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

PubMed

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.

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

PubMed

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, P<0.05 was considered statistically significant. 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. 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.

Gastrointestinal manifestations of Fabry disease: clinical response to enzyme replacement therapy.

PubMed

Banikazemi, Maryam; Ullman, Thomas; Desnick, Robert J

2005-08-01

Gastrointestinal symptoms are often an early and prominent manifestation of Fabry disease, an X-linked inborn error of metabolism caused by the deficient activity of the lysosomal enzyme, alpha-galactosidase A. This enzyme deficiency results in the progressive accumulation of globotriaosylceramide and other glycosphingolipids in tissue lysosomes throughout the body. In classically affected patients, glycosphingolipid accumulation in the vascular endothelium eventually culminates in life-threatening renal, cardiac, and cerebrovascular disease. In addition, over 50% of patients experience post-prandial abdominal pain and diarrhea that interferes with the ability to work and quality of life. Here, we describe four males aged 17-40 years with classic Fabry disease and severe gastrointestinal symptoms who participated in clinical trials of enzyme replacement therapy with agalsidase beta (Fabrazyme, 1 mg/kg every 2 weeks). Before therapy, the three adult patients experienced post-prandial abdominal pain, bloating, and severe diarrhea with 7-10 bowel movements per day every day and the 17-year-old had weekly episodes of diarrhea with six bowel movements per day. Other symptoms included vomiting, food intolerance, and poor weight gain. All patients took medications for these symptoms (diphenoxylate-atropine [Lomotil], ranitidine hydrochloride [Zantac], or sulfasalazine). After 6-7 months of agalsidase beta therapy, all patients reported "no or only occasional" abdominal pain or diarrhea, had discontinued their gastrointestinal medications, and had gained 3-8 kg. These marked improvements in gastrointestinal symptoms have persisted for over 3 years of treatment. In such patients, enzyme replacement at 1 mg/kg effects an early and significant clinical improvement in the gastrointestinal manifestations of Fabry disease.

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I

PubMed Central

Dickson, Patricia; Peinovich, Maryn; McEntee, Michael; Lester, Thomas; Le, Steven; Krieger, Aimee; Manuel, Hayden; Jabagat, Catherine; Passage, Merry; Kakkis, Emil D.

2008-01-01

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human α-l-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of α-l-iduronidase–specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9–44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases. PMID:18654665

Enzyme Replacement for Craniofacial Skeletal Defects and Craniosynostosis in Murine Hypophosphatasia

PubMed Central

Liu, Jin; Campbell, Cassie; Nam, Hwa Kyung; Caron, Alexandre; Yadav, Manisha C; Millán, José Luis; Hatch, Nan E.

2015-01-01

Hypophosphatasia (HPP) is an inborn-error-of-metabolism disorder characterized by deficient bone and tooth mineralization due to loss-of function mutations in the gene (Alpl) encoding tissue-nonspecific alkaline phosphatase (TNAP). Alpl−/− mice exhibit many characteristics seen in infantile HPP including long bone and tooth defects, vitamin B6 responsive seizures and craniosynostosis. Previous reports demonstrated that a mineral-targeted form of TNAP rescues long bone, verterbral and tooth mineralization defects in Alpl−/− mice. Here we report that enzyme replacement with mineral-targeted TNAP (asfotase-alfa) also prevents craniosynostosis (the premature fusion of cranial bones) and additional craniofacial skeletal abnormalities in Alpl−/− mice. Craniosynostosis, cranial bone volume and density, and craniofacial shape abnormalities were assessed by microsocopy, histology, digital caliper measurements and micro CT. We found that craniofacial shape defects, cranial bone mineralization and craniosynostosis were corrected in Alpl−/− mice injected daily subcutaneously starting at birth with recombinant enzyme. Analysis of Alpl−/− calvarial cells indicates that TNAP deficiency leads to aberrant osteoblastic gene expression and diminished proliferation. Some but not all of these cellular abnormalities were rescued by treatment with inorganic phosphate. These results confirm an essential role for TNAP in craniofacial skeletal development and demonstrate the efficacy of early postnatal mineral-targeted enzyme replacement for preventing craniofacial abnormalities including craniosynostosis in murine infantile HPP. PMID:25959417

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

PubMed

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.

/sup 67/Ga citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

/sup 67/Ga citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n . 30) and in 71% of patients with inactive disease (n . 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r..436; p less than .005). The frequency of abnormalmore » /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical indentification of inactive sacoidosis.« less

Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A)

PubMed Central

Lin, Hsiang-Yu; Liu, Hao-Chuan; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Hsu, Ting-Rong; Shen, Chia-I; Li, Shao-Tzu; Li, Cheng-Fang; Lee, Li-Hong; Lee, Pi-Chang; Huang, Chun-Kai; Chiang, Chuan-Chi; Lin, Ching-Yuang; Lin, Shuan-Pei; Niu, Dau-Ming

2013-01-01

Objective Current studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A). Design Retrospective cohort study. Setting Tertiary medical centre. Participants 21 patients with cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with classic Fabry disease (4 men and 11 women) treated with biweekly intravenous infusions of agalsidase β (1 mg/kg) or agalsidase α (0.2 mg/kg) for at least 6 months. Outcome measures These data were collected at the time before enzyme replacement therapy (ERT) began and followed up after ERT for at least 6 months, including patient demographics, medical history, parameter changes of cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3) and Mainz Severity Score Index. Results After 6–39 months of ERT, plasma lyso-Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with cardiac-type and classic Fabry disease, respectively, which indicated an improvement of disease severity. For patients with cardiac-type Fabry disease, echocardiography revealed the reduction or stabilisation of left ventricular mass index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively, as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type. Most patients showed stable renal function after ERT. There were statistically significant improvements (p<0.05) between the data at baseline and those after ERT for values of plasma lyso-Gb3, LVMI, IVS, LPW and Mainz Severity Score Index. No severe clinical events were reported during the treatment. Conclusions ERT is beneficial and appears to be safe for Taiwanese patients with cardiac-type Fabry disease, as well as for those with the classic type. PMID:23864212

Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL.

PubMed

Offner, Fritz; Samoilova, Olga; Osmanov, Evgenii; Eom, Hyeon-Seok; Topp, Max S; Raposo, João; Pavlov, Viacheslav; Ricci, Deborah; Chaturvedi, Shalini; Zhu, Eugene; van de Velde, Helgi; Enny, Christopher; Rizo, Aleksandra; Ferhanoglu, Burhan

2015-10-15

This phase 2 study evaluated whether substituting bortezomib for vincristine in frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy could improve efficacy in non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL), centrally confirmed by immunohistochemistry (Hans method). In total, 164 patients were randomized 1:1 to receive six 21-day cycles of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), all IV day 1, prednisone 100 mg/m(2) orally days 1-5, plus either bortezomib 1.3 mg/m(2) IV days 1, 4, 8, 11 (rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib [VR-CAP]; n = 84) or vincristine 1.4 mg/m(2) (maximum 2 mg) IV day 1 (R-CHOP; n = 80). There were no significant differences between VR-CAP and R-CHOP in complete response rate (64.5%, 66.2%; odds ratio [OR], 0.91; P = .80), overall response rate (93.4%, 98.6%; OR, 0.21; P = .11), progression-free survival (hazard ratio [HR], 1.12; P = .76), or overall survival (HR, 0.89; P = .75). Rates of grade ≥3 adverse events (AEs; 88%, 89%), serious AEs (38%, 34%), discontinuations due to AEs (7%, 3%), and deaths due to AEs (2%, 5%) were similar with VR-CAP and R-CHOP. Grade ≥3 peripheral neuropathy rates were 6% and 3%, respectively. VR-CAP did not improve efficacy vs R-CHOP in non-GCB DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT01040871. © 2015 by The American Society of Hematology.

A biochemical and physicochemical comparison of two recombinant enzymes used for enzyme replacement therapies of hunter syndrome.

PubMed

Chung, Yo Kyung; Sohn, Young Bae; Sohn, Jong Mun; Lee, Jieun; Chang, Mi Sun; Kwun, Younghee; Kim, Chi Hwa; Lee, Jin Young; Yook, Yeon Joo; Ko, Ah-Ra; Jin, Dong-Kyu

2014-05-01

Mucopolysaccharidosis II (MPS II, Hunter syndrome; OMIM 309900) is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to accumulation of glycosaminoglycans (GAGs). For enzyme replacement therapy (ERT) of Hunter syndrome, two recombinant enzymes, idursulfase (Elaprase(®), Shire Human Genetic Therapies, Lexington, MA) and idursulfase beta (Hunterase(®), Green Cross Corporation, Yongin, Korea), are currently available in Korea. To compare the biochemical and physicochemical differences between idursulfase and idursulfase beta, we examined the formylglycine (FGly) content, specific enzyme activity, mannose-6-phosphate (M6P) content, sialic acid content, and in vitro cell uptake activity of normal human fibroblasts of these two enzymes.The FGly content, which determines the enzyme activity, of idursulfase beta was significantly higher than that of idursulfase (79.4 ± 0.9 vs. 68.1 ± 2.2 %, P < 0.001). In accordance with the FGly content, the specific enzyme activity of idursulfase beta was significantly higher than that of idursulfase (42.6 ± 1.1 vs. 27.8 ± 0.9 nmol/min/μg protein, P < 0.001). The levels of M6P and sialic acid were not significantly different (2.4 ± 0.1 vs 2.4 ± 0.3 mol/mol protein for M6P and 12.3 ± 0.7 vs. 12.4 ± 0.4 mol/mol protein for sialic acid). However, the cellular uptake activity of the normal human fibroblasts in vitro showed a significant difference (Kuptake, 5.09 ± 0.96 vs. 6.50 ± 1.28 nM protein, P = 0.017).In conclusion, idursulfase beta exhibited significantly higher specific enzyme activity than idursulfase, resulting from higher FGly content. These biochemical differences may be partly attributed to clinical efficacy. However, long-term clinical evaluations of Hunter syndrome patients treated with these two enzymes will be needed to demonstrate the clinical implications of significant difference of the enzyme activity and the FGly content.

Retrospective study of long-term outcomes of enzyme replacement therapy in Fabry disease: Analysis of prognostic factors

PubMed Central

Biegstraaten, Marieke; Hughes, Derralynn A.; Mehta, Atul; Elliott, Perry M.; Oder, Daniel; Watkinson, Oliver T.; Vaz, Frédéric M.; van Kuilenburg, André B. P.; Wanner, Christoph; Hollak, Carla E. M.

2017-01-01

Despite enzyme replacement therapy, disease progression is observed in patients with Fabry disease. Identification of factors that predict disease progression is needed to refine guidelines on initiation and cessation of enzyme replacement therapy. To study the association of potential biochemical and clinical prognostic factors with the disease course (clinical events, progression of cardiac and renal disease) we retrospectively evaluated 293 treated patients from three international centers of excellence. As expected, age, sex and phenotype were important predictors of event rate. Clinical events before enzyme replacement therapy, cardiac mass and eGFR at baseline predicted an increased event rate. eGFR was the most important predictor: hazard ratios increased from 2 at eGFR <90 ml/min/1.73m2 to 4 at eGFR <30, compared to patients with an eGFR >90. In addition, men with classical disease and a baseline eGFR <60 ml/min/1.73m2 had a faster yearly decline (-2.0 ml/min/1.73m2) than those with a baseline eGFR of >60. Proteinuria was a further independent risk factor for decline in eGFR. Increased cardiac mass at baseline was associated with the most robust decrease in cardiac mass during treatment, while presence of cardiac fibrosis predicted a stronger increase in cardiac mass (3.36 gram/m2/year). Of other cardiovascular risk factors, hypertension significantly predicted the risk for clinical events. In conclusion, besides increasing age, male sex and classical phenotype, faster disease progression while on enzyme replacement therapy is predicted by renal function, proteinuria and to a lesser extent cardiac fibrosis and hypertension. PMID:28763515

Guanidinylated Neomycin Conjugation Enhances Intranasal Enzyme Replacement in the Brain.

PubMed

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.

Enzyme replacement therapy in Fabry disease: influence on cardiac manifestations.

PubMed

Caballero, L; Climent, V; Hernández-Romero, D; Quintanilla, M A; de la Morena, G; Marín, F

2010-01-01

Fabry disease (FD) is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of different cells and tissues, causing principally ventricular hypertrophy, renal failure and cerebrovascular accidents, reducing lifespan both in hemizygous males and heterozygous females. Residual enzyme activity might lead to slow progression of the disease and result in the so-called cardiac or renal variants with delayed presentation. Two different forms of alpha-galactosidase A enzyme replacement therapies (ERT) are available for the treatment of FD, one genetically engineered in human cell line (agalsidase alfa, Replagal, Shire) and the other produced in a Chinese hamster ovary cell line (agalsidase beta, Fabrazyme, Genzyme). Although both proteins are structurally and functionally very similar, with the same amino acid sequence as the native human enzyme, they differ in the pattern of glycosilation of the protein depending on the originating cell line. Studies with both preparations have described a reduction in plasma, urinary sediment and tissue levels of Gb3, a decrease in the frequency of pain crisis and a reduction in left ventricular mass and improvement or stabilization of renal function. Studies have generally shown the greatest benefit when treatment is started at an early stage of the disease before extensive fibrosis or other irreversible tissue damage takes place. However, more data are needed to document long-term treatment outcomes. The aim of the present review is to provide an update overview of the two different forms of ERT for FD, their clinical effects in cardiac manifestations and their possible differences in terms of efficacy, side effects and safety profiles.

Long-Term Safety and Efficacy of Enzyme Replacement Therapyfor Fabry Disease

PubMed Central

Wilcox, William R.; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E.; Desnick, Robert J.; Germain, Dominique P.

2004-01-01

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human α-galactosidase A (rh-αGalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-αGalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh-αGalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30–36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh-αGalA IgG antibody titers. Among seroconverted patients, after 30–36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had ⩾4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30–36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile. PMID:15154115

A replaceable dual-enzyme capillary microreactor using magnetic beads and its application for simultaneous detection of acetaldehyde and pyruvate.

PubMed

Shi, Jing; Zhao, Wenwen; Chen, Yuanfang; Guo, Liping; Yang, Li

2012-07-01

A novel replaceable dual-enzyme capillary microreactor was developed and evaluated using magnetic fields to immobilize the alcohol dehydrogenase (ADH)- and lactate dehydrogenase (LDH)-coated magnetic beads at desired positions in the capillary. The dual-enzyme assay was achieved by measuring the two consumption peaks of the coenzyme β-nicotinamide adenine dinucleotide (NADH), which were related to the ADH reaction and LDH reaction. The dual-enzyme capillary microreactor was constructed using magnetic beads without any modification of the inner surface of the capillary, and showed great stability and reproducibility. The electrophoretic resolution for different analytes can be easily controlled by altering the relative distance of different enzyme-coated magnetic beads. The apparent K(m) values for acetaldehyde with ADH-catalyzed reaction and for pyruvate with LDH-catalyzed reaction were determined. The detection limits for acetaldehyde and pyruvate determination are 0.01 and 0.016 mM (S/N = 3), respectively. The proposed method was successfully applied to simultaneously determine the acetaldehyde and pyruvate contents in beer samples. The results indicated that combing magnetic beads with CE is of great value to perform replaceable and controllable multienzyme capillary microreactor for investigation of a series of enzyme reactions and determination of multisubstrates. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

Alfadhel, Majid; Sirrs, Sandra

2011-01-01

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.

Enzyme replacement therapy in classical infantile pompe disease: results of a ten-month follow-up study.

PubMed

Klinge, L; Straub, V; Neudorf, U; Voit, T

2005-02-01

Infantile Pompe disease (IPD) is a fatal, autosomal recessive muscle-wasting disorder. Due to a deficiency of the lysosomal enzyme acid alpha-glucosidase patients develop a generalized myopathy, diaphragmatic weakness, and cardiomyopathy leading to death usually within the first year of life. So far there is no therapy available. We report on the safety and efficacy of transgenically derived recombinant human precursor acid alpha-glucosidase (rhGAA) in a 10-month follow-up study in two children with IPD who previously completed a 48-week course of enzyme replacement therapy (ERT) with the same medication at the same dose in a phase II clinical trial. Under this therapy cardiac status and muscle strength had improved, leading to survival beyond the age of one year. These results, together with data from two other phase II clinical trials encouraged further evaluation of the long-term safety and efficacy of enzyme replacement therapy in patients with infantile-onset Pompe disease. During the 10-month follow-up period, ERT was well-tolerated and neither patient experienced a single infusion-associated reaction. The initial improvements in cardiac size and function, as measured by left ventricular mass index and the fractional shortening, were maintained in both patients, and a continued improvement of motor function, as measured by the Alberta infant motor scale, was observed.

Enzyme replacement therapy for Fabry disease: lessons from two alpha-galactosidase A orphan products and one FDA approval.

PubMed

Desnick, Robert J

2004-07-01

Two virtually identical products have been developed for enzyme replacement therapy for the treatment of Fabry disease, which is a rare and debilitating genetic disease caused by decreased activity of the lysosomal enzyme alpha-galactosidase A. Lack of this enzyme results in progressive tissue accumulation of globotriaosylceramide (GL-3), resulting in life-threatening renal, cardiac and cerebrovascular complications. Both enzyme replacement products, agalsidase alfa (Replagal; Transkaryotic Therapies, Cambridge, MA, USA) and agalsidase beta (Fabrazyme; Genzyme Corporation, Cambridge, MA, USA), were approved by the European Agency for the Evaluation of Medicinal Products in 2001; agalsidase alfa at a recommended dose of 0.2 mg/kg and agalsidase beta at a recommended dose of 1 mg/kg. In the US, however, orphan drug laws dictated that only one of these products could be approved. In April 2003, after a rigorous evaluation of both products by the US FDA, this approval was granted to agalsidase beta. This decision reflected clinical trial design, how dosages were determined, antibody effects and the ability of each product to demonstrate either clinical efficacy or reduction of tissue storage of GL-3 in major organs of pathology when administered at the recommended dosage. The process also highlighted important issues in the evaluation of drugs to treat life-threatening genetic diseases for which the pathological basis is well-defined.

Long-term safety and efficacy of enzyme replacement therapy for Fabry disease.

PubMed

Wilcox, William R; Banikazemi, Maryam; Guffon, Nathalie; Waldek, Stephen; Lee, Philip; Linthorst, Gabor E; Desnick, Robert J; Germain, Dominique P

2004-07-01

Elsewhere, we reported the safety and efficacy results of a multicenter phase 3 trial of recombinant human alpha -galactosidase A (rh-alpha GalA) replacement in patients with Fabry disease. All 58 patients who were enrolled in the 20-wk phase 3 double-blind, randomized, and placebo-controlled study received subsequently 1 mg/kg of rh-alpha GalA (agalsidase beta, Fabrazyme, Genzyme Corporation) biweekly in an ongoing open-label extension study. Evidence of long-term efficacy, even in patients who developed IgG antibodies against rh- alpha GalA, included the continuously normal mean plasma globotriaosylceramide (GL-3) levels during 30 mo of the extension study and the sustained capillary endothelial GL-3 clearance in 98% (39/40) of patients who had a skin biopsy taken after treatment for 30 mo (original placebo group) or 36 mo (original enzyme-treated group). The mean serum creatinine level and estimated glomerular filtration rate also remained stable after 30-36 mo of treatment. Infusion-associated reactions decreased over time, as did anti-rh- alpha GalA IgG antibody titers. Among seroconverted patients, after 30-36 mo of treatment, seven patients tolerized (no detectable IgG antibody), and 59% had > or =4-fold reductions in antibody titers. As of 30 mo into the extension trial, three patients were withdrawn from the study because of positive serum IgE or skin tests; however, all have been rechallenged successfully at the time of this report. Thus, enzyme replacement therapy for 30-36 mo with agalsidase beta resulted in continuously decreased plasma GL-3 levels, sustained endothelial GL-3 clearance, stable kidney function, and a favorable safety profile.

Bronchoalveolar lavage, serum angiotensin-converting enzyme, and /sup 67/Ga scanning in extrathoracic sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallaert, B.; Ramon, P.; Fournier, E.

1982-11-01

Results of bronchoalveolar lavage (BAL), 67Ga scanning, and serum angiotensin-converting enzyme (SACE) assay are compared in the assessment of pulmonary involvement in ten cases of extrathoracic sarcoidosis. Standard clinical, radiologic, and pulmonary function tests detected no pulmonary changes in these patients, but BAL demonstrated an increased alveolar lymphocytosis in eight of ten cases. SACE levels were increased in two cases, and the thoracic gallium uptake was normal in all cases. BAL appears to be the best technique for diagnosing latent pulmonary involvement in extrathoracic sarcoidosis.

Enzyme replacement therapy for murine hypophosphatasia.

PubMed

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.

Enzyme architecture: the effect of replacement and deletion mutations of loop 6 on catalysis by triosephosphate isomerase.

PubMed

Zhai, Xiang; Go, Maybelle K; O'Donoghue, AnnMarie C; Amyes, Tina L; Pegan, Scott D; Wang, Yan; Loria, J Patrick; Mesecar, Andrew D; Richard, John P

2014-06-03

Two mutations of the phosphodianion gripper loop in chicken muscle triosephosphate isomerase (cTIM) were examined: (1) the loop deletion mutant (LDM) formed by removal of residues 170-173 [Pompliano, D. L., et al. (1990) Biochemistry 29, 3186-3194] and (2) the loop 6 replacement mutant (L6RM), in which the N-terminal hinge sequence of TIM from eukaryotes, 166-PXW-168 (X = L or V), is replaced by the sequence from archaea, 166-PPE-168. The X-ray crystal structure of the L6RM shows a large displacement of the side chain of E168 from that for W168 in wild-type cTIM. Solution nuclear magnetic resonance data show that the L6RM results in significant chemical shift changes in loop 6 and surrounding regions, and that the binding of glycerol 3-phosphate (G3P) results in chemical shift changes for nuclei at the active site of the L6RM that are smaller than those of wild-type cTIM. Interactions with loop 6 of the L6RM stabilize the enediolate intermediate toward the elimination reaction catalyzed by the LDM. The LDM and L6RM result in 800000- and 23000-fold decreases, respectively, in kcat/Km for isomerization of GAP. Saturation of the LDM, but not the L6RM, by substrate and inhibitor phosphoglycolate is detected by steady-state kinetic analyses. We propose, on the basis of a comparison of X-ray crystal structures for wild-type TIM and the L6RM, that ligands bind weakly to the L6RM because a large fraction of the ligand binding energy is utilized to overcome destabilizing electrostatic interactions between the side chains of E168 and E129 that are predicted to develop in the loop-closed enzyme. Similar normalized yields of DHAP, d-DHAP, and d-GAP are formed in LDM- and L6RM-catalyzed reactions of GAP in D2O. The smaller normalized 12-13% yield of DHAP and d-DHAP observed for the mutant cTIM-catalyzed reactions compared with the 79% yield of these products for wild-type cTIM suggests that these mutations impair the transfer of a proton from O-2 to O-1 at the initial

Fabry disease, enzyme replacement therapy and the significance of antibody responses.

PubMed

Deegan, Patrick B

2012-03-01

Fabry disease is an X-linked disorder caused by a deficiency of α-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide in tissues throughout the body. Cardiac, renal and neurological manifestations are common and life expectancy is significantly reduced relative to the general population. Management of Fabry disease involves the administration of intravenous enzyme replacement therapy (ERT). Two forms - agalsidase alfa and agalsidase beta - have been licensed in certain jurisdictions and are generally well tolerated; however, some patients develop antibodies to the infused enzyme, which may impair the efficacy and safety of treatment. Agalsidase alfa and agalsidase beta are produced in different systems; this leads to certain differences in post-translational modification that may affect immunogenicity. Immunoglobulin (Ig) G antibodies have frequently been reported in patients with Fabry disease receiving ERT; IgG responses are reported in a greater proportion of patients receiving agalsidase beta than in patients receiving agalsidase alfa. IgE antibodies are less common than IgG antibodies, and have not been observed in patients receiving agalsidase alfa. However, these data are difficult to interpret due to methodological differences in the assessment of seropositivity, and in the doses of enzyme used. The clinical impact of the development of IgG antibodies to ERT in patients with Fabry disease remains unclear, due to lack of data and to the marked heterogeneity of patients both in terms of disease manifestations and response to therapy. Further studies that examine the development of antibodies in patients with Fabry disease and the potential impact of such antibodies on the outcome of ERT are necessary.

Enzyme Replacement Therapy for Murine Hypophosphatasia*

PubMed Central

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

Enzyme replacement therapy on hypophosphatasia mouse model

PubMed Central

Montaño, Adriana M.; Shimada, Tsutomu; Sly, William S.

2013-01-01

Hypophosphatasia (HPP) is an inborn error of metabolism caused by deficiency of the tissue-nonspecific alkaline phosphatase (TNSALP), resulting in a defect of bone mineralization. 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. Enzyme replacement therapy (ERT) for HPP by functional TNSALP is one of the therapeutic options. The C-terminal-anchorless human recombinant TNSALP derived from Chinese hamster ovary cell lines was purified. TNSALP-null mice (Akp2−/−), an infantile model of HPP, were treated from birth using TNSALP and vitamin B6 diet. Long-term efficacy studies of ERT consisted of every 3 days subcutaneous or intravenous injections till 28 days old (dose 20 U/g) and subsequently every 3 days intravenous injections for 6 months (dose 10 U/g). We assessed therapeutic effect by growth and survival rates, fertility, skeletal manifestations, and radiographic and pathological finding. Treated Akp2−/− mice grew normally till 4 weeks and appeared well with a minimum skeletal abnormality as well as absence of epilepsy, compared with untreated mice which died by 3 weeks old. The prognosis of TNSALP-treated Akp2−/− mice was improved substantially: 1) prolonged life span over 6 months, 2) improvement of the growth, and 3) normal fertility. After 6 months of treatment, we found moderate hypomineralization with abnormal proliferative chondrocytes in growth plate and articular cartilage. In conclusion, ERT with human native TNSALP improves substantial clinical manifestations in Akp2−/− mice, suggesting that ERT with anchorless TNSALP is also a potential therapy for HPP. PMID:23978959

Characterization of Bulk GaN Crystals Grown From Solution at Near Atmospheric Pressure

DTIC Science & Technology

2010-01-01

pressureN.Y. Garces a,n, B.N. Feigelson a, J.A. Freitas Jra, Jihyun Kimb, R.L. Myers-Ward a, E.R. Glaser a a Naval Research Laboratory, Codes 6877, 6882...Lee, I.J. Song, Appl. Phys. Lett. 79 (2001) 2570. [13] J.A. Freitas Jr., W.J. Moore, B.V. Shanabrook, G.C.B. Braga, S.K. Lee, S.S. Park , J.Y. Han...Morkoc, S.S. Park , K.Y. Lee, Appl. Phys. Lett. 78 (2001) 3041. [17] J.A. Freitas Jr., G.C.B. Braga, W.J. Moore, J.G. Tischler, J.C. Culbertson, M

Enzyme replacement prevents enamel defects in hypophosphatasia mice

PubMed Central

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

Fabry disease in children: agalsidase-beta enzyme replacement therapy.

PubMed

Borgwardt, L; Feldt-Rasmussen, U; Rasmussen, A K; Ballegaard, M; Meldgaard Lund, A

2013-05-01

Fabry disease is a rare, multiorgan disease. The most serious complications involve the kidney, brain and heart. This study aims to assess the effect of enzyme replacement therapy (ERT) using agalsidase-beta in children with Fabry disease. We carried out a nationwide, descriptive and observational retrospective cohort study of 10 children (9-16 years at baseline), who underwent regular systematic investigations for 1-8 years after initiation of ERT with agalsidase-beta (Fabryzyme®, Genzyme). Ophthalmological, echocardiographic abnormalities and hypohidrosis were found at baseline and during the follow-up period. Serious kidney, heart or brain involvement had not developed at the last follow-up examination. For the majority of the patients improvements were found concerning headache, acroparaesthesias and gastrointestinal pain during the follow-up period. The level of energy and physical activity also increased. Treatment with agalsidase-beta was associated with a reduction of neuropathic and abdominal pain and headache. Although all aspects of the Fabry pain phenotype cannot be treated with ERT, the observed effects were clinically significant in the lives of the majority of Fabry children and together with the absence of serious Fabry manifestations at last follow-up, we argue that early initiation of ERT may be considered. © 2012 John Wiley & Sons A/S.

OsGA2ox5, a Gibberellin Metabolism Enzyme, Is Involved in Plant Growth, the Root Gravity Response and Salt Stress

PubMed Central

Shan, Chi; Mei, Zhiling; Duan, Jianli; Chen, Haiying; Feng, Huafeng; Cai, Weiming

2014-01-01

Gibberellin (GA) 2-oxidases play an important role in the GA catabolic pathway through 2β-hydroxylation. There are two classes of GA2oxs, i.e., a larger class of C19-GA2oxs and a smaller class of C20-GA2oxs. In this study, the gene encoding a GA 2-oxidase of rice, Oryza sativa GA 2-oxidase 5 (OsGA2ox5), was cloned and characterized. BLASTP analysis showed that OsGA2ox5 belongs to the C20-GA2oxs subfamily, a subfamily of GA2oxs acting on C20-GAs (GA12, GA53). Subcellular localization of OsGA2ox5-YFP in transiently transformed onion epidermal cells revealed the presence of this protein in both of the nucleus and cytoplasm. Real-time PCR analysis, along with GUS staining, revealed that OsGA2ox5 is expressed in the roots, culms, leaves, sheaths and panicles of rice. Rice plants overexpressing OsGA2ox5 exhibited dominant dwarf and GA-deficient phenotypes, with shorter stems and later development of reproductive organs than the wild type. The dwarfism phenotype was partially rescued by the application of exogenous GA3 at a concentration of 10 µM. Ectopic expression of OsGA2ox5 cDNA in Arabidopsis resulted in a similar phenotype. Real-time PCR assays revealed that both GA synthesis-related genes and GA signaling genes were expressed at higher levels in transgenic rice plants than in wild-type rice; OsGA3ox1, which encodes a key enzyme in the last step of the bioactive GAs synthesis pathway, was highly expressed in transgenic rice. The roots of OsGA2ox5-ox plants exhibited increased starch granule accumulation and gravity responses, revealing a role for GA in root starch granule development and gravity responses. Furthermore, rice and Arabidopsis plants overexpressing OsGA2ox5 were more resistant to high-salinity stress than wild-type plants. These results suggest that OsGA2ox5 plays important roles in GAs homeostasis, development, gravity responses and stress tolerance in rice. PMID:24475234

OsGA2ox5, a Gibberellin Metabolism Enzyme, Is Involved in Plant Growth, the Root Gravity Response and Salt Stress

NASA Astrophysics Data System (ADS)

Cai, Weiming; Shan, Chi

Gibberellin (GA) 2-oxidases play an important role in the GA catabolic pathway through 2b-hydroxylation. There are two classes of GA2oxs, i.e., a larger class of C19-GA2oxs and a smaller class of C20-GA2oxs. In this study, the gene encoding a GA 2-oxidase of rice, Oryza sativa GA 2-oxidase 5 (OsGA2ox5), was cloned and characterized. BLASTP analysis showed that OsGA2ox5 belongs to the C20-GA2oxs subfamily, a subfamily of GA2oxs acting on C20-GAs (GA12, GA53). Subcellular localization of OsGA2ox5-YFP in transiently transformed onion epidermal cells revealed the presence of this protein in both of the nucleus and cytoplasm. Real-time PCR analysis, along with GUS staining, revealed that OsGA2ox5 is expressed in the roots, culms, leaves, sheaths and panicles of rice. Rice plants overexpressing OsGA2ox5 exhibited dominant dwarf and GAdeficient phenotypes, with shorter stems and later development of reproductive organs than the wild type. The dwarfism phenotype was partially rescued by the application of exogenous GA3 at a concentration of 10 mM. Ectopic expression of OsGA2ox5 cDNA in Arabidopsis resulted in a similar phenotype. Real-time PCR assays revealed that both GA synthesis-related genes and GA signaling genes were expressed at higher levels in transgenic rice plants than in wild-type rice; OsGA3ox1, which encodes a key enzyme in the last step of the bioactive GAs synthesis pathway, was highly expressed in transgenic rice. The roots of OsGA2ox5-ox plants exhibited increased starch granule accumulation and gravity responses, revealing a role for GA in root starch granule development and gravity responses. Furthermore, rice and Arabidopsis plants overexpressing OsGA2ox5 were more resistant to high-salinity stress than wild-type plants. These results suggest that OsGA2ox5 plays important roles in GAs homeostasis, development, gravity responses and stress tolerance in rice.

OsGA2ox5, a gibberellin metabolism enzyme, is involved in plant growth, the root gravity response and salt stress.

PubMed

Shan, Chi; Mei, Zhiling; Duan, Jianli; Chen, Haiying; Feng, Huafeng; Cai, Weiming

2014-01-01

Gibberellin (GA) 2-oxidases play an important role in the GA catabolic pathway through 2β-hydroxylation. There are two classes of GA2oxs, i.e., a larger class of C₁₉-GA2oxs and a smaller class of C₂₀-GA2oxs. In this study, the gene encoding a GA 2-oxidase of rice, Oryza sativa GA 2-oxidase 5 (OsGA2ox5), was cloned and characterized. BLASTP analysis showed that OsGA2ox5 belongs to the C₂₀-GA2oxs subfamily, a subfamily of GA2oxs acting on C₂₀-GAs (GA₁₂, GA₅₃). Subcellular localization of OsGA2ox5-YFP in transiently transformed onion epidermal cells revealed the presence of this protein in both of the nucleus and cytoplasm. Real-time PCR analysis, along with GUS staining, revealed that OsGA2ox5 is expressed in the roots, culms, leaves, sheaths and panicles of rice. Rice plants overexpressing OsGA2ox5 exhibited dominant dwarf and GA-deficient phenotypes, with shorter stems and later development of reproductive organs than the wild type. The dwarfism phenotype was partially rescued by the application of exogenous GA3 at a concentration of 10 µM. Ectopic expression of OsGA2ox5 cDNA in Arabidopsis resulted in a similar phenotype. Real-time PCR assays revealed that both GA synthesis-related genes and GA signaling genes were expressed at higher levels in transgenic rice plants than in wild-type rice; OsGA3ox1, which encodes a key enzyme in the last step of the bioactive GAs synthesis pathway, was highly expressed in transgenic rice. The roots of OsGA2ox5-ox plants exhibited increased starch granule accumulation and gravity responses, revealing a role for GA in root starch granule development and gravity responses. Furthermore, rice and Arabidopsis plants overexpressing OsGA2ox5 were more resistant to high-salinity stress than wild-type plants. These results suggest that OsGA2ox5 plays important roles in GAs homeostasis, development, gravity responses and stress tolerance in rice.

Enzyme replacement therapy in newborn mucopolysaccharidosis IVA mice: early treatment rescues bone lesions?

PubMed Central

Tomatsu, Shunji; Montaño, Adriana M.; Oikawa, Hirotaka; Dung, Vu Chi; Hashimoto, Amiko; Oguma, Toshihiro; Takahashi, Tatsuo; Shimada, Tsutomu; Orii, Tadao; Sly, William S.

2014-01-01

We treated mucopolysaccharidosis IVA (MPS IVA) mice to assess the effects of long-term enzyme replacement therapy (ERT) initiated at birth, since adult mice treated by ERT showed little improvement in bone pathology (1). To conduct ERT in newborn mice, we used recombinant human N-acetylgalactosamine-6-sulfate sulfatase (GALNS) produced in a CHO cell line. First, to observe the tissue distribution pattern, a dose of 250 units/g body weight was administered intravenously in MPS IVA mice at day 2 or 3. The infused enzyme was primarily recovered in liver and spleen, with detectable activity in bone and brain. Second, newborn ERT was conducted after tissue distribution study. The first injection of newborn ERT was performed intravenously, the second to fourth weekly injections were intraperitoneal, and the remaining injections from 5th to 14th week were intravenous into the tail vein. MPS IVA mice treated with GALNS showed clearance of lysosomal storage in liver, spleen, and sinus lining cells in bone marrow. The column structure of the growth plate was organized better than adult mice treated with ERT; however, hyaline and fibrous cartilage cells in femur, spine, ligaments, discs, synovium, and periosteum still had storage materials to some extent. Heart valves were refractory to the treatment. Levels of serum keratan sulfate were kept normal in newborn ERT mice. In conclusion, the enzyme, which enters the cartilage before the cartilage cell layer becomes mature, prevents disorganization of column structure. Early treatment from birth leads to partial remission of bone pathology in MPS IVA mouse. PMID:24953405

Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature.

PubMed

Pisani, Antonio; Visciano, Bianca; Roux, Graciana Diez; Sabbatini, Massimo; Porto, Caterina; Parenti, Giancarlo; Imbriaco, Massimo

2012-11-01

Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency of the hydrolytic enzyme alpha galactosidase A, with consequent accumulation of globotrioasoyl ceramide in cells and tissues of the body, resulting in a multi-system pathology including end organ failure. In the classical phenotype, cardiac failure, renal failure and stroke result in a reduced median life expectancy. The current causal treatment for Fabry disease is the enzyme replacement therapy (ERT): two different products, Replagal (agalsidase alfa) and Fabrazyme (agalsidase beta), have been commercially available in Europe for almost 10 years and they are both indicated for long-term treatment. In fact, clinical trials, observational studies and registry data have provided many evidences for safety and efficacy of ERT in improving symptoms of pain, gastrointestinal disturbances, hypohidrosis, left ventricular mass index, glomerular filtration rate and quality of life. Few data are available on comparison of the two treatments and on the clinical course of the disease. This article reviews the published evidence for clinical efficacy of the two available enzyme preparations. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed Central

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

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

PubMed

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.

Installation Boundary Fence Replacement: Upland Areas: Environmental Assessment

DTIC Science & Technology

2004-05-27

Moody Air Force Base, GA Environmental Assessment Installation Boundary Fence Replacement INSTALLATION BOUNDARY...347 CES/CEV),3485 Georgia Street,Moody AFB, GA ,31699 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Moody Air Force Base, GA Environmental Assessment

Adaptation of a Control Center Development Environment for Industrial Process Control

NASA Technical Reports Server (NTRS)

Killough, Ronnie L.; Malik, James M.

1994-01-01

In the control center, raw telemetry data is received for storage, display, and analysis. This raw data must be combined and manipulated in various ways by mathematical computations to facilitate analysis, provide diversified fault detection mechanisms, and enhance display readability. A development tool called the Graphical Computation Builder (GCB) has been implemented which provides flight controllers with the capability to implement computations for use in the control center. The GCB provides a language that contains both general programming constructs and language elements specifically tailored for the control center environment. The GCB concept allows staff who are not skilled in computer programming to author and maintain computer programs. The GCB user is isolated from the details of external subsystem interfaces and has access to high-level functions such as matrix operators, trigonometric functions, and unit conversion macros. The GCB provides a high level of feedback during computation development that improves upon the often cryptic errors produced by computer language compilers. An equivalent need can be identified in the industrial data acquisition and process control domain: that of an integrated graphical development tool tailored to the application to hide the operating system, computer language, and data acquisition interface details. The GCB features a modular design which makes it suitable for technology transfer without significant rework. Control center-specific language elements can be replaced by elements specific to industrial process control.

Cardiomyopathy and response to enzyme replacement therapy in a male mouse model for Fabry disease.

PubMed

Nguyen Dinh Cat, Aurelie; Escoubet, Brigitte; Agrapart, Vincent; Griol-Charhbili, Violaine; Schoeb, Trenton; Feng, Wenguang; Jaimes, Edgar; Warnock, David G; Jaisser, Frederic

2012-01-01

Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, (predominately globotriaosylceramide; GL-3) in lysosomes, as well as other cellular compartments and the extracellular space. Our aim was to characterize the cardiac phenotype of male knock-out mice that are deficient in alpha-galactosidase A activity, as a model for Fabry disease and test the efficacy of Enzyme Replacement Therapy with agalsidase-beta. Male mice (3-4 months of age) were characterized with awake blood pressure and heart rate measurements, cardiac echocardiography and electrocardiography measurements under light anesthesia, histological studies and molecular studies with real-time polymerase chain reaction. The Fabry knock-out mouse has bradycardia and lower blood pressure than control wild type (CB7BL/6J) mice. In Fabry knock-out mice, the cardiomyopathy associated mild hypertrophy at echography with normal systolic LV function and mild diastolic dysfunction. Premature atrial contractions were more frequent in without conduction defect. Heart weight normalized to tibial length was increased in Fabry knock-out mice. Ascending aorta dilatation was observed. Molecular studies were consistent with early stages of cardiac remodeling. A single dose of agalsidase-beta (3 mg/kg) did not affect the LV hypertrophy, function or heart rate, but did improve the mRNA signals of early cardiac remodeling. In conclusion, the alpha-galactosidase A deficient mice at 3 to 4 months of age have cardiac and vascular alterations similar to that described in early clinical stage of Fabry disease in children and adolescents. Enzyme replacement therapy affects cardiac molecular remodeling after a single dose.

