation in body weight between treatments in initial and end of the experiment (p > 0.05. There was significant decrease in feed intake by increasing level of CM (p 0.05. However, the egg shell thickness showed significantly decreased with increasing levels of canola meal in the diet  (p < 0.05. According to this study results, 30% replacement of SBM by CM in the diet (contained 10% CM has no adverse effect on quail’s performance.

  10. Modified prokaryotic glucose isomerase enzymes with altered pH activity profiles

    NARCIS (Netherlands)

    Lambeir, Anne-Marie; Lasters, Ignace; Mrabet, Nadir; Quax, Wim; Van Der Laan, Jan M.; Misset, Onno

    1994-01-01

    A method for selecting amino acid residues is disclosed which upon replacement will give rise to an enzyme with an altered pH optimum. The method is specific for metalloenzymes which are inactivated at low pH due to the dissociation of the metal ions. The method is based on altering the pKa of the

  11. Recent advances in enzyme extraction strategies: A comprehensive review.

    Science.gov (United States)

    Nadar, Shamraja S; Pawar, Rohini G; Rathod, Virendra K

    2017-08-01

    The increasing interest of industrial enzymes demands for development of new downstream strategies for maximizing enzyme recovery. The significant efforts have been focused on the development of newly adapted technologies to purify enzymes in catalytically active form. Recently, an aqueous two phase system (ATPS) is emerged as powerful tools for efficient extraction and purification of enzymes due to their versatility, lower cost, process integration capability and easy scale-up. The present review gives an overview of effect of parameters such as tie line length, pH, neutral salts, properties of polymer and salt involved in traditional polymer/polymer and polymer/salt ATPS for enzyme recovery. Further, advanced ATPS have been developed based on alcohols, surfactants, micellar compounds to avoid tedious recovery steps for getting desired enzyme. In order to improve the selectivity and efficiency of ATPS, recent approaches of conventional ATPS combined with different techniques like affinity ligands, ionic liquids, thermoseparating polymers and microfluidic device based ATPS have been reviewed. Moreover, three phase partitioning is also highlighted for enzymes enrichment as a blooming technology for efficiently integrated bioseparation techniques. At the end, it includes an overview of CLEAs technology and organic-inorganic nanoflowers preparation as novel strategies for simultaneous extraction, purification and immobilization of enzymes. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Soluble inhibitors/deactivators of cellulase enzymes from lignocellulosic biomass.

    Science.gov (United States)

    Kim, Youngmi; Ximenes, Eduardo; Mosier, Nathan S; Ladisch, Michael R

    2011-04-07

    Liquid hot water, steam explosion, and dilute acid pretreatments of lignocellulose generate soluble inhibitors which hamper enzymatic hydrolysis as well as fermentation of sugars to ethanol. Toxic and inhibitory compounds will vary with pretreatment and include soluble sugars, furan derivatives (hydroxymethyl fulfural, furfural), organic acids (acetic, formic and, levulinic acid), and phenolic compounds. Their effect is seen when an increase in the concentration of pretreated biomass in a hydrolysis slurry results in decreased cellulose conversion, even though the ratio of enzyme to cellulose is kept constant. We used lignin-free cellulose, Solka Floc, combined with mixtures of soluble components released during pretreatment of wood, to prove that the decrease in the rate and extent of cellulose hydrolysis is due to a combination of enzyme inhibition and deactivation. The causative agents were extracted from wood pretreatment liquid using PEG surfactant, activated charcoal or ethyl acetate and then desorbed, recovered, and added back to a mixture of enzyme and cellulose. At enzyme loadings of either 1 or 25mg protein/g glucan, the most inhibitory components, later identified as phenolics, decreased the rate and extent of cellulose hydrolysis by half due to both inhibition and precipitation of the enzymes. Full enzyme activity occurred when the phenols were removed. Hence detoxification of pretreated woods through phenol removal is expected to reduce enzyme loadings, and therefore reduce enzyme costs, for a given level of cellulose conversion. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. MMIC Replacement for Gunn Diode Oscillators

    Science.gov (United States)