Cardiomyopathy and Response to Enzyme Replacement Therapy in a Male Mouse Model for Fabry Disease

PubMed Central

Nguyen Dinh Cat, Aurelie; Escoubet, Brigitte; Agrapart, Vincent; Griol-Charhbili, Violaine; Schoeb, Trenton; Feng, Wenguang; Jaimes, Edgar; Warnock, David G.; Jaisser, Frederic

2012-01-01

Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, (predominately globotriaosylceramide; GL-3) in lysosomes, as well as other cellular compartments and the extracellular space. Our aim was to characterize the cardiac phenotype of male knock-out mice that are deficient in alpha-galactosidase A activity, as a model for Fabry disease and test the efficacy of Enzyme Replacement Therapy with agalsidase-beta. Male mice (3–4 months of age) were characterized with awake blood pressure and heart rate measurements, cardiac echocardiography and electrocardiography measurements under light anesthesia, histological studies and molecular studies with real-time polymerase chain reaction. The Fabry knock-out mouse has bradycardia and lower blood pressure than control wild type (CB7BL/6J) mice. In Fabry knock-out mice, the cardiomyopathy associated mild hypertrophy at echography with normal systolic LV function and mild diastolic dysfunction. Premature atrial contractions were more frequent in without conduction defect. Heart weight normalized to tibial length was increased in Fabry knock-out mice. Ascending aorta dilatation was observed. Molecular studies were consistent with early stages of cardiac remodeling. A single dose of agalsidase-beta (3 mg/kg) did not affect the LV hypertrophy, function or heart rate, but did improve the mRNA signals of early cardiac remodeling. In conclusion, the alpha-galactosidase A deficient mice at 3 to 4 months of age have cardiac and vascular alterations similar to that described in early clinical stage of Fabry disease in children and adolescents. Enzyme replacement therapy affects cardiac molecular remodeling after a single dose. PMID:22574107

Long Circulating Enzyme Replacement Therapy Rescues Bone Pathology in Mucopolysaccharidosis VII Murine Model

PubMed Central

Rowan, Daniel J.; Tomatsu, Shunji; Grubb, Jeffrey H.; Haupt, Bisong; Montaño, Adriana M.; Oikawa, Hirotaka; Sosa, Catalina; Chen, Anping; Sly, William S.

2012-01-01

Mucopolysaccharidosis (MPS) type VII is a lysosomal storage disease caused by deficiency of the lysosomal enzyme β-glucuronidase (GUS), leading to accumulation of glycosaminoglycans (GAGs). Enzyme replacement therapy (ERT) effectively clears GAG storage in the viscera. Recent studies showed that a chemically modified form of GUS (PerT-GUS), which escaped clearance by mannose 6-phosphate and mannose receptors and showed prolonged circulation, reduced CNS storage more effectively than native GUS. Clearance of storage in bone has been limited due to the avascularity of the growth plate. To evaluate the effectiveness of long-circulating PerT-GUS in reducing the skeletal pathology, we treated MPS VII mice for 12 weeks beginning at 5 weeks of age with PerT-GUS or native GUS and used micro-CT, radiographs, and quantitative histopathological analysis for assessment of bones. Micro-CT findings showed PerT-GUS treated mice had a significantly lower BMD. Histopathological analysis also showed reduced storage material and a more organized growth plate in PerT-GUS treated mice compared with native GUS treated mice. Long term treatment with PerT-GUS from birth up to 57 weeks also significantly improved bone lesions demonstrated by micro-CT, radiographs and quantitative histopathological assay. In conclusion, long-circulating PerT-GUS provides a significant impact to rescue of bone lesions and CNS involvement. PMID:22902520

Severe infusion reactions to fabry enzyme replacement therapy: rechallenge after tracheostomy.

PubMed

Nicholls, K; Bleasel, K; Becker, G

2012-01-01

A 34-year-old male patient with Fabry disease (OMIM 301500) commenced enzyme replacement therapy (ERT) with Agalsidase alfa, with positive clinical response. Infusion reactions, initially mild and easily managed, commenced during his 13th infusion, and continued over the next 3 years. Severity of reactions subsequently increased despite very slow infusion, extended prophylactic medication and attempted desensitisation, requiring regular intensive care unit (ICU) admissions. Facial oedema and flushing, throat tightness, headache and joint pain typically occurred 4-36 h after completion of most infusions, responding rapidly to subcutaneous adrenaline. Low titre specific IgG seroconversion was noted at 12 months, with subsequent reversion to negative after 5 years, despite persistence of infusion reactions. Specific IgE and skin testing was negative. Trial of ERT product switch to Agalsidase-beta resulted in no improvement in reactions. At 5 years, ERT was ceased in the face of recurrent ICU readmissions. In the face of progressive clinical deterioration, he underwent tracheostomy to allow recommencement of ERT. Two years later, he has clinically improved on regular attenuated dose Agalsidase-beta, administered by slow infusion in a local hospital setting.

Role of cardiac MRI in evaluating patients with Anderson-Fabry disease: assessing cardiac effects of long-term enzyme replacement therapy.

PubMed

Messalli, G; Imbriaco, M; Avitabile, G; Russo, R; Iodice, D; Spinelli, L; Dellegrottaglie, S; Cademartiri, F; Salvatore, M; Pisani, A

2012-02-01

Anderson-Fabry disease is a multisystemic disorder of lipid metabolism secondary to X-chromosome alterations and is frequently associated with cardiac manifestations such as left ventricular (LV) hypertrophy, gradually leading to an alteration in cardiac performance. The purpose of this study was to monitor, using magnetic resonance imaging (MRI), any changes produced by enzyme replacement therapy with agalsidase beta at the cardiac level in patients with Anderson-Fabry disease. Sixteen (ten men, six women) patients with genetically confirmed Anderson-Fabry disease underwent cardiac MRI before starting enzyme replacement therapy (baseline study) and after 48 months of treatment with agalsidase beta at the dose of 1 mg/kg (follow-up study). After 48 months of treatment, a significant reduction in LV mass and wall thickness was observed: 187±59 g vs. 149±44 g, and 16±3 mm vs. 13±3 mm, respectively. A significant reduction in T2 relaxation time was noted at the level of the interventricular septum (81±3 ms vs. 67±7 ms), at the apical level (80±8 ms vs. 63±6 ms) and at the level of the lateral wall (82±8 ms vs. 63±10 ms) (p<0.05). No significant variation was observed in ejection fraction between the two studies (65±3% vs. 64±2%; p>0.05) (mean bias 1.0); however, an improvement was noted in the New York Heart Association (NYHA) class of the majority of patients (12/16) (p<0.05). In patients with Anderson-Fabry disease undergoing enzyme replacement therapy with agalsidase beta, MRI documented a significant reduction in myocardial T2 relaxation time, a significant decrease in maximal myocardial thickness and in total LV mass. MRI did not reveal significant improvements in LV global systolic function; however, improvement in NYHA functional class was noted, consistent with improved diastolic function.

[Enzyme replacement therapy in patients with Fabry disease: state of the art and review of the literature].

PubMed

Riccio, Eleonora; Capuano, Ivana; Visciano, Bianca; Marchetiello, Cristina; Petrillo, Fortunato; Pisani, Antonio

2013-01-01

Anderson-Fabry disease is a hereditary X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha galactosidase A. It results in the accumulation of the glycosphingolypid globotrioasoyl ceramide (Gb3 in different cells and organs, resulting in a multi-system pathology including end organ failure. Patients with Fabry disease present clinically with cardiac, renal and neurological involvement; both life expectancy and quality of life are severely compromised. The current causal treatment for Fabry disease is enzyme replacement therapy (ERT), available since 2001. The two recombinant preparations available for ERT are agalsidase alfa (Replagal) and agalsidase beta (Fabrazyme). They have both been showed to have positive effect on kidney and heart, on the symptoms of pain and quality of life. Few data to date are available on comparison of the two preparations of ERT. This article reviews evidence of the literature and shows our personal experience about the safety and efficacy of ERT.

Toward reducing immunogenicity of enzyme replacement therapy: altering the specificity of human β-glucuronidase to compensate for α-iduronidase deficiency.

PubMed

Chuang, Huai-Yao; Suen, Ching-Shu; Hwang, Ming-Jing; Roffler, Steve R

2015-11-01

Enzyme replacement therapy (ERT) is an effective treatment for many patients with lysosomal storage disorders caused by deficiency in enzymes involved in cell metabolism. However, immune responses that develop against the administered enzyme in some patients can hinder therapeutic efficacy and cause serious side effects. Here we investigated the feasibility of a general approach to decrease ERT immunogenicity by altering the specificity of a normal endogenous enzyme to compensate for a defective enzyme. We sought to identify human β-glucuronidase variants that display α-iduronidase activity, which is defective in mucopolysaccharidosis (MPS) type I patients. A human β-glucuronidase library was screened by the Enzyme Cleavable Surface-Tethered All-purpose Screen sYstem to isolate variants that exhibited 100-290-fold greater activity against the α-iduronidase substrate 4-methylumbelliferyl α-l-iduronide and 7900-24 500-fold enzymatic specificity shift when compared with wild-type β-glucuronidase. In vitro treatment of MPS I cells with the β-glucuronidase variants significantly restored lysosome appearance similar to treatment with α-iduronidase. Our study suggests that β-glucuronidase variants can be isolated to display α-iduronidase activity and produce significant phenotype improvement of MPS I cells. This strategy may represent a possible approach to produce enzymes that display therapeutic benefits with potentially less immunogenicity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Recent advances of high voltage AlGaN/GaN power HFETs

NASA Astrophysics Data System (ADS)

Uemoto, Yasuhiro; Ueda, Tetsuzo; Tanaka, Tsuyoshi; Ueda, Daisuke

2009-02-01

We review our recent advances of GaN-based high voltage power transistors. These are promising owing to low on-state resistance and high breakdown voltage taking advantages of superior material properties. However, there still remain a couple of technical issues to be solved for the GaN devices to replace the existing Si-based power devices. The most critical issue is to achieve normally-off operation which is strongly desired for the safety operation, however, it has been very difficult because of the built-in polarization electric field. Our new device called GIT (Gate Injection Transistor) utilizing conductivity modulation successfully achieves the normally-off operation keeping low on-state resistance. The fabricated GIT on a Si substrate exhibits threshold voltage of +1.0V. The obtained on-state resistance and off-state breakdown voltage were 2.6mΩ•cm2 and 800V, respectively. Remaining technical issue is to further increase the breakdown voltage. So far, the reported highest off-state breakdown voltage of AlGaN/GaN HFETs has been 1900V. Overcoming these issues by a novel device structure, we have demonstrated the world highest breakdown voltages of 10400V using thick poly-crystalline AlN as a passivation film and Via-holes through sapphire which enable very efficient layout of the lateral HFET array avoiding any undesired breakdown of passivation films. Since conventional wet or dry etching cannot be used for chemically stable sapphire, high power pulsed laser is used to form the via-holes. The presented GaN power devices demonstrate that GaN is advantageous for high voltage power switching applications replacing currently used Si-based power MOSFETs and IGBTs.

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

PubMed Central

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

2017-01-01

Objective 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. Design 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. Results 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, p<0.00001; I2=89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I2=86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. Conclusions 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. PMID:27941156

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

PubMed

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, p<0.00001; I 2 =89%) and placebo (83.2±5.5 vs 67.4±7.0, p=0.0001; I 2 =86%). PERT improved coefficient of nitrogen absorption, reduced faecal fat excretion, faecal nitrogen excretion, faecal weight and abdominal pain, without significant adverse events. Follow-up studies demonstrated that PERT increased serum nutritional parameters, improved GI symptoms and quality of life without significant adverse events. High-dose or enteric-coated enzymes showed a trend to greater effectiveness than low-dose or non-coated comparisons, respectively. Subgroup, sensitive and meta-regression 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/.

76 FR 70530 - Suspension of Preparation of Environmental Impact Statement for the Proposed Replacement General...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-14

... Environmental Impact Statement for the Proposed Replacement General Aviation Airport, Mesquite, Clark County, NV... Environmental Impact Statement (EIS) for a proposed Replacement General Aviation (GA) Airport in Mesquite, Clark... General Aviation (GA) Airport, for the City of Mesquite in eastern Clark County, Nevada. The City [[Page...

Enzyme replacement therapy and fatigue in adults with Pompe disease.

PubMed

Güngör, Deniz; de Vries, Juna M; Brusse, Esther; Kruijshaar, Michelle E; Hop, Wim C J; Murawska, Magda; van den Berg, Linda E M; Reuser, Arnold J J; van Doorn, Pieter A; Hagemans, Marloes L C; Plug, Iris; van der Ploeg, Ans T

2013-06-01

Pompe disease is a hereditary metabolic myopathy, for which enzyme replacement therapy (ERT) has been available since 2006. We investigated whether ERT reduces fatigue in adult patients with Pompe disease. In this prospective international observational survey, we used the Fatigue Severity Scale (FSS) to measure fatigue. Repeated measures ANOVA was used to analyze the data over time. In a subgroup of patients, we also evaluated muscle strength using the Medical Research Council Scale, measured pulmonary function as Forced Vital Capacity, and assessed depression using the Hospital Anxiety and Depression Scale. We followed 163 patients for a median period of 4 years before ERT and for 3 years during ERT. Before ERT, the mean FSS score remained stable at around 5.3 score points; during ERT, scores improved significantly by 0.13 score points per year (p < 0.001). Fatigue decreased mainly in women, in older patients and in those with shorter disease duration. Patients' improvements in fatigue were moderately correlated with the effect of ERT on depression (r 0.55; CI 95% 0.07 to 0.70) but not with the effect of ERT on muscle strength or pulmonary function. Fatigue is a common and disabling problem in patients with early and advanced stages of Pompe disease. Our finding that ERT helps to reduce fatigue is therefore important for this patient population, irrespective of the mechanisms underlying this effect. Copyright © 2013 Elsevier Inc. All rights reserved.

A prospective 10-year study of individualized, intensified enzyme replacement therapy in advanced Fabry disease.

PubMed

Schiffmann, Raphael; Swift, Caren; Wang, Xuan; Blankenship, Derek; Ries, Markus

2015-11-01

To test the hypothesis that more frequent enzyme replacement therapy (ERT) slows the decline in kidney function in adult patients with Fabry disease. A single center open label 10-year prospective clinical trial of 12 patients with advanced Fabry disease who, after having experienced an ongoing decline in renal function after 2-4 years of receiving ERT at the approved dose of 0.2 mg/kg agalsidase alfa every other week (EOW), were switched to weekly (EW) ERT at the same dose. We used linear regression to fit each individual patient's longitudinal estimated glomerular filtration rate (eGFR) record in order to compare the deterioration rates between EOW and EW ERT. For the entire group, mean slope on agalsidase alfa every 2 weeks was -7.92 ± 2.88 ml/min/1.73 m(2)/year and 3.84 ± 4.08 ml/min/1.73 m(2)/year on weekly enzyme infusions (p = 0.01, two-tailed paired t test). Three patients (25 %) completed the entire study with relatively preserved renal function while 50 % of patients reached end-stage renal disease (ESRD) during the 10 years of this study. The estimated average delay to ESRD was 13.8 years [n = 11; 95 % CI 0.66, 27]. One patient had a positive eGFR slope on weekly infusions while the patient with the highest antibody titer had a steeper slope after switching. Mean globotriaosylceramide concentrations in urine and plasma as well as urine protein excretion remained unchanged. Weekly enzyme infusions slow the decline of renal function in a subgroup of more severe patients thus showing that existing ERT can be further optimized.

Antiproteinuric therapy and fabry nephropathy: sustained reduction of proteinuria in patients receiving enzyme replacement therapy with agalsidase-beta.

PubMed

Tahir, Hindia; Jackson, Leslie L; Warnock, David G

2007-09-01

This report describes an open-label, nonrandomized, prospective evaluation of the effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy on patients who have Fabry disease and also received enzyme replacement therapy with agalsidase-beta, given at 1 mg/kg body wt every 2 wk. Previous placebo-controlled phase III and phase IV trials with agalsidase-beta demonstrated clearing of globotriaosylceramide from vascular endothelia but little effect on proteinuria or progressive loss of kidney function in patients with Fabry disease and severe chronic kidney disease marked by overt proteinuria and/or estimated GFR <60 ml/min per 1.73 m2. Angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker therapy is the standard of care for patients with proteinuric kidney diseases, but their use is challenging in patients with Fabry disease and low or low-normal baseline systemic BP. A group of patients with Fabry disease were treated with antiproteinuric therapy, in conjunction with agalsidase-beta; sustained reductions in proteinuria with stabilization of kidney function were achieved in a group of six patients who had severe Fabry nephropathy; the progression rate was -0.23 +/- 1.12 ml/min per 1.73 m2 per yr with 30 mo of follow-up.

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

PubMed

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) on daily feed intake, rate of weight gain, feed to gain ratio, nitrogen retention, faecal nitrogen, total nitrogen output and nitrogen digestibility. The weight gained by rabbits fed on 0, 25 and 50 % were all comparable (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) effect of supplement added on the body weight gain of the experimental animals. There was significant effect (p < 0.05) of the diet on the obtained feed to gain ratio. However, there was no significant effect (p > 0.05) of the treatment on urinary nitrogen. Significant (p < 0.05) effects of supplementation was observed on the feed intake, weight gain, feed to gain

CD77 levels over enzyme replacement treatment in Fabry Disease Family (V269M).

PubMed

Pereira, Ester Miranda; Silva, Adalberto Socorro da; Silva, Raimundo Nonato da; Monte Neto, José Tiburcio; Nascimento, Fernando F do; Sousa, Jackeline L M; Costa Filho, Henrique César Saraiva de Arêa Leão; Sales Filho, Herton Luiz Alves; Labilloy, Anatalia; Monte, Semiramis Jamil Hadad do

2018-06-04

Fabry disease (FD) is a disorder caused by mutations in the gene encoding for lysosomal enzyme α-galactosidase A (α-GAL). Reduced α-GAL activity leads to progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. The recent report of increased expression of CD77 in blood cells of patients with FD indicated that this molecule can be used as a potential marker for monitoring enzyme replacement therapy (ERT). The purpose of this study was to evaluate the CD77 levels throughout ERT in FD patients (V269M mutation). We evaluated the fluctuations in PBMC (peripheral blood mononuclear cell) membrane CD77 expression in FD patients undergoing ERT and correlated these levels with those observed in different cell types. A greater CD77 expression was found in phagocytes of patients compared to controls at baseline. Interestingly, the variability in CD77 levels is larger in patients at baseline (340 - 1619 MIF) and after 12 months of ERT (240 - 530 MIF) compared with the control group (131 - 331 MFI). Furthermore, by analyzing the levels of CD77 in phagocytes from patients throughout ERT, we found a constant decrease in CD77 levels. The increased CD77 levels in the phagocytes of Fabry carriers together with the decrease in CD77 levels throughout ERT suggest that measuring CD77 levels in phagocytes is a promising tool for monitoring the response to ERT in FD.

A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease.

PubMed

Lee, Karen; Jin, Xiaoying; Zhang, Kate; Copertino, Lorraine; Andrews, Laura; Baker-Malcolm, Jennifer; Geagan, Laura; Qiu, Huawei; Seiger, Keirsten; Barngrover, Debra; McPherson, John M; Edmunds, Tim

2003-04-01

Fabry disease is a lysosomal storage disease arising from deficiency of the enzyme alpha-galactosidase A. Two recombinant protein therapeutics, Fabrazyme (agalsidase beta) and Replagal (agalsidase alfa), have been approved in Europe as enzyme replacement therapies for Fabry disease. Both contain the same human enzyme, alpha-galactosidase A, but they are produced using different protein expression systems and have been approved for administration at different doses. To determine if there is recognizable biochemical basis for the different doses, we performed a comparison of the two drugs, focusing on factors that are likely to influence biological activity and availability. The two drugs have similar glycosylation, both in the type and location of the oligosaccharide structures present. Differences in glycosylation were mainly limited to the levels of sialic acid and mannose-6-phosphate present, with Fabrazyme having a higher percentage of fully sialylated oligosaccharides and a higher level of phosphorylation. The higher levels of phosphorylated oligomannose residues correlated with increased binding to mannose-6-phosphate receptors and uptake into Fabry fibroblasts in vitro. Biodistribution studies in a mouse model of Fabry disease showed similar organ uptake. Likewise, antigenicity studies using antisera from Fabry patients demonstrated that both drugs were indistinguishable in terms of antibody cross-reactivity. Based on these studies and present knowledge regarding the influence of glycosylation on protein biodistribution and cellular uptake, the two protein preparations appear to be functionally indistinguishable. Therefore, the data from these studies provide no rationale for the use of these proteins at different therapeutic doses.

[Electroacupuncture intervention combined with general anesthesia for 80 cases of heart valve replacement surgery under cardiopulmonary bypass].

PubMed

Chi, Hao; Zhou, Wen-Xiong; Wu, Yao-Yao; Chen, Tong-Yu; Ge, Wen; Yuan, Lan; Shen, Wei-Dong; Zhou, Jia

2014-02-01

To determine whether electroacupuncture (EA) intervention combined with general anesthesia (GA) strategy can reduce early post-operative morbidity and medical costs in patients undergoing heart valve replacement operation under cardiopulmonary bypass. A total of 160 heart valve replacement surgery patients undergoing cardiopulmonary bypass were randomly divided into GA and EA + GA groups (n = 80 in each group). Patients of the GA group were given with intravenous injection of Fentanyl, Midazolam, Vecuronium Bromide, etc. and routine tracheal intubation. EA (3-4 Hz, 2.0-2.2 mA) was applied to bilateral Zhongfu (LU 1), Chize (LU 5) and Ximen (PC 4) beginning about 20 mm before the surgery in the EA + GA group. Endotracheal intubation was not employed but only prepared as a standby for patients of the EA + GA group. The dosage of narcotic drugs, duration of surgery, duration of aertic blockage, rate of cardiac re-beating, volumes of post-operative blood transfusion, discharge volume, cases of post-operative pulmonary infection, vocal cord injury, and the time of first bed-off, first eating and duration in intensive care unit (IOU) residence. etc. were recorded. The successful rates of heart valve replacement surgery were similar in both GA and EA + GA groups. Compared with the GA group, the dosages of Fentanyl, Midazolam and Vecuronium of the EA + GA group were significantly lower (P < 0.05, P < 0.01), the numbers of patients needing blood-transfusion, antibiotics treatment, and suffering from pulmonary infection were fewer, the time of first bed-off and duration of hospitalizetion and IOU residence were considerably shorter (P < 0.05, P < 0.01) and the total medical cost was obviously lower (P < 0.05) in the EA + GA group. EA combined with general anesthesia strategy for heart valve replacement surgery without endotracheal intubation is safe and can reduce post-operative morbidity and medical costs in patients undergoing heart valve replacement surgery under

Enzyme Replacement Therapy Prevents Dental Defects in a Model of Hypophosphatasia

PubMed Central

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

2011-01-01

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 B6-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-FcD10). sALP-FcD10 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. PMID:21212313

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

PubMed

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.

Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy.

PubMed

van Breemen, Mariëlle J; Rombach, Saskia M; Dekker, Nick; Poorthuis, Ben J; Linthorst, Gabor E; Zwinderman, Aeilko H; Breunig, Frank; Wanner, Christoph; Aerts, Johannes M; Hollak, Carla E

2011-01-01

Fabry disease is treated by two-weekly infusions with α-galactosidase A, which is deficient in this X-linked globotriaosylceramide (Gb3) storage disorder. Elevated plasma globotriaosylsphingosine (lysoGb3) is a hallmark of classical Fabry disease. We investigated effects of enzyme replacement therapy (ERT) on plasma levels of lysoGb3 and Gb3 in patients with classical Fabry disease treated with agalsidase alfa at 0.2mg/kg, agalsidase beta at 0.2mg/kg or at 1.0mg/kg bodyweight. Each treatment regimen led to prominent reductions of plasma lysoGb3 in Fabry males within 3 months (P=0.0313), followed by relative stability later on. Many males developed antibodies against α-galactosidase A, particularly those treated with agalsidase beta. Patients with antibodies tended towards smaller correction in plasma lysoGb3 concentration, whereas treatment with high dose agalsidase beta allowed a reduction comparable to patients without antibodies. Pre-treatment plasma lysoGb3 concentrations of Fabry females were relatively low. In all females and with each treatment regimen, ERT gave reduction or stabilisation of plasma lysoGb3. Our investigation revealed that ERT of Fabry patients reduces plasma lysoGb3, regardless of the recombinant enzyme used. This finding shows that ERT can correct a characteristic biochemical abnormality in Fabry patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

PubMed

Politei, J; Schenone, A B; Cabrera, G; Heguilen, R; Szlago, M

2016-01-01

We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Positively selected amino acid replacements within the RuBisCO enzyme of oak trees are associated with ecological adaptations.

PubMed

Hermida-Carrera, Carmen; Fares, Mario A; Fernández, Ángel; Gil-Pelegrín, Eustaquio; Kapralov, Maxim V; Mir, Arnau; Molins, Arántzazu; Peguero-Pina, José Javier; Rocha, Jairo; Sancho-Knapik, Domingo; Galmés, Jeroni

2017-01-01

Phylogenetic analysis by maximum likelihood (PAML) has become the standard approach to study positive selection at the molecular level, but other methods may provide complementary ways to identify amino acid replacements associated with particular conditions. Here, we compare results of the decision tree (DT) model method with ones of PAML using the key photosynthetic enzyme RuBisCO as a model system to study molecular adaptation to particular ecological conditions in oaks (Quercus). We sequenced the chloroplast rbcL gene encoding RuBisCO large subunit in 158 Quercus species, covering about a third of the global genus diversity. It has been hypothesized that RuBisCO has evolved differentially depending on the environmental conditions and leaf traits governing internal gas diffusion patterns. Here, we show, using PAML, that amino acid replacements at the residue positions 95, 145, 251, 262 and 328 of the RuBisCO large subunit have been the subject of positive selection along particular Quercus lineages associated with the leaf traits and climate characteristics. In parallel, the DT model identified amino acid replacements at sites 95, 219, 262 and 328 being associated with the leaf traits and climate characteristics, exhibiting partial overlap with the results obtained using PAML.

Positively selected amino acid replacements within the RuBisCO enzyme of oak trees are associated with ecological adaptations

PubMed Central

Hermida-Carrera, Carmen; Fares, Mario A.; Fernández, Ángel; Gil-Pelegrín, Eustaquio; Kapralov, Maxim V.; Mir, Arnau; Molins, Arántzazu; Peguero-Pina, José Javier; Rocha, Jairo; Sancho-Knapik, Domingo

2017-01-01

Phylogenetic analysis by maximum likelihood (PAML) has become the standard approach to study positive selection at the molecular level, but other methods may provide complementary ways to identify amino acid replacements associated with particular conditions. Here, we compare results of the decision tree (DT) model method with ones of PAML using the key photosynthetic enzyme RuBisCO as a model system to study molecular adaptation to particular ecological conditions in oaks (Quercus). We sequenced the chloroplast rbcL gene encoding RuBisCO large subunit in 158 Quercus species, covering about a third of the global genus diversity. It has been hypothesized that RuBisCO has evolved differentially depending on the environmental conditions and leaf traits governing internal gas diffusion patterns. Here, we show, using PAML, that amino acid replacements at the residue positions 95, 145, 251, 262 and 328 of the RuBisCO large subunit have been the subject of positive selection along particular Quercus lineages associated with the leaf traits and climate characteristics. In parallel, the DT model identified amino acid replacements at sites 95, 219, 262 and 328 being associated with the leaf traits and climate characteristics, exhibiting partial overlap with the results obtained using PAML. PMID:28859145

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

PubMed Central

2014-01-01

Background 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 paper, we assess the cost-effectiveness of enzyme replacement therapy in infantile Pompe disease. Methods A patient simulation model was used to compare costs and effects of ERT with costs of effects of supportive therapy (ST). The model was filled with data on survival, quality of life and costs. For both arms of the model, data on survival were obtained from international literature. In addition, survival as observed among 20 classic-infantile Dutch patients, who all received ERT, was used. Quality of life was measured using the EQ-5D and assumed to be the same in both treatment groups. Costs included the costs of ERT (which depend on a child’s weight), infusions, costs of other health care utilization, and informal care. A lifetime time horizon was used, with 6-month time cycles. Results Life expectancy was significantly longer in the ERT group than in the ST group. On average, ST receiving patients were modelled not to survive the first half year of life; whereas the life expectancy in the ERT patients was modelled to be almost 14 years. Lifetime incremental QALYs were 6.8. Incremental costs were estimated to be € 7.0 million, which primarily consisted of treatment costs (95%). The incremental costs per QALY were estimated to be € 1.0 million (range sensitivity analyses: € 0.3 million - € 1.3 million). The incremental cost per life year gained was estimated to be € 0.5 million. Conclusions The incremental costs per QALY ratio is far above the conventional threshold values. Results from univariate and probabilistic sensitivity analyses showed the robustness of the results. PMID:24884717

Uneventful pregnancy outcome after enzyme replacement therapy with agalsidase beta in a heterozygous female with Fabry disease: A case report.

PubMed

Germain, Dominique P; Bruneval, Patrick; Tran, Thi-Chien; Balouet, Pierre; Richalet, Bernard; Benistan, Karelle

2010-01-01

No reproductive studies have been performed with enzyme replacement therapy (ERT) for Fabry disease (FD, OMIM 301500), a lysosomal storage disorder. Therefore, use during pregnancy is theoretically contraindicated. We report the first case of agalsidase beta treatment throughout pregnancy. High-range proteinuria remained stable and the patient gave birth to a healthy boy after an uncomplicated pregnancy. The decision to administer ERT during pregnancy should be made on an individual basis, considering the FD status and possible risks. Copyright 2009 Elsevier Masson SAS. All rights reserved.

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

PubMed

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 <.01). Although the study was not powered to detect differences in mortality, mortality was significantly lower in the intervention group treated with pancreatic enzymes (18.6% vs 37.8%; P < .05). 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.

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

PubMed

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 < 0.05). In conclusion, it is suggested that DCP supplemented with enzymes can be used as an energy source in laying hen diets up to 30% without showing negative effects on nutrient digestibility, productive performance, or egg quality.

Characterization of an Mg-implanted GaN p-i-n Diode

DTIC Science & Technology

2016-03-31

unintentionally doped GaN layer was grown by metal organic chemical vapor deposition (MOCVD) on a n+ Ga -face c-oriented GaN substrate. The as-grown MOCVD film...their proper lattice sites. In the case of Mg implanted GaN , the Mg must replace Ga to result in p-type material. In many other semiconductor...Characterization of an Mg-implanted GaN p-i-n Diode Travis J. Anderson, Jordan D. Greenlee, Boris N. Feigelson, Karl D. Hobart, and Francis J

Ultra-Thin, Triple-Bandgap GaInP/GaAs/GaInAs Monolithic Tandem Solar Cells

NASA Technical Reports Server (NTRS)

Wanlass, M. W.; Ahrenkiel, S. P.; Albin, D. S.; Carapella, J. J.; Duda, A.; Emery, K.; Geisz, J. F.; Jones, K.; Kurtz, Sarah; Moriarty, T.;

Magnetic properties of doped Mn-Ga alloys made by mechanical milling and heat treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Daniel R.; National High Magnetic Field Laboratory, Tallahassee, FL 32310; Han, Ke

2016-05-15

Mn-Ga alloys have shown hard magnetic properties, even though these alloys contain no rare-earth metals. However, much work is needed before rare-earth magnets can be replaced. We have examined the magnetic properties of bulk alloys made with partial replacement of both the Mn and Ga elements in the Mn{sub 0.8}Ga{sub 0.2} system. Bulk samples of Mn-Ga-Bi, Mn-Ga-Al, Mn-Fe-Ga and Mn-(FeB)-Ga alloys were fabricated and studied using mechanically milling and heat treatments while altering the atomic percentage of the third element between 2.5 and 20 at%. The ternary alloy exhibits all hard magnetic properties at room temperature with large coercivity. Annealedmore » Mn-Ga-X bulk composites exhibit high coercivities up to 16.6 kOe and remanence up to 9.8 emu/g, that is increased by 115% over the binary system.« less

Investigation of efficiency enhancement in InGaN MQW LED with compositionally step graded GaN/InAlN/GaN multi-layer barrier

NASA Astrophysics Data System (ADS)

Prajoon, P.; Anuja Menokey, M.; Charles Pravin, J.; Ajayan, J.; Rajesh, S.; Nirmal, D.

2018-04-01

The advantage of InGaN multiple Quantum well (MQW) Light emitting diode (LED) on a SiC substrate with compositionally step graded GaN/InAlN/GaN multi-layer barrier (MLB) is studied. The Internal quantum efficiency, Optical power, current-voltage characteristics, spontaneous emission rate and carrier distribution profile in the active region are investigated using Sentaurus TCAD simulation. An analytical model is also developed to describe the QW carrier injection efficiency, by including carrier leakage mechanisms like carrier overflow, thermionic emission and tunnelling. The enhanced electron confinement, reduced carrier asymmetry, and suppressed carrier overflow in the active region of the MLB MQW LED leads to render a superior performance than the conventional GaN barrier MQW LED. The simulation result also elucidates the efficiency droop behaviour in the MLB MQW LED, it suggests that the efficiency droop effect is remarkably improved when the GaN barrier is replaced with GaN/InAlN/GaN MLB barrier. The analysis shows a dominating behaviour of carrier escape mechanism due to tunnelling. Moreover, the lower lattice mismatching of SiC substrate with GaN epitaxial layer is attributed with good crystal quality and reduced polarization effect, ultimately enhances the optical performance of the LEDs.

Cost-effectiveness of enzyme replacement therapy for Fabry disease.

PubMed

Rombach, Saskia M; Hollak, Carla E M; Linthorst, Gabor E; Dijkgraaf, Marcel G W

2013-02-19

The cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care was evaluated in the Dutch cohort of patients with Fabry disease. Cost-effectiveness analysis was performed using a life-time state-transition model. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort consisting of males and females aged 5-78 years. Intervention with ERT (either agalsidase alfa or agalsidase beta) was compared to the standard medical care. The main outcome measures were years without end organ damage (renal, cardiac en cerebrovascular complications), quality adjusted life years (QALYs), and costs. Over a 70 year lifetime, an untreated Fabry patient will generate 55.0 years free of end-organ damage (53.5 years in males, 56.9 years in females) and 48.6 QALYs (47.8 in males, 49.7 in females). Starting ERT in a symptomatic patient increases the number of years free of end-organ damage by 1.5 year (1.6 in males, 1.3 in females), while the number of QALYs gained increases by a similar amount (1.7 in males, 1.4 in females). The costs of ERT starting in the symptomatic stage are between €9 - €10 million (£ 7.9 - £ 8.8 million, $13.0- $14.5 million) during a patient's lifetime. Consequently, the extra costs per additional year free of end-organ damage and the extra costs per additional QALY range from €5.5 - €7.5 million (£ 4.8 - £ 6.6 million, $ 8.0 - $ 10.8 million), undiscounted. In symptomatic patients with Fabry disease, ERT has limited effect on quality of life and progression to end organ damage. The pharmaco-economic evaluation shows that this modest effectiveness drives the costs per QALY and the costs per year free of end-organ damage to millions of euros. Differentiation of patients who may benefit from ERT should be improved to enhance cost-effectiveness.

Tonic B-cell receptor signaling in diffuse large B-cell lymphoma.

PubMed

Havranek, Ondrej; Xu, Jingda; Köhrer, Stefan; Wang, Zhiqiang; Becker, Lisa; Comer, Justin M; Henderson, Jared; Ma, Wencai; Man Chun Ma, John; Westin, Jason R; Ghosh, Dipanjan; Shinners, Nicholas; Sun, Luhong; Yi, Allen F; Karri, Anusha R; Burger, Jan A; Zal, Tomasz; Davis, R Eric

2017-08-24

We used clustered regularly interspaced short palindromic repeats/Cas9-mediated genomic modification to investigate B-cell receptor (BCR) signaling in cell lines of diffuse large B-cell lymphoma (DLBCL). Three manipulations that altered BCR genes without affecting surface BCR levels showed that BCR signaling differs between the germinal center B-cell (GCB) subtype, which is insensitive to Bruton tyrosine kinase inhibition by ibrutinib, and the activated B-cell (ABC) subtype. Replacing antigen-binding BCR regions had no effect on BCR signaling in GCB-DLBCL lines, reflecting this subtype's exclusive use of tonic BCR signaling. Conversely, Y188F mutation in the immunoreceptor tyrosine-based activation motif of CD79A inhibited tonic BCR signaling in GCB-DLBCL lines but did not affect their calcium flux after BCR cross-linking or the proliferation of otherwise-unmodified ABC-DLBCL lines. CD79A-GFP fusion showed BCR clustering or diffuse distribution, respectively, in lines of ABC and GCB subtypes. Tonic BCR signaling acts principally to activate AKT, and forced activation of AKT rescued GCB-DLBCL lines from knockout (KO) of the BCR or 2 mediators of tonic BCR signaling, SYK and CD19. The magnitude and importance of tonic BCR signaling to proliferation and size of GCB-DLBCL lines, shown by the effect of BCR KO, was highly variable; in contrast, pan-AKT KO was uniformly toxic. This discrepancy was explained by finding that BCR KO-induced changes in AKT activity (measured by gene expression, CXCR4 level, and a fluorescent reporter) correlated with changes in proliferation and with baseline BCR surface density. PTEN protein expression and BCR surface density may influence clinical response to therapeutic inhibition of tonic BCR signaling in DLBCL. © 2017 by The American Society of Hematology.

Cardiac energy metabolism is disturbed in Fabry disease and improves with enzyme replacement therapy using recombinant human galactosidase A.

PubMed

Machann, Wolfram; Breunig, Frank; Weidemann, Frank; Sandstede, Jörn; Hahn, Dietbert; Köstler, Herbert; Neubauer, Stefan; Wanner, Christoph; Beer, Meinrad

2011-03-01

In vitro studies have shown impairment of energy metabolism in cardiac fibroblasts from Fabry patients. A recent in vivo study reported an association between cardiac energy metabolism and increased myocardial mass in Fabry patients. We therefore assessed possible disturbances of cardiac energy metabolism in Fabry patients by in vivo (31)P-MR-spectroscopy. Additionally, the effect of enzyme replacement therapy (ERT) on cardiac energetics was tested. Twenty-three patients (41 ± 9 years; 10 females) with genetically proven Fabry disease were examined with a 1.5 T Scanner, and compared with an age-matched healthy control group. Eight patients underwent ERT and had follow-up examinations after 3 and 14 months. The high-energy phosphate molecules phosphocreatine (PCr) and adenosine triphosphate (ATP) were quantified in localized 31P-spectra by SLOOP (spectral localization with optimum point spread function). Cine- and late gadolinium enhancement (LGE) studies were also performed. When compared with healthy controls, Fabry patients demonstrated reduced PCr- (6.1 ± 1.9 vs. 8.8 ± 2.6 mmol/kg; P = 0.003) and ATP concentrations (3.9 ± 1.5 vs. 4.6 ± 1.0 mmol/kg; P = 0.048). During ERT, PCr concentrations increased (7.1 ± 1.5 mmol/kg vs. 6.1 ± 1.9; P < 0.05) and left ventricular mass decreased (215 ± 55 vs. 185 ± 45 g; P = 0.012). Disturbances in cardiac energetics were not correlated to the presence or absence of cardiac fibrosis on LGE. Cardiac energy metabolism is disturbed in Fabry disease; this may play an important role in the pathogenesis of Fabry cardiomyopathy. Enzyme replacement therapy ameliorates energetic depression.

[Molecular mechanism of AtGA3OX1 and AtGA3OX2 genes affecting secondary wall thickening in stems in Arabidopsis].

PubMed

Wang, Zeng-Guang; Chai, Guo-Hua; Wang, Zhi-Yao; Tang, Xian-Feng; Sun, Chang-Jiang; Zhou, Gong-Ke; Ma, San-Mei

2013-05-01

Bioactive gibberellins (GAs) are a type of important plant growth regulators, which play the key roles in multiple processes, such as seed germination, leaf expansion, flowering, fruit bearing, and stem development. Its biosynthesis is regulated by a variety of enzymes including gibberellin 3-oxidase that is a key rate-limiting enzyme. In Arabidopsis, gibberellin 3-oxidase consists of four members, of which AtGA3OX1 and AtGA3OX2 are highly expressed in stems, suggesting the potential roles in the stem development played by the two genes. To date, there are few studies on AtGA3OX1 and AtGA3OX2 regulating secondary wall thickening in stems. In this study, we used the atga3ox1atga3ox2 double mutant as the materials to study the effects of AtGA3OX1 and AtGA3OX2 genes on secondary wall thickening in stems. The results indicated that simulations repression of AtGA3OX1 and AtGA3OX2 genes resulted in significantly reduction of secondary wall thickening of fiber cells, but not that of vessel cells. Three main components (cellulose, hemicelluloses, and lignin) were also dramatically suppressed in the double mutants. qRT-PCR analysis demonstrated that the expressions of secondary wall biosynthetic genes and the associated transcription factors were obviously affected in AtGA3OX1 and AtGA3OX2 double mutant. Therefore, we presume that Arabidopsis AtGA3OX1 and AtGA3OX2 genes might activate the expression of these transcription factors, thus regulate secondary wall thickening in stems. Together, our results provide a theoretical basis for enhancing the lodging resistance of food crops and improving the biomass of energy plants by genetically engineering Arabidopsis AtGA3OX homologs.

High temperature superconductor NB3Ga

NASA Technical Reports Server (NTRS)

Vieland, L. J.; Wicklund, A. W.

1973-01-01

The discovery of superconductivity at 20.3 K in the Nb-Ga system by applying chemical vapor deposition (CVD) techniques to the materials preparation problem is reported. Films on ceramic substrates have been grown with superconducting onsets of up to 20.3 K. Critical fields at 4.2 K in excess of 300 kG and alpha's of 1100,000 T-A/sq cm have been obtained. The results confirm that the outstanding properties of Nb-Ga are due to an equilibrium configuration of the system, namely, the stoichiometric A-15 compound Nb3Ga, which is stable at relatively low temperatures. Practical materials preparation problems center on the codeposition of an adjacent Nb5Ga3 phase and the requirement that the deposition temperature be low. Some ternary alloys were also prepared, with part of the Ga replaced by Sn, Sb, Al, or Ge.

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

PubMed

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

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

PubMed

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.

Dose response of bone-targeted enzyme replacement for murine hypophosphatasia

PubMed Central

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

2011-01-01

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-FcD10, 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 8.2 mg/kg for 43 days. 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 ED80 (the dose prevents the bone defects in 80% of mice) was 3.2, 2.8 and 2.9 mg/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 PPi concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP. 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. PMID:21458605

The effectiveness of dietary sunflower meal and exogenous enzyme on growth, digestive enzymes, carcass traits, and blood chemistry of broilers.

PubMed

Alagawany, Mahmoud; Attia, Adel I; Ibrahim, Zenat A; Mahmoud, Reda A; El-Sayed, Sabry A

2017-05-01

High costs of conventional protein feed sources including soybean meal (SBM) generated the need for finding other alternatives. Thus, the present study was designed to evaluate the impact of graded replacements of SBM by sunflower seed meal (SFM) with or without enzyme supplementation on growth performance, digestive enzymes, carcass traits, and blood profile of broiler chickens. A total of 240 unsexed 1-week-old broiler chicks (Hubbard) were randomly divided into eight treatment groups of 30 chicks each in five replicates each of six chicks in a factorial design (4 × 2) arrangement, including four levels of SFM (0, 25, 50, and 75% replacing SBM) and two levels of enzyme (0- or 0.1-g/kg diet) supplementation. Performance traits including feed conversion ratio, body weight, and weight gain were significantly (P < 0.01) improved with increasing SFM up to 50% substitution for SBM or with enzyme supplementation in broiler diet during the experiment. However, feed intake of broiler chicks was decreased with enzyme supplementation (P < 0.05). The activities of digestive enzymes (protease and amylase) were significantly (P < 0.05) influenced and enhanced by SFM and enzyme inclusion in diets, respectively. The activities of protease and amylase were improved with SFM diet supplemented with 0.1 g/kg enzyme in comparison with those with the un-supplemented diet. The evaluated carcass traits were not statistically (P > 0.05) influenced by feeding SFM meal or enzyme addition. Biochemical blood parameters were significantly (P < 0.01) affected by SFM, enzyme, or their interaction in broiler diets, except for globulin that was not affected by dietary enzyme. It is concluded that increasing SFM level in the diet up to 50% replacing SBM with the supplementation of enzyme improved the growth performance and enhanced positively carcass traits as well as the activity of digestive enzymes in broiler chickens.

Growth and Characterisation of GaAs/AlGaAs Core-shell Nanowires for Optoelectronic Device Applications

NASA Astrophysics Data System (ADS)

Jiang, Nian

III-V semiconductor nanowires have been investigated as key components for future electronic and optoelectronic devices and systems due to their direct band gap and high electron mobility. Amongst the III-V semiconductors, the planar GaAs material system has been extensively studied and used in industries. Accordingly, GaAs nanowires are the prime candidates for nano-scale devices. However, the electronic performance of GaAs nanowires has yet to match that of state-of-the-art planar GaAs devices. The present deficiency of GaAs nanowires is typically attributed to the large surface-to- volume ratio and the tendency for non-radiative recombination centres to form at the surface. The favoured solution of this problem is by coating GaAs nanowires with AlGaAs shells, which replaces the GaAs surface with GaAs/AlGaAs interface. This thesis presents a systematic study of GaAs/AlGaAs core-shell nanowires grown by metal organic chemical vapour deposition (MOCVD), including understanding the growth, and characterisation of their structural and optical properties. The structures of the nanowires were mainly studied by scanning electron microscopy and transmis- sion electron microscopy (TEM). A procedure of microtomy was developed to prepare the cross-sectional samples for the TEM studies. The optical properties were charac- terised by photoluminescence (PL) spectroscopy. Carrier lifetimes were measured by time-resolved PL. The growth of AlGaAs shell was optimised to obtain the best optical properties, e.g. the strongest PL emission and the longest minority carrier lifetimes. (Abstract shortened by ProQuest.).

Gallium Nitrate Is Efficacious in Murine Models of Tuberculosis and Inhibits Key Bacterial Fe-Dependent Enzymes

PubMed Central

Olakanmi, Oyebode; Kesavalu, Banurekha; Pasula, Rajamouli; Abdalla, Maher Y.; Schlesinger, Larry S.

2013-01-01

Acquiring iron (Fe) is critical to the metabolism and growth of Mycobacterium tuberculosis. Disruption of Fe metabolism is a potential approach for novel antituberculous therapy. Gallium (Ga) has many similarities to Fe. Biological systems are often unable to distinguish Ga3+ from Fe3+. Unlike Fe3+, Ga3+ cannot be physiologically reduced to Ga2+. Thus, substituting Ga for Fe in the active site of enzymes may render them nonfunctional. We previously showed that Ga inhibits growth of M. tuberculosis in broth and within cultured human macrophages. We now report that Ga(NO3)3 shows efficacy in murine tuberculosis models. BALB/c SCID mice were infected intratracheally with M. tuberculosis, following which they received daily intraperitoneal saline, Ga(NO3)3, or NaNO3. All mice receiving saline or NaNO3 died. All Ga(NO3)3-treated mice survived. M. tuberculosis CFU in the lungs, liver, and spleen of the NaNO3-treated or saline-treated mice were significantly higher than those in Ga-treated mice. When BALB/c mice were substituted for BALB/c SCID mice as a chronic (nonlethal) infection model, Ga(NO3)3 treatment significantly decreased lung CFU. To assess the mechanism(s) whereby Ga inhibits bacterial growth, the effect of Ga on M. tuberculosis ribonucleotide reductase (RR) (a key enzyme in DNA replication) and aconitase activities was assessed. Ga decreased M. tuberculosis RR activity by 50 to 60%, but no additional decrease in RR activity was seen at Ga concentrations that completely inhibited mycobacterial growth. Ga decreased aconitase activity by 90%. Ga(NO3)3 shows efficacy in murine M. tuberculosis infection and leads to a decrease in activity of Fe-dependent enzymes. Additional work is warranted to further define Ga's mechanism of action and to optimize delivery forms for possible therapeutic uses in humans. PMID:24060870

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

PubMed

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.

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

PubMed Central

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

Improvement of dysphagia in a child affected by Pompe disease treated with enzyme replacement therapy

PubMed Central

2013-01-01

Aim Dysphagia is a known complication in Pompe Disease (PD), a severe metabolic myopathy due to alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) with alglucosidase alfa is the only approved therapy for PD. Presently no data are available on the effects of ERT on dysphagia in PD patients. The aim of this work is to evaluate the course of this complication in a 6 years old boy affected by PD after treatment with ERT. Methods Dysphagia was assessed by Videofluoroscopic Swallowing Study (VFSS) at baseline, before the start of ERT and after 36 months of therapy. We used the Dysphagia Severity Rating Scale (DSS) to define the severity grade of dysphagia. Results VFSS performed at baseline revealed complete incoordination of oral stage swallowing which was classified as a grade 1 dysphagia according to DSS. After 36 months of treatment VFSS revealed normal swallowing, classified as grade 0 by DSS. Conclusion Our results suggest that ERT is effective in improving dysphagia. VFSS may be a useful tool to investigate and monitor swallowing disorders in patients affected by PD. PMID:23668440

Enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs in mucopolysaccharidosis I mice.

PubMed

Baldo, Guilherme; Mayer, Fabiana Q; Martinelli, Bárbara Z; de Carvalho, Talita G; Meyer, Fabiola S; de Oliveira, Patrícia G; Meurer, Luise; Tavares, Angela; Matte, Ursula; Giugliani, Roberto

2013-05-01

Since we previously observed that in patients with mucopolysaccharidosis (MPS) the storage of undegraded glycosaminoglycans (GAG) occurs from birth, in the present study we aimed to compare normal, untreated MPS I mice (knockout for alpha-l-iduronidase-IDUA), and MPS I mice treated with enzyme replacement therapy (ERT, Laronidase, 1.2mg/kg every 2 weeks) started from birth (ERT-neo) or from 2 months of age (ERT-ad). All mice were sacrificed at 6 months. Both treatments were equally effective in normalizing GAG levels in the viscera but had no detectable effect on the joint. Heart function was also improved with both treatments. On the other hand, mice treated from birth presented better outcomes in the difficult-to-treat aortas and heart valves. Surprisingly, both groups had improvements in behavior tests, and normalization of GAG levels in the brain and IDUA injection resulted in detectable levels of enzyme in the brain tissue 1h after administration. ERT-ad mice developed significantly more anti-IDUA-IgG antibodies, and mice that didn't develop antibodies had better performances in behavior tests, indicating that development of antibodies may reduce enzyme bioavailability. Our results suggest that ERT started from birth leads to better outcomes in the aorta and heart valves, as well as a reduction in antibody levels. Some poor vascularized organs, such as the joints, had partial or no benefit and ancillary therapies might be needed for patients. The results presented here support the idea that ERT started from birth leads to better treatment outcomes and should be considered whenever possible, a observation that gains relevance as newborn screening programs are being considered for MPS and other treatable lysosomal storage disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Enhanced mobility in vertically scaled N-polar high-electron-mobility transistors using GaN/InGaN composite channels

NASA Astrophysics Data System (ADS)

Li, Haoran; Wienecke, Steven; Romanczyk, Brian; Ahmadi, Elaheh; Guidry, Matthew; Zheng, Xun; Keller, Stacia; Mishra, Umesh K.

2018-02-01

A GaN/InGaN composite channel design for vertically scaled N-polar high-electron-mobility transistor (HEMT) structures is proposed and demonstrated by metal-organic chemical vapor deposition. In a conventional N-polar HEMT structure, as the channel thickness (tch) decreases, the sheet charge density (ns) decreases, the electric field in the channel increases, and the centroid of the two-dimensional electron gas (2DEG) moves towards the back-barrier/channel interface, resulting in stronger scattering and lower electron mobility (μ). In this study, a thin InGaN layer was introduced in-between the channel and the AlGaN cap to increase the 2DEG density and reduce the electric field in the channel and therefore increase the electron mobility. The dependence of μ on the InGaN thickness (tInGaN) and the indium composition (xIn) was investigated for different channel thicknesses. With optimized tInGaN and xIn, significant improvements in electron mobility were observed. For a 6 nm channel HEMT structure, the electron mobility increased from 606 to 1141 cm2/(V.s) when the 6 nm thick pure GaN channel was replaced by the 4 nm GaN/2 nm In0.1Ga0.9N composite channel.

Development of a screen-printed carbon electrode based disposable enzyme sensor strip for the measurement of glycated albumin.

PubMed

Hatada, Mika; Tsugawa, Wakako; Kamio, Eri; Loew, Noya; Klonoff, David C; Sode, Koji

2017-02-15

Glycated proteins, such as glycated hemoglobin (HbA1c) or glycated albumin (GA) in the blood, are essential indicators of glycemic control for diabetes mellitus. Since GA, compared to HbA1c, is more sensitive to short term changes in glycemic levels, GA is expected to be used as an alternative or together with HbA1c as a surrogate marker indicator for glycemic control. In this paper we report the development of a sensing system for measuring GA by combining an enzyme analysis method, which is already used in clinical practice, with electrochemical principles. We used fructosyl amino acid oxidase, hexaammineruthenium(III) chloride as the electron mediator, and an inexpensive and economically attractive screen-printed carbon electrode. We used chronoamperometry to measure protease-digested GA samples. The developed sensor strips were able to measure protease-digested samples containing GA in very small sample volumes (1.3μL) within about 1min. We also prepared enzyme sensor strips suitable for clinical use in which the enzyme and the mediator were deposited and dried on. This sensor system showed a clear correlation between the GA concentration and the resulting current. The strips were stable following 3 months of storage at 37°C. We conclude that this disposable enzyme sensor strip system for measuring GA is suitable for point-of-care test (POCT) applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimum Design of ARC-less InGaP/GaAs DJ Solar Cell with Hetero Tunnel Junction

NASA Astrophysics Data System (ADS)

Abbasian, Sobhan; Sabbaghi-Nadooshan, Reza

2018-07-01

The operation of hetero In0.49Ga0.51P-Al0.7Ga0.3As tunnel diodes has been evaluated, and an approach for optimizing the back surface field (BSF) layer of a InGaP/GaAs dual-junction (DJ) solar cell developed. The results show that the hetero In0.49Ga0.51P-Al0.7Ga0.3As tunnel diode transferred more electrons and holes and showed less recombination between the top and bottom cells with increased efficiency ( η) in the InGaP/GaAs DJ solar cell. To achieve higher open-circuit voltage ( V oc), GaAs semiconductor was investigated to match with Al0.52In0.48P with bandgap of 2.4 eV, and replacement of the bottom cell in the InGaP/GaAs DJ solar cell with such an Al0.52In0.48P-GaAs heterojunction increased the photogeneration in this region. In the next step, addition of a BSF layer to the top cell required two BSF layers in the bottom cell to optimize the short-circuit current ( J sc) and η. The thickness and doping of the BSF layers were increased to obtain the highest η for the cell. The proposed structure was then compared with previous works. The proposed structure yielded V oc = 2.46 V, J sc = 30 mA/cm2, fill factor (FF) = 88.61%, and η = 65.51% under AM1.5 (1 sun) illumination.

Computerized cognitive testing in patients with type I Gaucher disease: effects of enzyme replacement and substrate reduction.

PubMed

Elstein, Deborah; Guedalia, Judith; Doniger, Glen M; Simon, Ely S; Antebi, Vered; Arnon, Yael; Zimran, Ari

2005-02-01

Because of concern for drug-induced cognitive dysfunction during clinical trials using substrate reduction therapy (miglustat) in type 1 Gaucher disease and because it has been suggested that some patients with type 1 Gaucher disease may develop neurocognitive impairment as part of the natural history, two different batteries of neuropsychological tests were devised to examine these issues. Using these tests, cognitive function was assessed in patients treated with miglustat, in patients receiving enzyme replacement (standard care for symptomatic patients), and in untreated (milder) patients. For this study, 55/60 patients exposed to miglustat in Israel participated in psychologist-administered testing; 36/55 participated in computerized testing. Of these, 31 enzyme-treated patients and 22 untreated patients participated in the psychologist-administered testing, and 15 enzyme-treated patients and 18 untreated patients participated in computerized testing. The psychologist-administered battery consisted of 18 standard neuropsychological subtests specific to executive and visuospatial functioning. The computerized battery (Mindstreams, NeuroTrax Corp., New York, NY) consisted of 10 subtests tapping multiple cognitive domains. Between-group analyses for each modality compared cognitive performance. In the psychologist-administered testing, patients exposed to miglustat performed significantly less well than the other groups in 5/18 subtests. On the computerized tests, all patients performed comparably to normal controls. Scores in patients exposed to miglustat were higher than in untreated patients, particularly in visuospatial function, whereas enzyme-treated patients performed less well. However, with the exception of visuospatial function, these results were not statistically significant. It is unclear why different testing methods yielded discordant results. Any dysfunction suggested by the current study is apparently subtle and of doubtful clinical relevance

Altered biodistribution of Ga-67 by intramuscular gold salts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moult, R.G.; Bekerman, C.

1989-11-01

The authors observed a deviation from the normal scintigraphic pattern of Ga-67 citrate biodistribution. An 8-year-old black girl with juvenile rheumatoid arthritis, who had been treated with intramuscular injections of gold salts, had a Ga-67 study as part of her workup. The study demonstrated no hepatic uptake, but showed elevated skeletal and renal activity. This characteristic biodistribution of Ga-67 may be due to inhibition of lysosomal enzymes by gold and/or to accumulation of gold in lysosomes. To study these possibilities, the authors reviewed the mechanisms of Ga-67 localization and gold metabolism. Alteration of the Ga-67 citrate scintigraphic pattern due tomore » earlier treatment with gold salts has not been reported previously.« less

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

PubMed

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.

Enzyme Architecture: Self-Assembly of Enzyme and Substrate Pieces of Glycerol-3-Phosphate Dehydrogenase into a Robust Catalyst of Hydride Transfer.

PubMed

Reyes, Archie C; Amyes, Tina L; Richard, John P

2016-11-23

The stabilization of the transition state for hlGPDH-catalyzed reduction of DHAP due to the action of the phosphodianion of DHAP and the cationic side chain of R269 is between 12.4 and 17 kcal/mol. The R269A mutation of glycerol-3-phosphate dehydrogenase (hlGPDH) results in a 9.1 kcal/mol destabilization of the transition state for enzyme-catalyzed reduction of dihydroxyacetone phosphate (DHAP) by NADH, and there is a 6.7 kcal/mol stabilization of this transition state by 1.0 M guanidine cation (Gua + ) [J. Am. Chem. Soc. 2015, 137, 5312-5315]. The R269A mutant shows no detectable activity toward reduction of glycolaldehyde (GA), or activation of this reaction by 30 mM HPO 3 2- . We report the unprecedented self-assembly of R269A hlGPDH, dianions (X 2- = FPO 3 2- , HPO 3 2- , or SO 4 2- ), Gua + and GA into a functioning catalyst of the reduction of GA, and fourth-order reaction rate constants k cat /K GA K X K Gua . The linear logarithmic correlation (slope = 1.0) between values of k cat /K GA K X for dianion activation of wildtype hlGPDH-catalyzed reduction of GA and k cat /K GA K X K Gua shows that the electrostatic interaction between exogenous dianions and the side chain of R269 is not significantly perturbed by cutting hlGPDH into R269A and Gua + pieces. The advantage for connection of hlGPDH (R269A mutant + Gua + ) and substrate pieces (GA + HP i ) pieces, (ΔG S ‡ ) HPi+E+Gua = 5.6 kcal/mol, is nearly equal to the sum of the advantage to connection of the substrate pieces, (ΔG S ‡ ) GA+HPi = 3.3 kcal/mol, for wildtype hlGPDH-catalyzed reaction of GA + HP i , and for connection of the enzyme pieces, (ΔG S ‡ ) E+Gua = 2.4 kcal/mol, for Gua + activation of the R269A hlGPDH-catalyzed reaction of DHAP.

Ocular lesions in canine mucopolysaccharidosis I and response to enzyme replacement therapy.

PubMed

Newkirk, Kim M; Atkins, Rosalie M; Dickson, Patti I; Rohrbach, Barton W; McEntee, Michael F

2011-07-11

Mucopolysaccharidosis I (MPS I) is an inherited metabolic disorder resulting from deficiency of α-L-iduronidase and lysosomal accumulation of glycosaminoglycans (GAG) in multiple tissues. Accumulation of GAG in corneal stromal cells causes corneal opacity and reduced vision. The purpose of this study was to determine the extent of ocular GAG accumulation and investigate the effectiveness of intravenous enzyme replacement therapy (ERT) on corneal GAG accumulation in dogs. Ocular tissues were obtained from 58 dogs with mucopolysaccharidosis I and four unaffected controls. Affected dogs received either low-dose ERT, high-dose ERT, or no treatment; some low-dose dogs also received intrathecal treatments. Histologic severity of corneal stromal GAG accumulation was scored. Accumulation of GAG was found in corneal stromal cells and scleral fibroblasts but not in corneal epithelium, endothelium, ciliary epithelium, choroid, retina, retinal pigment epithelium, or optic nerve. Corneal GAG accumulation increased in severity with increasing age. Although low-dose ERT did not significantly reduce corneal stromal GAG accumulation in comparison with untreated animals, high-dose ERT did result in significantly less GAG accumulation compared with the untreated dogs (adjusted P = 0.0143) or the low-dose ERT group (adjusted P = 0.0031). Intrathecal treatments did not significantly affect GAG accumulation. Dogs that began ERT shortly after birth also had significantly less (P < 0.0001) GAG accumulation in the corneal stroma than dogs with a later onset of treatment. These data suggest that high-dose, intravenous ERT is effective at preventing and/or clearing corneal stromal GAG accumulation, particularly if initiated early after birth.

A Thermally Stable NiZn/Ta/Ni Scheme to Replace AuBe/Au Contacts in High-Efficiency AlGaInP-Based Light-Emitting Diodes

NASA Astrophysics Data System (ADS)

Kim, Dae-Hyun; Park, Jae-Seong; Kang, Daesung; Seong, Tae-Yeon

2017-08-01

We developed NiZn/(Ta/)Ni ohmic contacts to replace expensive AuBe/Au contacts commonly used in high-efficiency AlGaInP-based light-emitting diodes (LEDs), and compared the electrical properties of the two contact types. Unlike the AuBe/Au (130 nm/100 nm) contact, the NiZn/Ta/Ni (130 nm/20 nm/100 nm) contact shows improved electrical properties after being annealed at 500°C, with a contact resistivity of 5.2 × 10-6 Ω cm2. LEDs with the NiZn/Ta/Ni contact exhibited a 4.4% higher output power (at 250 mW) than LEDs with the AuBe/Au contact. In contrast to the trend for the AuBe/Au contact, the Ga 2 p core level for the NiZn/Ta/Ni contact shifted toward lower binding energies after being annealed at 500°C. Auger electron spectroscopy (AES) depth profiles showed that annealing the AuBe/Au samples caused the outdiffusion of both Be and P atoms into the metal contact, whereas in the NiZn/Ta/Ni samples, Zn atoms indiffused into the GaP layer. The annealing-induced electrical degradation and ohmic contact formation mechanisms are described and discussed on the basis of the results of x-ray photoemission spectroscopy and AES.

Replacement of the Endogenous Starch Debranching Enzymes ISA1 and ISA2 of Arabidopsis with the Rice Orthologs Reveals a Degree of Functional Conservation during Starch Synthesis

PubMed Central

Streb, Sebastian; Zeeman, Samuel C.

2014-01-01

This study tested the interchangeability of enzymes in starch metabolism between dicotyledonous and monocotyledonous plant species. Amylopectin - a branched glucose polymer - is the major component of starch and is responsible for its semi-crystalline property. Plants synthesize starch with distinct amylopectin structures, varying between species and tissues. The structure determines starch properties, an important characteristic for cooking and nutrition, and for the industrial uses of starch. Amylopectin synthesis involves at least three enzyme classes: starch synthases, branching enzymes and debranching enzymes. For all three classes, several enzyme isoforms have been identified. However, it is not clear which enzyme(s) are responsible for the large diversity of amylopectin structures. Here, we tested whether the specificities of the debranching enzymes (ISA1 and ISA2) are major determinants of species-dependent differences in amylopectin structure by replacing the dicotyledonous Arabidopsis isoamylases (AtISA1 and AtISA2) with the monocotyledonous rice (Oryza sativa) isoforms. We demonstrate that the ISA1 and ISA2 are sufficiently well conserved between these species to form heteromultimeric chimeric Arabidopsis/rice isoamylase enzymes. Furthermore, we were able to reconstitute the endosperm-specific rice OsISA1 homomultimeric complex in Arabidopsis isa1isa2 mutants. This homomultimer was able to facilitate normal rates of starch synthesis. The resulting amylopectin structure had small but significant differences in comparison to wild-type Arabidopsis amylopectin. This suggests that ISA1 and ISA2 have a conserved function between plant species with a major role in facilitating the crystallization of pre-amylopectin synthesized by starch synthases and branching enzymes, but also influencing the final structure of amylopectin. PMID:24642810

Digestive Enzyme Supplementation in Gastrointestinal Diseases.

PubMed

Ianiro, Gianluca; Pecere, Silvia; Giorgio, Valentina; Gasbarrini, Antonio; Cammarota, Giovanni

2016-01-01

Digestive enzymes are able to break down proteins and carbohydrates and lipids, and their supplementation may play a role in the management of digestive disorders, from lactose intolerance to cystic fibrosis. To date, several formulations of digestive enzymes are available on the market, being different each other in terms of enzyme type, source and origin, and dosage. This review, performed through a non-systematic search of the available literature, will provide an overview of the current knowledge of digestive enzyme supplementation in gastrointestinal disorders, discussion of the use of pancreatic enzymes, lactase (β-galactosidase) and conjugated bile acids, and also exploring the future perspective of digestive enzyme supplementation. Currently, the animal-derived enzymes represent an established standard of care, however the growing study of plant-based and microbe-derived enzymes offers great promise in the advancement of digestive enzyme therapy. New frontiers of enzyme replacement are being evaluated also in the treatment of diseases not specifically related to enzyme deficiency, whereas the combination of different enzymes might constitute an intriguing therapeutic option in the future.

Solvent effects on enzymes - Implications for extraterrestrial life.

NASA Technical Reports Server (NTRS)

Heinrich, M. R.

1972-01-01

Review of several studies on the alterations taking place in the structure, catalytic activity, specificity, and stability of an enzyme when some or all of the water in the medium is replaced by another solvent. These studies show the utility of solvents as a tool for probing enzyme function. They also suggest that solvents other than water should be investigated as media for controlling and directing enzyme reactions.

Epitaxial growth and magnetic properties of ultraviolet transparent Ga2O3/(Ga1-xFex)2O3 multilayer thin films.

PubMed

Guo, Daoyou; An, Yuehua; Cui, Wei; Zhi, Yusong; Zhao, Xiaolong; Lei, Ming; Li, Linghong; Li, Peigang; Wu, Zhenping; Tang, Weihua

2016-04-28

Multilayer thin films based on the ferromagnetic and ultraviolet transparent semiconductors may be interesting because their magnetic/electronic/photonic properties can be manipulated by the high energy photons. Herein, the Ga2O3/(Ga1-xFex)2O3 multilayer epitaxial thin films were obtained by alternating depositing of wide band gap Ga2O3 layer and Fe ultrathin layer due to inter diffusion between two layers at high temperature using the laser molecular beam epitaxy technique. The multilayer films exhibits a preferred growth orientation of crystal plane, and the crystal lattice expands as Fe replaces Ga site. Fe ions with a mixed valence of Fe(2+) and Fe(3+) are stratified distributed in the film and exhibit obvious agglomerated areas. The multilayer films only show a sharp absorption edge at about 250 nm, indicating a high transparency for ultraviolet light. What's more, the Ga2O3/(Ga1-xFex)2O3 multilayer epitaxial thin films also exhibits room temperature ferromagnetism deriving from the Fe doping Ga2O3.

Polar and semipolar GaN/Al0.5Ga0.5N nanostructures for UV light emitters

NASA Astrophysics Data System (ADS)

Brault, J.; Rosales, D.; Damilano, B.; Leroux, M.; Courville, A.; Korytov, M.; Chenot, S.; Vennéguès, P.; Vinter, B.; De Mierry, P.; Kahouli, A.; Massies, J.; Bretagnon, T.; Gil, B.

2014-06-01

AlxGa1-xN-based ultra-violet (UV) light emitting diodes (LEDs) are seen as the best solution for the replacement of traditional mercury lamp technology. By adjusting the Al concentration, a large emission spectrum range from 360 nm (GaN) down to 200 nm (AlN) can be covered. Owing to the large density of defects typically present in AlxGa1-xN materials usually grown on sapphire substrates, LED efficiencies still need to be improved. Taking advantage of the 3D carrier confinement, quantum dots (QDs) are among the solutions currently under investigation to improve the performances of UV LEDs. The objectives of this work are to present and discuss the morphological and optical properties of GaN nanostructures grown by molecular beam epitaxy on the (0 0 0 1) and the (11-22) orientations of Al0.5Ga0.5N. In particular, the dependence of the morphological properties of the nanostructures on the growth conditions and the surface orientation will be presented. The optical characteristics as a function of the nanostructure design (size, shape and dimensionality) will also be shown and discussed. The electroluminescence characteristics of a first series of QD-based GaN/Al0.5Ga0.5N LEDs grown on the polar (0 0 0 1) plane will be investigated.

AmeriFlux US-Me1 Metolius - Eyerly burn

DOE Data Explorer

Law, Bev [Oregon State University

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site US-Me1 Metolius - Eyerly burn. Site Description - An intermediate aged ponderosa pine forest that was severely burned in the 2002 Eyerly wildfire. All trees were killed (stand replacing event). Irvine et al (2007) GCB 13 (8), 1748–1760.

Enzyme replacement therapy with agalsidase beta improves cardiac involvement in Fabry's disease.

PubMed

Spinelli, L; Pisani, A; Sabbatini, M; Petretta, M; Andreucci, M V; Procaccini, D; Lo Surdo, N; Federico, S; Cianciaruso, B

2004-08-01

Fabry's disease is an X-linked lysosomal storage disease caused by a deficiency of alpha-galactosidase that results in an accumulation of neutral glycosphingolipids throughout the body, including the cardiovascular system. Fabry cardiomyopathy, characterized by progressive severe concentric left ventricular (LV) hypertrophy, is very frequent and is the most important cause of death in affected patients. Enzyme replacement therapy (ERT) allows a specific treatment for this disease, however, there are very few data on the effectiveness of therapy on cardiac involvement. Nine patients with Fabry cardiac disease were studied on basal condition and after 6 and 12 months of treatment with algasidase beta (Fabrazyme). A complete clinical, electrocardiographic and echocardiographic evaluation was performed in all patients. Interpretable Doppler recordings of transmitral flow and pulmonary flow velocity curves were also acquired. At baseline, the patients with Fabry's disease had increased LV septum and posterior wall thickness, normal LV fractional shortening, LV ejection fraction, normal Doppler parameters of mitral inflow but a duration of pulmonary vein flow velocity wave exceeding that of the mitral wave at atrial systole. ERT did not affect heart rate and arterial pressure. LV internal diameters did not change, there was a slight but not significant decrease in the LV posterior wall thickening and a progressive decrease in the interventricular septum thickening (p < 0.025) and in LV mass (p < 0.001) The difference in duration between pulmonary vein flow velocity wave and mitral wave at atrial systole significantly decreased (p < 0.001). These results suggest that ERT in patients with Fabry cardiomyopathy is able to reduce the LV mass and ameliorate the LV stiffness. Copyright 2004 Blackwell Munksgaard

Enzyme replacement therapy in a patient with Fabry disease and the development of IgE antibodies against agalsidase beta but not agalsidase alpha.

PubMed

Tanaka, Akemi; Takeda, Taisuke; Hoshina, Takao; Fukai, Kazuyoshi; Yamano, Tsunekazu

2010-12-01

Fabry disease is an X-linked inherited lysosomal storage disorder caused by an inborn deficiency of the enzyme α-galactosidase A. Enzyme replacement therapy (ERT) with agalsidase alpha or beta isozymes is an effective treatment. Cross-reactivity of immunoglobulin G (IgG) antibodies with agalsidase alpha and beta has been reported, but no such reaction has been recorded for IgE antibodies. We present the case of a patient with Fabry disease who developed antiagalsidase beta IgE antibodies without cross-reactivity to agalsidase alpha. A 17-year-old boy with Fabry disease had suffered from severe atopic dermatitis since infancy, and he complained for several years of peripheral pain during the summer months and when exercising. Fabry disease was confirmed by family history and a positive enzyme test, and ERT was commenced. Following infusion of agalsidase beta (1.0 mg/kg), the patient complained of a high temperature in his hands and feet, and purulent eczema developed. The infusion dose was reduced to 0.2 mg/kg, but the hyperthermia did not change, although its duration decreased. After three infusions, eosinophilia developed (9.4%; 573 cells/μl blood) and remained unresolved after four infusions with agalsidase beta. Treatment with this enzyme was discontinued, and agalsidase alpha (0.2 mg/kg) started. This produced immediate resolution of the eosinophilia, which has been maintained during follow-up. In conclusion, this patient developed IgE antibodies against agalsidase beta, which demonstrated no cross-reactivity to agalsidase alpha. These findings emphasize the importance of analyzing IgE antibodies against both enzymes when patients exhibit severe infusion-related events.

Crosslinked Enzyme Aggregates in Hierarchically-Ordered Mesoporous Silica: A Simple and Effective Method for Enzyme Stabilization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Moon Il; Kim, Jungbae; Lee, Jinwoo

2007-02-01

alpha-chymotrypsin (CT) and lipase (LP) were immobilized in hierarchically-ordered mesocellular mesoporous silica (HMMS) in a simple but effective way for the enzyme stabilization, which was achieved by the enzyme adsorption followed by glutaraldehyde (GA) crosslinking. This resulted in the formation of nanometer scale crosslinked enzyme aggregates (CLEAs) entrapped in the mesocellular pores of HMMS (37 nm), which did not leach out of HMMS through narrow mesoporous channels (13 nm). CLEA of alpha-chymotrypsin (CLEA-CT) in HMMS showed a high enzyme loading capacity and significantly increased enzyme stability. No activity decrease of CLEA-CT was observed for two weeks under even rigorously shakingmore » condition, while adsorbed CT in HMMS and free CT showed a rapid inactivation due to the enzyme leaching and presumably autolysis, respectively. With the CLEA-CT in HMMS, however, there was no tryptic digestion observed suggesting that the CLEA-CT is not susceptible to autolysis. Moreover, CLEA of lipase (CLEA-LP) in HMMS retained 30% specific activity of free lipase with greatly enhanced stability. This work demonstrates that HMMS can be efficiently employed as host materials for enzyme immobilization leading to highly enhanced stability of the immobilized enzymes with high enzyme loading and activity.« less

Mutations in the F-box gene SNEEZY result in decreased arabidopsis GA signaling

USDA-ARS?s Scientific Manuscript database

We previously reported that the SLEEPY1 (SLY1) homolog, F-box gene SNEEZY/SLEEPY2 (SNE/SLY2), can partly replace SLY1 in gibberellin (GA) hormone signaling through interaction with DELLAs RGA and GAI. To determine whether SNE normally functions in GA signaling, we characterized the phenotypes of tw...

Coupled Effect of Elevated Temperature and Cooling Conditions on the Properties of Ground Clay Brick Mortars

NASA Astrophysics Data System (ADS)

Ali Abd El Aziz, Magdy; Abdelaleem, Salh; Heikal, Mohamed

2013-12-01

When a concrete structure is exposed to fire and cooling, some deterioration in its chemical resistivity and mechanical properties takes place. This deterioration can reach a level at which the structure may have to be thoroughly renovated or completely replaced. In this investigation, four types of cement mortars, ground clay bricks (GCB)/sand namely 0/3, 1/2, 2/1 and 3/0, were used. Three different cement contents were used: 350, 400 and 450 kg/m3. All the mortars were prepared and cured in tap water for 3 months and then kept in laboratory atmospheric conditions up to 6 months. The specimens were subjected to elevated temperatures up to 700°C for 3h and then cooled by three different conditions: water, furnace, and air cooling. The results show that all the mortars subjected to fire, irrespective of cooling mode, suffered a significant reduction in compressive strength. However, the mortars cooled in air exhibited a relativity higher reduction in compressive strength rather than those water or furnace cooled. The mortars containing GCB/sand (3/0) and GCB/sand (1/2) exhibited a relatively higher thermal stability than the others.

Phage lytic enzymes targeting streptococci

USDA-ARS?s Scientific Manuscript database

Streptococcal pathogens contribute to a wide variety of human and livestock diseases. There is a need for new antimicrobials to replace over-used conventional antibiotics. Bacteriophage (viruses that infect bacteria) endolysins (enzymes that help degrade the bacterial cell wall) are ideal candidat...

Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome

PubMed Central

Tomatsu, Shunji; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Shimada, Tsutomu; Bober, Michael B; Chinen, Yasutsugu; Yabe, Hiromasa; Montaño, Adriana M; Giugliani, Roberto; Kubaski, Francyne; Yasuda, Eriko; Rodríguez-López, Alexander; Espejo-Mojica, Angela J; Sánchez, Oscar F; Mason, Robert W; Barrera, Luis A; Mackenzie, William G; Orii, Tadao

2015-01-01

Patients with mucopolysaccharidosis IVA (MPS IVA) can present with systemic skeletal dysplasia, leading to a need for multiple orthopedic surgical procedures, and often become wheelchair bound in their teenage years. Studies on patients with MPS IVA treated by enzyme replacement therapy (ERT) showed a sharp reduction on urinary keratan sulfate, but only modest improvement based on a 6-minute walk test and no significant improvement on a 3-minute climb-up test and lung function test compared with the placebo group, at least in the short-term. Surgical remnants from ERT-treated patients did not show reduction of storage materials in chondrocytes. The impact of ERT on bone lesions in patients with MPS IVA remains limited. ERT seems to be enhanced in a mouse model of MPS IVA by a novel form of the enzyme tagged with a bone-targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month-old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21 (DE3) (erGALNS) and in the methylotrophic yeast Pichia pastoris (prGALNS) has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT), beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS

Epitaxial growth and magnetic properties of ultraviolet transparent Ga2O3/(Ga1−xFex)2O3 multilayer thin films

PubMed Central

Guo, Daoyou; An, Yuehua; Cui, Wei; Zhi, Yusong; Zhao, Xiaolong; Lei, Ming; Li, Linghong; Li, Peigang; Wu, Zhenping; Tang, Weihua

2016-01-01

Multilayer thin films based on the ferromagnetic and ultraviolet transparent semiconductors may be interesting because their magnetic/electronic/photonic properties can be manipulated by the high energy photons. Herein, the Ga2O3/(Ga1−xFex)2O3 multilayer epitaxial thin films were obtained by alternating depositing of wide band gap Ga2O3 layer and Fe ultrathin layer due to inter diffusion between two layers at high temperature using the laser molecular beam epitaxy technique. The multilayer films exhibits a preferred growth orientation of crystal plane, and the crystal lattice expands as Fe replaces Ga site. Fe ions with a mixed valence of Fe2+ and Fe3+ are stratified distributed in the film and exhibit obvious agglomerated areas. The multilayer films only show a sharp absorption edge at about 250 nm, indicating a high transparency for ultraviolet light. What’s more, the Ga2O3/(Ga1−xFex)2O3 multilayer epitaxial thin films also exhibits room temperature ferromagnetism deriving from the Fe doping Ga2O3. PMID:27121446

Catalytically Active Guanylyl Cyclase B Requires Endoplasmic Reticulum-mediated Glycosylation, and Mutations That Inhibit This Process Cause Dwarfism.

PubMed

Dickey, Deborah M; Edmund, Aaron B; Otto, Neil M; Chaffee, Thomas S; Robinson, Jerid W; Potter, Lincoln R

2016-05-20

C-type natriuretic peptide activation of guanylyl cyclase B (GC-B), also known as natriuretic peptide receptor B or NPR2, stimulates long bone growth, and missense mutations in GC-B cause dwarfism. Four such mutants (L658F, Y708C, R776W, and G959A) bound (125)I-C-type natriuretic peptide on the surface of cells but failed to synthesize cGMP in membrane GC assays. Immunofluorescence microscopy also indicated that the mutant receptors were on the cell surface. All mutant proteins were dephosphorylated and incompletely glycosylated, but dephosphorylation did not explain the inactivation because the mutations inactivated a "constitutively phosphorylated" enzyme. Tunicamycin inhibition of glycosylation in the endoplasmic reticulum or mutation of the Asn-24 glycosylation site decreased GC activity, but neither inhibition of glycosylation in the Golgi by N-acetylglucosaminyltransferase I gene inactivation nor PNGase F deglycosylation of fully processed GC-B reduced GC activity. We conclude that endoplasmic reticulum-mediated glycosylation is required for the formation of an active catalytic, but not ligand-binding domain, and that mutations that inhibit this process cause dwarfism. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Agents for replacement of NAD+/NADH system in enzymatic reactions

DOEpatents

Fish, Richard H.; Kerr, John B.; Lo, Christine H.

2004-04-06

Novel agents acting as co-factors for replacement of NAD(P).sup.+ /NAD(P)H co-enzyme systems in enzymatic oxido-reductive reactions. Agents mimicking the action of NAD(P).sup.+ /NAD(P)H system in enzymatic oxidation/reduction of substrates into reduced or oxidized products. A method for selection and preparation of the mimicking agents for replacement of NAD(P).sup.+ /NAD(P)H system and a device comprising co-factors for replacement of NAD(P).sup.+ /NAD(P)H system.

Cost-effectiveness of enzyme replacement therapy for type 1 Gaucher disease

PubMed Central

2014-01-01

Objective To evaluate the cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care without ERT in the Dutch cohort of patients with type 1 Gaucher disease (GD I). Design Cost-effectiveness analysis was performed using a life-time state-transition model of the disease’s natural course. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort. Setting The tertiary referral center for Gaucher disease in the Netherlands. Participants The Dutch cohort of patients with GD I. Intervention ERT versus standard medical care without ERT in symptomatic patients. Main outcome measures Years free of end organ damage (YFEOD) (splenectomy, bone complication, malignancy, multiple complications), quality adjusted life years (QALY), and costs. Results Over an 85 year lifetime, an untreated GD I patient will generate 48.9 YFEOD and 55.86 QALYs. Starting ERT in a symptomatic patient increases the YFEOD by 12.8 years, while the number of QALYs gained increases by 6.27. The average yearly ERT medication costs range between €124,000 and €258,000 per patient. The lifetime costs of ERT starting in the symptomatic stage are €5,716,473 against €171,780 without ERT, a difference of €5,544,693. Consequently, the extra costs per additional YFEOD or per additional QALY are €434,416 and €884,994 respectively. After discounting effects by 1.5% and costs by 4% and under a reasonable scenario of ERT unit cost reduction by 25%, these incremental cost-effectiveness ratios could decrease to €149,857 and €324,812 respectively. Discussion ERT is a highly potential drug for GD I with substantial health gains. The conservatively estimated incremental cost-effectiveness ratios are substantially lower than for Pompe and Fabry disease. We suggest that the high effectiveness has contributed importantly to acceptance of reimbursement of ERT for GD I. The present study may

The Role of Pancreatic Enzyme Replacement Therapy in Unresectable Pancreatic Cancer: A Prospective Cohort Study.