    Crowe, Thomas W.; Porterfield, David

    2011-01-01

    An all-solid-state replacement for high-frequency Gunn diode oscillators (GDOs) has been proposed for use in NASA s millimeter- and submillimeter-wave sensing instruments. Highly developed microwave oscillators are used to achieve a low-noise and highly stable reference signal in the 10-40-GHz band. Compact amplifiers and high-power frequency multipliers extend the signal to the 100-500-GHz band with minimal added phase noise and output power sufficient for NASA missions. This technology can achieve improved output power and frequency agility, while maintaining phase noise and stability comparable to other GDOs. Additional developments of the technology include: a frequency quadrupler to 145 GHz with 18 percent efficiency and 15 percent fixed tuned bandwidth; frequency doublers featuring 124, 240, and 480 GHz; an integrated 874-GHz subharmonic mixer with a mixer noise temperature of 3,000 K DSB (double sideband) and mixer conversion loss of 11.8 dB DSB; a high-efficiency frequency tripler design with peak output power of 23 mW and 14 mW, and efficiency of 16 and 13 percent, respectively; millimeter-wave integrated circuit (MMIC) power amplifiers to the 30-40 GHz band with high DC power efficiency; and an 874-GHz radiometer suitable for airborne observation with state-of-the-art sensitivity at room temperature and less than 5 W of total power consumption.

  14. Hormone replacement therapy in cancer survivors: Utopia?

    Science.gov (United States)

    Angioli, Roberto; Luvero, Daniela; Armento, Grazia; Capriglione, Stella; Plotti, Francesco; Scaletta, Giuseppe; Lopez, Salvatore; Montera, Roberto; Gatti, Alessandra; Serra, Giovan Battista; Benedetti Panici, Pierluigi; Terranova, Corrado

    2018-04-01

    As growing of old women population, menopausal women will also increase: an accurate estimation of postmenopausal population is an essential information for health care providers considering that with aging, the incidence of all cancers is expected to increase. Hormone replacement therapy (HRT) has proven to be highly effective in alleviating menopausal symptoms such as hot flashes, night sweats, dyspareunia, sexual disorders, and insomnia and in preventing osteoporosis. According to preclinical data, estrogen and progesterone are supposed to be involved in the induction and progression of breast and endometrial cancers. Similarly, in epithelial ovarian cancer (EOC), the pathogenesis seems to be at least partly hormonally influenced. Is HRT in gynecological cancer survivors possible? The literature data are controversial. Many clinicians remain reluctant to prescribe HRT for these patients due to the fear of relapse and the risk to develop coronary heart disease or breast cancer. Before the decision to use HRT an accurate counselling should be mandatory in order to individualizing on the basis of potential risks and benefits, including a close follow-up. Nevertheless, we do believe that with strong informed consent doctors may individually consider to prescribe some course of HRT in order to minimize menopausal symptoms and disease related to hormonal reduction. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Process optimized minimally invasive total hip replacement

    Directory of Open Access Journals (Sweden)

    Philipp Gebel

    2012-02-01

    Full Text Available The purpose of this study was to analyse a new concept of using the the minimally invasive direct anterior approach (DAA in total hip replacement (THR in combination with the leg positioner (Rotex- Table and a modified retractor system (Condor. We evaluated retrospectively the first 100 primary THR operated with the new concept between 2009 and 2010, regarding operation data, radiological and clinical outcome (HOOS. All surgeries were perfomed in a standardized operation technique including navigation. The average age of the patients was 68 years (37 to 92 years, with a mean BMI of 26.5 (17 to 43. The mean time of surgery was 80 min. (55 to 130 min. The blood loss showed an average of 511.5 mL (200 to 1000 mL. No intra-operative complications occurred. The postoperative complication rate was 6%. The HOOS increased from 43 points pre-operatively to 90 (max 100 points 3 months after surgery. The radiological analysis showed an average cup inclination of 43° and a leg length discrepancy in a range of +/- 5 mm in 99%. The presented technique led to excellent clinic results, showed low complication rates and allowed correct implant positions although manpower was saved.

  16. Surfactant replacement therapy--economic impact.

    Science.gov (United States)

    Pejaver, R K; al Hifzi, I; Aldussari, S

    2001-06-01

    Surfactant replacement is an effective treatment for neonatal respiratory distress syndrome. (RDS). As widespread use of surfactant is becoming a reality, it is important to assess the economic implications of this new form of therapy. A comparison study was carried out at the Neonatal Intensive Care Unit (NICU) of Northwest Armed Forces Hospital, Saudi Arabia. Among 75 infants who received surfactant for RDS and similar number who were managed during time period just before the surfactant was available, but by set criteria would have made them eligible for surfactant. All other management modalities except surfactant were the same for all these babies. Based on the intensity of monitoring and nursing care required by the baby, the level of care was divided as: Level IIIA, IIIB, Level II, Level I. The cost per day per bed for each level was calculated, taking into account the use of hospital immovable equipment, personal salaries of nursing, medical, ancillary staff, overheads and maintenance, depreciation and replacement costs. Medications used, procedures done, TPN, oxygen, were all added to individual patient's total expenditure. 75 infants in the Surfactant group had 62 survivors. They spent a total of 4300 days in hospital. (av 69.35) Out of which 970 d (av 15.65 per patient) were ventilated days. There were 56 survivors in the non-surfactant group of 75. They had spent a total of 5023 days in the hospital (av 89.69/patient) out of which 1490 were ventilated days (av 26.60 d). Including the cost of surfactant (two doses), cost of hospital stay for each infant taking the average figures of stay would be SR 118, 009.75 per surfactant treated baby and SR 164, 070.70 per non-surfactant treated baby. The difference of 46,061 SR is 39.03% more in non-surfactant group. One Saudi rial = 8 Rs (approx at the time study was carried out.) Medical care cost varies from place to place. However, it is definitely cost-effective where surfactant is concerned. Quality adjusted

  17. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis.

    Science.gov (United States)

    Elahi, Maqsood M; Choi, Charles H; Konda, Subbareddy; Shake, Jay G

    2015-01-01

    This report describes a patient's self-substitution of nattokinase for the vitamin K antagonist warfarin after aortic valve replacement with a mechanical prosthesis. Nattokinase is an enzyme derived from a popular fermented soybean preparation in Japan (natto), which has fibrinolytic properties and is gaining popularity in nontraditional health journals and nonmedical health websites as an over-the-counter thrombolytic. After nearly a year of use of nattokinase without warfarin, the patient developed thrombus on the mechanical valve and underwent successful repeat valve replacement. We believe this is the first documented case of nattokinase being used as a substitute for warfarin after valve replacement, and we strongly discourage its use for this purpose.

  18. The future of rapid bridge deck replacement.

    Science.gov (United States)

    2015-06-01

    Replacing aging, deteriorated infrastructure often requires road closures and traffic detours which impose : inconvenience and delay on commerce and members of the motoring public. Accelerated bridge construction : techniques often use precast member...

  19. Proper Installation of Replacement Windows | Efficient Windows

    Science.gov (United States)

    Collaborative Foundry Foundry New Construction Windows Window Selection Tool Selection Process Design Guidance Installation Replacement Windows Window Selection Tool Assessing Options Selection Process Design Guidance Installation Understanding Windows Benefits Design Considerations Measuring

  20. Assessing Window Replacement Options | Efficient Windows Collaborative

    Science.gov (United States)

    Foundry Foundry New Construction Windows Window Selection Tool Selection Process Design Guidance Installation Replacement Windows Window Selection Tool Assessing Options Selection Process Design Guidance Installation Understanding Windows Benefits Design Considerations Measuring Performance Performance Standards

  1. Logistic Vehicle System Replacement Cost Estimate

    National Research Council Canada - National Science Library

    Stinson, Margaret

    1998-01-01

    The Logistics Vehicle System (LVS) was originally fielded from 1985-1989. Most of the LVS fleet will reach end-of-service life in 2005, therefore the goal of the Logistics Vehicle System Replacement (LVSR...

  2. Nuclear facilities: repair and replacement technologies

    International Nuclear Information System (INIS)

    2005-01-01

    The oldest operating reactors are more than 35 years old and are now facing major maintenance operations. The first replacement of a pressurizer took place in autumn 2005 at the St-Lucie plant (Usa) while steam generators have been currently replaced since 1983. Nuclear industry has to adapt to this new market by proposing innovative technological solutions in the reactor maintenance field. This document gathers the 9 papers presented at the conference. The main improvements concern repair works on internal components of PWR-type reactors, the replacement of major components of the primary coolant circuit and surface treatments to limit the propagation of damages. The first paper shows that adequate design and feedback experience are good assets to manage the ageing of a nuclear unit. Another paper shows that a new repair method of a relief valve can avoid its replacement. (A.C.)