PubMed

Saito, Tomotaka; Hirano, Kenji; Isayama, Hiroyuki; Nakai, Yousuke; Saito, Kei; Umefune, Gyotane; Akiyama, Dai; Watanabe, Takeo; Takagi, Kaoru; Hamada, Tsuyoshi; Takahara, Naminatsu; Uchino, Rie; Mizuno, Suguru; Kogure, Hirofumi; Matsubara, Saburo; Yamamoto, Natsuyo; Tada, Minoru; Koike, Kazuhiko

2017-03-01

Although patients with pancreatic cancer (PC) are prone to exocrine pancreatic insufficiency, there are little evidence about pancreatic enzyme replacement therapy (PERT) in patients with PC, especially those receiving chemotherapy. This is a prospective consecutive observational study of PERT in patients with unresectable PC. We prospectively enrolled patients receiving chemotherapy for unresectable PC from April 2012 to February 2014 and prescribed oral pancrelipase of 48,000 lipase units per meal (pancrelipase group). N-benzoyl-tryrosyl para-aminobenzoic acid test was performed at baseline. Patients receiving chemotherapy before April 2012 were retrospectively studied as a historical cohort. Data on the nutritional markers at baseline and 16 weeks were extracted, and serial changes, defined as the ratio of markers at 16 weeks/baseline, were compared between 2 groups. A total of 91 patients (46 in the pancrelipase group and 45 in the historical cohort) were analyzed. N-benzoyl-tryrosyl para-aminobenzoic acid test was low in 94% of the pancrelipase group. Serial change in the pancrelipase group versus historical cohort was 1.01 versus 0.95 in body mass index (P < 0.001) and 1.03 versus 0.97 in serum albumin (P = 0.131). The rate of exocrine pancreatic insufficiency in unresectable PC was high, and PERT can potentially improve the nutritional status during chemotherapy.

Clinical benefit in Fabry patients given enzyme replacement therapy--a case series.

PubMed

Guffon, N; Fouilhoux, A

2004-01-01

Fabry disease is a rare lysosomal storage disorder resulting from deficient activity of alpha-galactosidase A and subsequent pathological accumulation of glycosphingolipids throughout the body. Traditionally, Fabry disease was managed symptomatically, but the introduction of enzyme replacement therapies (ERTs) (agalsidase beta (Fabrazyme); agalsidase alfa (Replagal)) has transformed treatment of this disorder. Clinical studies of both compounds have demonstrated clearance of glycosphingolipds from key tissues. To explore whether substrate clearance translates into clinical benefit, a retrospective survey of 17 patients (mean age 34.7 years) treated with agalsidase beta (1 mg/kg every 2 weeks) was undertaken, using an eight-item retrospective questionnaire developed specifically to assess the effect of ERT on the symptoms of Fabry disease. Pain severity, heat tolerance, physical activity, fatigue and psychological status were scored using a 10-point visual analogue scale (e.g. for pain severity: 1=none, 10=strong). Answers to all other questions were quantitative. Changes in mean scores were 4.69 to 2.25 (p =0.012) for pain severity; 4.38 to 2.21 (p =0.019) for number of pain crises per month; 8.69 to 2.98 (p =0.097) for duration of pain crises in hours; 2.76 to 5.76 (p =0.002) for heat tolerance; 3.28 to 2.51 (p =0.058) for bowel movements per day; 2.47 to 4.47 (p =0.007) for frequency of physical activity; 5.53 to 3.71 (p =0.046) for fatigue, and 5.82 to 8.12 (p =0.005) for psychological status. All patients improved in at least one aspect, although the degree of improvement across patients and aspects varied widely; reasons for this remain unclear. Despite the inherent bias involved in retrospective questionnaires, we believe that the findings are encouraging. A prospective version of the questionnaire is currently under validation.

Antibody Epitope of Human α-Galactosidase A Revealed by Affinity Mass Spectrometry: A Basis for Reversing Immunoreactivity in Enzyme Replacement Therapy of Fabry Disease.

PubMed

Kukacka, Zdenek; Iurascu, Marius; Lupu, Loredana; Rusche, Hendrik; Murphy, Mary; Altamore, Lorenzo; Borri, Fabio; Maeser, Stefan; Papini, Anna Maria; Hennermann, Julia; Przybylski, Michael

2018-05-08

α-Galactosidase (αGal) is a lysosomal enzyme that hydrolyses the terminal α-galactosyl moiety from glycosphingolipids. Mutations in the encoding genes for αGal lead to defective or misfolded enzyme, which results in substrate accumulation and subsequent organ dysfunction. The metabolic disease caused by a deficiency of human α-galactosidase A is known as Fabry disease or Fabry-Anderson disease, and it belongs to a larger group known as lysosomal storage diseases. An effective treatment for Fabry disease has been developed by enzyme replacement therapy (ERT), which involves infusions of purified recombinant enzyme in order to increase enzyme levels and decrease the amounts of accumulated substrate. However, immunoreactivity and IgG antibody formation are major, therapy-limiting, and eventually life-threatening complications of ERT. The present study focused on the epitope determination of human α-galactosidase A against its antibody formed. Here we report the identification of the epitope of human αGal(309-332) recognized by a human monoclonal anti-αGal antibody, using a combination of proteolytic excision of the immobilized immune complex and surface plasmon resonance biosensing mass spectrometry. The epitope peptide, αGal(309-332), was synthesized by solid-phase peptide synthesis. Determination of its affinity by surface plasmon resonance analysis revealed a high binding affinity for the antibody (K D =39×10 -9  m), which is nearly identical to that of the full-length enzyme (K D =16×10 -9  m). The proteolytic excision affinity mass spectrometry method is shown here to be an efficient tool for epitope identification of an immunogenic lysosomal enzyme. Because the full-length αGal and the antibody epitope showed similar binding affinities, this provides a basis for reversing immunogenicity upon ERT by: 1) treatment of patients with the epitope peptide to neutralize antibodies, or 2) removal of antibodies by apheresis, and thus significantly

Expression cloning of a gibberellin 20-oxidase, a multifunctional enzyme involved in gibberellin biosynthesis.

PubMed Central

Lange, T; Hedden, P; Graebe, J E

1994-01-01

In the biosynthetic pathway to the gibberellins (GAs), carbon-20 is removed by oxidation to give the C19-GAs, which include the biologically active plant hormones. We report the isolation of a cDNA clone encoding a GA 20-oxidase [gibberellin, 2-oxoglutarate:oxygen oxidoreductase (20-hydroxylating, oxidizing) EC 1.14.11.-] by screening a cDNA library from developing cotyledons of pumpkin (Cucurbita maxima L.) for expression of this enzyme. When mRNA from either the cotyledons or the endosperm was translated in vitro using rabbit reticulocyte lysates, the products contained GA12 20-oxidase activity. A polyclonal antiserum was raised against the amino acid sequence of a peptide released by tryptic digestion of purified GA 20-oxidase from the endosperm. A cDNA expression library in lambda gt11 was prepared from cotyledon mRNA and screened with the antiserum. The identity of positive clones was confirmed by the demonstration of GA12 20-oxidase activity in single bacteriophage plaques. Recombinant protein from a selected clone catalyzed the three-step conversions of GA12 to GA25 and of GA53 to GA17, as well as the formation of the C19-GAs, GA1, GA9, and GA20, from their respective aldehyde precursors, GA23, GA24, and GA19. The nucleotide sequence of the cDNA insert contains an open reading frame of 1158 nt encoding a protein of 386 amino acid residues. The predicted M(r) (43,321) and pI (5.3) are similar to those determined experimentally for the native GA 20-oxidase. Furthermore, the derived amino acid sequence includes sequences obtained from the N terminus and two tryptic peptides from the native enzyme. It also contains regions that are highly conserved in a group of non-heme Fe-containing dioxygenases. Images PMID:8078921

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

PubMed Central

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.

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

PubMed

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.

Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

PubMed

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.

In situ monitoring of myenteric neuron activity using acetylcholinesterase-modified AlGaN/GaN solution-gate field-effect transistors.

PubMed

Müntze, Gesche Mareike; Pouokam, Ervice; Steidle, Julia; Schäfer, Wladimir; Sasse, Alexander; Röth, Kai; Diener, Martin; Eickhoff, Martin

2016-03-15

The response characteristics of acetylcholinesterase-modified AlGaN/GaN solution-gate field-effect transistors (AcFETs) are quantitatively analyzed by means of a kinetic model. The characterization shows that the covalent enzyme immobilization process yields reproducible AcFET characteristics with a Michaelis constant KM of (122 ± 4) μM for the immobilized enzyme layer. The increase of KM by a factor of 2.4 during the first four measurement cycles is attributed to partial denaturation of the enzyme. The AcFETs were used to record the release of acetylcholine (ACh) by neuronal tissue cultivated on the gate area upon stimulation by rising the extracellular K(+) concentration. The neuronal tissue constituted of isolated myenteric neurons from four to 12 days old Wistar rats, or sections from the muscularis propria containing the myenteric plexus from adult rats. For both cases the AcFET response was demonstrated to be related to the activity of the immobilized acetylcholinesterase using the reversible acetylcholinesterase blocker donepezil. A concentration response curve of this blocking agent revealed a half maximal inhibitory concentration of 40 nM which is comparable to values measured by complementary in vitro methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Switch from agalsidase beta to agalsidase alfa in the enzyme replacement therapy of patients with Fabry disease in Latin America.

PubMed

Ripeau, Diego; Amartino, Hernán; Cedrolla, Martín; Urtiaga, Luis; Urdaneta, Bella; Cano, Marilis; Valdez, Rita; Antongiovanni, Norberto; Masllorens, Francisca

2017-01-01

There are currently two available enzyme replacement therapies for Fabry disease and little information regarding efficacy and safety of switching therapies. Between 2009 and 2012 there was a worldwide shortage of agalsidase beta and patients on that enzyme were switched to agalsidase alfa. This retrospective observational study assessed a 2-year period of efficacy and safety in a population of Fabry patients, in Argentina (30 patients) and Venezuela (3 patients), who switched therapies from algasidase beta to agalsidase alfa. Thirty-three patients completed 24-months follow-up after the switch (age 32.4 ± 2.0, range 10.0-55.9 years; male: female 23:10). Measures of renal function such as estimated glomerular filtration rate remained almost unchanged in 31 patients without end stage renal disease over the 2 years after switching and urine protein excretion continued stable. Cardiac functional parameters: left ventricular mass index, interventricular septum, left ventricular posterior wall showed no significant change from baseline in the 33 patients. Quality of life, pain and disease severity scores were mostly unchanged after 24-months and agalsidase alfa was generally well tolerated. Our findings showed there is no significant change in the efficacy measured through the renal or cardiac function, quality of life, pain, disease severity scoring and safety for at least 2 years after switching from agalsidase beta to agalsidase alfa.

Agrobotanical attributes, nitrogen-fixation, enzyme activities and nutraceuticals and tyrosinase enzyme of hyacinth bean (Lablab purpureus L.) - a bio-functional medicinal legume.

USDA-ARS?s Scientific Manuscript database

Hyacinth bean (Lablab purpureus L.) accessions of different origins received from USDA, ARS, Plant Genetic Resources Conservation Unit, Griffin, GA, U.S.A. were evaluated for agrobotanical attributes, enzyme activities, nutraceuticals and quality in pot culture at AMU, Aligarh, Uttar Pradesh. Fresh ...

Plant-based oral delivery of β-glucocerebrosidase as an enzyme replacement therapy for Gaucher's disease.

PubMed

Shaaltiel, Yoseph; Gingis-Velitski, Svetlana; Tzaban, Salit; Fiks, Nadia; Tekoah, Yoram; Aviezer, David

2015-10-01

Gaucher's disease (GD), a lysosomal storage disorder caused by mutations in the gene encoding glucocerebrosidase (GCD), is currently treated by enzyme replacement therapy (ERT) using recombinant GCD that is administered intravenously every 2 weeks. However, intravenous administration includes discomfort or pain and might cause local and systemic infections that may lead to low patient compliance. An orally administered drug has the potential to alleviate these problems. In this study, we describe the potential use of plant cells as a vehicle for the oral delivery of recombinant human GCD (prGCD) expressed in carrot cells. The in vitro results demonstrate that the plant cells protect the recombinant protein in the gastric fluids and may enable absorption into the blood. Feeding experiments, with rat and pig as model animals, using carrot cells containing prGCD, show that active recombinant prGCD was found in the digestive tract and blood system and reached both, liver and spleen, the target organs in GD. These results demonstrate that the oral administration of proteins encapsulated in plant cells is feasible. Specifically, carrot cells containing recombinant human prGCD can be used as an oral delivery system and are a feasible alternative to intravenous administration of ERT for GD. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Effect of coffee filtrate, methylglyoxal, glyoxal, and caffeine on Salmonella typhimurium and S. enteritidis survival in ground chicken breasts.

PubMed

Maletta, Anne B; Were, Lilian M

2012-02-01

The antimicrobial effect of roasted coffee filtrate (CF) and dicarbonyls on Salmonella Typhimurium and Salmonella Enteritidis in raw ground chicken breast meat (GCB) was investigated. Coffee was brewed and filtered before addition to GCB. Coffee filtrate with and without added caffeine, methylglyoxal, and/or glyoxal was added to GCB and then inoculated with Salmonella Typhimurium and Salmonella Enteritidis. Ground chicken samples were stomached with peptone water at days 1, 3, 5, and 7, plated on XLD agar with a TSA overlay, and Salmonella survivors were enumerated. CF alone gave less than a 1 Log reduction in all runs compared to control GCB with no treatment. Methylglyoxal (2.28 mg/g GCB) had the greatest antimicrobial effect against Salmonella Typhimurium and Salmonella Enteritidis in GCB with average Log reductions of 2.27 to 3.23, respectively, over the 7 d duration of the experiment compared to control GCB with no treatment. A 1 Log reduction was observed in GCB with CF, 0.93 mg glyoxal, and 1 mg caffeine/g chicken compared to the control and GCB with only CF. Heat-produced coffee compounds could potentially reduce Salmonella in retail ground chicken and chicken products. © 2011 Institute of Food Technologists®

Improved InGaN/GaN light-emitting diodes with a p-GaN/n-GaN/p-GaN/n-GaN/p-GaN current-spreading layer.

PubMed

Zhang, Zi-Hui; Tan, Swee Tiam; Liu, Wei; Ju, Zhengang; Zheng, Ke; Kyaw, Zabu; Ji, Yun; Hasanov, Namig; Sun, Xiao Wei; Demir, Hilmi Volkan

2013-02-25

This work reports both experimental and theoretical studies on the InGaN/GaN light-emitting diodes (LEDs) with optical output power and external quantum efficiency (EQE) levels substantially enhanced by incorporating p-GaN/n-GaN/p-GaN/n-GaN/p-GaN (PNPNP-GaN) current spreading layers in p-GaN. Each thin n-GaN layer sandwiched in the PNPNP-GaN structure is completely depleted due to the built-in electric field in the PNPNP-GaN junctions, and the ionized donors in these n-GaN layers serve as the hole spreaders. As a result, the electrical performance of the proposed device is improved and the optical output power and EQE are enhanced.

Cerebellar Alterations and Gait Defects as Therapeutic Outcome Measures for Enzyme Replacement Therapy in α-Mannosidosis

PubMed Central

Damme, Markus; Stroobants, Stijn; Walkley, Steven U.; Lüllmann-Rauch, Renate; D`Hooge, Rudi; Fogh, Jens; Saftig, Paul; Lübke, Torben; Blanz, Judith

2011-01-01

α-Mannosidosis is a rare lysosomal storage disease with accumulation of undegraded mannosyl-linked oligosaccharides in cells throughout the body, most notably in the CNS. This leads to a broad spectrum of neurological manifestations, including progressive intellectual impairment, disturbed motor functions and cerebellar atrophy. To develop therapeutic outcome measures for enzyme replacement therapy (ERT) that could be used for human patients, a gene knockout model of α-mannosidosis in mice was analyzed for CNS pathology and motor deficits. In the cerebellar molecular layer, α-mannosidosis mice display clusters of activated Bergman glia, infiltration of phagocytic macrophages and accumulation of free cholesterol and gangliosides (GM1), notably in regions lacking Purkinje cells. α-mannosidosis brain lysates also displayed increased expression of Lamp1 and hyperglycosylation of the cholesterol binding protein NPC2. Detailed assessment of motor function revealed age-dependent gait defects in the mice that resemble the disturbed motor function in human patients. Short-term ERT partially reversed the observed cerebellar pathology with fewer activated macrophages and astrocytes but unchanged levels of hyperglycosylated NPC2, gangliosides and cholesterol. The present study demonstrates cerebellar alterations in α-mannosidosis mice that relate to the motor deficits and pathological changes seen in human patients and can be used as therapeutic outcome measures. PMID:21157375

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

PubMed

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.

Comparative investigation of InGaP/GaAs/GaAsBi and InGaP/GaAs heterojunction bipolar transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Yi-Chen; Tsai, Jung-Hui, E-mail: jhtsai@nknucc.nknu.edu.tw; Chiang, Te-Kuang

2015-10-15

In this article the characteristics of In{sub 0.49}Ga{sub 0.51}P/GaAs/GaAs{sub 0.975}Bi{sub 0.025} and In{sub 0.49}Ga{sub 0.51}P/GaAs heterojunction bipolar transistor (HBTs) are demonstrated and compared by two-dimensional simulated analysis. As compared to the traditional InGaP/GaAs HBT, the studied InGaP/GaAs/GaAsBi HBT exhibits a higher collector current, a lower base-emitter (B–E) turn-on voltage, and a relatively lower collector-emitter offset voltage of only 7 mV. Because the more electrons stored in the base is further increased in the InGaP/GaAs/GaAsBi HBT, it introduces the collector current to increase and the B–E turn-on voltage to decrease for low input power applications. However, the current gain is slightlymore » smaller than the traditional InGaP/GaAs HBT attributed to the increase of base current for the minority carriers stored in the GaAsBi base.« less

Long-term outcome of enzyme-replacement therapy in advanced Fabry disease: evidence for disease progression towards serious complications

PubMed Central

Weidemann, F; Niemann, M; Störk, S; Breunig, F; Beer, M; Sommer, C; Herrmann, S; Ertl, G; Wanner, C

2013-01-01

Objective The long-term effects of enzyme-replacement therapy (ERT) in Fabry disease are unknown. Thus, the aim of this study was to determine whether ERT in patients with advanced Fabry disease affects progression towards ‘hard’ clinical end-points in comparison with the natural course of the disease. Methods A total of 40 patients with genetically proven Fabry disease (mean age 40 ± 9 years; n = 9 women) were treated prospectively with ERT for 6 years. In addition, 40 subjects from the Fabry Registry, matched for age, sex, chronic kidney disease stage and previous transient ischaemic attack (TIA), served as a comparison group. The main outcome was a composite of stroke, end-stage renal disease (ESRD) and death. Secondary outcomes included changes in myocardial left ventricular (LV) wall thickness and replacement fibrosis, change in glomerular filtration rate (GFR), new TIA and change in neuropathic pain. Results During a median follow-up of 6.0 years (bottom and top quartiles: 5.1, 7.2), 15 events occurred in 13 patients (n = 7 deaths, n = 4 cases of ESRD and n = 4 strokes). Sudden death occurred (n = 6) only in patients with documented ventricular tachycardia and myocardial replacement fibrosis. The annual progression of myocardial LV fibrosis in the entire cohort was 0.6 ± 0.7%. As a result, posterior end-diastolic wall thinning was observed (baseline, 13.2 ± 2.0 mm; follow-up, 11.4 ± 2.1 mm; P < 0.01). GFR decreased by 2.3 ± 4.6 mL min−1 per year. Three patients experienced a TIA. The major clinical symptom was neuropathic pain (n = 37), and this symptom improved in 25 patients. The event rate was not different between the ERT group and the untreated (natural history) group of the Fabry Registry. Conclusion Despite ERT, clinically meaningful events including sudden cardiac death continue to develop in patients with advanced Fabry disease. PMID:23586858

The Mismetallation of Enzymes during Oxidative Stress*

PubMed Central

Imlay, James A.

2014-01-01

Mononuclear iron enzymes can tightly bind non-activating metals. How do cells avoid mismetallation? The model bacterium Escherichia coli may control its metal pools so that thermodynamics favor the correct metallation of each enzyme. This system is disrupted, however, by superoxide and hydrogen peroxide. These species oxidize ferrous iron and thereby displace it from many iron-dependent mononuclear enzymes. Ultimately, zinc binds in its place, confers little activity, and imposes metabolic bottlenecks. Data suggest that E. coli compensates by using thiols to extract the zinc and by importing manganese to replace the catalytic iron atom. Manganese resists oxidants and provides substantial activity. PMID:25160623

High-resolution depth profile of the InGaP-on-GaAs heterointerface by FE-AES and its relationship to device properties

NASA Astrophysics Data System (ADS)

Ichikawa, O.; Fukuhara, N.; Hata, M.; Nakano, T.; Sugiyama, M.; Shimogaki, Y.; Nakano, Y.

2007-01-01

At InGaP-on-GaAs heterointerface, transition layer is formed during metalorganic vapor phase epitaxy (MOVPE) growth that can affect device properties. Many studies of this transition layer have been done but the characterization methods used are not direct measures of the atomic structure at the heterointerface. In this study, we investigated the abruptness and thickness of the InGaP-on-GaAs transition layers by field-emission Auger electron spectroscopy, by which a depth profile with a resolution of abruptness of 30 Å or below can be obtained. The group V switching position relative to that of In goes deeper into the GaAs with increasing PH 3 supply, suggesting an initial, quick replacement of As atoms with P atoms followed by a slow P diffusion into the bulk GaAs. Changes of abruptness of the As or P profiles at the heterointerface with varying PH 3 supply on the GaAs surface are not observed. Furthermore, we evaluated the effect of the GaAsP-like transition layers on the turn-on voltage of an InGaP emitter HBT. A linear relationship is shown between the shift of the group V switching position and the HBT turn-on voltage, which is consistent with the assumption that current flow decreases at the transition layer. Calculated difference of conduction band energy between InGaP and the transition layer is 0.15 eV for the sample with ordered InGaP and 0.04 eV for disordered InGaP, is consistent with the difference of the band gap energies between ordered and disordered InGaP. Calculated P compositions are 0.52 and 0.35, respectively.

GaAs Optoelectronic Integrated-Circuit Neurons

NASA Technical Reports Server (NTRS)

Lin, Steven H.; Kim, Jae H.; Psaltis, Demetri

1992-01-01

Monolithic GaAs optoelectronic integrated circuits developed for use as artificial neurons. Neural-network computer contains planar arrays of optoelectronic neurons, and variable synaptic connections between neurons effected by diffraction of light from volume hologram in photorefractive material. Basic principles of neural-network computers explained more fully in "Optoelectronic Integrated Circuits For Neural Networks" (NPO-17652). In present circuits, devices replaced by metal/semiconductor field effect transistors (MESFET's), which consume less power.

On the effect of N-GaN/P-GaN/N-GaN/P-GaN/N-GaN built-in junctions in the n-GaN layer for InGaN/GaN light-emitting diodes.

PubMed

Kyaw, Zabu; Zhang, Zi-Hui; Liu, Wei; Tan, Swee Tiam; Ju, Zhen Gang; Zhang, Xue Liang; Ji, Yun; Hasanov, Namig; Zhu, Binbin; Lu, Shunpeng; Zhang, Yiping; Sun, Xiao Wei; Demir, Hilmi Volkan

2014-01-13

N-GaN/P-GaN/N-GaN/P-GaN/N-GaN (NPNPN-GaN) junctions embedded between the n-GaN region and multiple quantum wells (MQWs) are systematically studied both experimentally and theoretically to increase the performance of InGaN/GaN light emitting diodes (LEDs) in this work. In the proposed architecture, each thin P-GaN layer sandwiched in the NPNPN-GaN structure is completely depleted due to the built-in electric field in the NPNPN-GaN junctions, and the ionized acceptors in these P-GaN layers serve as the energy barriers for electrons from the n-GaN region, resulting in a reduced electron over flow and enhanced the current spreading horizontally in the n- GaN region. These lead to increased optical output power and external quantum efficiency (EQE) from the proposed device.

Clinical observations on enzyme replacement therapy in patients with Fabry disease and the switch from agalsidase beta to agalsidase alfa.

PubMed

Lin, Hsiang-Yu; Huang, Yu-Hsiu; Liao, Hsuan-Chieh; Liu, Hao-Chuan; Hsu, Ting-Rong; Shen, Chia-I; Li, Shao-Tzu; Li, Cheng-Fang; Lee, Li-Hong; Lee, Pi-Chang; Huang, Chun-Kai; Chiang, Chuan-Chi; Lin, Shuan-Pei; Niu, Dau-Ming

2014-04-01

Fabry disease is an X-linked inherited lysosomal storage disease that can be treated with the enzymes of agalsidase beta (Fabrazyme) and agalsidase alfa (Replagal). Since June 2009, viral contamination of Genzyme's production facility has resulted in a worldwide shortage of agalsidase beta, leading to the switch to agalsidase alfa for patients with Fabry disease in Taiwan. The medical records were retrospectively reviewed for nine male patients with Fabry disease from the start of agalsidase beta treatment until the switch to agalsidase alfa for at least 1 year. After 12-112 months of enzyme replacement therapy (ERT), decreased plasma globotriaosylsphingosine (lyso-Gb3) was found in five out of seven patients, indicating improvement in disease severity. Among the six patients with available echocardiographic data at baseline and after ERT, all six experienced reductions of left ventricular mass index. Renal function, including microalbuminuria and estimated glomerular filtration rate, showed stability after ERT. Mainz Severity Score Index scores revealed that all nine patients remained stable at 12 months after switching to agalsidase alfa. ERT improved or stabilized cardiac status and stabilized renal function, while reducing plasma lyso-Gb3. ERT was well tolerated, even among the three patients who had hypersensitivity reactions. The switch of ERT from agalsidase beta to agalsidase alfa appears to be safe after 1 year of follow-up for Taiwanese patients with Fabry disease. Copyright © 2013. Published by Elsevier B.V.

Safety and efficacy of enzyme replacement therapy with agalsidase beta: an international, open-label study in pediatric patients with Fabry disease.

PubMed

Wraith, J Edmond; Tylki-Szymanska, Anna; Guffon, Nathalie; Lien, Y Howard; Tsimaratos, Michel; Vellodi, Ashok; Germain, Dominique P

2008-04-01

To evaluate the safety and explore the efficacy of enzyme replacement therapy with agalsidase beta (recombinant human alpha-galactosidase A; Fabrazyme [Genzyme Corporation, Cambridge, MA]) in pediatric patients with Fabry disease, a genetic disorder in which deficient endogenous enzyme causes pathogenic tissue accumulation of globotriaosylceramide (GL-3). Fourteen male and 2 female patients, 8 to 16 years old, were treated in this open-label study. A 12-week observation period to collect baseline data preceded the 48-week treatment period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No primary efficacy end point was specified. Before treatment, results of skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation in superficial dermal capillary endothelial cells; with treatment, these cells were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and in all available week-48 biopsies. With treatment, reports of gastrointestinal symptoms declined steadily. Patient diaries documented significant reductions in school absences due to sickness. Agalsidase beta was generally well tolerated; most treatment-related adverse events were mild or moderate infusion-associated reactions involving rigors, fever, or rhinitis. Agalsidase beta safely and effectively reduced the GL-3 accumulation in dermal endothelium already evident in children with Fabry disease. Early intervention may prevent irreversible end-organ damage from chronic GL-3 deposition.

Zinc-blende MnN bilayer formation on the GaN(111) surface

NASA Astrophysics Data System (ADS)

Gutierrez-Ojeda, S. J.; Guerrero-Sánchez, J.; Garcia-Diaz, R.; Ramirez-Torres, A.; Takeuchi, Noboru; H. Cocoletzi, Gregorio

2017-07-01

Atomic layers of manganese nitride, deposited on the cubic gallium nitride (111) surface, are investigated using spin polarized periodic density functional theory calculations. The adsorption of a manganese atom has been evaluated at different high symmetry sites. Incorporation into the GaN substrate by replacing gallium atoms drives the formation of a site in which the displaced Ga atom forms bonds with Ga atoms at the surface. This energetically favorable configuration shows a ferromagnetic alignment. Surface formation energy calculations demonstrate that when a full Mn ML is incorporated into the GaN structure, a Ga ML on top of a MnN bilayer may be formed for very Ga-rich conditions. On the other hand, when a full Mn ML is deposited on top of the nitrogen terminated surface, an epitaxial MnN bilayer is formed with antiferromagnetic characteristics. Density of states and partial density of states are reported to show the antiferromagnetic alignment in both structures. This behavior is mainly induced by the Mn-d orbitals.

Heterologous expression and transcript analysis of gibberellin biosynthetic genes of grasses reveals novel functionality in the GA3ox family.

PubMed

Pearce, Stephen; Huttly, Alison K; Prosser, Ian M; Li, Yi-dan; Vaughan, Simon P; Gallova, Barbora; Patil, Archana; Coghill, Jane A; Dubcovsky, Jorge; Hedden, Peter; Phillips, Andrew L

2015-06-05

The gibberellin (GA) pathway plays a central role in the regulation of plant development, with the 2-oxoglutarate-dependent dioxygenases (2-ODDs: GA20ox, GA3ox, GA2ox) that catalyse the later steps in the biosynthetic pathway of particularly importance in regulating bioactive GA levels. Although GA has important impacts on crop yield and quality, our understanding of the regulation of GA biosynthesis during wheat and barley development remains limited. In this study we identified or assembled genes encoding the GA 2-ODDs of wheat, barley and Brachypodium distachyon and characterised the wheat genes by heterologous expression and transcript analysis. The wheat, barley and Brachypodium genomes each contain orthologous copies of the GA20ox, GA3ox and GA2ox genes identified in rice, with the exception of OsGA3ox1 and OsGA2ox5 which are absent in these species. Some additional paralogs of 2-ODD genes were identified: notably, a novel gene in the wheat B genome related to GA3ox2 was shown to encode a GA 1-oxidase, named as TaGA1ox-B1. This enzyme is likely to be responsible for the abundant 1β-hydroxylated GAs present in developing wheat grains. We also identified a related gene in barley, located in a syntenic position to TaGA1ox-B1, that encodes a GA 3,18-dihydroxylase which similarly accounts for the accumulation of unusual GAs in barley grains. Transcript analysis showed that some paralogs of the different classes of 2-ODD were expressed mainly in a single tissue or at specific developmental stages. In particular, TaGA20ox3, TaGA1ox1, TaGA3ox3 and TaGA2ox7 were predominantly expressed in developing grain. More detailed analysis of grain-specific gene expression showed that while the transcripts of biosynthetic genes were most abundant in the endosperm, genes encoding inactivation and signalling components were more highly expressed in the seed coat and pericarp. The comprehensive expression and functional characterisation of the multigene families encoding the 2-ODD

The health of loblolly pine stands at Fort Benning, GA

Treesearch

Soung-Ryoul Ryu; G. Geoff Wang; Joan L. Walker

2013-01-01

Approximately two-thirds of the red-cockaded woodpecker (Picoides borealis) (RCW) groups at Fort Benning, GA, depend on loblolly pine (Pinus taeda) stands for nesting or foraging. However, loblolly pine stands are suspected to decline. Forest managers want to replace loblolly pine with longleaf pine (P. palustris...

Regulation and therapeutic targeting of peptide-activated receptor guanylyl cyclases

PubMed Central

Potter, Lincoln R.

2016-01-01

Cyclic GMP is a ubiquitous second messenger that regulates a wide array of physiologic processes such as blood pressure, long bone growth, intestinal fluid secretion, phototransduction and lipolysis. Soluble and single-membrane-spanning enzymes called guanylyl cyclases (GC) synthesize cGMP. In humans, the latter group consists of GC-A, GC-B, GC-C, GC-E and GC-F, which are also known as NPR-A, NPR-B, StaR, Ret1-GC and Ret2-GC, respectively. Membrane GCs are activated by peptide ligands such as atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP), guanylin, uroguanylin, heat stable enterotoxin and GC-activating proteins. Nesiritide and carperitide are clinically approved peptide-based drugs that activate GC-A. CD-NP is an experimental heart failure drug that primarily activates GC-B but also activates GC-A at high concentrations and is resistant to degradation. Inactivating mutations in GC-B cause acromesomelic dysplasia type Maroteaux dwarfism and chromosomal mutations that increase CNP concentrations are associated with Marfanoid-like skeletal overgrowth. Pump-based CNP infusions increase skeletal growth in a mouse model of the most common type of human dwarfism, which supports CNP/GC-B-based therapies for short stature diseases. Linaclotide is a peptide activator of GC-C that stimulates intestinal motility and is in late-stage clinical trials for the treatment of chronic constipation. This review discusses the discovery of cGMP, guanylyl cyclases, the general characteristics and therapeutic applications of GC-A, GC-B and GC-C, and emphasizes the regulation of transmembrane guanylyl cyclases by phosphorylation and ATP. PMID:21185863

Use of GaN as a Scintillating Ionizing Radiation Detector

NASA Astrophysics Data System (ADS)

Wensman, Johnathan; Guardala, Noel; Mathur, Veerendra; Alasagas, Leslie; Vanhoy, Jeffrey; Statham, John; Marron, Daniel; Millett, Marshall; Marsh, Jarrod; Currie, John; Price, Jack

2017-09-01

Gallium nitride (GaN) is a III/V direct bandgap semiconductor which has been used in light emitting diodes (LEDs) since the 1990s. Currently, due to a potential for increased efficiency, GaN is being investigated as a replacement for silicon in power electronics finding potential uses ranging from data centers to electric vehicles. In addition to LEDs and power electronics though, doped GaN can be used as a gamma insensitive fast neutron detector due to the direct band-gap, light propagation properties, and response to ionizing radiations. Investigation of GaN as a semiconductor scintillator for use in a radiation detection system involves mapping the response function of the detector crystal over a range of photon and neutron energies, and measurements of light generation in the GaN crystal due to proton, alpha, and nitrogen projectiles. In this presentation we discuss the measurements made to date, and plausible interpretations of the response functions. This work funded in part by the Naval Surface Warfare Center, Carderock Division In-house Laboratory Independent Research program.

Deleterious effects of interruption followed by reintroduction of enzyme replacement therapy on a lysosomal storage disorder.

PubMed

Schneider, Ana Paula; Matte, Ursula; Pasqualim, Gabriela; Tavares, Angela Maria Vicente; Mayer, Fabiana Quoos; Martinelli, Barbara; Ribas, Graziela; Vargas, Carmen Regla; Giugliani, Roberto; Baldo, Guilherme

2016-10-01

Temporary interruption of enzyme replacement therapy (ERT) in patients with different lysosomal storage disorders may happen for different reasons (adverse reactions, issues with reimbursement, logistic difficulties, and so forth), and the impact of the interruption is still uncertain. In the present work, we studied the effects of the interruption of intravenous ERT (Laronidase, Genzyme) followed by its reintroduction in mice with the prototypical lysosomal storage disorder mucopolysaccharidosis type I, comparing to mice receiving continuous treatment, untreated mucopolysaccharidosis type I mice, and normal mice. In the animals which treatment was temporarily interrupted, we observed clear benefits of treatment in several organs (liver, lung, heart, kidney, and testis) after reintroduction, but a worsening in the thickness of the aortic wall was detected. Furthermore, these mice had just partial improvements in behavioral tests, suggesting some deterioration in the brain function. Despite worsening is some disease aspects, urinary glycosaminoglycans levels did not increase during interruption, which indicates that this biomarker commonly used to monitor treatment in patients should not be used alone to assess treatment efficacy. The deterioration observed was not caused by the development of serum antienzyme antibodies. All together our results suggest that temporary ERT interruption leads to deterioration of function in some organs and should be avoided whenever possible. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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.

High-luminance LEDs replace incandescent lamps in new applications

NASA Astrophysics Data System (ADS)

Evans, David L.

1997-04-01

The advent of high luminance AlInGaP and InGaN LED technologies has prompted the use of LED devices in new applications formally illuminated by incandescent lamps. The luminous efficiencies of these new LED technologies equals or exceeds that attainable with incandescent sources, with reliability factors that far exceed those of incandescent sources. The need for a highly efficient, dependable, and cost effective replacement for incandescent lamps is being fulfilled with high luminance LED lamps. This paper briefly described some of the new applications incorporating high luminance LED lamps, traffic signals and roadway signs for traffic management, automotive exterior lighting, active matrix and full color displays for commercial advertising, and commercial aircraft panel lighting and military aircraft NVG compatible lighting.

Photoelectrochemical NADH Regeneration using Pt-Modified p -GaAs Semiconductor Electrodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stufano, Paolo; Paris, Aubrey R.; Bocarsly, Andrew

Cofactor regeneration in enzymatic reductions is crucial for the application of enzymes to both biological and energy-related catalysis. Specifically, regenerating NADH from NAD + is of great interest, and using electrochemistry to achieve this end is considered a promising option. Here in this paper, we report the first example of photoelectrochemical NADH regeneration at the illuminated (λ >600 nm), metal-modified p-type semiconductor electrode Pt/p-GaAs. Although bare p-GaAs electrodes produce only enzymatically inactive NAD 2, NADH was produced at the illuminated Pt-modified p-GaAs surface. At low overpotential (–0.75 V vs. Ag/AgCl), Pt/p-GaAs exhibited a seven-fold greater Faradaic efficiency for the formationmore » of NADH than Pt alone, with reduced competition from the hydrogen evolution reaction. Improved Faradaic efficiency and low overpotential suggest the possible utility of Pt/p-GaAs in energy-related NADH-dependent enzymatic processes.« less

Photoelectrochemical NADH Regeneration using Pt-Modified p -GaAs Semiconductor Electrodes

DOE PAGES

Stufano, Paolo; Paris, Aubrey R.; Bocarsly, Andrew

2017-02-22

Cofactor regeneration in enzymatic reductions is crucial for the application of enzymes to both biological and energy-related catalysis. Specifically, regenerating NADH from NAD + is of great interest, and using electrochemistry to achieve this end is considered a promising option. Here in this paper, we report the first example of photoelectrochemical NADH regeneration at the illuminated (λ >600 nm), metal-modified p-type semiconductor electrode Pt/p-GaAs. Although bare p-GaAs electrodes produce only enzymatically inactive NAD 2, NADH was produced at the illuminated Pt-modified p-GaAs surface. At low overpotential (–0.75 V vs. Ag/AgCl), Pt/p-GaAs exhibited a seven-fold greater Faradaic efficiency for the formationmore » of NADH than Pt alone, with reduced competition from the hydrogen evolution reaction. Improved Faradaic efficiency and low overpotential suggest the possible utility of Pt/p-GaAs in energy-related NADH-dependent enzymatic processes.« less

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

PubMed

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.

Reduction of Plasma Globotriaosylsphingosine Levels After Switching from Agalsidase Alfa to Agalsidase Beta as Enzyme Replacement Therapy for Fabry Disease.

PubMed

Goker-Alpan, Ozlem; Gambello, Michael J; Maegawa, Gustavo H B; Nedd, Khan J; Gruskin, Daniel J; Blankstein, Larry; Weinreb, Neal J

2016-01-01

Agalsidase alfa and agalsidase beta, recombinant enzyme preparations for treatment of Fabry disease (FD), have different approved dosing schedules: 0.2 mg/kg and 1.0 mg/kg every other week (EOW), respectively. This open-label, multicenter, exploratory phase 4 study evaluated plasma globotriaosylsphingosine (lyso-GL-3) and plasma and urine globotriaosylceramide (GL-3) levels at baseline and 2, 4, and 6 months after the switch from agalsidase alfa (0.2 mg/kg EOW for ≥12 months) to agalsidase beta (1.0 mg/kg EOW) in 15 male patients with FD. Immunoglobulin (Ig)G antidrug antibody titers were assessed, and safety was monitored throughout the study. Plasma lyso-GL-3 concentrations decreased significantly within 2 months after switch and reductions continued through month 6 (mean absolute changes, -12.8, -16.1, and -16.7 ng/mL at 2, 4, and 6 months, respectively; all P < 0.001). The mean percentage reduction from baseline was 39.5% (P < 0.001) at month 6. For plasma GL-3, the mean absolute change from baseline (-0.9 μg/mL) and percentage reduction (17.9%) at month 6 were both significant (P < 0.05). Urine GL-3 measurements showed intra-patient variability and changes from baseline were not significant. No clinical outcomes were assessed in this 6-month study, and, therefore, no conclusions can be drawn regarding the correlation of observed reductions in glycosphingolipid concentrations with clinically relevant outcomes. There were no differences in IgG antidrug antibody titers between the two enzymes. The switch from agalsidase alfa to agalsidase beta was well tolerated. Plasma lyso-GL-3 and GL-3 levels reduced after switching from agalsidase alfa to agalsidase beta, indicating that agalsidase beta has a greater pharmacodynamic effect on these markers at the recommended dose. These data further support the use of agalsidase beta 1.0 mg/kg EOW as enzyme replacement therapy in FD.

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

PubMed

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.

Salicylic-Acid-Induced Chilling- and Oxidative-Stress Tolerance in Relation to Gibberellin Homeostasis, C-Repeat/Dehydration-Responsive Element Binding Factor Pathway, and Antioxidant Enzyme Systems in Cold-Stored Tomato Fruit.

PubMed

Ding, Yang; Zhao, Jinhong; Nie, Ying; Fan, Bei; Wu, Shujuan; Zhang, Yu; Sheng, Jiping; Shen, Lin; Zhao, Ruirui; Tang, Xuanming

2016-11-02

Effects of salicylic acid (SA) on gibberellin (GA) homeostasis, C-repeat/dehydration-responsive element binding factor (CBF) pathway, and antioxidant enzyme systems linked to chilling- and oxidative-stress tolerance in tomato fruit were investigated. Mature green tomatoes (Solanum lycopersicum L. cv. Moneymaker) were treated with 0, 0.5, and 1 mM SA solution for 15 min before storage at 4 °C for 28 days. In comparison to 0 or 0.5 mM SA, 1 mM SA significantly decreased the chilling injury (CI) index in tomato fruit. In the SA-treated fruit, the upregulation of GA biosynthetic gene (GA3ox1) expression was followed by gibberellic acid (GA 3 ) surge and DELLA protein degradation. CBF1 participated in the SA-modulated tolerance and stimulated the expression of GA catabolic gene (GA2ox1). Furthermore, 1 mM SA enhanced activities of antioxidant enzymes and, thus, reduced reactive oxygen species accumulation. Our findings suggest that SA might protect tomato fruit from CI and oxidative damage through regulating GA metabolism, CBF1 gene expression, and antioxidant enzyme activities.

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

PubMed

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.

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

PubMed

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.