  3. Guide to optimized replacement of equipment seals

    International Nuclear Information System (INIS)

    Gleason, J.F.

    1990-03-01

    A reevaluation of current scheduled replacement intervals of polymeric seals in plant equipment can achieve significant benefits. Information is provided which has the potential for increasing replacement intervals based on better information on how seals have performed through unique nuclear industry tests to qualify equipment, improved elastomers and increased knowledge of the failure mechanisms and related performance. The research was performed by reviewing applications of elastomeric seals in nuclear plants and practice associated with defining seal replacement intervals in the nuclear power and other industries. Performance indicators and how they predict degradation of seals were evaluated. Guidelines and a flow chart for reevaluating seal replacement intervals are provided. 29 refs., 38 figs., 8 tabs

  4. Inhibition and kinetic studies of lignin degrading enzymes of Ganoderma boninense by naturally occurring phenolic compounds.

    Science.gov (United States)

    Surendran, Arthy; Siddiqui, Yasmeen; Saud, Halimi Mohd; Ali, Nusaibah Syd; Manickam, Sivakumar

    2018-05-22

    Lignolytic (Lignin degrading) enzyme, from oil palm pathogen Ganoderma boninense Pat. (Syn G. orbiforme (Ryvarden), is involved in the detoxification and the degradation of lignin in the oil palm and is the rate-limiting step in the infection process of this fungus. Active inhibition of lignin degrading enzymes secreted by G. boninense by various naturally occurring phenolic compounds and estimation of efficiency on pathogen suppression was aimed at. In our work, ten naturally occurring phenolic compounds were evaluated for their inhibitory potential towards the lignolytic enzymes of G.boninense. Additionally, the lignin degrading enzymes were characterised. Most of the peholic compounds exhibited an uncompetitive inhibition towards the lignin degrading enzymes. Benzoic acid was the superior inhibitor to the production of lignin degrading enzymes, when compared between the ten phenolic compounds. The inhibitory potential of the phenolic compounds toward the lignin degrading enzymes are higher than that of the conventional metal ion inhibitor. The lignin degrading enzymes were stable in a wide range of pH but were sensitive to higher to temperature. The study demonstrated the inhibitor potential of ten naturally occurring phenolic compounds toward the lignin degrading enzymes of G. boninense with different efficacies. The study has shed a light towards a new management strategy to control BSR in oil palm. It serves as replacement for the existing chemical control. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Can Clouds replace Grids? Will Clouds replace Grids?

    International Nuclear Information System (INIS)

    Shiers, J D

    2010-01-01

    The world's largest scientific machine - comprising dual 27km circular proton accelerators cooled to 1.9 o K and located some 100m underground - currently relies on major production Grid infrastructures for the offline computing needs of the 4 main experiments that will take data at this facility. After many years of sometimes difficult preparation the computing service has been declared 'open' and ready to meet the challenges that will come shortly when the machine restarts in 2009. But the service is not without its problems: reliability - as seen by the experiments, as opposed to that measured by the official tools - still needs to be significantly improved. Prolonged downtimes or degradations of major services or even complete sites are still too common and the operational and coordination effort to keep the overall service running is probably not sustainable at this level. Recently 'Cloud Computing' - in terms of pay-per-use fabric provisioning - has emerged as a potentially viable alternative but with rather different strengths and no doubt weaknesses too. Based on the concrete needs of the LHC experiments - where the total data volume that will be acquired over the full lifetime of the project, including the additional data copies that are required by the Computing Models of the experiments, approaches 1 Exabyte - we analyze the pros and cons of Grids versus Clouds. This analysis covers not only technical issues - such as those related to demanding database and data management needs - but also sociological aspects, which cannot be ignored, neither in terms of funding nor in the wider context of the essential but often overlooked role of science in society, education and economy.

  6. Can Clouds replace Grids? Will Clouds replace Grids?

    Energy Technology Data Exchange (ETDEWEB)

    Shiers, J D, E-mail: Jamie.Shiers@cern.c [CERN, 1211 Geneva 23 (Switzerland)

    2010-04-01

    The world's largest scientific machine - comprising dual 27km circular proton accelerators cooled to 1.9{sup o}K and located some 100m underground - currently relies on major production Grid infrastructures for the offline computing needs of the 4 main experiments that will take data at this facility. After many years of sometimes difficult preparation the computing service has been declared 'open' and ready to meet the challenges that will come shortly when the machine restarts in 2009. But the service is not without its problems: reliability - as seen by the experiments, as opposed to that measured by the official tools - still needs to be significantly improved. Prolonged downtimes or degradations of major services or even complete sites are still too common and the operational and coordination effort to keep the overall service running is probably not sustainable at this level. Recently 'Cloud Computing' - in terms of pay-per-use fabric provisioning - has emerged as a potentially viable alternative but with rather different strengths and no doubt weaknesses too. Based on the concrete needs of the LHC experiments - where the total data volume that will be acquired over the full lifetime of the project, including the additional data copies that are required by the Computing Models of the experiments, approaches 1 Exabyte - we analyze the pros and cons of Grids versus Clouds. This analysis covers not only technical issues - such as those related to demanding database and data management needs - but also sociological aspects, which cannot be ignored, neither in terms of funding nor in the wider context of the essential but often overlooked role of science in society, education and economy.

  7. Can Clouds replace Grids? Will Clouds replace Grids?

    Science.gov (United States)

    Shiers, J. D.

    2010-04-01

    The world's largest scientific machine - comprising dual 27km circular proton accelerators cooled to 1.9oK and located some 100m underground - currently relies on major production Grid infrastructures for the offline computing needs of the 4 main experiments that will take data at this facility. After many years of sometimes difficult preparation the computing service has been declared "open" and ready to meet the challenges that will come shortly when the machine restarts in 2009. But the service is not without its problems: reliability - as seen by the experiments, as opposed to that measured by the official tools - still needs to be significantly improved. Prolonged downtimes or degradations of major services or even complete sites are still too common and the operational and coordination effort to keep the overall service running is probably not sustainable at this level. Recently "Cloud Computing" - in terms of pay-per-use fabric provisioning - has emerged as a potentially viable alternative but with rather different strengths and no doubt weaknesses too. Based on the concrete needs of the LHC experiments - where the total data volume that will be acquired over the full lifetime of the project, including the additional data copies that are required by the Computing Models of the experiments, approaches 1 Exabyte - we analyze the pros and cons of Grids versus Clouds. This analysis covers not only technical issues - such as those related to demanding database and data management needs - but also sociological aspects, which cannot be ignored, neither in terms of funding nor in the wider context of the essential but often overlooked role of science in society, education and economy.

  8. Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

    Science.gov (United States)

    Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

    2016-01-01

    Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

  9. Machine replacement, Network Externalities and Investment Cycles

    OpenAIRE

    Juan Ruiz

    2003-01-01

    This paper presents a model where agents decide on the timing of replacement of ageing machines. The optimal replacement policy for an agent is influenced by other agents' decisions because the productivity of a particular vintage displays network externalities that set in with a lag. In equilibrium, agents follow innovation cycles with a frequency that is lower than optimal, so there is too much delay. One extreme case is the possibility of inefficient collapse: for some parameters there is ...

  10. Equipment Replacement Decision Making: Opportunities and Challenges

    OpenAIRE

    Fan, Wei (David); Gemar, Mason D.; Machemehl, Randy

    2012-01-01

    The primary function of equipment managers is to replace the right equipment at the right time and at the lowest overall cost. In this paper, the opportunities and challenges associated with equipment replacement optimization (ERO) are discussed in detail. First, a comprehensive review of the state-of-the art and state-of-the practice literature for the ERO problem is conducted. Second, a dynamic programming (DP) based optimization solution methodology is presented to solve the ERO problem. T...

  11. Does Online Marketing Truly Replace Traditional Marketing?

    OpenAIRE

    Gunawan, Emilia Margareth

    2013-01-01

    This review explains the way how online marketing has been replacing traditional marketing in terms of marketing mix. This replacement might happen, because online marketing can give advantages, i.e., offering on-time delivery, increasing effectiveness of two way interactions between buyer and seller, and creating online communities (Szmigin, et al, 2005). The transition of atoms to bits format reflects that tangible products in traditional marketing is being digitalized. The marketing strate...