Synthesis and properties of γ-Ga2O3-Al2O3 solid solutions

NASA Astrophysics Data System (ADS)

Afonasenko, T. N.; Leont'eva, N. N.; Talzi, V. P.; Smirnova, N. S.; Savel'eva, G. G.; Shilova, A. V.; Tsyrul'nikov, P. G.

2017-10-01

The textural and structural properties of mixed oxides Ga2O3-Al2O3, obtained via impregnating γ-Al2O3 with a solution of Ga(NO3)3 and subsequent heat treatment, are studied. According to the results from X-ray powder diffraction, gallium ions are incorporated into the structure of aluminum oxide to form a solid solution of spinel-type γ-Ga2O3-Al2O3 up to a Ga2O3 content of 50 wt % of the total weight of the sample, accompanied by a reduction in the specific surface area, volume, and average pore diameter. It is concluded that when the Ga2O3 content exceeds 50 wt %, the β-Ga2O3 phase is observed along with γ-Ga2O3-Al2O3 solid solution. 71Ga and 27Al NMR spectroscopy shows that gallium replaces aluminum atoms from the tetrahedral position to the octahedral coordination in the structure of γ-Ga2O3-Al2O3.

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

PubMed Central

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

Comparison of trap characteristics between AlGaN/GaN and AlGaN/InGaN/GaN heterostructure by frequency dependent conductance measurement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chakraborty, Apurba, E-mail: apurba.chakraborty86@gmail.com; Biswas, Dhrubes; Advanced Technology Development Centre, IIT Kharagpur, Kharagpur 721302

2015-02-23

Frequency dependent conductance measurement is carried out to observe the trapping effect in AlGaN/InGaN/GaN double heterostructure and compared that with conventional AlGaN/GaN single heterostructure. It is found that the AlGaN/InGaN/GaN diode structure does not show any trapping effect, whereas single heterostructure AlGaN/GaN diode suffers from two kinds of trap energy states in near depletion to higher negative voltage bias region. This conductance behaviour of AlGaN/InGaN/GaN heterostructure is owing to more Fermi energy level shift from trap energy states at AlGaN/InGaN junction compare to single AlGaN/GaN heterostructure and eliminates the trapping effects. Analysis yielded interface trap energy state in AlGaN/GaN ismore » to be with time constant of (33.8–76.5) μs and trap density of (2.38–0.656) × 10{sup 12 }eV{sup −1} cm{sup −2} in −3.2 to −4.8 V bias region, whereas for AlGaN/InGaN/GaN structure no interface energy states are found and the extracted surface trap energy concentrations and time constants are (5.87–4.39) ×10{sup 10} eV{sup −1} cm{sup −2} and (17.8–11.3) μs, respectively, in bias range of −0.8–0.0 V.« less

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

PubMed

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.

Biocatalysts based on nanozeolite-enzyme complexes: Effects of alkoxysilane surface functionalization and biofuel production using microalgae lipids feedstock.

PubMed

de Vasconcellos, Adriano; Miller, Alex Henrique; Aranda, Donato A G; Nery, José Geraldo

2018-05-01

Nanozeolites with different crystallographic structures (Nano/TS1, Nano/GIS, Nano/LTA, Nano/BEA, Nano/X, and Nano-X/Ni), functionalized with (3-aminopropyl)trimethoxysilane (APTMS) and crosslinked with glutaraldehyde (GA), were studied as solid supports for Thermomyces lanuginosus lipase (TLL) immobilization. Physicochemical characterizations of the surface-functionalized nanozeolites and nanozeolite-enzyme complexes were performed using XRD, SEM, AFM, ATR-FTIR, and zeta potential measurements. The experimental enzymatic activity results indicated that the nanozeolitic supports functionalized with APTMS and GA immobilized larger amounts of enzymes and provided higher enzymatic activities, compared to unfunctionalized supports. Correlations were observed among the nanozeolite surface charges, the enzyme immobilization efficiencies, and the biocatalyst activities. The catalytic performance and reusability of these enzyme-nanozeolite complexes were evaluated in the ethanolysis transesterification of microalgae oil to fatty acid ethyl esters (FAEEs). TLL immobilized on the nanozeolite supports functionalized with APTMS and GA provided the most efficient biocatalysis, with FAEEs yields above 93% and stability during five reaction cycles. Lower FAEEs yields and poorer catalytic stability were found for nanozeolite-enzyme complexes prepared only by physical adsorption. The findings indicated the viability of designing highly efficient biocatalysts for biofuel production by means of chemical modulation of nanozeolite surfaces. The high biocatalyst catalytic efficiency observed in ethanolysis reactions using a lipid feedstock that does not compete with food production is an advantage that should encourage the industrial application of these biocatalysts. Copyright © 2018 Elsevier B.V. All rights reserved.

Enzyme replacement therapy stabilized white matter lesion progression in Fabry disease.

PubMed

Fellgiebel, Andreas; Gartenschläger, Martin; Wildberger, Kerstin; Scheurich, Armin; Desnick, Robert J; Sims, Katherine

2014-01-01

The central nervous system manifestations in Fabry disease (FD) include progressive white matter lesions (WMLs) and stroke. Due to progressive microvascular involvement, men and women with FD over 35 years of age develop WMLs. Moreover, the prevalence of stroke has been estimated to be 12 times higher in FD compared with the general population. Enzyme replacement therapy (ERT) is available and has shown beneficial effects on renal, cardiac, and peripheral nerve function in FD, but the ERT effect on the progression of WMLs, or the reduction in cerebrovascular events, remains unknown. The WML burden and the effect of agalsidase beta 1 mg/kg biweekly on WML progression were assessed longitudinally in a Phase 4 agalsidase-beta placebo-controlled analysis of untreated and treated FD patients with mild-to-moderate renal involvement (serum creatinine measurements of ≥1.2 mg/dl and <3.0 mg/dl). The primary end point was the difference in the number of patients with increased WML burden between the agalsidase beta and placebo groups at the end of treatment. The diameters of the WMLs were determined manually using axial flow-attenuated-inversion-recovery-weighted magnetic resonance imaging (MRI) scans taken at baseline and follow-up. MRI scans from 41 FD patients (mean age 43.9, age range 20-68, 3 females; n=25 on ERT, n=16 on placebo) were analyzed. WML burden was present in 63% of patients at baseline, increased over a mean of 27 months (range 12-33 months) follow-up, and correlated with left ventricular hypertrophy (LVPW). Patients with previous or recent strokes (n=11, 39-68 years) showed an increase in the number of WMLs (p=0.005). A greater proportion of younger patients (≤50 years) on ERT (n=18) had stable WML burden compared with younger patients in the placebo group (n=13): 44% (8 of 18) versus 31% (4 of 13), p=0.014. The number needed to treat was 8. This FD patient cohort, with mild-to-moderate renal involvement, had a significant WML burden and high inter

Surface structures of L10-MnGa (001) by scanning tunneling microscopy and first-principles theory

NASA Astrophysics Data System (ADS)

Corbett, J. P.; Guerrero-Sanchez, J.; Richard, A. L.; Ingram, D. C.; Takeuchi, N.; Smith, A. R.

2017-11-01

We report on the surface reconstructions of L10-ordered MnGa (001) thin films grown by molecular beam epitaxy on a 50 nm Mn3N2 (001) layer freshly grown on a magnesium oxide (001) substrate. Scanning tunneling microscopy, Auger electron spectroscopy, and reflection high energy electron diffraction are combined with first-principles density functional theory calculations to determine the reconstructions of the L10-ordered MnGa (001) surface. We find two lowest energy reconstructions of the MnGa (001) face: a 1 × 1 Ga-terminated structure and a 1 × 2 structure with a Mn replacing a Ga in the 1 × 1 Ga-terminated surface. The 1 × 2 reconstruction forms a row structure along [100]. The manganese:gallium stoichiometry within the surface based on theoretical modeling is in good agreement with experiment. Magnetic moment calculations for the two lowest energy structures reveal important surface and bulk effects leading to oscillatory total magnetization for ultra-thin MnGa (001) films.

Spatially resolved In and As distributions in InGaAs/GaP and InGaAs/GaAs quantum dot systems.

PubMed

Shen, J; Song, Y; Lee, M L; Cha, J J

2014-11-21

InGaAs quantum dots (QDs) on GaP are promising for monolithic integration of optoelectronics with Si technology. To understand and improve the optical properties of InGaAs/GaP QD systems, detailed measurements of the QD atomic structure as well as the spatial distributions of each element at high resolution are crucial. This is because the QD band structure, band alignment, and optical properties are determined by the atomic structure and elemental composition. Here, we directly measure the inhomogeneous distributions of In and As in InGaAs QDs grown on GaAs and GaP substrates at the nanoscale using energy dispersive x-ray spectral mapping in a scanning transmission electron microscope. We find that the In distribution is broader on GaP than on GaAs, and as a result, the QDs appear to be In-poor using a GaP matrix. Our findings challenge some of the assumptions made for the concentrations and distributions of In within InGaAs/GaAs or InGaAs/GaP QD systems and provide detailed structural and elemental information to modify the current band structure understanding. In particular, the findings of In deficiency and inhomogeneous distribution in InGaAs/GaP QD systems help to explain photoluminescence spectral differences between InGaAs/GaAs and InGaAs/GaP QD systems.

Enzyme replacement therapy in Japanese Fabry disease patients: the results of a phase 2 bridging study.

PubMed

Eto, Y; Ohashi, T; Utsunomiya, Y; Fujiwara, M; Mizuno, A; Inui, K; Sakai, N; Kitagawa, T; Suzuki, Y; Mochizuki, S; Kawakami, M; Hosoya, T; Owada, M; Sakuraba, H; Saito, H

2005-01-01

Fabry Disease (alpha-galactosidase A deficiency) is an X-linked hereditary disorder leading to the pathological accumulation of globotriaosylceramide (GL-3) in lysosomes, particularly in the vascular endothelium of the kidney, heart and brain. We report the results of an open-label phase 2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta (Fabrazyme) treatment of Fabry patients in the Japanese population, relative to safety and efficacy. The study design mirrored the design of the completed phase 3 clinical trial that led to approval of the product agalsidase beta. The 13 Japanese, male Fabry patients enrolled in the study received the enzyme replacement therapy over a period of 20 weeks as biweekly infusions. All selected efficacy end points showed improvements that were comparable with findings from the phase 3 study. These improvements included reductions of GL-3 accumulation in both kidney and skin capillary endothelial cells to (near) normal levels (92% of patients). Kidney and plasma GL-3 levels decreased by 51.9% and 100%, respectively, by ELISA. Renal function remained normal. Fabry-associated pain, and quality of life, showed improvement over baseline in multiple categories. Related adverse events were mild or moderate in intensity and mostly infusion-associated (fever and rigors). As expected, IgG antibody formation was observed in 85% of the patients, but had no effect on treatment response. These results suggest that treatment with agalsidase beta is safe and effective in Japanese patients with Fabry disease. With regard to safety and efficacy, no differences were observed as compared to the caucasian population.

Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: a pilot study.

PubMed

Mignani, Renzo; Panichi, Vincenzo; Giudicissi, Antonio; Taccola, Daniele; Boscaro, Francesca; Feletti, Carlo; Moneti, Gloriano; Cagnoli, Leonardo

2004-04-01

We sought to assess the safety and efficacy of enzyme replacement therapy (ERT) with recombinant human-alpha-galactosidase A (rh-alpha-Gal A) in kidney transplant recipients with Fabry disease, a previously unstudied population. Three male kidney transplant recipients with biochemically, genetically, and histologically confirmed Fabry disease and documented Fabry myocardiopathy received the rh-alpha-Gal A, agalsidase beta, 1 mg/kg of body weight every 2 weeks by intravenous infusion and were monitored biochemically, clinically, and electrocardiographically and echocardiographically for 18 months. Patients showed biochemical, clinical/functional, and morphologic response to ERT. Plasma globotriaosylceramide decreased 23% to 50%. Extremity pain resolved within 2 months in the patient with this manifestation. On echocardiography, left ventricular mass, end diastolic diameter (EDD), and cardiac contractility, shown by ejection fraction (EF), improved in 2 of the 3 patients receiving essentially all planned infusions. EDD and EF remained basically stable, but cardiac morphologic abnormalities progressed in the other patient, who had a 5-month interruption in ERT after the initial month. Mild mitral insufficiency persisted in all patients, as did atrial fibrillation in the affected individual. After a combined total of 116 infusions, no treatment-related adverse event, intolerance, or seroconversion was seen. Renal function remained stable and the immunosuppression regimen unchanged in all patients. Our pilot study provides preliminary evidence that ERT with agalsidase beta, 1 mg/kg every 2 weeks, is safe and often effective against extra-renal manifestations in kidney transplant patients with Fabry disease. Studies with longer courses of this and higher doses of ERT are merited in this population.

Measurement of HbA1c in Gingival Crevicular Blood Using a High Pressure Liquid Chromatography Procedure

PubMed Central

Pesce, Michael A.; Strauss, Shiela M.; Rosedale, Mary; Netterwald, Jane; Wang, Hangli

2016-01-01

Objectives To validate an ion exchange high-pressure liquid chromatography (HPLC) method for measuring glycated hemoglobin (HbA1c) in gingival crevicular blood (GCB) spotted on filter paper, for use in screening dental patients for diabetes. Methods We collected the GCB specimens for this study from the oral cavities of patients during dental visits, using rigorous strategies to obtain GCB that was as free of debris as possible. The analytical performance of the HPLC method was determined by measuring the precision, linearity, carryover, stability of HbA1c in GCB, and correlation of HbA1c results in GCB specimens with finger-stick blood (FSB) specimens spotted on filter paper. Results The coefficients of variation (CVs) for the inter- and intrarun precision of the method were less than 2.0%. Linearity ranged between 4.2% and 12.4%; carryover was less than 2.0%, and the stability of the specimen was 6 days at 4°C and as many as 14 days at −70°C. Linear regression analysis comparing the HbA1c results in GCB with FSB yielded a correlation coefficient of 0.993, a slope of 0.981, and an intercept of 0.13. The Bland-Altman plot showed no difference in the HbA1c results from the GCB and FSB specimens at normal, prediabetes, and diabetes HbA1c levels. Conclusion We validated an HPLC method for measuring HbA1c in GCB; this method can be used to screen dental patients for diabetes. PMID:26489673

Measurement of HbA1c in Gingival Crevicular Blood Using a High-Pressure Liquid Chromatography Procedure.

PubMed

Pesce, Michael A; Strauss, Shiela M; Rosedale, Mary; Netterwald, Jane; Wang, Hangli

2015-01-01

To validate an ion exchange high-pressure liquid chromatography (HPLC) method for measuring glycated hemoglobin (HbA1c) in gingival crevicular blood (GCB) spotted on filter paper, for use in screening dental patients for diabetes. We collected the GCB specimens for this study from the oral cavities of patients during dental visits, using rigorous strategies to obtain GCB that was as free of debris as possible. The analytical performance of the HPLC method was determined by measuring the precision, linearity, carryover, stability of HbA1c in GCB, and correlation of HbA1c results in GCB specimens with finger-stick blood (FSB) specimens spotted on filter paper. The coefficients of variation (CVs) for the inter- and intrarun precision of the method were less than 2.0%. Linearity ranged between 4.2% and 12.4%; carryover was less than 2.0%, and the stability of the specimen was 6 days at 4°C and as many as 14 days at -70°C. Linear regression analysis comparing the HbA1c results in GCB with FSB yielded a correlation coefficient of 0.993, a slope of 0.981, and an intercept of 0.13. The Bland-Altman plot showed no difference in the HbA1c results from the GCB and FSB specimens at normal, prediabetes, and diabetes HbA1c levels. We validated an HPLC method for measuring HbA1c in GCB; this method can be used to screen dental patients for diabetes. Copyright© by the American Society for Clinical Pathology (ASCP).

Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis.

PubMed

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-06-01

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.

Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis

PubMed Central

Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

2011-01-01

To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. PMID:21487393

Static and dynamic half-life and lifetime molecular turnover of enzymes.

PubMed

Miyawaki, Osato; Kanazawa, Tsukasa; Maruyama, Chika; Dozen, Michiko

2017-01-01

The static half-life of an enzyme is the half-life of a free enzyme not working without substrate and the dynamic half-life is that of an active enzyme working with plenty amount of substrate. These two half-lives were measured and compared for glucoamylase (GA) and β-galactosidase (BG). The dynamic half-life was much longer than the static half-life by one to three orders of magnitude for both enzymes. For BG, the half-life of the enzyme physically entrapped in a membrane reactor was also measured. In this case also, the half-life of BG in the membrane reactor was much longer than the free enzyme without substrate. These results suggest the large difference in stabilities between the free enzyme and the enzyme-substrate complex. This may be related to the natural enzyme metabolism. According to the difference in half-life, the lifetime molecular turnover (LMT), which is the number of product molecules produced by a single molecule of enzyme until it loses its activity completely, was much higher by one to four orders of magnitude for the active enzyme than the free enzyme. The concept of LMT, proposed here, will be important in bioreactor operations with or without immobilization. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Performance Analysis of GaN Capping Layer Thickness on GaN/AlGaN/GaN High Electron Mobility Transistors.

PubMed

Sharma, N; Periasamy, C; Chaturvedi, N

2018-07-01

In this paper, we present an investigation of the impact of GaN capping layer and AlGaN layer thickness on the two-dimensional (2D)-electron mobility and the carrier concentration which was formed close to the AlGaN/GaN buffer layer for Al0.25Ga0.75N/GaN and GaN/Al0.25Ga0.75N/GaN heterostructures deposited on sapphire substrates. The results of our analysis clearly indicate that expanding the GaN capping layer thickness from 1 nm to 100 nm prompts an increment in the electron concentration at hetero interface. As consequence of which drain current was additionally increments with GaN cap layer thicknesses, and eventually saturates at approximately 1.85 A/mm for capping layer thickness greater than 40 nm. Interestingly, for the same structure, the 2D-electron mobility, decrease monotonically with GaN capping layer thickness, and saturate at approximately 830 cm2/Vs for capping layer thickness greater than 50 nm. A device with a GaN cap layer didn't exhibit gate leakage current. Furthermore, it was observed that the carrier concentration was first decrease 1.03 × 1019/cm3 to 6.65 × 1018/cm3 with AlGaN Layer thickness from 5 to 10 nm and after that it increases with the AlGaN layer thickness from 10 to 30 nm. The same trend was followed for electric field distributions. Electron mobility decreases monotonically with AlGaN layer thickness. Highest electron mobility 1354 cm2/Vs were recorded for the AlGaN layer thickness of 5 nm. Results obtained are in good agreement with published experimental data.

Systems-Wide Prediction of Enzyme Promiscuity Reveals a New Underground Alternative Route for Pyridoxal 5’-Phosphate Production in E. coli

DOE PAGES

Oberhardt, Matthew A.; Zarecki, Raphy; Reshef, Leah; ...

2016-01-28

Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such enzymes is an important open question in biology. Here we develop a genome-wide method, PROPER, that uses a permissive PSI-BLAST approach to predict promiscuous activities of metabolic genes. Enzyme promiscuity is typically studied experimentally using multicopy suppression, in which over-expression of a promiscuous ‘replacer’ gene rescues lethality caused by inactivation of a ‘target’ gene. We use PROPER to predict multicopy suppression in Escherichia coli, achieving highly significant overlap with published cases (hypergeometric p = 4.4e-13). We then validate three novel predictedmore » target-replacer gene pairs in new multicopy suppression experiments. We next go beyond PROPER and develop a network-based approach, GEM-PROPER, that integrates PROPER with genome-scale metabolic modeling to predict promiscuous replacements via alternative metabolic pathways. GEM-PROPER predicts a new indirect replacer (thiG) for an essential enzyme (pdxB) in production of pyridoxal 5’-phosphate (the active form of Vitamin B 6), which we validate experimentally via multicopy suppression. Here, we perform a structural analysis of thiG to determine its potential promiscuous active site, which we validate experimentally by inactivating the pertaining residues and showing a loss of replacer activity. Thus, this study is a successful example where a computational investigation leads to a network-based identification of an indirect promiscuous replacement of a key metabolic enzyme, which would have been extremely difficult to identify directly.« less

Microbial keratinases: industrial enzymes with waste management potential.

PubMed

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.

Different predictive values of interim 18F-FDG PET/CT in germinal center like and non-germinal center like diffuse large B-cell lymphoma.

PubMed

Kim, Jihyun; Lee, Jeong-Ok; Paik, Jin Ho; Lee, Won Woo; Kim, Sang Eun; Song, Yoo Sung

2017-01-01

Diffuse large B-cell lymphoma (DLBCL) is a pathologically heterogeneous disease with different prognoses according to its molecular profiles. Despite the broad usage of 18 F-fluoro-2-dexoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT), previous studies that have investigated the value of interim 18 F-FDG PET/CT in DLBCL have given the controversial results. The purpose of this study was to evaluate the prognostic value of interim 18 F-FDG PET/CT in DLBCL according to germinal center B cell-like (GCB) and non-GCB molecular profiling. We enrolled 118 newly diagnosed DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Interim 18 F-FDG PET/CT scans performed after 2 or 3 cycles of R-CHOP treatment were evaluated based on the Lugano response criteria. Patients were grouped as GCB or non-GCB molecular subtypes according to immunohistochemistry results of CD10, BCL6, and MUM1, based on Hans' algorithm. In total 118 DLBCL patients, 35 % were classified as GCB, and 65 % were classified as non-GCB. Interim PET/CT was negative in 70 %, and positive in 30 %. During the median follow-up period of 23 months, the positive interim 18 F-FDG PET/CT group showed significantly inferior progression free survival (PFS) compared to the negative interim 18 F-FDG PET/CT group (P = 0.0004) in entire patients. A subgroup analysis according to molecular profiling demonstrated significant difference of PFS between the positive and negative interim 18 F-FDG PET groups in GCB subtype of DLBCL (P = 0.0001), but there was no significant difference of PFS between the positive and negative interim 18 F-FDG PET groups in non-GCB subtype of DLBCL. Interim 18 F-FDG PET/CT scanning had a significant predictive value for disease progression in patients with the GCB subtype of DLBCL treated with R-CHOP, but not in those with the non-GCB subtype. Therefore, molecular profiles of DLBCL should be considered for

Enzyme replacement for GM1-gangliosidosis: Uptake, lysosomal activation, and cellular disease correction using a novel β-galactosidase:RTB lectin fusion.

PubMed

Condori, Jose; Acosta, Walter; Ayala, Jorge; Katta, Varun; Flory, Ashley; Martin, Reid; Radin, Jonathan; Cramer, Carole L; Radin, David N

2016-02-01

cleaved and rapidly degraded. The activated β-gal was still detected at 48h suggesting interactions with protective protein/cathepsin A. Uptake-saturation analyses indicated that the RTB adsorptive-mediated mechanisms of β-gal:RTB supported significantly greater accumulation of β-galactose activity in fibroblasts compared to the receptor-mediated mechanisms of the mammalian cell-derived β-gal. These data demonstrate that plant-made β-gal:RTB functions as an effective replacement enzyme for GM1-gangliosidosis - delivering enzyme into cells, enabling essential lysosomal processing, and mediating disease substrate clearance at the cellular level. RTB provides novel uptake behaviors and thus may provide new receptor-independent strategies that could broadly impact lysosomal disease treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Differences in the cytogenetic alteration profiles of diffuse large B-cell lymphoma among Chinese and American patients.

PubMed

Chen, Yan; Dave, Bhavana J; Zhu, Xiongzeng; Chan, Wing C; Iqbal, Javeed; Sanger, Warren G; Fu, Kai

2013-05-01

To study the similarities and differences of cytogenetic alterations in diffuse large B-cell lymphoma (DLBCL) between Asian and Caucasian patients, we compared the cytogenetic profiles of Chinese and American DLBCL cases by analyzing conventional karyotypes and select fluorescence in situ hybridization (FISH) findings. We used interphase FISH analyses to determine the incidence of the t(14;18) and BCL6 and MYC rearrangements. Immunohistochemical analysis was used to categorize the lymphomas into the germinal center B-cell-like (GCB) or non-GCB-DLBCL subtypes, according to the Hans algorithm. Our data suggested that Chinese patients had cytogenetic profiles for GCB-DLBCL that differed from those of their American counterparts; specifically, the Chinese GCB patients exhibited greater frequencies of BCL6 rearrangements and gains of 1q and 11q but lower incidence of the t(14;18). Non-GCB-DLBCL in both the Chinese and American patients was characterized by recurrent gains of 3/3q and 18/18q. The incidences of both BCL6 rearrangement and t(14;18) were similar in Chinese and American non-GCB-DLBCL cases. Copyright © 2013 Elsevier Inc. All rights reserved.

Developing Low-Noise GaAs JFETs For Cryogenic Operation

NASA Technical Reports Server (NTRS)

Cunningham, Thomas J.

1995-01-01

Report discusses aspects of effort to develop low-noise, low-gate-leakage gallium arsenide-based junction field-effect transistors (JFETs) for operation at temperature of about 4 K as readout amplifiers and multiplexing devices for infrared-imaging devices. Transistors needed to replace silicon transistors, relatively noisy at 4 K. Report briefly discusses basic physical principles of JFETs and describes continuing process of optimization of designs of GaAs JFETs for cryogenic operation.

Neuraxial anesthesia improves long-term survival after total joint replacement: a retrospective nationwide population-based study in Taiwan.

PubMed

Chen, Wei-Hung; Hung, Kuo-Chuan; Tan, Ping-Heng; Shi, Hon-Yi

2015-04-01

This study explored the effects of general (GA) and neuraxial (NA) anesthesia on the outcomes of primary total joint replacement (TJR) in terms of postoperative mortality, length of stay (LOS), and hospital treatment costs. From 1997 to 2010, this nationwide population-based study retrospectively evaluated 7,977 patients in Taiwan who underwent primary total hip or knee replacement. We generated two propensity-score-matched subgroups, each containing an equal number of patients who underwent TJR with either GA or NA. Of the 7,977 patients, 2,990 (37.5%) underwent GA and 4,987 (62.5%) underwent NA. Propensity-score matching was used to create comparable GA and NA groups adjusted for age, sex, comorbidities, surgery type, hospital volume, and surgeon volume. Survival over the first three years following surgery was similar. The proportion of patients alive up to 14 years postoperatively for those undergoing NA was 58.2% (95% confidence interval [CI] 50.4 to 66.0), and for those undergoing GA it was 57.3% (95% CI 51.4 to 63.2). Neuraxial anesthesia was associated with lower median [interquartile range; IQR] hospital treatment cost ($4,079 [3,805-4,444] vs $4,113 [3,812-4,568]; P < 0.001) and shorter median [IQR] LOS (8 [7-10] days vs 8 [6-10] days, respectively; P = 0.024). Our results support the use of NA for primary TJR. The improvements in hospital costs persist even when anesthesia costs are removed. The mechanism underlying the association between NA and long-term survival is unknown.

Theoretical study for heterojunction surface of NEA GaN photocathode dispensed with Cs activation

NASA Astrophysics Data System (ADS)

Xia, Sihao; Liu, Lei; Wang, Honggang; Wang, Meishan; Kong, Yike

2016-09-01

For the disadvantages of conventional negative electron affinity (NEA) GaN photocathodes activated by Cs or Cs/O, new-type NEA GaN photocathodes with heterojunction surface dispensed with Cs activation are investigated based on first-principle study with density functional theory. Through the growth of an ultrathin n-type GaN cap layer on p-type GaN emission layer, a p-n heterojunction is formed on the surface. According to the calculation results, it is found that Si atoms tend to replace Ga atoms to result in an n-type doped cap layer which contributes to the decreasing of work function. After the growth of n-type GaN cap layer, the atom structure near the p-type emission layer is changed while that away from the surface has no obvious variations. By analyzing the E-Mulliken charge distribution of emission surface with and without cap layer, it is found that the positive charge of Ga and Mg atoms in the emission layer decrease caused by the cap layer, while the negative charge of N atom increases. The conduction band moves downwards after the growth of cap layer. Si atom produces donor levels around the valence band maximum. The absorption coefficient of GaN emission layer decreases and the reflectivity increases caused by n-type GaN cap layer.

Gallium as a Therapeutic Agent: A Thermodynamic Evaluation of the Competition between Ga(3+) and Fe(3+) Ions in Metalloproteins.

PubMed

Nikolova, Valia; Angelova, Silvia; Markova, Nikoleta; Dudev, Todor

2016-03-10

Gallium has been employed (in the form of soluble salts) to fight various forms of cancer, infectious, and inflammatory diseases. The rationale behind this lies in the ability of Ga(3+) cation to mimic closely in appearance the native ferric ion, Fe(3+), thus interfering with the biological processes requiring ferric cofactors. However, Ga(3+) ion cannot participate in redox reactions and, when substituting for the "native" Fe(3+) ion in the enzyme active site, renders it inactive. Although a significant body of information on the Ga(3+)-Fe(3+) competition in biological systems has been accumulated, the intimate mechanism of the process is still not well understood and several questions remain: What are the basic physical principles governing the competition between the two trivalent cations in proteins? What type of metal centers are the most likely targets for gallium therapy? To what extent are the Fe(3+)-binding sites in the key enzyme ribonucleotide reductase vulnerable to Ga(3+) substitution? Here, we address these questions by studying the competition between Ga(3+) and Fe(3+) ions in model metal binding sites of various compositions and charge states. The results obtained are in line with available experimental data and shed light on the intimate mechanism of the Ga(3+)/Fe(3+) selectivity in various model metal binding sites and biological systems such as serum transferrin and ribonucleotide reductase.

Fabrication of full-color GaN-based light-emitting diodes on nearly lattice-matched flexible metal foils.

PubMed

Kim, Hyeryun; Ohta, Jitsuo; Ueno, Kohei; Kobayashi, Atsushi; Morita, Mari; Tokumoto, Yuki; Fujioka, Hiroshi

2017-05-18

GaN-based light-emitting diodes (LEDs) have been widely accepted as highly efficient solid-state light sources capable of replacing conventional incandescent and fluorescent lamps. However, their applications are limited to small devices because their fabrication process is expensive as it involves epitaxial growth of GaN by metal-organic chemical vapor deposition (MOCVD) on single crystalline sapphire wafers. If a low-cost epitaxial growth process such as sputtering on a metal foil can be used, it will be possible to fabricate large-area and flexible GaN-based light-emitting displays. Here we report preparation of GaN films on nearly lattice-matched flexible Hf foils using pulsed sputtering deposition (PSD) and demonstrate feasibility of fabricating full-color GaN-based LEDs. It was found that introduction of low-temperature (LT) grown layers suppressed the interfacial reaction between GaN and Hf, allowing the growth of high-quality GaN films on Hf foils. We fabricated blue, green, and red LEDs on Hf foils and confirmed their normal operation. The present results indicate that GaN films on Hf foils have potential applications in fabrication of future large-area flexible GaN-based optoelectronics.

Thermophilic Enzyme or Mesophilic Enzyme with Enhanced Thermostability: Can We Draw a Line?

PubMed

Jing, Xiaomin; Evangelista Falcon, Wilfredo; Baudry, Jerome; Serpersu, Engin H

2017-07-27

Aminoglycoside nucleotidyltransferase 4' (ANT) is a homodimeric enzyme that modifies the C4'-OH site of aminoglycoside antibiotics by nucleotidylation. A few single- and double-residue mutants of this enzyme (T130K, D80Y, and D80Y/T130K) from Bacillus stearothermophilus show increased thermostability. This article investigates how such residue replacements, which are distant from the active site and monomer-monomer interface, result in various changes of the thermostability of the enzyme. In this work, we show that the thermodynamic properties of enzyme-ligand complexes and protein dynamics may be indicators of a thermophilic behavior. Our data suggests that one of the single-site mutants of ANT, D80Y, may be a thermophilic protein and the other thermostable mutant, T130K, is actually a more heat-stable variant of the mesophilic wild type (WT) with a higher T m . Our data also suggest that T130K and D80Y adopt different global dynamics strategies to achieve different levels of thermostability enhancement and that the differences between the properties of the species can be described in terms of global dynamics rather than in terms of specific structural features. Thermophilicity of the D80Y comes at the cost of less favorable thermodynamic parameters for ligand binding relative to WT. On the other hand, the T130K species exhibits the same affinity to ligands and the same thermodynamic parameters of complex formation as the WT enzyme. These observations suggest that a quantitative characterization of ligand binding and protein dynamics can be used to differentiate thermophilic proteins from their simply more heat-stable mesophilic counterparts.

Structure of (Ga2O3)2(ZnO)13 and a unified description of the homologous series (Ga2O3)2(ZnO)(2n + 1).

PubMed

Michiue, Yuichi; Kimizuka, Noboru; Kanke, Yasushi; Mori, Takao

2012-06-01

The structure of (Ga(2)O(3))(2)(ZnO)(13) has been determined by a single-crystal X-ray diffraction technique. In the monoclinic structure of the space group C2/m with cell parameters a = 19.66 (4), b = 3.2487 (5), c = 27.31 (2) Å, and β = 105.9 (1)°, a unit cell is constructed by combining the halves of the unit cell of Ga(2)O(3)(ZnO)(6) and Ga(2)O(3)(ZnO)(7) in the homologous series Ga(2)O(3)(ZnO)(m). The homologous series (Ga(2)O(3))(2)(ZnO)(2n + 1) is derived and a unified description for structures in the series is presented using the (3+1)-dimensional superspace formalism. The phases are treated as compositely modulated structures consisting of two subsystems. One is constructed by metal ions and another is by O ions. In the (3 + 1)-dimensional model, displacive modulations of ions are described by the asymmetric zigzag function with large amplitudes, which was replaced by a combination of the sawtooth function in refinements. Similarities and differences between the two homologous series (Ga(2)O(3))(2)(ZnO)(2n + 1) and Ga(2)O(3)(ZnO)(m) are clarified in (3 + 1)-dimensional superspace. The validity of the (3 + 1)-dimensional model is confirmed by the refinements of (Ga(2)O(3))(2)(ZnO)(13), while a few complex phenomena in the real structure are taken into account by modifying the model.

A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

PubMed Central

Persu, Alexandre; Lambert, Michel; Deinum, Jaap; Cossu, Marta; de Visscher, Nathalie; Irenge, Leonid; Ambroise, Jerôme; Minon, Jean-Marc; Nesterovitch, Andrew B.; Churbanov, Alexander; Popova, Isolda A.; Danilov, Sergei M.; Danser, A. H. Jan; Gala, Jean-Luc

2013-01-01

Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. PMID:23560051

Fishmeal replacement with Spirulina Platensis and Chlorella vulgaris in African catfish (Clarias gariepinus) diet: Effect on antioxidant enzyme activities and haematological parameters.

PubMed

Raji, Ameenat Abiodun; Alaba, Peter Adeniyi; Yusuf, Hindatu; Abu Bakar, Noor Hidayati; Mohd Taufek, Norhidayah; Muin, Hasniyati; Alias, Zazali; Milow, Pozi; Abdul Razak, Shaharudin

2018-05-25

This study explored fishmeal replacement with two freshwater microalgae: Spirulina Platensis and Chlorella vulgaris in African catfish (Clarias gariepinus) diet. The effect of inclusion of the two microalgae on biomarkers of oxidative stress, haematological parameters, enzyme activities and growth performance were investigated. The juvenile fish were given 3 distinct treatments with isonitrogenous (35.01-36.57%) and isoenergetic (417.24-422.27 Kcal 100 g - 1) diets containing 50% S. platensis (50SP), 75% S. platensis (75SP), 50% C. vulgaris (50CL), 75% C. vulgaris (75CL) and 100% fishmeal (100% FM) was used as the control diet. The result shows that all the diets substituted with both S. platensis, and C. vulgaris boosted the growth performance based on specific growth rate (SGR) and body weight gain (BDWG) when compared with the control diet. The feed conversion ratio (FCR) and protein efficiency ratio (PER) was significantly influenced by all the supplementations. The haematological analysis of the fish shows a significant increase in the value of red and white blood cells upon supplementation with 50SP and 50CL but decrease slightly when increased to 75SP and 75CL. Furthermore, the value of haematocrit and haemoglobin also increased upon supplementation with 50SP and 50CL but decrease slightly when increased to 75SP and 75CL. The white blood cell (WBC), red blood cell (RBC) increased, while total cholesterol (TCL), and Plasma glucose levels decreased significantly upon supplementation of algae. This is a clear indication that S. platensis and C. vulgaris are a promising replacement for fishmeal, which is a source protein in the C. gariepinus diet. Copyright © 2018 Elsevier Ltd. All rights reserved.

AlGaAs/InGaAs/AlGaAs double pulse doped pseudomorphic high electron mobility transistor structures on InGaAs substrates

NASA Astrophysics Data System (ADS)

Hoke, W. E.; Lyman, P. S.; Mosca, J. J.; McTaggart, R. A.; Lemonias, P. J.; Beaudoin, R. M.; Torabi, A.; Bonner, W. A.; Lent, B.; Chou, L.-J.; Hsieh, K. C.

1997-10-01

Double pulse doped AlGaAs/InGaAs/AlGaAs pseudomorphic high electron mobility transistor (PHEMT) structures have been grown on InxGa1-xAs (x=0.025-0.07) substrates using molecular beam epitaxy. A strain compensated, AlGaInAs/GaAs superlattice was used for improved resistivity and breakdown. Excellent electrical and optical properties were obtained for 110-Å-thick InGaAs channel layers with indium concentrations up to 31%. A room temperature mobility of 6860 cm2/V s with 77 K sheet density of 4.0×1012cm-2 was achieved. The InGaAs channel photoluminescence intensity was equivalent to an analogous structure on a GaAs substrate. To reduce strain PHEMT structures with a composite InGaP/AlGaAs Schottky layer were also grown. The structures also exhibited excellent electrical and optical properties. Transmission electron micrographs showed planar channel interfaces for highly strained In0.30Ga0.70As channel layers.

Local structure investigation of Ga and Yb dopants in Co 4 Sb 12 skutterudites

DOE PAGES

Hu, Yanyun; Chen, Ning; Clancy, J. P.; ...

2017-12-29

We report our x-ray absorption spectroscopy studies at both Ga K-edge and Yb L 2-edge to elucidate the local structure of Ga and Yb dopants in Yb xGa yCo 4Sb 12. Our extended x-ray absorption fine structure (EXAFS) data confirm that Ga atoms occupy two crystallographic sites: one is the 24g site replacing Sb, and the other is the 2a site in the off-center void position. We find that the occupancy ratio of these two sites varies significantly as a function of the filling fraction of additional Yb, which exclusively occupies the 2a on-center site. At low concentrations of Yb,more » Ga 24g and Ga 2a dopants coexist and they form a charge-compensated compound defect proposed by Qiu et al. [Adv. Mater. 23, 3194 (2013)]. The Ga 24g occupancy increases gradually with increasing Yb concentration, and almost all Ga occupies the 24g site for the highest Yb concentration (x = 0.4). In addition to the local crystal structure evidence provided by our EXAFS data, we also present x-ray absorption near-edge structure (XANES) spectra, which show a small Ga K-edge energy shift as a function of Yb concentration consistent with the change from predominantly Ga 2a to Ga 24g states. Our result suggests that the increased solubility of Yb in Yb-Ga co-doped Co 4Sb 12 skutterudites is due to the increased Ga 24g electron acceptor, and thus provides an important strategy to optimize the carrier concentration in partially filled skutterudites.« less

Local structure investigation of Ga and Yb dopants in Co 4 Sb 12 skutterudites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Yanyun; Chen, Ning; Clancy, J. P.

We report our x-ray absorption spectroscopy studies at both Ga K-edge and Yb L 2-edge to elucidate the local structure of Ga and Yb dopants in Yb xGa yCo 4Sb 12. Our extended x-ray absorption fine structure (EXAFS) data confirm that Ga atoms occupy two crystallographic sites: one is the 24g site replacing Sb, and the other is the 2a site in the off-center void position. We find that the occupancy ratio of these two sites varies significantly as a function of the filling fraction of additional Yb, which exclusively occupies the 2a on-center site. At low concentrations of Yb,more » Ga 24g and Ga 2a dopants coexist and they form a charge-compensated compound defect proposed by Qiu et al. [Adv. Mater. 23, 3194 (2013)]. The Ga 24g occupancy increases gradually with increasing Yb concentration, and almost all Ga occupies the 24g site for the highest Yb concentration (x = 0.4). In addition to the local crystal structure evidence provided by our EXAFS data, we also present x-ray absorption near-edge structure (XANES) spectra, which show a small Ga K-edge energy shift as a function of Yb concentration consistent with the change from predominantly Ga 2a to Ga 24g states. Our result suggests that the increased solubility of Yb in Yb-Ga co-doped Co 4Sb 12 skutterudites is due to the increased Ga 24g electron acceptor, and thus provides an important strategy to optimize the carrier concentration in partially filled skutterudites.« less

Phosphor-Free InGaN White Light Emitting Diodes Using Flip-Chip Technology

PubMed Central

Li, Ying-Chang; Chang, Liann-Be; Chen, Hou-Jen; Yen, Chia-Yi; Pan, Ke-Wei; Huang, Bohr-Ran; Kuo, Wen-Yu; Chow, Lee; Zhou, Dan; Popko, Ewa

2017-01-01

Monolithic phosphor-free two-color gallium nitride (GaN)-based white light emitting diodes (LED) have the potential to replace current phosphor-based GaN white LEDs due to their low cost and long life cycle. Unfortunately, the growth of high indium content indium gallium nitride (InGaN)/GaN quantum dot and reported LED’s color rendering index (CRI) are still problematic. Here, we use flip-chip technology to fabricate an upside down monolithic two-color phosphor-free LED with four grown layers of high indium quantum dots on top of the three grown layers of lower indium quantum wells separated by a GaN tunneling barrier layer. The photoluminescence (PL) and electroluminescence (EL) spectra of this white LED reveal a broad spectrum ranging from 475 to 675 nm which is close to an ideal white-light source. The corresponding color temperature and color rendering index (CRI) of the fabricated white LED, operated at 350, 500, and 750 mA, are comparable to that of the conventional phosphor-based LEDs. Insights of the epitaxial structure and the transport mechanism were revealed through the TEM and temperature dependent PL and EL measurements. Our results show true potential in the Epi-ready GaN white LEDs for future solid state lighting applications. PMID:28772792

Electron mobility in InGaN channel heterostructure field effect transistor structures with different barriers

NASA Astrophysics Data System (ADS)

Xie, J.; Leach, J. H.; Ni, X.; Wu, M.; Shimada, R.; Özgür, Ü.; Morkoç, H.