  12. Infective endocarditis following percutaneous pulmonary valve replacement

    DEFF Research Database (Denmark)

    Cheung, Gary; Vejlstrup, Niels; Ihlemann, Nikolaj

    2013-01-01

    Infective endocarditis (IE) following percutaneous pulmonary valve replacement (PPVR) with the Melody valve is rarely reported. Furthermore, there are challenges in this diagnosis; especially echocardiographic evidence of vegetation within the prosthesis may be difficult.......Infective endocarditis (IE) following percutaneous pulmonary valve replacement (PPVR) with the Melody valve is rarely reported. Furthermore, there are challenges in this diagnosis; especially echocardiographic evidence of vegetation within the prosthesis may be difficult....

  13. Quantitative site-specific phosphoproteomics of Trichoderma reesei signaling pathways upon induction of hydrolytic enzyme production

    NARCIS (Netherlands)

    Nguyen, E.V.; Imanishi, S.Y.; Haapaniemi, P.; Yadav, A.; Saloheimo, M.; Corthals, G.L.; Pakula, T.M.

    2016-01-01

    The filamentous fungus Trichoderma reesei is used for industrial production of secreted enzymes including carbohydrate active enzymes, such as cellulases and hemicellulases. The production of many of these enzymes by T. reesei is influenced by the carbon source it grows on, where the regulation

  14. Enzymes and Enzyme Activity Encoded by Nonenveloped Viruses.

    Science.gov (United States)

    Azad, Kimi; Banerjee, Manidipa; Johnson, John E

    2017-09-29

    Viruses are obligate intracellular parasites that rely on host cell machineries for their replication and survival. Although viruses tend to make optimal use of the host cell protein repertoire, they need to encode essential enzymatic or effector functions that may not be available or accessible in the host cellular milieu. The enzymes encoded by nonenveloped viruses-a group of viruses that lack any lipid coating or envelope-play vital roles in all the stages of the viral life cycle. This review summarizes the structural, biochemical, and mechanistic information available for several classes of enzymes and autocatalytic activity encoded by nonenveloped viruses. Advances in research and development of antiviral inhibitors targeting specific viral enzymes are also highlighted.

  15. Essential Specification Elements for Heat Exchanger Replacement

    Energy Technology Data Exchange (ETDEWEB)

    Bower, L.

    2015-07-01

    Performance upgrade and equipment degradation are the primary impetuses for a nuclear power plant to engage in the large capital cost project of heat exchanger replacement. Along with attention to these issues, consideration of heat exchanger Codes and Standards, material improvements, thermal redesign, and configuration are essential for developing User’s Design Specifications for successful replacement projects. The User’s Design Specification is the central document in procuring ASME heat exchangers. Properly stated objectives for the heat exchanger replacement are essential for obtaining the materials, configurations and thermal designs best suited for the nuclear power plant. Additionally, the code of construction required and the applied manufacturing standard (TEMA or HEI) affects how the heat exchanger may be designed or configured to meet the replacement goals. Knowledge of how Codes and Standards affect design and configuration details will aid in writing the User’s Design Specification. Joseph Oat Corporation has designed and fabricated many replacement heat exchangers for the nuclear power industry. These heat exchangers have been constructed per ASME Section III to various Code-Years or ASME Section VIII-1 to the current Code-Year also in accordance with TEMA and HEI. These heat exchangers have been a range of like-for-like replacement to complete thermal, material and configuration redesigns. Several examples of these heat exchangers with their Code, Standard and specification implications are presented. (Author.

  16. International examples of steam generator replacement

    International Nuclear Information System (INIS)

    Wiechmann, K.

    1993-01-01

    Since 1979-1980 a total of twelve nuclear power plants world-wide have had their steam generators replaced. The replacement of the Combustion steam generators in the Millstone-2 plant in the United States was completed very recently. Steam generator replacement activities are going on at present in four plants. In North Anna, the steam generators have been under replacement since January 1990. In Japan, preparations have been started for Genkai-1. Since January 1992, the two projects in Beznau-1, Switzerland, and Doel-3, Belgium, have bee planned and executed in parallel. Why steam generator replacement? There are a number of defect mechanisms which give rise to the need for early steam generator replacement. One of the main reasons is the use of Inconel-600 as material for the heating tubes. Steam generator heating tubes made of Inconel-600 have been known to exhibit their first defects due to stress corrosion cracking after less than one year of operation. (orig.) [de