2007-12-01

InGaN possesses higher electron mobility and velocity than GaN, and therefore is expected to lead to relatively better performances for heterostructure field effect transistors (HFETs). However, the reported mobilities for AlGaN /InGaN HFETs are lower than GaN channel HFETs. To address this issue, we studied the effect of different barriers on the Hall mobility for InGaN channel HFETs grown by metal organic chemical vapor deposition. Unlike the conventional AlGaN barrier, the AlInN barrier can be grown at the same temperature as the InGaN channel layer, alleviating some of the technological roadblocks. Specifically, this avoids possible degradation of the thin InGaN channel during AlGaN growth at high temperatures; and paves the way for better interfaces. An undoped In0.18Al0.82N/AlN/In0.04Ga0.96N HFET structure exhibited a μH=820cm2/Vs, with a ns=2.12×1013cm-2 at room temperature. Moreover, with an In-doped AlGaN barrier, namely, Al0.24In0.01Ga0.75N, grown at 900°C, the μH increased to 1230cm2/Vs with a ns of 1.09×1013cm-2 for a similar InGaN channel. Furthermore, when the barrier was replaced by Al0.25Ga0.75N grown at 1030°C, μH dropped to 870cm2/Vs with ns of 1.26×1013cm-2 at room temperature. Our results suggest that to fully realize the potential of the InGaN channel HFETs, AlInN or AlInGaN should be used as the barrier instead of the conventional AlGaN barrier.

Photoelectrochemical response of GaN, InGaN, and GaNP nanowire ensembles

NASA Astrophysics Data System (ADS)

Philipps, Jan M.; Hölzel, Sara; Hille, Pascal; Schörmann, Jörg; Chatterjee, Sangam; Buyanova, Irina A.; Eickhoff, Martin; Hofmann, Detlev M.

2018-05-01

The photoelectrochemical responses of GaN, GaNP, and InGaN nanowire ensembles are investigated by the electrical bias dependent photoluminescence, photocurrent, and spin trapping experiments. The results are explained in the frame of the surface band bending model. The model is sufficient for InGaN nanowires, but for GaN nanowires the electrochemical etching processes in the anodic regime have to be considered additionally. These processes lead to oxygen rich surface (GaxOy) conditions as evident from energy dispersive X-ray fluorescence. For the GaNP nanowires, a bias dependence of the carrier transfer to the electrolyte is not reflected in the photoluminescence response, which is tentatively ascribed to a different origin of radiative recombination in this material as compared to (In)GaN. The corresponding consequences for the applications of the materials for water splitting or pH-sensing will be discussed.

Preclinical toxicity evaluation of erythrocyte-encapsulated thymidine phosphorylase in BALB/c mice and beagle dogs: an enzyme-replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy.

PubMed

Levene, Michelle; Coleman, David G; Kilpatrick, Hugh C; Fairbanks, Lynette D; Gangadharan, Babunilayam; Gasson, Charlotte; Bax, Bridget E

2013-01-01

Erythrocyte-encapsulated thymidine phosphorylase (EE-TP) is currently under development as an enzyme replacement therapy for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), an autosomal recessive disorder caused by a deficiency of thymidine phosphorylase. The rationale for the development of EE-TP is based on the pathologically elevated metabolites (thymidine and deoxyuridine) being able to freely diffuse across the erythrocyte membrane where the encapsulated enzyme catalyses their metabolism to the normal products. The systemic toxic potential of EE-TP was assessed when administered intermittently by iv bolus injection to BALB/c mice and Beagle dogs for 4 weeks. The studies consisted of one control group receiving sham-loaded erythrocytes twice weekly and two treated groups, one dosed once every 2 weeks and the other dosed twice per week. The administration of EE-TP to BALB/c mice resulted in thrombi/emboli in the lungs and spleen enlargement. These findings were also seen in the control group, and there was no relationship to the number of doses administered. In the dog, transient clinical signs were associated with EE-TP administration, suggestive of an immune-based reaction. Specific antithymidine phosphorylase antibodies were detected in two dogs and in a greater proportion of mice treated once every 2 weeks. Nonspecific antibodies were detected in all EE-TP-treated animals. In conclusion, these studies do not reveal serious toxicities that would preclude a clinical trial of EE-TP in patients with MNGIE, but caution should be taken for infusion-related reactions that may be related to the production of nonspecific antibodies or a cell-based immune response.

Influence of internal electric fields on band gaps in short period GaN/GaAlN and InGaN/GaN polar superlattices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorczyca, I., E-mail: iza@unipress.waw.pl; Skrobas, K.; Suski, T.

2015-08-21

The electronic structures of short period mGaN/nGa{sub y}Al{sub 1−y}N and mIn{sub y}Ga{sub 1-y}N/nGaN superlattices grown along the wurtzite c axis have been calculated for different alloy compositions y and various small numbers m of well- and n of barrier-monolayers. The general trends in gap behavior can, to a large extent, be related to the strength of the internal electric field, E, in the GaN and InGaN quantum wells. In the GaN/GaAlN superlattices, E reaches 4 MV/cm, while in the InGaN/GaN superlattices, values as high as E ≈ 6.5 MV/cm are found. The strong electric fields are caused by spontaneous and piezoelectric polarizations,more » the latter contribution dominating in InGaN/GaN superlattices. The influence of different arrangements of In atoms (indium clustering) on the band gap values in InGaN/GaN superlattices is examined.« less

Influence of internal electric fields on band gaps in short period GaN/GaAlN and InGaN/GaN polar superlattices

NASA Astrophysics Data System (ADS)

Gorczyca, I.; Skrobas, K.; Suski, T.; Christensen, N. E.; Svane, A.

2015-08-01

The electronic structures of short period mGaN/nGayAl1-yN and mInyGa1-yN/nGaN superlattices grown along the wurtzite c axis have been calculated for different alloy compositions y and various small numbers m of well- and n of barrier-monolayers. The general trends in gap behavior can, to a large extent, be related to the strength of the internal electric field, E, in the GaN and InGaN quantum wells. In the GaN/GaAlN superlattices, E reaches 4 MV/cm, while in the InGaN/GaN superlattices, values as high as E ≈ 6.5 MV/cm are found. The strong electric fields are caused by spontaneous and piezoelectric polarizations, the latter contribution dominating in InGaN/GaN superlattices. The influence of different arrangements of In atoms (indium clustering) on the band gap values in InGaN/GaN superlattices is examined.

Efficient Ga(As)Sb quantum dot emission in AlGaAs by GaAs intermediate layer

NASA Astrophysics Data System (ADS)

Loeber, Thomas Henning; Richter, Johannes; Strassner, Johannes; Heisel, Carina; Kimmle, Christina; Fouckhardt, Henning

2013-03-01

Ga(As)Sb quantum dots (QDs) are epitaxially grown in AlGaAs/GaAs in the Stranski-Krastanov mode. In the recent past we achieved Ga(As)Sb QDs in GaAs with an extremely high dot density of 9.8•1010 cm-2 by optimization of growth temperature, Sb/Ga flux pressure ratio, and coverage. Additionally, the QD emission wavelength could be chosen precisely with these growth parameters in the range between 876 and 1035 nm. Here we report a photoluminescence (PL) intensity improvement for the case with AlGaAs barriers. Again growth parameters and layer composition are varied. The aluminium content is varied between 0 and 90%. Reflectance anisotropy spectroscopy (RAS) is used as insitu growth control to determine growth rate, layer thickness, and AlGaAs composition. Ga(As)Sb QDs, directly grown in AlxGa1-xAs emit no PL signal, even with a very low x ≈ 0.1. With additional around 10 nm thin GaAs intermediate layers between the Ga(As)Sb QDs and the AlGaAs barriers PL signals are detected. Samples with 4 QD layers and AlxGa1-xAs/GaAs barriers in between are grown. The thickness and composition of the barriers are changed. Depending on these values PL intensity is more than 4 times as high as in the case with simple GaAs barriers. With these results efficient Ga(As)Sb QD lasers are realized, so far only with pure GaAs barriers. Our index-guided broad area lasers operate continuous-wave (cw) @ 90 K, emit optical powers of more than 2•50 mW and show a differential quantum efficiency of 54% with a threshold current density of 528 A/cm2.

Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, R.G.; Bekerman, C.; Sicilian, L.

1982-09-01

Gallium 67 citrate scans and serum angiotension converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestation. /sup 67/Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with /sup 67/Ga uptake score (r = .436; p < .005). The frequency ofmore » abnormal /sup 67/Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal /sup 67/Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). /sup 67/Ga scans can be used to support the clinical identification of inactive sarcoidosis.« less

Photoreflectance from GaAs and GaAs/GaAs interfaces

NASA Astrophysics Data System (ADS)

Sydor, Michael; Angelo, James; Wilson, Jerome J.; Mitchel, W. C.; Yen, M. Y.

1989-10-01

Photoreflectance from semi-insulating GaAs, and GaAs/GaAs interfaces, is discussed in terms of its behavior with temperature, doping, epilayer thickness, and laser intensity. Semi-insulating substrates show an exciton-related band-edge signal below 200 K and an impurity-related photoreflectance above 400 K. At intermediate temperatures the band-edge signal from thin GaAs epilayers contains a contribution from the epilayer-substrate interface. The interface effect depends on the epilayer's thickness, doping, and carrier mobility. The effect broadens the band-edge photoreflectance by 5-10 meV, and artifically lowers the estimates for the critical-point energy, ECP, obtained through the customary third-derivative functional fit to the data.

Effect of high density H 2 plasmas on InGaP/GaAs and AlGaAs/GaAs HEMTs

NASA Astrophysics Data System (ADS)

Ren, F.; Kopf, R. F.; Kuo, J. M.; Lothian, J. R.; Lee, J. W.; Pearton, S. J.; Shul, R. J.; Constantine, C.; Johnson, D.

1998-05-01

InGaP/GaAs and AlGaAs/GaAs high electron mobility transistors have been exposed to inductively coupled plasma or electron cyclotron resonance H 2 plasmas as a function of pressure, source power and rf chuck power. The transconductance, gate ideality factor and saturated drain-source current are all degraded by the plasma treatment. Two mechanisms are identified: passivation of Si dopants in the InGaP or AlGaAs donor layers by H 0 and lattice disorder created by H + and H 2+ ion bombardment. HEMTs are found to be more susceptible to plasma-induced degradation than heterojunction bipolar transistors.

Local structure investigation of Ga and Yb dopants in Co4Sb12 skutterudites

NASA Astrophysics Data System (ADS)

Hu, Yanyun; Chen, Ning; Clancy, J. P.; Salvador, James R.; Kim, Chang-Yong; Shi, Xiaoya; Li, Qiang; Kim, Young-June

2017-12-01

We report comprehensive x-ray absorption spectroscopy studies at both the Ga K edge and Yb L2 edge to elucidate the local structure of Ga and Yb dopants in YbxGayCo4Sb12 . Our extended x-ray absorption fine structure (EXAFS) data confirm that Ga atoms occupy two crystallographic sites: one is the 24 g site replacing Sb, and the other is the 2 a site in the off-center void position. We find that the occupancy ratio of these two sites varies significantly as a function of the filling fraction of additional Yb, which exclusively occupies the 2 a on-center site. At low concentrations of Yb, Ga24 g and Ga2 a dopants coexist and they form a charge-compensated compound defect proposed by Qiu et al. [Adv. Funct. Mater. 23, 3194 (2013), 10.1002/adfm.201202571]. The Ga24 g occupancy increases gradually with increasing Yb concentration, and almost all Ga occupies the 24 g site for the highest Yb concentration studied (x =0.4 ). In addition to the local structural evidence provided by our EXAFS data, we also present x-ray absorption near-edge structure (XANES) spectra, which show a small Ga K -edge energy shift as a function of Yb concentration consistent with the change from predominantly Ga2 a to Ga24 g states. Our result suggests that the increased solubility of Yb in Yb-Ga co-doped Co4Sb12 skutterudites is due to the increased Ga24 g electron acceptor, and thus provides an important strategy to optimize the carrier concentration in partially filled skutterudites.

The beneficial effects of long-term enzyme replacement therapy on cardiac involvement in Japanese Fabry patients.

PubMed

Hongo, Kenichi; Ito, Keiichi; Date, Taro; Anan, Ikuko; Inoue, Yasunori; Morimoto, Satoshi; Ogawa, Kazuo; Kawai, Makoto; Kobayashi, Hiroshi; Kobayashi, Masahisa; Ida, Hiroyuki; Ohashi, Toya; Taniguchi, Ikuo; Yoshimura, Michihiro; Eto, Yoshikatsu

2018-06-01

Fabry disease is a hereditary disorder that occurs due to the reduction or absence of alpha-galactosidase A activity, which leads to cardiac involvement including left ventricular hypertrophy (LVH). Enzyme replacement therapy (ERT) provides better patient outcomes by preventing serious complications. However, there have been very few studies on the long-term effects of ERT on the cardiac manifestations in Japanese Fabry patients. We retrospectively analyzed the data from the medical records of 42 Fabry patients (male, n = 17; female, n = 25) who were followed at Jikei University Hospital, and in whom the long-term effects of ERT could be evaluated (median follow-up period: male, 11 years; female, 8 years). The slope of the left ventricular mass (LVM) increase was 3.02 ± 3.41 g/m 2 /year in males and 1.69 ± 2.73 g/m 2 /year in females. In a subgroup analysis, the slopes of males with and without LVH did not differ to a statistically significant extent; however, the slope in female patients without LVH was significantly smaller than that of female patients with LVH. We then compared our data to the natural historical data that have previously been reported. In comparison to the previously reported data, we found a significant reduction in the LVM changes (g/height 2.7 /year) of patients who received long-term ERT (male, 4.07 ± 1.03 to 1.25 ± 1.39; female, 2.31 ± 0.81 to 0.78 ± 1.23). Long-term ERT effectively prevents LVH in Fabry patients. This effect was also observed in the patients with LVH prior to the initiation of ERT. Copyright © 2018 Elsevier Inc. All rights reserved.

Connected Au network in annealed Ni/Au thin films on p-GaN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, S. P.; Jang, H. W.; Noh, D. Y.

2007-11-12

We report the formation of a connected Au network in annealed Ni/Au thin films on p-GaN, which was studied by scanning electron microscopy, transmission electron microscopy, and synchrotron x-ray diffraction. As the Ni was oxidized into NiO upon annealing at 530 deg. C in air, the Au layer was transformed to an interconnected network with an increased thickness. During annealing, Ni atoms diffuse out onto the Au through defects to form NiO, while Au atoms replace the Ni positions. The Au network grows downward until it reaches the p-GaN substrate, and NiO columns fill the space between the Au network.

Rapid thermal anneal in InP, GaAs and GaAs/GaAlAs

NASA Astrophysics Data System (ADS)

Descouts, B.; Duhamel, N.; Godefroy, S.; Krauz, P.

Ion implantation in semiconductors provides a doping technique with several advantages over more conventional doping methods and is now extensively used for device applications, e.g. field effect transistors (MESFET GaAs, MIS (InP), GaAs/GaAlAs heterojunction bipolar transistors (HBT). Because of the lattice disorder produced by the implantation, the dopant must be made electrically active by a postimplant anneal. As the device performances are very dependent on its electrical characteristics, the anneal is a very important stage of the process. Rapid anneal is known to provide less exodiffusion and less induffusion of impurities compared to conventional furnace anneal, so this technique has been used in this work to activate an n-type dopant (Si) in InP and a p-type dopant (Mg) in GaAs and GaAs/GaAIAs. These two ions have been chosen to realize implanted MIS InP and the base contacts for GaAs/GaAlAs HBTs. The experimental conditions to obtain the maximum electrical activity in these two cases will be detailed. For example, although we have not been able to obtain a flat profile in Mg + implanted GaAs/GaAlAs heterostructure by conventional thermal anneal, rapid thermal anneal gives a flat hole profile over a depth of 0.5 μm with a concentration of 1 x 10 19 cm -3.

Expensive drugs for rare disorders: to treat or not to treat? The case of enzyme replacement therapy for mucopolysaccharidosis VI.

PubMed

Schlander, M; Beck, M

2009-05-01

Mucopolysaccharidosis VI (MPS VI) is a very rare, chronically debilitating lysosomal storage disorder that develops in people with an enzyme deficiency. Clinical characteristics and progression rates vary widely between patients. The recent introduction of enzyme replacement therapy (ERT) has improved considerably the lives of patients with MPS VI, at an annual cost of treatment between euro 150,000 and euro 450,000 per patient. This Commentary article addresses the controversial topic of granting reimbursement for expensive treatment options for orphan diseases, such as MPS VI. The discussion reflects clinical, economic and ethical aspects and incorporates insights from the relevant literature (based on a Medline search to September 2008) on MPS VI, efficacy of ERT, orphan drugs, and the economics and ethics of health-care prioritisation. Although ERT for MPS VI received marketing authorisation in the European Union in January 2006, patients' access to this therapy varies geographically due to differences between national reimbursement schemes for orphan drugs. Some inclusion and exclusion criteria for treatment of MPS VI patients with ERT appear arbitrary and may contribute to the exclusion from treatment of patients who could benefit in the long term. Reimbursement schemes which rely on proof of short-term treatment effectiveness may discriminate against slowly progressive patients, as health gain can often not be confirmed over a short period of time in these patients. Conventional cost-effectiveness analysis remains silent on crucial issues related to budgetary impact, i.e. opportunity cost from a system perspective, and fair access to treatment. To prevent patients from being deprived of effective treatment, it is suggested that inclusion and exclusion criteria for treatment should be primarily based on a careful individual assessment of expected long-term clinical benefits. Once treatment has been agreed to as the correct option on clinical grounds, it is

Pancreatic enzyme replacement therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis: a 1-year disease management study on symptom control and quality of life.

PubMed

D'Haese, Jan G; Ceyhan, Güralp O; Demir, Ihsan Ekin; Layer, Peter; Uhl, Waldemar; Löhr, Matthias; Rychlik, Reinhard; Pirilis, Konstantinos; Zöllner, York; Gradl, Birgit; Foerster, Douglas; Möbius, Julia; Henniges, Friederike; Friess, Helmut

2014-08-01

Exocrine pancreatic insufficiency (EPI) is frequent in patients with chronic pancreatitis (CP). This 1-year, prospective, multicenter, observational, disease management study aimed to assess symptom improvement and quality of life in patients with CP with EPI who were receiving pancreatic enzyme replacement. Patients with CP and chronic EPI were either assigned to cohort 1 that consisted of patients already taking pancreatin (Kreon; Abbott Arzneimittel GmbH, Hannover, Germany) or cohort 2 that consisted of patients with newly diagnosed EPI without prior pancreatic enzyme treatment. Symptoms were documented, and quality of life was assessed using the gastrointestinal quality of life index (GIQLI) at baseline, 6 months, and 1 year. A total of 294 patients were evaluated (cohort 1, n = 206; cohort 2, n = 88). The proportion of patients experiencing gastrointestinal symptoms and recurrent pain after 1 year was significantly reduced in both cohorts (P < 0.001). The alleviation of symptoms was reflected in GIQLI score improvements at 1 year in both cohorts (P < 0.001), independent of CP severity and etiology. Improvements in GIQLI score were more pronounced in cohort 2 (P < 0.001). Pancreatin demonstrated symptom relief and improvement in quality of life in patients with CP-related EPI in this disease management study.

AlGaN-Cladding-Free m-Plane InGaN/GaN Laser Diodes with p-Type AlGaN Etch Stop Layers

NASA Astrophysics Data System (ADS)

Farrell, Robert M.; Haeger, Daniel A.; Hsu, Po Shan; Hardy, Matthew T.; Kelchner, Kathryn M.; Fujito, Kenji; Feezell, Daniel F.; Mishra, Umesh K.; DenBaars, Steven P.; Speck, James S.; Nakamura, Shuji

2011-09-01

We present a new method of improving the accuracy and reproducibility of dry etching processes for ridge waveguide InGaN/GaN laser diodes (LDs). A GaN:Al0.09Ga0.91N etch rate selectivity of 11:1 was demonstrated for an m-plane LD with a 40 nm p-Al0.09Ga0.91N etch stop layer (ESL) surrounded by Al-free cladding layers, establishing the effectiveness of AlGaN-based ESLs for controlling etch depth in ridge waveguide InGaN/GaN LDs. These results demonstrate the potential for integrating AlGaN ESLs into commercial device designs where accurate control of the etch depth of the ridge waveguide is necessary for stable, kink-free operation at high output powers.

Influence of GaAs surface termination on GaSb/GaAs quantum dot structure and band offsets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zech, E. S.; Chang, A. S.; Martin, A. J.

2013-08-19

We have investigated the influence of GaAs surface termination on the nanoscale structure and band offsets of GaSb/GaAs quantum dots (QDs) grown by molecular-beam epitaxy. Transmission electron microscopy reveals both coherent and semi-coherent clusters, as well as misfit dislocations, independent of surface termination. Cross-sectional scanning tunneling microscopy and spectroscopy reveal clustered GaSb QDs with type I band offsets at the GaSb/GaAs interfaces. We discuss the relative influences of strain and QD clustering on the band offsets at GaSb/GaAs interfaces.

Comparison of alloy disorder scatterings in Ga- and N-polar AlGaN/GaN heterostructures

NASA Astrophysics Data System (ADS)

Kang, He; Li, Hui-Jie; Yang, Shao-Yan; Zhang, Wei; Zhu, Ming; Liu, Li; Li, Nan

2018-01-01

The two-dimensional electron gas (2DEG) mobilities limited by alloy disorder (AD) scattering in both Ga- and N-polar AlGaN/GaN heterostructures are investigated. It was found that the AD scattering limited electron mobility in N-polar heterostructures is on the order of 103-104 cm2/Vs, which is comparable to the optical phonon scattering at room-temperature. In comparison, the AD scattering in Ga-polar samples is much less important. Moreover, the electron mobility decreases with the 2DEG density in the Ga-polar device but shows a reverse trend in the N-polar counterpart. This is found to be caused by the rather different electric field distributions in Ga- and N-polar AlGaN/GaN heterostructures. In addition, we find that an AlN interlayer can effectively reduce the alloy scattering, mainly due to the large band offset between AlN and GaN. The calculated mobilities have been compared with the experiment results and good agreements are found. We believe that our results are important for the design of AlGaN/GaN heterostructure-based devices, especially the N-polar ones.

Cardiovascular testing in Fabry disease: exercise capacity reduction, chronotropic incompetence and improved anaerobic threshold after enzyme replacement.

PubMed

Lobo, T; Morgan, J; Bjorksten, A; Nicholls, K; Grigg, L; Centra, E; Becker, G

2008-06-01

The aim of this study was to document exercise capacity and serial electrocardiogram and echocardiograph findings in a cohort of Australian patients with Fabry disease, in relation to their history of enzyme replacement therapy (ERT). Fabry disease has multifactorial effects on the cardiovascular system. Most previous studies have focused on electrocardiographic and echocardiographic parameters. Exercise capacity can be used as an integrated measure of cardiovascular function and allows the effects of treatment to be monitored. A total of 38 patients (30 men and 8 women) with Fabry disease were monitored by 12-lead electrocardiograms every 6-12 months, and by annual standardized-protocol echocardiograms. Bicycle stress tests with VO(2) max measurement and once-only 6 minutes' walk tests were also carried out in subsets of patients whose general health status allowed testing. Seventy per cent of patients met electrocardiogram criteria for left ventricular hypertrophy. Left ventricular hypertrophy on echocardiograph was present in 64% of patients (80% of men). Exercise capacity was reduced in patients with Fabry disease compared with that predicted from normative population data. Mild improvement in anaerobic threshold was seen in the first year of ERT (14.1 +/- 3.0 to 15.8 +/- 3.0, P = 0.02), but no consistent further increase was seen beyond the first year. Most patients had resting bradycardia, with impaired ability to increase heart rate during exercise. Serial testing on ERT showed an improvement in anaerobic threshold but no significant change in VO(2) max. Male patients with Fabry disease were unable to attain predicted maximal heart rate on exercise or to achieve normal exercise levels. ERT was associated with a small improvement in anaerobic threshold over the first year.

Magnetometory of AlGaN/GaN heterostructure wafers

NASA Astrophysics Data System (ADS)

Tsubaki, K.; Maeda, N.; Saitoh, T.; Kobayashi, N.

2005-06-01

AlGaN/GaN heterostructure wafers are becoming a key technology for next generation cellar-phone telecommunication system because of their potential for high-performance microwave applications. Therefore, the electronic properties of a 2DEG in AlGaN/GaN heterostructures have recently been discussed. In this paper, we performed the extraordinary Hall effect measurement and the SQUID magnetometory of AlGaN/GaN heterostructure wafer at low temperature. The AlGaN/GaN heterostructures were grown by low-pressure metal-organic chemical vapour phase epitaxy on (0001) SiC substrate using AlN buffers. The electron mobility and electron concentration at 4.2 K are 9,540cm2/V s and 6.6 × 1012cm-2, respectively. In the extraordinary Hall effect measurement of AlGaN/GaN heterostructures, the hysteresis of Hall resistance appeared below 4.5 K and disappeared above 4.5 K. On the other hand, the hysteresis of magnetometric data obtained by SQUID magnetometory appears near zero magnetic field when the temperature is lower than 4.5 K. At the temperature larger than 4.5 K, the hysteresis of magnetometric data disappears. And the slopes of magnetometric data with respect to magnetic field become lower as obeying Currie-Weiss law and the Curie temperature TC is 4.5 K. Agreement of TC measured by the extraordinary Hall effect and the SQUID magnetometory implies the ferromagnetism at the AlGaN/GaN heterojunction. However, the conformation of the ferromagnetism of AlGaN/GaN heterostructure is still difficult and the detailed physical mechanism is still unclear.

Modeling and optimization of a double-well double-barrier GaN/AlGaN/GaN/AlGaN resonant tunneling diode

NASA Astrophysics Data System (ADS)

Liu, Yang; Gao, Bo; Gong, Min; Shi, Ruiying

2017-06-01

The influence of a GaN layer as a sub-quantum well for an AlGaN/GaN/AlGaN double barrier resonant tunneling diode (RTD) on device performance has been investigated by means of numerical simulation. The introduction of the GaN layer as the sub-quantum well turns the dominant transport mechanism of RTD from the 3D-2D model to the 2D-2D model and increases the energy difference between tunneling energy levels. It can also lower the effective height of the emitter barrier. Consequently, the peak current and peak-to-valley current difference of RTD have been increased. The optimal GaN sub-quantum well parameters are found through analyzing the electrical performance, energy band, and transmission coefficient of RTD with different widths and depths of the GaN sub-quantum well. The most pronounced electrical parameters, a peak current density of 5800 KA/cm2, a peak-to-valley current difference of 1.466 A, and a peak-to-valley current ratio of 6.35, could be achieved by designing RTD with the active region structure of GaN/Al0.2Ga0.8 N/GaN/Al0.2Ga0.8 N (3 nm/1.5 nm/1.5 nm/1.5 nm).

Curious Cases of the Enzymes.

PubMed

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.

Mechanism of action and interactions between xanthine oxidase inhibitors derived from natural sources of chlorogenic and ferulic acids.

PubMed

Gawlik-Dziki, Urszula; Dziki, Dariusz; Świeca, Michał; Nowak, Renata

2017-06-15

The aim of this study was to estimate the phenolic composition and xanthine oxidase (XO) inhibitory activity of green coffee beans (GCB) and wholemeal wheat flour (WF). Additionally, the type and strength of interaction (expressed as the combination index, CI) and mode of XO inhibition were analyzed. The major phenolic in GCB was 5-caffeoylquinic acid (39.92mg/g dw). The main phenolic acids in WF were trans- and cis-ferulic acids (257 and 165.57mg/100g dw, respectively). Both ferulic and chlorogenic acids individually inhibited XO, and for their combination moderate synergism was found. Buffer extractable compounds from GCB and WF demonstrated slight synergism (CI=0.92), while potentially bioaccessible and bioavailable compounds acted synergistically (CI=0.43 and 0.54, respectively). Buffer-extractable and potentially bioavailable phytochemicals from GCB acted uncompetitively, whereas potentially bioaccessible compounds acted as noncompetitive XO inhibitors. The addition of 3-5% of GCB to wheat bread significantly increased XO-inhibitory activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

An interfacial and comparative in vitro study of gastrointestinal lipases and Yarrowia lipolytica LIP2 lipase, a candidate for enzyme replacement therapy.

PubMed

Bénarouche, Anaïs; Point, Vanessa; Carrière, Frédéric; Cavalier, Jean-François

2014-07-01

Lipolytic activities of Yarrowia lipolytica LIP2 lipase (YLLIP2), human pancreatic (HPL) and dog gastric (DGL) lipases were first compared using lecithin-stabilized triacylglycerol (TAG) emulsions (Intralipid) at various pH and bile salt concentrations. Like DGL, YLLIP2 was able to hydrolyze TAG droplets covered by a lecithin monolayer, while HPL was not directly active on that substrate. These results were in good agreement with the respective kinetics of adsorption on phosphatidylcholine (PC) monomolecular films of the same three lipases, YLLIP2 being the most tensioactive lipase. YLLIP2 adsorption onto a PC monolayer spread at the air/water interface was influenced by pH-dependent changes in the enzyme/lipid interfacial association constant (KAds) which was optimum at pH 6.0 on long-chain egg PC monolayer, and at pH 5.0 on medium chain dilauroylphosphatidylcholine film. Using substrate monolayers (1,2-dicaprin, trioctanoin), YLLIP2 displayed the highest lipolytic activities on both substrates in the 25-35 mN m(-1) surface pressure range. YLLIP2 was active in a large pH range and displayed a pH-dependent activity profile combining DGL and HPL features at pH values found in the stomach (pH 3-5) and in the intestine (pH 6-7), respectively. The apparent maximum activity of YLLIP2 was observed at acidic pH 4-6 and was therefore well correlated with an efficient interfacial binding at these pH levels, whatever the type of interfaces (Intralipid emulsions, substrate or PC monolayers). All these findings support the use of YLLIP2 in enzyme replacement therapy for the treatment of pancreatic exocrine insufficiency, a pathological situation in which an acidification of intestinal contents occurs. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): Novel global treatment response model and outcomes in patients with alpha-mannosidosis.

PubMed

Harmatz, Paul; Cattaneo, Federica; Ardigò, Diego; Geraci, Silvia; Hennermann, Julia B; Guffon, Nathalie; Lund, Allan; Hendriksz, Christian J; Borgwardt, Line

2018-06-01

Alpha-mannosidosis is an ultra-rare monogenic disorder resulting from a deficiency in the lysosomal enzyme alpha-mannosidase, with a prevalence estimated to be as low as 1:1,000,000 live births. The resulting accumulation of mannose-rich oligosaccharides in all tissues leads to a very heterogeneous disorder with a continuum of clinical manifestations with no distinctive phenotypes. Long-term enzyme replacement therapy (ERT) with velmanase alfa is approved in Europe for the treatment of non-neurological manifestations in patients with mild to moderate alpha-mannosidosis. The clinical heterogeneity and rarity of the disease limit the sensitivity of single parameters to detect clinically relevant treatment effects. Thus, we propose a novel multiple variable responder analysis to evaluate the efficacy of ERT for alpha-mannosidosis and present efficacy analyses for velmanase alfa using this method. Global treatment response to velmanase alfa (defined by response to ≥2 domains comprising pharmacodynamic, functional, and quality of life outcomes) was applied post hoc to data from the pivotal placebo-controlled rhLAMAN-05 study and to the longer-term integrated data from all patients in the clinical development program (rhLAMAN-10). After 12 months of treatment, a global treatment response was achieved by 87% of patients receiving velmanase alfa (n = 15) compared with 30% of patients receiving placebo (n = 10). Longer-term data from all patients in the clinical program (n = 33) showed 88% of patients were global responders, including all (100%) pediatric patients (n = 19) and the majority (71%) of adult patients (n = 14). The responder analysis model demonstrates a clinically meaningful treatment effect with velmanase alfa and supports the early initiation and continued benefit of longer-term treatment of all patients with alpha-mannosidosis with this ERT. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease - A systematic literature review by a European panel of experts.

PubMed

Spada, Marco; Baron, Ralf; Elliott, Perry M; Falissard, Bruno; Hilz, Max J; Monserrat, Lorenzo; Tøndel, Camilla; Tylki-Szymańska, Anna; Wanner, Christoph; Germain, Dominique P

2018-04-26

Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease. A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients. Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life. Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage. Copyright © 2018. Published by Elsevier Inc.

Nanoscale characterization of GaN/InGaN multiple quantum wells on GaN nanorods by photoluminescence spectroscopy

NASA Astrophysics Data System (ADS)

Chen, Weijian; Wen, Xiaoming; Latzel, Michael; Yang, Jianfeng; Huang, Shujuan; Shrestha, Santosh; Patterson, Robert; Christiansen, Silke; Conibeer, Gavin

2017-02-01

GaN/InGaN multiple quantum wells (MQW) and GaN nanorods have been widely studied as a candidate material for high-performance light emitting diodes. In this study, GaN/InGaN MQW on top of GaN nanorods are characterized in nanoscale using confocal microscopy associated with photoluminescence spectroscopy, including steady-state PL, timeresolved PL and fluorescence lifetime imaging (FLIM). Nanorods are fabricated by etching planar GaN/InGaN MQWs on top of a GaN layer on a c-plane sapphire substrate. Photoluminescence efficiency from the GaN/InGaN nanorods is evidently higher than that of the planar structure, indicating the emission improvement. Time-resolved photoluminescence (TRPL) prove that surface defects on GaN nanorod sidewalls have a strong influence on the luminescence property of the GaN/InGaN MWQs. Such surface defects can be eliminated by proper surface passivation. Moreover, densely packed nanorod array and sparsely standing nanorods have been studied for better understanding the individual property and collective effects from adjacent nanorods. The combination of the optical characterization techniques guides optoelectronic materials and device fabrication.

Enhanced Thermionic Emission and Low 1/f Noise in Exfoliated Graphene/GaN Schottky Barrier Diode.

PubMed

Kumar, Ashutosh; Kashid, Ranjit; Ghosh, Arindam; Kumar, Vikram; Singh, Rajendra

2016-03-01

Temperature-dependent electrical transport characteristics of exfoliated graphene/GaN Schottky diodes are investigated and compared with conventional Ni/GaN Schottky diodes. The ideality factor of graphene/GaN and Ni/GaN diodes are measured to be 1.33 and 1.51, respectively, which is suggestive of comparatively higher thermionic emission current in graphene/GaN diode. The barrier height values for graphene/GaN diode obtained using thermionic emission model and Richardson plots are found to be 0.60 and 0.72 eV, respectively, which are higher than predicted barrier height ∼0.40 eV as per the Schottky-Mott model. The higher barrier height is attributed to hole doping of graphene due to graphene-Au interaction which shifts the Fermi level in graphene by ∼0.3 eV. The magnitude of flicker noise of graphene/GaN Schottky diode increases up to 175 K followed by its decrease at higher temperatures. This indicates that diffusion currents and barrier inhomogeneities dominate the electronic transport at lower and higher temperatures, respectively. The exfoliated graphene/GaN diode is found to have lower level of barrier inhomogeneities than conventional Ni/GaN diode, as well as earlier reported graphene/GaN diode fabricated using chemical vapor deposited graphene. The lesser barrier inhomogeneities in graphene/GaN diode results in lower flicker noise by 2 orders of magnitude as compared to Ni/GaN diode. Enhanced thermionic emission current, lower level of inhomogeneities, and reduced flicker noise suggests that graphene-GaN Schottky diodes may have the underlying trend for replacing metal-GaN Schottky diodes.

De novo active sites for resurrected Precambrian enzymes

NASA Astrophysics Data System (ADS)

Risso, Valeria A.; Martinez-Rodriguez, Sergio; Candel, Adela M.; Krüger, Dennis M.; Pantoja-Uceda, David; Ortega-Muñoz, Mariano; Santoyo-Gonzalez, Francisco; Gaucher, Eric A.; Kamerlin, Shina C. L.; Bruix, Marta; Gavira, Jose A.; Sanchez-Ruiz, Jose M.

2017-07-01

Protein engineering studies often suggest the emergence of completely new enzyme functionalities to be highly improbable. However, enzymes likely catalysed many different reactions already in the last universal common ancestor. Mechanisms for the emergence of completely new active sites must therefore either plausibly exist or at least have existed at the primordial protein stage. Here, we use resurrected Precambrian proteins as scaffolds for protein engineering and demonstrate that a new active site can be generated through a single hydrophobic-to-ionizable amino acid replacement that generates a partially buried group with perturbed physico-chemical properties. We provide experimental and computational evidence that conformational flexibility can assist the emergence and subsequent evolution of new active sites by improving substrate and transition-state binding, through the sampling of many potentially productive conformations. Our results suggest a mechanism for the emergence of primordial enzymes and highlight the potential of ancestral reconstruction as a tool for protein engineering.

Polarization compensation at low p-GaN doping density in InGaN/GaN p-i-n solar cells: Effect of InGaN interlayers

NASA Astrophysics Data System (ADS)

Saini, Basant; Adhikari, Sonachand; Pal, Suchandan; Kapoor, Avinsahi

2017-07-01

The effectiveness of polarization matching layer (PML) between i-InGaN/p-GaN is studied numerically for Ga-face InGaN/GaN p-i-n solar cell at low p-GaN doping (∼5e17 cm-3). The simulations are performed for four InxGa1-xN/GaN heterostructures (x = 10%, 15%, 20% and 25%), thus investigating the impact of PML for low as well as high indium containing absorber regions. Use of PML presents a suitable alternative to counter the effects of polarization-induced electric fields arising at low p-GaN doping density especially for absorber regions with high indium (>10%). It is seen that it not only mitigates the negative effects of polarization-induced electric fields but also reduces the high potential barriers existing at i-InGaN/p-GaN heterojunction. The improvement in photovoltaic properties of the heterostructures even at low p-GaN doping validates this claim.

GaSbBi/GaSb quantum well laser diodes

NASA Astrophysics Data System (ADS)

Delorme, O.; Cerutti, L.; Luna, E.; Narcy, G.; Trampert, A.; Tournié, E.; Rodriguez, J.-B.

2017-05-01

We report on the structural and optical properties of GaSbBi single layers and GaSbBi/GaSb quantum well heterostructures grown by molecular beam epitaxy on GaSb substrates. Excellent crystal quality and room-temperature photoluminescence are achieved in both cases. We demonstrate laser operation from laser diodes with an active zone composed of three GaSb0.885Bi0.115/GaSb quantum wells. These devices exhibit continuous-wave lasing at 2.5 μm at 80 K, and lasing under pulsed operation at room-temperature near 2.7 μm.

Enzymes approved for human therapy: indications, mechanisms and adverse effects.

PubMed

Baldo, Brian A

2015-02-01

Research and drug developments fostered under orphan drug product development programs have greatly assisted the introduction of efficient and safe enzyme-based therapies for a range of rare disorders. The introduction and regulatory approval of 20 different recombinant enzymes has enabled, often for the first time, effective enzyme-replacement therapy for some lysosomal storage disorders, including Gaucher (imiglucerase, taliglucerase, and velaglucerase), Fabry (agalsidase alfa and beta), and Pompe (alglucosidase alfa) diseases and mucopolysaccharidoses I (laronidase), II (idursulfase), IVA (elosulfase), and VI (galsulfase). Approved recombinant enzymes are also now used as therapy for myocardial infarction (alteplase, reteplase, and tenecteplase), cystic fibrosis (dornase alfa), chronic gout (pegloticase), tumor lysis syndrome (rasburicase), leukemia (L-asparaginase), some collagen-based disorders such as Dupuytren's contracture (collagenase), severe combined immunodeficiency disease (pegademase bovine), detoxification of methotrexate (glucarpidase), and vitreomacular adhesion (ocriplasmin). The development of these efficacious and safe enzyme-based therapies has occurred hand in hand with some remarkable advances in the preparation of the often specifically designed recombinant enzymes; the manufacturing expertise necessary for commercial production; our understanding of underlying mechanisms operative in the different diseases; and the mechanisms of action of the relevant recombinant enzymes. Together with information on these mechanisms, safety findings recorded so far on the various adverse events and problems of immunogenicity of the recombinant enzymes used for therapy are presented.

Self-organization of palladium nanoislands on GaN and AlxGa1-xN/GaN heterostructures

NASA Astrophysics Data System (ADS)

Stafiniak, Andrzej; Szymański, Tomasz; Paszkiewicz, Regina

2017-12-01

We report on systematic study on the dewetting process of thin Pd layer and self-organized Pd nano-islands on SiO2, GaN and AlxGa1-xN/GaN heterostructures with various Al content. The influence of factors such as the thickness of metal layer, type of top layer of AlGaN/GaN heterostructures, temperature and time of annealing process on the dimensions, shapes and density of Pd islands was analyzed. Comparing the behavior of self-organization of Pd islands on Al0.25Ga0.75N/GaN and SiO2 we can conclude that solid-state dewetting process on SiO2 occures much faster than on Al0.25Ga0.75N. For substrates with SiO2 this process requires less energy and can arise for thicker layer. On the Al0.25Ga0.75N surface the islands take more crystalline shape which is probably due to surface reconstruction of Pd-Ga alloy thin layer on interface. For thin metal layer the coalescence of islands into larger islands similar to Ostwald ripening mechanism was observed. Greater surface roughness of AlxGa1-xN/GaN heterostructures with higher Al content causes an increase of surface density of islands and the reduction of their sizes which improves the roundness. In case of GaN and AlxGa1-xN layers with Al content lower than 20%, the surface degradation caused by annealing process was observed. Probably, this is due to the decomposition of layers with gallium droplet formation on catalytic metal islands.