  17. A replaceable reflective film for solar concentrators

    Energy Technology Data Exchange (ETDEWEB)

    1991-09-01

    The 3M Company manufactures a silvered acrylic film called ECP-305 that is regarded as the preferred reflective film for use on stretched-membrane heliostats. However, ECP-305 will degrade in time, due to both corrosion of the silver layer and delamination at the film's silver-to-acrylic interface, and will eventually need to be replaced. 3M uses a very aggressive adhesive on this film, and once it is laminated, replacement is very difficult. The purpose of this investigation was the development of a replaceable reflector, a reflective film that can be easily removed and replaced. A replaceable reflector was successfully configured by laminating ECP-305 to the top surface of a smooth, dimensionally stable polymer film, with a removable adhesive applied to the underside of the polymer film. Several stages of screening and testing led to the selection of a 0.010-inch thick polycarbonate (GE 8030) as the best polymer film and a medium tack tape (3M Y-9425) was selected as the best removable adhesive. To demonstrate the feasibility of the replaceable reflector concept and to provide a real-time field test, the chosen construction was successfully applied to the 50-m{sup 2} SKI heliostat at the Central Receiver Test Facility at Sandia National Laboratories in Albuquerque. 4 refs., 13 figs., 7 tabs.

  18. A bivariate optimal replacement policy for a multistate repairable system

    International Nuclear Information System (INIS)

    Zhang Yuanlin; Yam, Richard C.M.; Zuo, Ming J.

    2007-01-01

    In this paper, a deteriorating simple repairable system with k+1 states, including k failure states and one working state, is studied. It is assumed that the system after repair is not 'as good as new' and the deterioration of the system is stochastic. We consider a bivariate replacement policy, denoted by (T,N), in which the system is replaced when its working age has reached T or the number of failures it has experienced has reached N, whichever occurs first. The objective is to determine the optimal replacement policy (T,N)* such that the long-run expected profit per unit time is maximized. The explicit expression of the long-run expected profit per unit time is derived and the corresponding optimal replacement policy can be determined analytically or numerically. We prove that the optimal policy (T,N)* is better than the optimal policy N* for a multistate simple repairable system. We also show that a general monotone process model for a multistate simple repairable system is equivalent to a geometric process model for a two-state simple repairable system in the sense that they have the same structure for the long-run expected profit (or cost) per unit time and the same optimal policy. Finally, a numerical example is given to illustrate the theoretical results

  19. Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates

    Science.gov (United States)

    Huang, Ruiqi; Hippauf, Frank; Rohrbeck, Diana; Haustein, Maria; Wenke, Katrin; Feike, Janie; Sorrelle, Noah; Piechulla, Birgit; Barkman, Todd J.

    2012-01-01

    In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (kcat/KM) for competing substrates, even though adaptive substitutions may affect KM and kcat separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities. PMID:22315396

  20. Rethinking fundamentals of enzyme action.

    Science.gov (United States)

    Northrop, D B

    1999-01-01

    Despite certain limitations, investigators continue to gainfully employ concepts rooted in steady-state kinetics in efforts to draw mechanistically relevant inferences about enzyme catalysis. By reconsidering steady-state enzyme kinetic behavior, this review develops ideas that allow one to arrive at the following new definitions: (a) V/K, the ratio of the maximal initial velocity divided by the Michaelis-Menten constant, is the apparent rate constant for the capture of substrate into enzyme complexes that are destined to yield product(s) at some later point in time; (b) the maximal velocity V is the apparent rate constant for the release of substrate from captured complexes in the form of free product(s); and (c) the Michaelis-Menten constant K is the ratio of the apparent rate constants for release and capture. The physiologic significance of V/K is also explored to illuminate aspects of antibiotic resistance, the concept of "perfection" in enzyme catalysis, and catalytic proficiency. The conceptual basis of congruent thermodynamic cycles is also considered in an attempt to achieve an unambiguous way for comparing an enzyme-catalyzed reaction with its uncatalyzed reference reaction. Such efforts promise a deeper understanding of the origins of catalytic power, as it relates to stabilization of the reactant ground state, stabilization of the transition state, and reciprocal stabilizations of ground and transition states.