Indium droplet formation in InGaN thin films with single and double heterojunctions prepared by MOCVD

PubMed Central

2014-01-01

Indium gallium nitride (InGaN) samples with single heterojunction (SH) and double heterojunction (DH) were prepared using metal-organic chemical vapor deposition. SH has a layer of InGaN thin film (thicknesses, 25, 50, 100, and 200 nm) grown on an uGaN film (thickness, 2 μm). The DH samples are distinguished by DH uGaN film (thickness, 120 nm) grown on the InGaN layer. Reciprocal space mapping measurements reveal that the DH samples are fully strained with different thicknesses, whereas the strain in the SH samples are significantly relaxed with the increasing thickness of the InGaN film. Scanning electron microscopy results show that the surface roughness of the sample increases when the sample is relaxed. High-resolution transmission electron microscopy images of the structure of indium droplets in the DH sample indicate that the thickness of the InGaN layer decreases with the density of indium droplets. The formation of these droplets is attributed to the insufficient kinetic energy of indium atom to react with the elements of group V, resulting to aggregation. The gallium atoms in the GaN thin film will not be uniformly replaced by indium atoms; the InGaN thin film has an uneven distribution of indium atoms and the quality of the epitaxial layer is degraded. PMID:25024692

Metal-interconnection-free integration of InGaN/GaN light emitting diodes with AlGaN/GaN high electron mobility transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Chao; Cai, Yuefei; Liu, Zhaojun

2015-05-04

We report a metal-interconnection-free integration scheme for InGaN/GaN light emitting diodes (LEDs) and AlGaN/GaN high electron mobility transistors (HEMTs) by combining selective epi removal (SER) and selective epitaxial growth (SEG) techniques. SER of HEMT epi was carried out first to expose the bottom unintentionally doped GaN buffer and the sidewall GaN channel. A LED structure was regrown in the SER region with the bottom n-type GaN layer (n-electrode of the LED) connected to the HEMTs laterally, enabling monolithic integration of the HEMTs and LEDs (HEMT-LED) without metal-interconnection. In addition to saving substrate real estate, minimal interface resistance between the regrownmore » n-type GaN and the HEMT channel is a significant improvement over metal-interconnection. Furthermore, excellent off-state leakage characteristics of the driving transistor can also be guaranteed in such an integration scheme.« less

Optimization of GaAs Nanowire Pin Junction Array Solar Cells by Using AlGaAs/GaAs Heterojunctions

NASA Astrophysics Data System (ADS)

Wu, Yao; Yan, Xin; Wei, Wei; Zhang, Jinnan; Zhang, Xia; Ren, Xiaomin

2018-04-01

We optimized the performance of GaAs nanowire pin junction array solar cells by introducing AlGaAs/GaAs heterejunctions. AlGaAs is used for the p type top segment for axial junctions and the p type outer shell for radial junctions. The AlGaAs not only serves as passivation layers for GaAs nanowires but also confines the optical generation in the active regions, reducing the recombination loss in heavily doped regions and the minority carrier recombination at the top contact. The results show that the conversion efficiency of GaAs nanowires can be greatly enhanced by using AlGaAs for the p segment instead of GaAs. A maximum efficiency enhancement of 8.42% has been achieved in this study. And for axial nanowire, by using AlGaAs for the top p segment, a relatively long top segment can be employed without degenerating device performance, which could facilitate the fabrication and contacting of nanowire array solar cells. While for radial nanowires, AlGaAs/GaAs nanowires show better tolerance to p-shell thickness and surface condition.

Optimization of GaAs Nanowire Pin Junction Array Solar Cells by Using AlGaAs/GaAs Heterojunctions.

PubMed

Wu, Yao; Yan, Xin; Wei, Wei; Zhang, Jinnan; Zhang, Xia; Ren, Xiaomin

2018-04-25

We optimized the performance of GaAs nanowire pin junction array solar cells by introducing AlGaAs/GaAs heterejunctions. AlGaAs is used for the p type top segment for axial junctions and the p type outer shell for radial junctions. The AlGaAs not only serves as passivation layers for GaAs nanowires but also confines the optical generation in the active regions, reducing the recombination loss in heavily doped regions and the minority carrier recombination at the top contact. The results show that the conversion efficiency of GaAs nanowires can be greatly enhanced by using AlGaAs for the p segment instead of GaAs. A maximum efficiency enhancement of 8.42% has been achieved in this study. And for axial nanowire, by using AlGaAs for the top p segment, a relatively long top segment can be employed without degenerating device performance, which could facilitate the fabrication and contacting of nanowire array solar cells. While for radial nanowires, AlGaAs/GaAs nanowires show better tolerance to p-shell thickness and surface condition.

Spin injection in epitaxial MnGa(111)/GaN(0001) heterostructures

NASA Astrophysics Data System (ADS)

Zube, Christian; Malindretos, Joerg; Watschke, Lars; Zamani, Reza R.; Disterheft, David; Ulbrich, Rainer G.; Rizzi, Angela; Iza, Michael; Keller, Stacia; DenBaars, Steven P.

2018-01-01

Ferromagnetic MnGa(111) layers were grown on GaN(0001) by molecular beam epitaxy. MnGa/GaN Schottky diodes with a doping level of around n = 7 × 1018 cm-3 were fabricated to achieve single step tunneling across the metal/semiconductor junction. Below the GaN layer, a thin InGaN quantum well served as optical spin detector ("spin-LED"). For electron spin injection from MnGa into GaN and subsequent spin transport through a 45 nm (70 nm) thick GaN layer, we observe a circular polarization of 0.3% (0.2%) in the electroluminescence at 80 K. Interface mixing, spin polarization losses during electrical transport in the GaN layer, and spin relaxation in the InGaN quantum well are discussed in relation with the low value of the optically detected spin polarization.

Meningiomas: A Comparative Study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for Molecular Imaging in Mice

PubMed Central

Soto-Montenegro, María Luisa; Peña-Zalbidea, Santiago; Mateos-Pérez, Jose María; Oteo, Marta; Romero, Eduardo; Morcillo, Miguel Ángel; Desco, Manuel

2014-01-01

Purpose The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three 68Ga-DOTA-labeled somatostatin analogues (68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE) using PET/CT in a murine model with subcutaneous meningioma xenografts. Methods The experiment was performed with 16 male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH-157MN). 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE were produced in a FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT scanner. The SUVmax of the liver and muscle, and the tumor-to-liver (T/L) and tumor-to-muscle (T/M) SUV ratios were computed. Kinetic analysis was performed using Logan graphical analysis for a two-tissue reversible compartmental model, and the volume of distribution (Vt) was determined. Results Hepatic SUVmax and Vt were significantly higher with 68Ga-DOTANOC than with 68Ga-DOTATOC and 68Ga-DOTATATE. No significant differences between tracers were found for SUVmax in tumor or muscle. No differences were found in the T/L SUV ratio between 68Ga-DOTATATE and 68Ga-DOTATOC, both of which had a higher fraction than 68Ga-DOTANOC. The T/M SUV ratio was significantly higher with 68Ga-DOTATATE than with 68Ga-DOTATOC and 68Ga-DOTANOC. The Vt for tumor was higher with 68Ga-DOTATATE than with 68Ga-DOTANOC and relatively similar to that of 68Ga-DOTATOC. Conclusions This study demonstrates, for the first time, the ability of the three radiolabeled somatostatin analogues tested to image a human meningioma cell line. Although Vt was relatively similar with 68Ga-DOTATATE and 68Ga-DOTATOC, uptake was higher with 68Ga-DOTATATE in the tumor than with 68Ga-DOTANOC and 68Ga-DOTATOC, suggesting a higher diagnostic value of 68Ga-DOTATATE for detecting meningiomas. PMID:25369268

Theoretical and experimental studies of electric field distribution in N-polar GaN/AlGaN/GaN heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gladysiewicz, M., E-mail: marta.gladysiewicz@pwr.edu.pl; Janicki, L.; Kudrawiec, R.

2015-12-28

Electric field distribution in N-polar GaN(channel)/AlGaN/GaN(buffer) heterostructures was studied theoretically by solving Schrodinger and Poisson equations in a self-consistent manner for various boundary conditions and comparing results of these calculations with experimental data, i.e., measurements of electric field in GaN(channel) and AlGaN layers by electromodulation spectroscopy. A very good agreement between theoretical calculations and experimental data has been found for the Fermi-level located at ∼0.3 eV below the conduction band at N-polar GaN surface. With this surface boundary condition, the electric field distribution and two dimensional electron gas concentration are determined for GaN(channel)/AlGaN/GaN(buffer) heterostructures of various thicknesses of GaN(channel) and AlGaNmore » layers.« less

Role of AlGaN/GaN interface traps on negative threshold voltage shift in AlGaN/GaN HEMT

NASA Astrophysics Data System (ADS)

Malik, Amit; Sharma, Chandan; Laishram, Robert; Bag, Rajesh Kumar; Rawal, Dipendra Singh; Vinayak, Seema; Sharma, Rajesh Kumar

2018-04-01

This article reports negative shift in the threshold-voltage in AlGaN/GaN high electron mobility transistor (HEMT) with application of reverse gate bias stress. The device is biased in strong pinch-off and low drain to source voltage condition for a fixed time duration (reverse gate bias stress), followed by measurement of transfer characteristics. Negative threshold voltage shift after application of reverse gate bias stress indicates the presence of more carriers in channel as compared to the unstressed condition. We propose the presence of AlGaN/GaN interface states to be the reason of negative threshold voltage shift, and developed a process to electrically characterize AlGaN/GaN interface states. We verified the results with Technology Computer Aided Design (TCAD) ATLAS simulation and got a good match with experimental measurements.

Pulmonary involvement in Fabry disease: effect of plasma globotriaosylsphingosine and time to initiation of enzyme replacement therapy.

PubMed

Franzen, Daniel; Haile, Sarah R; Kasper, David C; Mechtler, Thomas P; Flammer, Andreas J; Krayenbühl, Pierre A; Nowak, Albina

2018-01-01

Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by mutations of GLA gene leading to reduced α-galactosidase activity and resulting in a progressive accumulation of globotriaosylceramide (Gb3) and its deacylated derivative, globotriaosyl-sphingosine (Lyso-Gb3). Plasma Lyso-Gb3 levels serve as a disease severity and treatment monitoring marker during enzyme replacement therapy (ERT). Adult patients with AFD who had yearly pulmonary function tests between 1999 and 2015 were eligible for this observational study. Primary outcome measures were the change in z-score of forced expiratory volume in the first second (FEV 1 ) and FEV 1 /FVC over time. Plasma Lyso-Gb3 levels and the age of ERT initiation were investigated for their association with lung function decline. Fifty-three patients (42% male, median (range) age at diagnosis of AFD 34 (6-61) years in men, 34 (13-67) in women) were included. The greatest decrease of FEV 1 /FVC z-scores was observed in Classic men (-0.048 per year, 95% CI -0.081 to -0.014), compared with the Later-Onset men (+0.013,95% CI -0.055 to 0.082), Classic women (-0.008, 95% CI -0.035 to +0.020) and Later-Onset women (-0.013, 95% CI -0.084 to +0.058). Cigarette smoking (P=0.022) and late ERT initiation (P=0.041) were independently associated with faster FEV 1 decline. FEV 1 /FVC z-score decrease was significantly reduced after initiation of ERT initiation (-0.045 compared with -0.015, P=0.014). Furthermore, there was a trend towards a relevant influence of Lyso-Gb3 (P=0.098) on airflow limitation with age. Early ERT initiation seems to preserve pulmonary function. Plasma Lyso-Gb3 is maybe a useful predictor for airflow limitation. Classic men need a closer monitoring of the lung function.

Effects of Neonatal Enzyme Replacement Therapy and Simvastatin Treatment on Cervical Spine Disease in Mucopolysaccharidosis I Dogs

PubMed Central

Chiaro, Joseph A; O’Donnell, Patricia; Shore, Eileen M; Malhotra, Neil R; Ponder, Katherine P; Haskins, Mark E; Smith, Lachlan J

2014-01-01

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α-L-iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kypho-scoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT+SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT treated; and MPS I ERT+SIM treated. Animals were euthanized at one year-of-age. Intervertebral disc condition and spinal cord compression were evaluated from MRIs and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using microcomputed tomography, and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT+SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, while ERT treatment resulted in partial preservation of these properties. ERT+SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process, and that additional treatment with simvastatin does not

AlGaN/GaN high electron mobility transistors with selective area grown p-GaN gates

NASA Astrophysics Data System (ADS)

Yuliang, Huang; Lian, Zhang; Zhe, Cheng; Yun, Zhang; Yujie, Ai; Yongbing, Zhao; Hongxi, Lu; Junxi, Wang; Jinmin, Li

2016-11-01

We report a selective area growth (SAG) method to define the p-GaN gate of AlGaN/GaN high electron mobility transistors (HEMTs) by metal-organic chemical vapor deposition. Compared with Schottky gate HEMTs, the SAG p-GaN gate HEMTs show more positive threshold voltage (V th) and better gate control ability. The influence of Cp2Mg flux of SAG p-GaN gate on the AlGaN/GaN HEMTs has also been studied. With the increasing Cp2Mg from 0.16 μmol/min to 0.20 μmol/min, the V th raises from -0.67 V to -0.37 V. The maximum transconductance of the SAG HEMT at a drain voltage of 10 V is 113.9 mS/mm while that value of the Schottky HEMT is 51.6 mS/mm. The SAG method paves a promising way for achieving p-GaN gate normally-off AlGaN/GaN HEMTs without dry etching damage. Project supported by the National Natural Sciences Foundation of China (Nos. 61376090, 61306008) and the National High Technology Program of China (No. 2014AA032606).

Formation of target-specific binding sites in enzymes: solid-phase molecular imprinting of HRP

NASA Astrophysics Data System (ADS)

Czulak, J.; Guerreiro, A.; Metran, K.; Canfarotta, F.; Goddard, A.; Cowan, R. H.; Trochimczuk, A. W.; Piletsky, S.

2016-05-01

Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike complex protein engineering approaches commonly employed to generate affinity proteins, the method proposed can be used to produce protein-based ligands in a short time period using native protein molecules. These affinity materials are potentially useful tools especially for assays since they combine the catalytic properties of enzymes (for signaling) and molecular recognition properties of antibodies. We demonstrate this concept in an ELISA-format assay where HRP imprinted with vancomycin and ampicillin replaced traditional enzyme-antibody conjugates for selective detection of templates at micromolar concentrations. This approach can potentially provide a fast alternative to raising antibodies for targets that do not require high assay sensitivities; it can also find uses as a biochemical research tool, as a possible replacement for immunoperoxidase-conjugates.Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike

Metalorganic chemical vapor deposition growth of high-mobility AlGaN/AlN/GaN heterostructures on GaN templates and native GaN substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jr-Tai, E-mail: jrche@ifm.liu.se; Hsu, Chih-Wei; Forsberg, Urban

2015-02-28

Severe surface decomposition of semi-insulating (SI) GaN templates occurred in high-temperature H{sub 2} atmosphere prior to epitaxial growth in a metalorganic chemical vapor deposition system. A two-step heating process with a surface stabilization technique was developed to preserve the GaN template surface. Utilizing the optimized heating process, a high two-dimensional electron gas mobility ∼2000 cm{sup 2}/V·s was obtained in a thin AlGaN/AlN/GaN heterostructure with an only 100-nm-thick GaN spacer layer homoepitaxially grown on the GaN template. This technique was also demonstrated viable for native GaN substrates to stabilize the surface facilitating two-dimensional growth of GaN layers. Very high residual silicon andmore » oxygen concentrations were found up to ∼1 × 10{sup 20 }cm{sup −3} at the interface between the GaN epilayer and the native GaN substrate. Capacitance-voltage measurements confirmed that the residual carbon doping controlled by growth conditions of the GaN epilayer can be used to successfully compensate the donor-like impurities. State-of-the-art structural properties of a high-mobility AlGaN/AlN/GaN heterostructure was then realized on a 1 × 1 cm{sup 2} SI native GaN substrate; the full width at half maximum of the X-ray rocking curves of the GaN (002) and (102) peaks are only 21 and 14 arc sec, respectively. The surface morphology of the heterostructure shows uniform parallel bilayer steps, and no morphological defects were noticeable over the entire epi-wafer.« less

Reducing Threshold of Multi Quantum Wells InGaN Laser Diode by Using InGaN/GaN Waveguide

NASA Astrophysics Data System (ADS)

Abdullah, Rafid A.; Ibrahim, Kamarulazizi

2010-07-01

ISE TCAD (Integrated System Engineering Technology Computer Aided Design) software simulation program has been utilized to help study the effect of using InGaN/GaN as a waveguide instead of conventional GaN waveguide for multi quantum wells violet InGaN laser diode (LD). Simulation results indicate that the threshold of the LD has been reduced by using InGaN/GaN waveguide where InGaN/GaN waveguide increases the optical confinement factor which leads to increase the confinement carriers at the active region of the LD.

Predictions of ground states of LiGa and NaGa

NASA Astrophysics Data System (ADS)

Boldyrev, Alexander I.; Simons, Jack

1996-11-01

The ground and very low-lying excited states of LiGa and NaGa have been studied using high level ab initio techniques. At the QCISD(T)/6-311 + G(2df) level of theory, the 1Σ + state was found to be the most stable for both molecules. The equilibrium bond lengths and dissociation energies were found to be: R( LiGa) = 2.865 Å and D0(LiGa) = 22.3 kcal/mol and R( NaGa) = 3.174 Å and D0(NaGa) = 17.1 kcal/mol. Trends within the ground electronic states of LiB, NaB, LiAl, NaAl, LiGa and NaGa are discussed and predictions for related AlkM (Alk LiCs and MBTl) species are made.

Characterization and multi-step transketolase-ω-transaminase bioconversions in an immobilized enzyme microreactor (IEMR) with packed tube.

PubMed

Halim, Amanatuzzakiah Abdul; Szita, Nicolas; Baganz, Frank

2013-12-01

The concept of de novo metabolic engineering through novel synthetic pathways offers new directions for multi-step enzymatic synthesis of complex molecules. This has been complemented by recent progress in performing enzymatic reactions using immobilized enzyme microreactors (IEMR). This work is concerned with the construction of de novo designed enzyme pathways in a microreactor synthesizing chiral molecules. An interesting compound, commonly used as the building block in several pharmaceutical syntheses, is a single diastereoisomer of 2-amino-1,3,4-butanetriol (ABT). This chiral amino alcohol can be synthesized from simple achiral substrates using two enzymes, transketolase (TK) and transaminase (TAm). Here we describe the development of an IEMR using His6-tagged TK and TAm immobilized onto Ni-NTA agarose beads and packed into tubes to enable multi-step enzyme reactions. The kinetic parameters of both enzymes were first determined using single IEMRs evaluated by a kinetic model developed for packed bed reactors. The Km(app) for both enzymes appeared to be flow rate dependent, while the turnover number kcat was reduced 3 fold compared to solution-phase TK and TAm reactions. For the multi-step enzyme reaction, single IEMRs were cascaded in series, whereby the first enzyme, TK, catalyzed a model reaction of lithium-hydroxypyruvate (HPA) and glycolaldehyde (GA) to L-erythrulose (ERY), and the second unit of the IEMR with immobilized TAm converted ERY into ABT using (S)-α-methylbenzylamine (MBA) as amine donor. With initial 60mM (HPA and GA each) and 6mM (MBA) substrate concentration mixture, the coupled reaction reached approximately 83% conversion in 20 min at the lowest flow rate. The ability to synthesize a chiral pharmaceutical intermediate, ABT in relatively short time proves this IEMR system as a powerful tool for construction and evaluation of de novo pathways as well as for determination of enzyme kinetics. Copyright © 2013 The Authors. Published by

Carrier confinement effects of InxGa1-xN/GaN multi quantum disks with GaN surface barriers grown in GaN nanorods

NASA Astrophysics Data System (ADS)

Park, Youngsin; Chan, Christopher C. S.; Taylor, Robert A.; Kim, Nammee; Jo, Yongcheol; Lee, Seung W.; Yang, Woochul; Im, Hyunsik

2018-04-01

Structural and optical properties of InxGa1-xN/GaN multi quantum disks (QDisks) grown on GaN nanorods by molecular beam epitaxy have been investigated by transmission electron microscopy and micro-photoluminescence (PL) spectroscopy. Two types of InGaN QDisks were grown: a pseudo-3D confined InGaN pillar-type QDisks embedded in GaN nanorods; and QDisks in flanged cone type GaN nanorods. The PL emission peak and excitation dependent PL behavior of the pillar-type Qdisks differ greatly from those of the flanged cone type QDisks. Time resolved PL was carried out to probe the differences in charge carrier dynamics. The results suggest that by constraining the formation of InGaN QDisks within the centre of the nanorod, carriers are restricted from migrating to the surface, decreasing the surface recombination at high carrier densities.

An enzymatic biosensor based on three-dimensional ZnO nanotetrapods spatial net modified AlGaAs/GaAs high electron mobility transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Yu; Bioengineering Program, Lehigh University, Bethlehem, Pennsylvania 18015; Zhang, Xiaohui

2014-11-24

We designed and constructed three dimensional (3D) zinc oxide Nanotetrapods (T-ZnOs) modified AlGaAs/GaAs high electron mobility transistors (HEMTs) for enzymatic uric acid (UA) detection. The chemical vapor deposition synthesized T-ZnOs was distributed on the gate areas of HEMTs in order to immobilize uricase and improve the sensitivity of the HEMTs. Combining with the high efficiency of enzyme immobilization by T-ZnOs and high sensitivity from HEMT, the as-constructed uricase/T-ZnOs/HEMTs biosensor showed fast response towards UA at ∼1 s, wide linear range from 0.2 nM to 0.2 mM and the low detect limit at 0.2 nM. The results point out an avenue to design electronic devicemore » as miniaturized lab-on-chip device for high sensitive and specific in biomedical and clinical diagnosis applications.« less

Rational design of engineered microbial cell surface multi-enzyme co-display system for sustainable NADH regeneration from low-cost biomass.

PubMed

Han, Lei; Liang, Bo; Song, Jianxia

2018-02-01

As an important cofactor, NADH is essential for most redox reactions and biofuel cells. However, supply of exogenous NADH is challenged, due to the low production efficiency and high cost of NADH regeneration system, as well as low stability of NADH. Here, we constructed a novel cell surface multi-enzyme co-display system with ratio- and space-controllable manner as exogenous NADH regeneration system for the sustainable NADH production from low-cost biomass. Dockerin-fused glucoamylase (GA) and glucose dehydrogenase (GDH) were expressed and assembled on the engineered bacterial surfaces, which displayed protein scaffolds with various combinations of different cohesins. When the ratio of GA and GDH was 3:1, the NADH production rate of the whole-cell biocatalyst reached the highest level using starch as substrate, which was three times higher than that of mixture of free enzymes, indicating that the highly ordered spatial organization of enzymes would promote reactions, due to the ratio of enzymes and proximity effect. To confirm performance of the established NADH regeneration system, the highly efficient synthesis of L-lactic acid (L-LA) was conducted by the system and the yield of L-LA (16 g/L) was twice higher than that of the mixture of free enzymes. The multi-enzyme co-display system showed good stability in the cyclic utilization. In conclusion, the novel sustainable NADH system would provide a cost-effective strategy to regenerate cofactor from low-cost biomass.

Endothelial C-Type Natriuretic Peptide Acts on Pericytes to Regulate Microcirculatory Flow and Blood Pressure.

PubMed

Špiranec, Katarina; Chen, Wen; Werner, Franziska; Nikolaev, Viacheslav O; Naruke, Takashi; Koch, Franziska; Werner, Andrea; Eder-Negrin, Petra; Diéguez-Hurtado, Rodrigo; Adams, Ralf H; Baba, Hideo A; Schmidt, Hannes; Schuh, Kai; Skryabin, Boris V; Movahedi, Kiavash; Schweda, Frank; Kuhn, Michaela

2018-04-06

Background -Peripheral vascular resistance has a major impact on arterial blood pressure levels. Endothelial C-type natriuretic peptide (CNP) participates in the local regulation of vascular tone but the target cells remain controversial. The cGMP-producing guanylyl cyclase-B (GC-B) receptor for CNP is expressed in vascular smooth muscle cells (VSMC). However, whereas endothelial cell-specific CNP knockout mice are hypertensive, mice with deletion of GC-B in VSMC have unaltered blood pressure. Methods -We analyzed whether the vasodilating response to CNP changes along the vascular tree, i.e. whether the GC-B receptor is expressed in microvascular types of cells. Mice with a floxed GC-B ( Npr2 ) gene were interbred with Tie2-Cre or PDGF-Rβ-Cre ERT2 lines to develop mice lacking GC-B in endothelial cells or in precapillary arteriolar SMC and capillary pericytes. Intravital microscopy, (non)invasive hemodynamics, fluorescence energy transfer studies of pericyte's cAMP levels in situ and renal physiology were combined to dissect whether and how CNP/GC-B/cGMP signaling modulates microcirculatory tone and blood pressure. Results -Intravital microscopy studies revealed that the vasodilatatory effect of CNP increases towards small-diameter arterioles and capillaries. Consistently, CNP did not prevent endothelin-1-induced acute constrictions of proximal arterioles but fully reversed endothelin effects in precapillary arterioles and capillaries. Here, the GC-B receptor is expressed both in endothelial and mural cells, i.e. in pericytes. Notably, the vasodilatatory effects of CNP were preserved in mice with endothelial GC-B deletion but abolished in mice lacking GC-B in microcirculatory SMC and pericytes. CNP, via GC-B/cGMP signaling modulates two signaling cascades in pericytes: it activates cGMP-dependent protein kinase I to phosphorylate downstream targets such as the cytoskeleton-associated vasodilator activated phosphoprotein; and it inhibits phosphodiesterase 3A

Adherent and Invasive Escherichia coli Is Associated with Granulomatous Colitis in Boxer Dogs

PubMed Central

Simpson, Kenneth W.; Dogan, Belgin; Rishniw, Mark; Goldstein, Richard E.; Klaessig, Suzanne; McDonough, Patrick L.; German, Alex J.; Yates, Robin M.; Russell, David G.; Johnson, Susan E.; Berg, Douglas E.; Harel, Josee; Bruant, Guillaume; McDonough, Sean P.; Schukken, Ynte H.

2006-01-01

The mucosa-associated microflora is increasingly considered to play a pivotal role in the pathogenesis of inflammatory bowel disease. This study explored the possibility that an abnormal mucosal flora is involved in the etiopathogenesis of granulomatous colitis of Boxer dogs (GCB). Colonic biopsy samples from affected dogs (n = 13) and controls (n = 38) were examined by fluorescent in situ hybridization (FISH) with a eubacterial 16S rRNA probe. Culture, 16S ribosomal DNA sequencing, and histochemistry were used to guide subsequent FISH. GCB-associated Escherichia coli isolates were evaluated for their ability to invade and persist in cultured epithelial cells and macrophages as well as for serotype, phylogenetic group, genome size, overall genotype, and presence of virulence genes. Intramucosal gram-negative coccobacilli were present in 100% of GCB samples but not controls. Invasive bacteria hybridized with FISH probes to E. coli. Three of four GCB-associated E. coli isolates adhered to, invaded, and replicated within cultured epithelial cells. Invasion triggered a “splash”-type response, was decreased by cytochalasin D, genistein, colchicine, and wortmannin, and paralleled the behavior of the Crohn's disease-associated strain E. coli LF 82. GCB E. coli and LF 82 were diverse in serotype and overall genotype but similar in phylogeny (B2 and D), in virulence gene profiles (fyuA, irp1, irp2, chuA, fepC, ibeA, kpsMII, iss), in having a larger genome size than commensal E. coli, and in the presence of novel multilocus sequence types. We conclude that GCB is associated with selective intramucosal colonization by E. coli. E. coli strains associated with GCB and Crohn's disease have an adherent and invasive phenotype and novel multilocus sequence types and resemble E. coli associated with extraintestinal disease in phylogeny and virulence gene profile. PMID:16861666

Quantitative Systems Pharmacology Modeling of Acid Sphingomyelinase Deficiency and the Enzyme Replacement Therapy Olipudase Alfa Is an Innovative Tool for Linking Pathophysiology and Pharmacology.

PubMed

Kaddi, Chanchala D; Niesner, Bradley; Baek, Rena; Jasper, Paul; Pappas, John; Tolsma, John; Li, Jing; van Rijn, Zachary; Tao, Mengdi; Ortemann-Renon, Catherine; Easton, Rachael; Tan, Sharon; Puga, Ana Cristina; Schuchman, Edward H; Barrett, Jeffrey S; Azer, Karim

2018-06-19

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder with heterogeneous clinical manifestations, including hepatosplenomegaly and infiltrative pulmonary disease, and is associated with significant morbidity and mortality. Olipudase alfa (recombinant human acid sphingomyelinase) is an enzyme replacement therapy under development for the non-neurological manifestations of ASMD. We present a quantitative systems pharmacology (QSP) model supporting the clinical development of olipudase alfa. The model is multiscale and mechanistic, linking the enzymatic deficiency driving the disease to molecular-level, cellular-level, and organ-level effects. Model development was informed by natural history, and preclinical and clinical studies. By considering patient-specific pharmacokinetic (PK) profiles and indicators of disease severity, the model describes pharmacodynamic (PD) and clinical end points for individual patients. The ASMD QSP model provides a platform for quantitatively assessing systemic pharmacological effects in adult and pediatric patients, and explaining variability within and across these patient populations, thereby supporting the extrapolation of treatment response from adults to pediatrics. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

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

PubMed

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.

Carrier quenching in InGaP/GaAs double heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wells, Nathan P., E-mail: nathan.p.wells@aero.org; Driskell, Travis U.; Hudson, Andrew I.

2015-08-14

Photoluminescence measurements on a series of GaAs double heterostructures demonstrate a rapid quenching of carriers in the GaAs layer at irradiance levels below 0.1 W/cm{sup 2} in samples with a GaAs-on-InGaP interface. These results indicate the existence of non-radiative defect centers at or near the GaAs-on-InGaP interface, consistent with previous reports showing the intermixing of In and P when free As impinges on the InGaP surface during growth. At low irradiance, these defect centers can lead to sub-ns carrier lifetimes. The defect centers involved in the rapid carrier quenching can be saturated at higher irradiance levels and allow carrier lifetimes tomore » reach hundreds of nanoseconds. To our knowledge, this is the first report of a nearly three orders of magnitude decrease in carrier lifetime at low irradiance in a simple double heterostructure. Carrier quenching occurs at irradiance levels near the integrated Air Mass Zero (AM0) and Air Mass 1.5 (AM1.5) solar irradiance. Additionally, a lower energy photoluminescence band is observed both at room and cryogenic temperatures. The temperature and time dependence of the lower energy luminescence is consistent with the presence of an unintentional InGaAs or InGaAsP quantum well that forms due to compositional mixing at the GaAs-on-InGaP interface. Our results are of general interest to the photovoltaic community as InGaP is commonly used as a window layer in GaAs based solar cells.« less

Intra-articular Enzyme Replacement Therapy with rhIDUA is Safe, Well-Tolerated, and Reduces Articular GAG Storage in the Canine Model of Mucopolysaccharidosis Type I

PubMed Central

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

2014-01-01

Background 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. Methods Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for six 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 one month following the final injection. Results 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 was 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

Mechanism of internal browning of pineapple: The role of gibberellins catabolism gene (AcGA2ox) and GAs

PubMed Central

Zhang, Qin; Rao, Xiuwen; Zhang, Lubin; He, Congcong; Yang, Fang; Zhu, Shijiang

2016-01-01

Internal browning (IB), a physiological disorder (PD) that causes severe losses in harvested pineapple, can be induced by exogenous gibberellins (GAs). Over the years, studies have focused on roles of Gibberellin 2-oxidase (GA2oxs), the major GAs catabolic enzyme in plants, in the regulation of changes in morphology or biomass. However, whether GA2oxs could regulate PD has not been reported. Here, a full-length AcGA2ox cDNA was isolated from pineapple, with the putative protein sharing 23.59% to 72.92% identity with GA2oxs from five other plants. Pineapples stored at 5 °C stayed intact, while those stored at 20 °C showed severe IB. Storage at 5 °C enhanced AcGA2ox expression and decreased levels of a GAs (GA4) ‘compared with storage at 20 °C. However, at 20 °C, exogenous application of abscisic acid (ABA) significantly suppressed IB. ABA simultaneously upregulated AcGA2ox and reduced GA4. Ectopic expression of AcGA2ox in Arabidopsis resulted in reduced GA4, lower seed germination, and shorter hypocotyls and roots, all of which were restored by exogenous GA4/7. Moreover, in pineapple, GA4/7 upregulated polyphenol oxidase, while storage at 5 °C and ABA downregulated it. These results strongly suggest the involvement of AcGA2ox in regulation of GAs levels and a role of AcGA2ox in regulating IB. PMID:27982026

Silencing C19-GA 2-oxidases induces parthenocarpic development and inhibits lateral branching in tomato plants

PubMed Central

Martínez-Bello, Liliam; Moritz, Thomas; López-Díaz, Isabel

2015-01-01

Gibberellins (GAs) are phytohormones that regulate a wide range of developmental processes in plants. Levels of active GAs are regulated by biosynthetic and catabolic enzymes like the GA 2-oxidases (GA2oxs). In tomato (Solanum lycopersicum L.) C19 GA2oxs are encoded by a small multigenic family of five members with some degree of redundancy. In order to investigate their roles in tomato, the silencing of all five genes in transgenic plants was induced. A significant increase in active GA4 content was found in the ovaries of transgenic plants. In addition, the transgenic unfertilized ovaries were much bigger than wild-type ovaries (about 30 times) and a certain proportion (5–37%) were able to develop parthenocarpically. Among the GA2ox family, genes GA2ox1 and -2 seem to be the most relevant for this phenotype since their expression was induced in unfertilized ovaries and repressed in developing fruits, inversely correlating with ovary growth. Interestingly, transgenic lines exhibited a significant inhibition of branching and a higher content of active GA4 in axillary buds. This phenotype was reverted, in transgenic plants, by the application of paclobutrazol, a GA biosynthesis inhibitor, suggesting a role for GAs as repressors of branching. In summary, this work demonstrates that GA 2-oxidases regulate gibberellin levels in ovaries and axillary buds of tomato plants and their silencing is responsible for parthenocarpic fruit growth and branching inhibition. PMID:26093022

Internal stress-assisted epitaxial lift-off process for flexible thin film (In)GaAs solar cells on metal foil

NASA Astrophysics Data System (ADS)

Kim, Youngjo; Kim, Kangho; Jung, Sang Hyun; Kim, Chang Zoo; Shin, Hyun-Beom; Choi, JeHyuk; Kang, Ho Kwan

2017-12-01

Flexible thin film (In)GaAs solar cells are grown by metalorganic chemical vapor deposition on GaAs substrates and transferred to 30 μm thick Au foil by internal stress-assisted epitaxial lift-off processes. The internal stress is induced by replacing the solar cell epi-layers from GaAs to In0.015Ga0.985As, which has a slightly larger lattice constant. The compressive strained layer thickness was varied from 0 to 4.5 μm to investigate the influence of the internal stress on the epitaxial lift-off time. The etching time in the epitaxial lift-off process was reduced from 36 to 4 h by employing a GaAs/In0.015Ga0.985As heterojunction structure that has a compressive film stress of -59.0 MPa. We found that the partially strained epi-structure contributed to the much faster lateral etching rate with spontaneous bending. Although an efficiency degradation problem occurred in the strained solar cell, it was solved by optimizing the epitaxial growth conditions.

InGaAsN/GaAs heterojunction for multi-junction solar cells

DOEpatents

Kurtz, Steven R.; Allerman, Andrew A.; Klem, John F.; Jones, Eric D.

2001-01-01

An InGaAsN/GaAs semiconductor p-n heterojunction is disclosed for use in forming a 0.95-1.2 eV bandgap photodetector with application for use in high-efficiency multi-junction solar cells. The InGaAsN/GaAs p-n heterojunction is formed by epitaxially growing on a gallium arsenide (GaAs) or germanium (Ge) substrate an n-type indium gallium arsenide nitride (InGaAsN) layer having a semiconductor alloy composition In.sub.x Ga.sub.1-x As.sub.1-y N.sub.y with 0GaAs layer, with the InGaAsN and GaAs layers being lattice-matched to the substrate. The InGaAsN/GaAs p-n heterojunction can be epitaxially grown by either molecular beam epitaxy (MBE) or metalorganic chemical vapor deposition (MOCVD). The InGaAsN/GaAs p-n heterojunction provides a high open-circuit voltage of up to 0.62 volts and an internal quantum efficiency of >70%.

Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes.

PubMed

Hobbs, Paul M; Johnson, William G; Graham, David Y

2016-08-06

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endoscopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain.

Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes

PubMed Central

Hobbs, Paul M; Johnson, William G; Graham, David Y

2016-01-01

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endoscopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain. PMID:27602238

InGaN/GaN multilayer quantum dots yellow-green light-emitting diode with optimized GaN barriers.

PubMed

Lv, Wenbin; Wang, Lai; Wang, Jiaxing; Hao, Zhibiao; Luo, Yi

2012-11-07

InGaN/GaN multilayer quantum dot (QD) structure is a potential type of active regions for yellow-green light-emitting diodes (LEDs). The surface morphologies and crystalline quality of GaN barriers are critical to the uniformity of InGaN QD layers. While GaN barriers were grown in multi-QD layers, we used improved growth parameters by increasing the growth temperature and switching the carrier gas from N2 to H2 in the metal organic vapor phase epitaxy. As a result, a 10-layer InGaN/GaN QD LED is demonstrated successfully. The transmission electron microscopy image shows the uniform multilayer InGaN QDs clearly. As the injection current increases from 5 to 50 mA, the electroluminescence peak wavelength shifts from 574 to 537 nm.

Growth of β-Ga2O3 and GaN nanowires on GaN for photoelectrochemical hydrogen generation.

PubMed

Hwang, Jih-Shang; Liu, Tai-Yan; Chattopadhyay, Surjit; Hsu, Geng-Ming; Basilio, Antonio M; Chen, Han-Wei; Hsu, Yu-Kuei; Tu, Wen-Hsun; Lin, Yan-Gu; Chen, Kuei-Hsien; Li, Chien-Cheng; Wang, Sheng-Bo; Chen, Hsin-Yi; Chen, Li-Chyong

2013-02-08

Enhanced photoelectrochemical (PEC) performances of Ga(2)O(3) and GaN nanowires (NWs) grown in situ from GaN were demonstrated. The PEC conversion efficiencies of Ga(2)O(3) and GaN NWs have been shown to be 0.906% and 1.09% respectively, in contrast to their 0.581% GaN thin film counterpart under similar experimental conditions. A low crystallinity buffer layer between the grown NWs and the substrate was found to be detrimental to the PEC performance, but the layer can be avoided at suitable growth conditions. A band bending at the surface of the GaN NWs generates an electric field that drives the photogenerated electrons and holes away from each other, preventing recombination, and was found to be responsible for the enhanced PEC performance. The enhanced PEC efficiency of the Ga(2)O(3) NWs is aided by the optical absorption through a defect band centered 3.3 eV above the valence band of Ga(2)O(3). These findings are believed to have opened up possibilities for enabling visible absorption, either by tailoring ion doping into wide bandgap Ga(2)O(3) NWs, or by incorporation of indium to form InGaN NWs.

Red-emitting Ga/As,P///In,Ga/P heterojunction lasers

NASA Technical Reports Server (NTRS)

Kressel, H.; Nuese, C. J.; Olsen, G. H.

1978-01-01

The paper describes in detail the properties of vapor-grown double-heterojunction lasers of Ga(As,P)/(In,Ga)P with room-temperature threshold current densities as low as 3400 A/sq cm at 7000 A and 6600 A/sq cm at 6800 A. These thresholds are three to eight times smaller than those of (Al,Ga)As lasers in this wavelength range due to the shorter-wavelength direct-indirect transition in Ga(As,P). The optical and electrical characteristics of the Ga(As,P)/(In,Ga)P lasers are found to be similar to those of (Al,Ga)As, with fundamental transverse-mode operation to 70 C, and spontaneous carrier lifetimes between 5 and 8 nsec typically observed at low current densities.

Unexpected promotion of PCDD/F formation by enzyme-aided Cl2 bleaching in non-wood pulp and paper mill.

PubMed

Fang, Liping; Zheng, Minghui; Liu, Guorui; Zhao, Yuyang; Liu, Wenbin; Huang, Linyan; Guo, Li

2017-02-01

Enzyme-aided Cl 2 bleaching is widely considered as promising replacements for conventional Cl 2 bleaching in wood pulp and paper mills. However, the effects of using enzyme-aided bleaching on the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the non-wood pulp and paper mills are unclear. A field study was performed to investigate PCDD/F formation when enzyme-aided Cl 2 bleaching was used to replace conventional Cl 2 bleaching in non-wood pulp and paper mills. Unexpectedly, the PCDD/F toxic equivalents (TEQs) in solid samples were higher when using enzyme-aided bleaching (0.49-5.4 pg TEQ/g) than that using conventional Cl 2 bleaching (0.15-2.44 pg TEQ/g). Large amounts of octachlorodibenzo-p-dioxin were formed during the enzyme-aided bleaching process. This could have been because enzyme strongly promoted the release of organic molecules bound to lignin and thus accelerated the formation of octachlorodibenzo-p-dioxin through organic molecular precursors. Although enzyme-aided Cl 2 bleaching was previously considered to be efficient for reducing PCDD/F releases and to be the best available technologies and best environmental practices for wood pulp and paper mills, the results obtained in this study suggested the necessity and urgency to evaluate the suitability of enzyme-aided Cl 2 bleaching for non-wood pulp and paper mills that intensively practiced in developing countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Magnetometory Measurement of AlGaN/GaN 2DEG

NASA Astrophysics Data System (ADS)

Tsubaki, K.; Maeda, N.; Saitoh, T.; Kobayashi, N.

2004-03-01

AlGaN/GaN heterostructure devices have been attracting much attention because of their potential for high-performance microwave applications. Therefore, the electronic properties of a 2DEG in AlGaN/GaN heterostructures have recently been discussed. In this paper, we performed the magnetometory measurement of AlGaN/GaN 2DEG at low temperature. The AlGaN/GaN heterostructures were grown by low-pressure metal-organic chemical vapour phase epitaxy on (0001) SiC substrate using AlN buffers. The electron mobility and electron concentration at 4.2 K are 9,540 cm^2/Vs and 6.6 × 10^12 cm-2, respectively. When the temperature is lower than 4.5 K the hysteresis of magnetometric data is observed near zero magnetic field. At the temperature larger than 4.5 K, the hysteresis of magnetometric data disappears and the slope of magnetometric data with respect to magnetic field becomes lower as obeying Currie-Weiss law. In general the hysteresis and Currie-Weiss law behavior in magnetometric data imply the possibility of the ferromagnetism, but the conformation of the ferromagnetism of AlGaN/GaN heterostructure is still difficult and the detailed physical mechanism is still unclear.

Internal quantum efficiency in yellow-amber light emitting AlGaN-InGaN-GaN heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ngo, Thi Huong; Gil, Bernard; Valvin, Pierre

2015-09-21

We determine the internal quantum efficiency of strain-balanced AlGaN-InGaN-GaN hetero-structures designed for yellow-amber light emission, by using a recent model based on the kinetics of the photoluminescence decay initiated by Iwata et al. [J. Appl. Phys. 117, 075701 (2015)]. Our results indicate that low temperature internal quantum efficiencies sit in the 50% range and we measure that adding an AlGaN layer increases the internal quantum efficiency from 50% up to 57% with respect to the GaN-InGaN case. More dramatic, it almost doubles from 2.5% up to 4.3% at room temperature.

Asymmetric quantum-well structures for AlGaN/GaN/AlGaN resonant tunneling diodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Lin'an, E-mail: layang@xidian.edu.cn; Li, Yue; Wang, Ying

Asymmetric quantum-well (QW) structures including the asymmetric potential-barrier and the asymmetric potential-well are proposed for AlGaN/GaN/AlGaN resonant tunneling diodes (RTDs). Theoretical investigation gives that an appropriate decrease in Al composition and thickness for emitter barrier as well as an appropriate increase of both for collector barrier can evidently improve the negative-differential-resistance characteristic of RTD. Numerical simulation shows that RTD with a 1.5-nm-thick GaN well sandwiched by a 1.3-nm-thick Al{sub 0.15}Ga{sub 0.85}N emitter barrier and a 1.7-nm-thick Al{sub 0.25}Ga{sub 0.75}N collector barrier can yield the I-V characteristic having the peak current (Ip) and the peak-to-valley current ratio (PVCR) of 0.39 A andmore » 3.6, respectively, about double that of RTD with a 1.5-nm-thick Al{sub 0.2}Ga{sub 0.8}N for both barriers. It is also found that an introduction of InGaN sub-QW into the diode can change the tunneling mode and achieve higher transmission coefficient of electron. The simulation demonstrates that RTD with a 2.8-nm-thick In{sub 0.03}Ga{sub 0.97}N sub-well in front of a 2.0-nm-thick GaN main-well can exhibit the I-V characteristic having Ip and PVCR of 0.07 A and 11.6, about 7 times and double the value of RTD without sub-QW, respectively. The purpose of improving the structure of GaN-based QW is to solve apparent contradiction between the device structure and the device manufacturability of new generation RTDs for sub-millimeter and terahertz applications.« less

Process dependency on threshold voltage of GaN MOSFET on AlGaN/GaN heterostructure

NASA Astrophysics Data System (ADS)

Wang, Qingpeng; Jiang, Ying; Miyashita, Takahiro; Motoyama, Shin-ichi; Li, Liuan; Wang, Dejun; Ohno, Yasuo; Ao, Jin-Ping

2014-09-01

GaN metal-oxide-semiconductor field-effect transistors (MOSFETs) with recessed gate on AlGaN/GaN heterostructure are reported in which the drain and source ohmic contacts were fabricated on the AlGaN/GaN heterostructure and the electron channel was formed on the GaN buffer layer by removing the AlGaN barrier layer. Negative threshold voltages were commonly observed in all devices. To investigate the reasons of the negative threshold voltages, different oxide thickness, etching gas and bias power of inductively-coupled plasma (ICP) system were utilized in the fabrication process of the GaN MOSFETs. It is found that positive charges of around 1 × 1012 q/cm2 exist near the interface at the just threshold condition in both silane- and tetraethylorthosilicate (TEOS)-based devices. It is also found that the threshold voltages do not obviously change with the different etching gas (SiCl4, BCl3 and two-step etching of SiCl4/Cl2) at the same ICP bias power level (20-25 W) and will become deeper when higher bias power is used in the dry recess process which may be related to the much serious ion bombardment damage. Furthermore, X-ray photoelectron spectroscopy (XPS) experiments were done to investigate the surface conditions. It is found that N 1s peaks become lower with higher bias power of the dry etching process. Also, silicon contamination was found and could be removed by HNO3/HF solution. It indicates that the nitrogen vacancies are mainly responsible for the negative threshold voltages rather than the silicon contamination. It demonstrates that optimization of the ICP recess conditions and improvement of the surface condition are still necessary to realize enhancement-mode GaN MOSFETs on AlGaN/GaN heterostructure.

White emission from non-planar InGaN/GaN MQW LEDs grown on GaN template with truncated hexagonal pyramids.

PubMed

Lee, Ming-Lun; Yeh, Yu-Hsiang; Tu, Shang-Ju; Chen, P C; Lai, Wei-Chih; Sheu, Jinn-Kong

2015-04-06

Non-planar InGaN/GaN multiple quantum well (MQW) structures are grown on a GaN template with truncated hexagonal pyramids (THPs) featuring c-plane and r-plane surfaces. The THP array is formed by the regrowth of the GaN layer on a selective-area Si-implanted GaN template. Transmission electron microscopy shows that the InGaN/GaN epitaxial layers regrown on the THPs exhibit different growth rates and indium compositions of the InGaN layer between the c-plane and r-plane surfaces. Consequently, InGaN/GaN MQW light-emitting diodes grown on the GaN THP array emit multiple wavelengths approaching near white light.

InGaN/GaN multilayer quantum dots yellow-green light-emitting diode with optimized GaN barriers

PubMed Central

2012-01-01

InGaN/GaN multilayer quantum dot (QD) structure is a potential type of active regions for yellow-green light-emitting diodes (LEDs). The surface morphologies and crystalline quality of GaN barriers are critical to the uniformity of InGaN QD layers. While GaN barriers were grown in multi-QD layers, we used improved growth parameters by increasing the growth temperature and switching the carrier gas from N2 to H2 in the metal organic vapor phase epitaxy. As a result, a 10-layer InGaN/GaN QD LED is demonstrated successfully. The transmission electron microscopy image shows the uniform multilayer InGaN QDs clearly. As the injection current increases from 5 to 50 mA, the electroluminescence peak wavelength shifts from 574 to 537 nm. PMID:23134721

Improvement of Surge Protection by Using an AlGaN/GaN-Based Metal-Semiconductor-Metal Two-Dimensional Electron Gas Varactor

NASA Astrophysics Data System (ADS)

Ferng, Yi-Cherng; Chang, Liann-Be; Das, Atanu; Lin, Ching-Chi; Cheng, Chun-Yu; Kuei, Ping-Yu; Chow, Lee

2012-12-01

In this paper, a varactor with metal-semiconductor-metal diodes on top of the (NH4)2S/P2S5-treated AlGaN/GaN two-dimensional electron gas epitaxial structure (MSM-2DEG) is proposed to the surge protection for the first time. The sulfur-treated MSM-2DEG varactor properties, including current-voltage (I-V), capacitance-voltage (C-V), and frequency response of the proposed surge protection circuit, are presented. To verify its capability of surge protection, we replace the metal oxide varistor (MOV) and resistor (R) in a state-of-the-art surge protection circuit with the sulfur-treated MSM-2DEG varactor under the application conditions of system-level surge tests. The measured results show that the proposed surge protection circuit, consisted of a gas discharge arrester (GDA) and a sulfur-treated MSM-2DEG varactor, can suppress an electromagnetic pulse (EMP) voltage of 4000 to 360 V, a reduction of 91%, whereas suppression is to 1780 V, a reduction of 55%, when using only a GDA.

Inhibition and kinetic studies of cellulose- and hemicellulose-degrading enzymes of Ganoderma boninense by naturally occurring phenolic compounds.

PubMed

Surendran, A; Siddiqui, Y; Ali, N S; Manickam, S

2018-06-01

Ganoderma sp, the causal pathogen of the basal stem rot (BSR) disease of oil palm, secretes extracellular hydrolytic enzymes. These play an important role in the pathogenesis of BSR by nourishing the pathogen through the digestion of cellulose and hemicellulose of the host tissue. Active suppression of hydrolytic enzymes secreted by Ganoderma boninense by various naturally occurring phenolic compounds and estimation of their efficacy on pathogen suppression is focused in this study. Ten naturally occurring phenolic compounds were assessed for their inhibitory effect on the hydrolytic enzymes of G. boninense. The enzyme kinetics (V max and K m ) and the stability of the hydrolytic enzymes were also characterized. The selected compounds had shown inhibitory effect at various concentrations. Two types of inhibitions namely uncompetitive and noncompetitive were observed in the presence of phenolic compounds. Among all the phenolic compounds tested, benzoic acid was the most effective compound suppressive to the growth and production of hydrolytic enzymes secreted by G. boninense. The phenolic compounds as inhibitory agents can be a better replacement for the metal ions which are known as conventional inhibitors till date. The three hydrolytic enzymes were stable in a wide range of pH and temperature. These findings highlight the efficacy of the applications of phenolic compounds to control Ganoderma. The study has proved a replacement for chemical controls of G. boninense with naturally occurring phenolic compounds. © 2018 The Society for Applied Microbiology.

Effect of GA3 treatment on seed development and seed-related gene expression in grape.

PubMed

Cheng, Chenxia; Xu, Xiaozhao; Singer, Stacy D; Li, Jun; Zhang, Hongjing; Gao, Min; Wang, Li; Song, Junyang; Wang, Xiping

2013-01-01

The phytohormone gibberellic acid (GA3) is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes. In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars ('Kyoho' and 'Red Globe'), along with a seedless cultivar ('Thompson Seedless'), following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF), both 'Kyoho' and 'Red Globe' seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls. Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development.

Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis.

PubMed

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.

Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis

PubMed Central

Elahi, Maqsood M.; Choi, Charles H.; Konda, Subbareddy

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. PMID:25552810

GaAs quantum dots in a GaP nanowire photodetector

NASA Astrophysics Data System (ADS)

Kuyanov, P.; McNamee, S. A.; LaPierre, R. R.

2018-03-01

We report the structural, optical and electrical properties of GaAs quantum dots (QDs) embedded along GaP nanowires. The GaP nanowires contained p-i-n junctions with 15 consecutively grown GaAs QDs within the intrinsic region. The nanowires were grown by molecular beam epitaxy using the self-assisted vapor-liquid-solid process. The crystal structure of the NWs alternated between twinned ZB and WZ as the composition along the NW alternated between the GaP barriers and the GaAs QDs, respectively, leading to a polytypic structure with a periodic modulation of the NW sidewall facets. Photodetector devices containing QDs showed absorption beyond the bandgap of GaP in comparison to nanowires without QDs. Voltage-dependent measurements suggested a field emission process of carriers from the QDs.

Luminescence and luminescence quenching in Gd3(Ga,Al)5O12 scintillators doped with Ce3+.

PubMed

Ogiegło, Joanna M; Katelnikovas, Arturas; Zych, Aleksander; Jüstel, Thomas; Meijerink, Andries; Ronda, Cees R

2013-03-28

The optical properties of gadolinium gallium aluminum garnet, Gd3(Ga,Al)5O12, doped with Ce(3+) are investigated as a function of the Ga/Al ratio, aimed at an improved understanding of the energy flow and luminescence quenching in these materials. A decrease of both the crystal field strength and band gap with increasing content of Ga(3+) is observed and explained by the geometrical influence of Ga(3+) on the crystal field splitting of the 5d level in line with theoretical work of Muñoz-García et al. ( uñoz-García, A. B.; Seijo, L. Phys. Rev. B 2010, 82, 184118 ). Thermal quenching results in shorter decay times as well as reduced emission intensities for all samples in the temperature range from 100 to 500 K. An activation energy for emission quenching is calculated from the data. The band gap of the host is measured upon Ga substitution and the decrease in band gap is related to Ga(3+) substitution into tetrahedral sites after all octahedral sites are occupied in the garnet material. Based on the change in band gap and crystal field splitting, band diagrams can be constructed explaining the low thermal quenching temperatures in the samples with high Ga content. The highest luminescence intensity is found for Gd3(Ga,Al)5O12 with 40% of Al(3+) replaced by Ga(3+).

Physical and electrical characterizations of AlGaN/GaN MOS gate stacks with AlGaN surface oxidation treatment

NASA Astrophysics Data System (ADS)

Yamada, Takahiro; Watanabe, Kenta; Nozaki, Mikito; Shih, Hong-An; Nakazawa, Satoshi; Anda, Yoshiharu; Ueda, Tetsuzo; Yoshigoe, Akitaka; Hosoi, Takuji; Shimura, Takayoshi; Watanabe, Heiji

2018-06-01

The impacts of inserting ultrathin oxides into insulator/AlGaN interfaces on their electrical properties were investigated to develop advanced AlGaN/GaN metal–oxide–semiconductor (MOS) gate stacks. For this purpose, the initial thermal oxidation of AlGaN surfaces in oxygen ambient was systematically studied by synchrotron radiation X-ray photoelectron spectroscopy (SR-XPS) and atomic force microscopy (AFM). Our physical characterizations revealed that, when compared with GaN surfaces, aluminum addition promotes the initial oxidation of AlGaN surfaces at temperatures of around 400 °C, followed by smaller grain growth above 850 °C. Electrical measurements of AlGaN/GaN MOS capacitors also showed that, although excessive oxidation treatment of AlGaN surfaces over around 700 °C has an adverse effect, interface passivation with the initial oxidation of the AlGaN surfaces at temperatures ranging from 400 to 500 °C was proven to be beneficial for fabricating high-quality AlGaN/GaN MOS gate stacks.

Linear and nonlinear optical absorption coefficients and refractive index changes in GaN/Al{sub x}Ga{sub (1−x)}N double quantum wells operating at 1.55 μm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dakhlaoui, Hassen

2015-04-07

In the present paper, the linear and nonlinear optical absorption coefficients and refractive index changes between the ground and the first excited states in double GaN/Al{sub x}Ga{sub (1−x)}N quantum wells are studied theoretically. The electronic energy levels and their corresponding wave functions are obtained by solving Schrödinger-Poisson equations self-consistently within the effective mass approximation. The obtained results show that the optical absorption coefficients and refractive index changes can be red- and blue-shifted through varying the left quantum well width and the aluminum concentration x{sub b2} of the central barrier, respectively. These structural parameters are found to present optimum values formore » carrying out the transition of 0.8 eV (1.55 μm). Furthermore, we show that the desired transition can also be achieved by replacing the GaN in the left quantum well with Al{sub y}Ga{sub (1−y)}N and by varying the aluminum concentration y{sub Al}. The obtained results give a new degree of freedom in optoelectronic device applications such as optical fiber telecommunications operating at (1.55 μm)« less

40 CFR 180.1098 - Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium Gibberellate...

Code of Federal Regulations, 2013 CFR

2013-07-01

... and GA4 + GA7), and Sodium or Potassium Gibberellate]; exemption from the requirement of a tolerance... Tolerances § 180.1098 Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium... potassium gibberellate] in or on all food commodities when used as plant regulators on plants, seeds, or...

40 CFR 180.1098 - Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium Gibberellate...

Code of Federal Regulations, 2011 CFR

2011-07-01

... and GA4 + GA7), and Sodium or Potassium Gibberellate]; exemption from the requirement of a tolerance... Tolerances § 180.1098 Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium... potassium gibberellate] in or on all food commodities when used as plant regulators on plants, seeds, or...

40 CFR 180.1098 - Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium Gibberellate...

Code of Federal Regulations, 2014 CFR

2014-07-01

... and GA4 + GA7), and Sodium or Potassium Gibberellate]; exemption from the requirement of a tolerance... Tolerances § 180.1098 Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium... potassium gibberellate] in or on all food commodities when used as plant regulators on plants, seeds, or...

40 CFR 180.1098 - Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium Gibberellate...

Code of Federal Regulations, 2012 CFR

2012-07-01

... and GA4 + GA7), and Sodium or Potassium Gibberellate]; exemption from the requirement of a tolerance... Tolerances § 180.1098 Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium... potassium gibberellate] in or on all food commodities when used as plant regulators on plants, seeds, or...

40 CFR 180.1098 - Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium Gibberellate...

Code of Federal Regulations, 2010 CFR

2010-07-01

... and GA4 + GA7), and Sodium or Potassium Gibberellate]; exemption from the requirement of a tolerance... Tolerances § 180.1098 Gibberellins [Gibberellic Acids (GA3 and GA4 + GA7), and Sodium or Potassium... potassium gibberellate] in or on all food commodities when used as plant regulators on plants, seeds, or...

Fine structure of Fe-Co-Ga and Fe-Cr-Ga alloys with low Ga content

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kleinerman, Nadezhda M., E-mail: kleinerman@imp.uran.ru; Serikov, Vadim V., E-mail: kleinerman@imp.uran.ru; Vershinin, Aleksandr V., E-mail: kleinerman@imp.uran.ru

2014-10-27

Investigation of Ga influence on the structure of Fe-Cr and Fe-Co alloys was performed with the use of {sup 57}Fe Mössbauer spectroscopy and X-ray diffraction methods. In the alloys of the Fe-Cr system, doping with Ga handicaps the decomposition of solid solutions, observed in the binary alloys, and increases its stability. In the alloys with Co, Ga also favors the uniformity of solid solutions. The analysis of Mössbauer experiments gives some grounds to conclude that if, owing to liquation, clusterization, or initial stages of phase separation, there exist regions enriched in iron, some amount of Ga atoms prefer to entermore » the nearest surroundings of iron atoms, thus forming binary Fe-Ga regions (or phases)« less

Replacing -CH2CH2- with -CONH- does not significantly change rates of charge transport through Ag(TS)-SAM//Ga2O3/EGaIn junctions.

PubMed

Thuo, Martin M; Reus, William F; Simeone, Felice C; Kim, Choongik; Schulz, Michael D; Yoon, Hyo Jae; Whitesides, George M

2012-07-04

This paper describes physical-organic studies of charge transport by tunneling through self-assembled monolayers (SAMs), based on systematic variations of the structure of the molecules constituting the SAM. Replacing a -CH(2)CH(2)- group with a -CONH- group changes the dipole moment and polarizability of a portion of the molecule and has, in principle, the potential to change the rate of charge transport through the SAM. In practice, this substitution produces no significant change in the rate of charge transport across junctions of the structure Ag(TS)-S(CH(2))(m)X(CH(2))(n)H//Ga(2)O(3)/EGaIn (TS = template stripped, X = -CH(2)CH(2)- or -CONH-, and EGaIn = eutectic alloy of gallium and indium). Incorporation of the amide group does, however, increase the yields of working (non-shorting) junctions (when compared to n-alkanethiolates of the same length). These results suggest that synthetic schemes that combine a thiol group on one end of a molecule with a group, R, to be tested, on the other (e.g., HS~CONH~R) using an amide-based coupling provide practical routes to molecules useful in studies of molecular electronics.

Ga flux dependence of Er-doped GaN luminescent thin films

NASA Astrophysics Data System (ADS)

Lee, D. S.; Steckl, A. J.

2002-02-01

Er-doped GaN thin films have been grown on (111) Si substrates with various Ga fluxes in a radio frequency plasma molecular beam epitaxy system. Visible photoluminescence (PL) and electroluminescence (EL) emission at 537/558 nm and infrared (IR) PL emission at 1.5 μm from GaN:Er films exhibited strong dependence on the Ga flux. Both visible and IR PL and visible EL increase with the Ga flux up to the stoichiometric growth condition, as determined by growth rate saturation. Beyond this condition, all luminescence levels abruptly dropped to the detection limit with increasing Ga flux. The Er concentration, measured by secondary ion mass spectroscopy and Rutherford backscattering, decreases with increasing Ga flux under N-rich growth conditions and remains constant above the stoichiometric growth condition. X-ray diffraction indicated that the crystalline quality of the GaN:Er film was improved with increasing Ga flux up to stoichiometric growth condition and then saturated. Er ions in the films grown under N-rich conditions appear much more optically active than those in the films grown under Ga-rich conditions.

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

PubMed Central

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

High Piezoelectric Conversion Properties of Axial InGaN/GaN Nanowires.

PubMed

Jegenyes, Nikoletta; Morassi, Martina; Chrétien, Pascal; Travers, Laurent; Lu, Lu; Julien, Francois H; Tchernycheva, Maria; Houzé, Frédéric; Gogneau, Noelle

2018-05-25

We demonstrate for the first time the efficient mechanical-electrical conversion properties of InGaN/GaN nanowires (NWs). Using an atomic force microscope equipped with a modified Resiscope module, we analyse the piezoelectric energy generation of GaN NWs and demonstrate an important enhancement when integrating in their volume a thick In-rich InGaN insertion. The piezoelectric response of InGaN/GaN NWs can be tuned as a function of the InGaN insertion thickness and position in the NW volume. The energy harvesting is favoured by the presence of a PtSi/GaN Schottky diode which allows to efficiently collect the piezo-charges generated by InGaN/GaN NWs. Average output voltages up to 330 ± 70 mV and a maximum value of 470 mV per NW has been measured for nanostructures integrating 70 nm-thick InGaN insertion capped with a thin GaN top layer. This latter value establishes an increase of about 35% of the piezo-conversion capacity in comparison with binary p-doped GaN NWs. Based on the measured output signals, we estimate that one layer of dense InGaN/GaN-based NW can generate a maximum output power density of about 3.3 W/cm². These results settle the new state-of-the-art for piezo-generation from GaN-based NWs and offer a promising perspective for extending the performances of the piezoelectric sources.

Study of GaN nanorods converted from β-Ga2O3

NASA Astrophysics Data System (ADS)

Li, Yuewen; Xiong, Zening; Zhang, Dongdong; Xiu, Xiangqian; Liu, Duo; Wang, Shuang; Hua, Xuemei; Xie, Zili; Tao, Tao; Liu, Bin; Chen, Peng; Zhang, Rong; Zheng, Youdou

2018-05-01

We report here high-quality β-Ga2O3 nanorods (NRs) grown on sapphire substrates by hydrothermal method. Ammoniating the β-Ga2O3 NRs results in strain-free wurtzite gallium nitride (GaN) NRs. It was shown by XRD and Raman spectroscopy that β-Ga2O3 was partially converted to GaN/β-Ga2O3 at 1000 °C and then completely converted to GaN NRs at 1050 °C, as confirmed by high-resolution transmission electron microscopy (HRTEM). There is no band-edge emission of β-Ga2O3 in the cathodoluminescence spectrum, and only a deep-level broad emission observed at 3.68-3.73 eV. The band edge emission (3.39 eV) of GaN NRs converted from β-Ga2O3 can also be observed.

Engineering of electric field distribution in GaN(cap)/AlGaN/GaN heterostructures: theoretical and experimental studies

NASA Astrophysics Data System (ADS)

Gladysiewicz, M.; Janicki, L.; Misiewicz, J.; Sobanska, M.; Klosek, K.; Zytkiewicz, Z. R.; Kudrawiec, R.

2016-09-01

Polarization engineering of GaN-based heterostructures opens a way to develop advanced transistor heterostructures, although measurement of the electric field in such heterostructures is not a simple task. In this work, contactless electroreflectance (CER) spectroscopy has been applied to measure the electric field in GaN-based heterostructures. For a set of GaN(d  =  0, 5, 15, and 30 nm)/AlGaN(20 nm)/GaN(buffer) heterostructures a decrease of electric field in the GaN(cap) layer from 0.66 MV cm-1 to 0.27 MV cm-1 and an increase of the electric field in the AlGaN layer from 0.57 MV cm-1 to 0.99 MV cm-1 have been observed with the increase in the GaN(cap) thickness from 5-30 nm. For a set of GaN(20 nm)/AlGaN(d  =  10, 20, 30, and 40 nm)/GaN(buffer) heterostructures a decrease of the electric field in the AlGaN layer from 1.77 MV cm-1 to 0.64 MV cm-1 and an increase of the electric field in the GaN layer from 0.57 MV cm-1 to 0.99 MV cm-1 were observed with the increase in the AlGaN thickness from 10-40 nm. To determine the distribution of the electric field in these heterostructures the Schrödinger and Poisson equations are solved in a self-consistent manner and matched with experimental data. It is shown that the built-in electric field in the GaN(cap) and AlGaN layers obtained from measurements does not reach values of electric field resulting only from polarization effects. The measured electric fields are smaller due to a screening of polarization effects by free carriers, which are inhomogeneously distributed across the heterostructure and accumulate at interfaces. The results clearly demonstrate that CER measurements supported by theoretical calculations are able to determine the electric field distribution in GaN-based heterostructures quantitatively, which is very important for polarization engineering in this material system.

Ultralow-voltage-drop GaN/InGaN/GaN tunnel junctions with 12% indium content

NASA Astrophysics Data System (ADS)

Akyol, Fatih; Zhang, Yuewei; Krishnamoorthy, Sriram; Rajan, Siddharth

2017-12-01

We report a combination of highly doped layers and polarization engineering that achieves highly efficient blue-transparent GaN/InGaN/GaN tunnel junctions (In content = 12%). NPN diode structures with a low voltage drop of 4.04 V at 5 kA/cm2 and a differential resistance of 6.51 × 10-5 Ω·cm2 at 3 kA/cm2 were obtained. The tunnel junction design with n++-GaN (Si: 5 × 1020 cm-3)/3 nm p++-In0.12Ga0.88N (Mg: 1.5 × 1020 cm-3)/p++-GaN (Mg: 5 × 1020 cm-3) showed the best device performance. Device simulations agree well with the experimentally determined optimal design. The combination of low In composition and high doping can facilitate lower tunneling resistance for blue-transparent light-emitting diodes.

White light emission of monolithic InGaN/GaN grown on morphology-controlled, nanostructured GaN templates.

PubMed

Song, Keun Man; Kim, Do-Hyun; Kim, Jong-Min; Cho, Chu-Young; Choi, Jehyuk; Kim, Kahee; Park, Jinsup; Kim, Hogyoug

2017-06-02

We demonstrated an InGaN/GaN-based, monolithic, white light-emitting diode (LED) without phosphors by using morphology-controlled active layers formed on multi-facet GaN templates containing polar and semipolar surfaces. The nanostructured surface morphology was controlled by changing the growth time, and distinct multiple photoluminescence peaks were observed at 360, 460, and 560 nm; these features were caused by InGaN/GaN-based multiple quantum wells (MQWs) on the nanostructured facets. The origin of each multi-peak was related to the different indium (In) compositions in the different planes of the quantum wells grown on the nanostructured GaN. The emitting units of MQWs in the LED structures were continuously connected, which is different from other GaN-based nanorod or nanowire LEDs. Therefore, the suggested structure had a larger active area. From the electroluminescence spectrum of the fabricated LED, monolithic white light emission with CIE color coordinates of x = 0.306 and y = 0.333 was achieved via multi-facet control combined with morphology control of the metal organic chemical vapor deposition-selective area growth of InGaN/GaN MQWs.

White light emission of monolithic InGaN/GaN grown on morphology-controlled, nanostructured GaN templates

NASA Astrophysics Data System (ADS)

Song, Keun Man; Kim, Do-Hyun; Kim, Jong-Min; Cho, Chu-Young; Choi, Jehyuk; Kim, Kahee; Park, Jinsup; Kim, Hogyoug

2017-06-01

We demonstrated an InGaN/GaN-based, monolithic, white light-emitting diode (LED) without phosphors by using morphology-controlled active layers formed on multi-facet GaN templates containing polar and semipolar surfaces. The nanostructured surface morphology was controlled by changing the growth time, and distinct multiple photoluminescence peaks were observed at 360, 460, and 560 nm; these features were caused by InGaN/GaN-based multiple quantum wells (MQWs) on the nanostructured facets. The origin of each multi-peak was related to the different indium (In) compositions in the different planes of the quantum wells grown on the nanostructured GaN. The emitting units of MQWs in the LED structures were continuously connected, which is different from other GaN-based nanorod or nanowire LEDs. Therefore, the suggested structure had a larger active area. From the electroluminescence spectrum of the fabricated LED, monolithic white light emission with CIE color coordinates of x = 0.306 and y = 0.333 was achieved via multi-facet control combined with morphology control of the metal organic chemical vapor deposition-selective area growth of InGaN/GaN MQWs.

Sc(2)MgGa(2) and Y(2)MgGa(2).

PubMed

Sahlberg, Martin; Andersson, Yvonne

2009-03-01

Scandium magnesium gallide, Sc(2)MgGa(2), and yttrium magnesium gallide, Y(2)MgGa(2), were synthesized from the corresponding elements by heating under an argon atmosphere in an induction furnace. These intermetallic compounds crystallize in the tetragonal Mo(2)FeB(2)-type structure. All three crystallographically unique atoms occupy special positions and the site symmetries of (Sc/Y, Ga) and Mg are m2m and 4/m, respectively. The coordinations around Sc/Y, Mg and Ga are pentagonal (Sc/Y), tetragonal (Mg) and triangular (Ga) prisms, with four (Mg) or three (Ga) additional capping atoms leading to the coordination numbers [10], [8+4] and [6+3], respectively. The crystal structure of Sc(2)MgGa(2 )was determined from single-crystal diffraction intensities and the isostructural Y(2)MgGa(2) was identified from powder diffraction data.

Investigation of GaAs/Al(x)Ga(1-x)As and In(y)Ga(1-y)As/GaAs superlattices on Si substrates

NASA Technical Reports Server (NTRS)

Reddy, U. K.; Ji, G.; Huang, D.; Munns, G.; Morkoc, H.

1987-01-01

The optical properties of lattice-matched GaAs/Al(x)Ga(1-x)As and In(y)Ga(1-y)As/GaAs strained-layer superlattices grown on Si substrates have been studied using the photoreflectance technique. These preliminary results show that good quality III-IV epilayers can be grown on Si. The experimental data were compared with calculations based on the envelope-function approximation and fitted to the third-derivative functional form of reflectance modulation theory.

Formation of two-dimensionally confined superparamagnetic (Mn, Ga)As nanocrystals in high-temperature annealed (Ga, Mn)As/GaAs superlattices.

PubMed

Sadowski, Janusz; Domagala, Jaroslaw Z; Mathieu, Roland; Kovacs, Andras; Dłużewski, Piotr

2013-05-15

The annealing-induced formation of (Mn, Ga)As nanocrystals in (Ga, Mn)As/GaAs superlattices was studied by x-ray diffraction, transmission electron microscopy and magnetometry. The superlattice structures with 50 Å thick (Ga, Mn)As layers separated by 25, 50 and 100 Å thick GaAs spacers were grown by molecular beam epitaxy at low temperature (250 °C), and then annealed at high temperatures of 400, 560 and 630 °C. The high-temperature annealing causes decomposition to a (Ga, Mn)As ternary alloy and the formation of (Mn, Ga)As nanocrystals inside the GaAs matrix. The nanocrystals are confined in the planes that were formerly occupied by (Ga, Mn)As layers for the up to 560 °C annealing and diffuse throughout the GaAs spacer layers at 630 °C annealing. The two-dimensionally confined nanocrystals exhibit a superparamagnetic behavior which becomes high-temperature ferromagnetism (~350 K) upon diffusion.

Magnetoresistance Study in a GaAs/InGaAs/GaAs Delta-Doped Quantum Well

NASA Astrophysics Data System (ADS)

Hasbun, J. E.

1997-03-01

The magnetoresistance of a GaAs/Ga_0.87In_0.13As/GaAs with an electron concentration of N_s=6.3x10^11cm-2 is calculated at low temperature for a magnetic field range of 2-30 tesla and low electric field. The results obtained for the magnetotransport are compared with the experimental work of Herfort et al.(J. Herfort, K.-J. Friedland, H. Kostial, and R. Hey, Appl. Phys. Lett. V66, 23 (1995)). While the logitudinal magnetoresistance agrees reasonably well with experiment, the Hall resistance slope reflects a classical shape; however, its second derivative seems to show oscillations that are consistent with the Hall effect plateaus seen experimentally. Albeit with a much higher electron concentration, earlier calculationsfootnote J. Hasbun, APS Bull. V41, 419 (1996) for an Al_0.27Ga_0.73/GaAs /Al_0.27Ga_0.73As quantum well shows similar behavior. This work has been carried out with the use of a quantum many body approach employed in earlier work(J. Hasbun, APS Bull. V41, 1659 (1996)).

Ectopic expression of specific GA2 oxidase mutants promotes yield and stress tolerance in rice.

PubMed

Lo, Shuen-Fang; Ho, Tuan-Hua David; Liu, Yi-Lun; Jiang, Mirng-Jier; Hsieh, Kun-Ting; Chen, Ku-Ting; Yu, Lin-Chih; Lee, Miin-Huey; Chen, Chi-Yu; Huang, Tzu-Pi; Kojima, Mikiko; Sakakibara, Hitoshi; Chen, Liang-Jwu; Yu, Su-May

2017-07-01

A major challenge of modern agricultural biotechnology is the optimization of plant architecture for enhanced productivity, stress tolerance and water use efficiency (WUE). To optimize plant height and tillering that directly link to grain yield in cereals and are known to be tightly regulated by gibberellins (GAs), we attenuated the endogenous levels of GAs in rice via its degradation. GA 2-oxidase (GA2ox) is a key enzyme that inactivates endogenous GAs and their precursors. We identified three conserved domains in a unique class of C 20 GA2ox, GA2ox6, which is known to regulate the architecture and function of rice plants. We mutated nine specific amino acids in these conserved domains and observed a gradient of effects on plant height. Ectopic expression of some of these GA2ox6 mutants moderately lowered GA levels and reprogrammed transcriptional networks, leading to reduced plant height, more productive tillers, expanded root system, higher WUE and photosynthesis rate, and elevated abiotic and biotic stress tolerance in transgenic rice. Combinations of these beneficial traits conferred not only drought and disease tolerance but also increased grain yield by 10-30% in field trials. Our studies hold the promise of manipulating GA levels to substantially improve plant architecture, stress tolerance and grain yield in rice and possibly in other major crops. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Effect of high moisture storage of pearl millet (Pennisetum typhoides) with or without feed enzymes on growth and nutrient utilization in broiler chickens.

PubMed

Manwar, Satish Jagannath; Mandal, Asit Baran

2009-08-01

Effect of reconstitution of pearl millet with or without enzymes on its utilization in broiler chickens was studied. The pearl millet grains were reconstituted by adding water to raise the moisture level to 30%, followed by storage in sealed plastic buckets with or without feed enzymes (0.5 g/kg) for 21 days at room temperature (25 degrees C). Subsequently, the grains were sun-dried to reduce the moisture content up to 10% to avoid mould growth. Nine dietary treatments were formulated incorporating pearl millet either raw with or without enzymes or reconstituted with or without enzymes in maize-soya based control diet replacing maize at 50 and 75% levels. The birds fed on diets containing enzyme reconstituted pearl millet accrued higher body weight than maize based control diet. Addition of enzymes to raw pearl-millet based diet improved the body weight gain significantly. The reconstitution of pearl millet with or without enzymes increased (P < 0.01) the dietary nitrogen corrected apparent metabolizable energy (AMEn) values and the highest improvement (6.11%) was recorded in diets containing pearl millet reconstituted with enzymes at 75% level of maize replacement. The percent nitrogen retention in pearl millet based diets was comparable to maize based control diet. It may be concluded that the supplementation of the feed enzymes or reconstitution of pearl millet may improve the utilization of pearl millet in broiler chickens.

Microbial Enzyme Production Using Lignocellulosic Food Industry Wastes as Feedstock: A Review

PubMed Central

Ravindran, Rajeev; Jaiswal, Amit K.

2016-01-01

Enzymes are of great importance in the industry due to their substrate and product specificity, moderate reaction conditions, minimal by-product formation and high yield. They are important ingredients in several products and production processes. Up to 30% of the total production cost of enzymes is attributed to the raw materials costs. The food industry expels copious amounts of processing waste annually, which is mostly lignocellulosic in nature. Upon proper treatment, lignocellulose can replace conventional carbon sources in media preparations for industrial microbial processes, such as enzyme production. However, wild strains of microorganisms that produce industrially important enzymes show low yield and cannot thrive on artificial substrates. The application of recombinant DNA technology and metabolic engineering has enabled researchers to develop superior strains that can not only withstand harsh environmental conditions within a bioreactor but also ensure timely delivery of optimal results. This article gives an overview of the current complications encountered in enzyme production and how accumulating food processing waste can emerge as an environment-friendly and economically feasible solution for a choice of raw material. It also substantiates the latest techniques that have emerged in enzyme purification and recovery over the past four years. PMID:28952592

[The Russian consensus on the diagnosis and treatment of chronic pancreatitis: Enzyme replacement therapy].

PubMed

Khatkov, I E; Maev, I V; Bordin, D S; Kucheryavyi, Yu A; Abdulkhakov, S R; Alekseenko, S A; Alieva, E I; Alikhanov, R B; Bakulin, I G; Baranovsky, A Yu; Beloborodova, E V; Belousova, E A; Buriev, I M; Bystrovskaya, E V; Vertyankin, S V; Vinokurova, L V; Galperin, E I; Gorelov, A V; Grinevich, V B; Danilov, M V; Darvin, V V; Dubtsova, E A; Dyuzheva, T G; Egorov, V I; Efanov, M G; Zakharova, N V; Zagainov, V E; Ivashkin, V T; Izrailov, R E; Korochanskaya, N V; Kornienko, E A; Korobka, V L; Kokhanenko, N Yu; Livzan, M A; Loranskaya, I D; Nikolskaya, K A; Osipenko, M F; Okhlobystin, A V; Pasechnikov, V D; Plotnikova, E Yu; Polyakova, S I; Sablin, O A; Simanenkov, V I; Ursova, N I; Tsvirkun, V V; Tsukanov, V V; Shabunin, A V

Russian National Research Medical University, Ministry of Health of Russia, Moscow; 26A.M. Nikiforov All-Russian Center of Emergency and Radiation Medicine, Russian Ministry for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters, Saint Petersburg; 27Research Institute for Medical Problems of the North, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk; 28S.P. Botkin City Clinical Hospital, Moscow Healthcare Department, Moscow; 29Tver State Medical University, Ministry of Health of Russia, Tver The Russian consensus on the diagnosis and treatment of chronic pancreatitis has been prepared on the initiative of the Russian Pancreatology Club to clarify and consolidate the opinions of Russian specialists (gastroenterologists, surgeons, and pediatricians) on the most significant problems of diagnosis and treatment of chronic pancreatitis. This article continues a series of publications explaining the most significant interdisciplinary consensus statements and deals with enzyme replacement therapy.

Evaluation of plant biomass resources available for replacement of fossil oil

PubMed Central

Henry, Robert J

2010-01-01

The potential of plants to replace fossil oil was evaluated by considering the scale of production required, the area of land needed and the types of plants available. High yielding crops (50 tonnes/ha) that have a high conversion efficiency (75%) would require a global land footprint of around 100 million ha to replace current (2008) oil consumption. Lower yielding or less convertible plants would require a larger land footprint. Domestication of new species as dedicated energy crops may be necessary. A systematic analysis of higher plants and their current and potential uses is presented. Plant biotechnology provides tools to improve the prospects of replacing oil with plant-derived biomass by increasing the amount of biomass produced per unit area of land and improving the composition of the biomass to increase the efficiency of conversion to biofuel and biomaterials. Options for the production of high value coproducts and the expression of processing aids such as enzymes in the plant may add further value to plants as bioenergy resources. PMID:20070873

Ga for Zn Cation Exchange Allows for Highly Luminescent and Photostable InZnP-Based Quantum Dots

PubMed Central

2017-01-01

In this work, we demonstrate that a preferential Ga-for-Zn cation exchange is responsible for the increase in photoluminescence that is observed when gallium oleate is added to InZnP alloy QDs. By exposing InZnP QDs with varying Zn/In ratios to gallium oleate and monitoring their optical properties, composition, and size, we conclude that Ga3+ preferentially replaces Zn2+, leading to the formation of InZnP/InGaP core/graded-shell QDs. This cation exchange reaction results in a large increase of the QD photoluminescence, but only for InZnP QDs with Zn/In ≥ 0.5. For InP QDs that do not contain zinc, Ga is most likely incorporated only on the quantum dot surface, and a PL enhancement is not observed. After further growth of a GaP shell and a lattice-matched ZnSeS outer shell, the cation-exchanged InZnP/InGaP QDs continue to exhibit superior PL QY (over 70%) and stability under long-term illumination (840 h, 5 weeks) compared to InZnP cores with the same shells. These results provide important mechanistic insights into recent improvements in InP-based QDs for luminescent applications. PMID:28706347

Evaluation of a Hypocrea jecorina enzyme preparation for hydrolysis of Tifton 85 bermudagrass.

PubMed

Ximenes, E A; Brandon, S K; Doran-Peterson, J

2008-03-01

Tifton 85 bermudagrass, developed at the ARS-USDA in Tifton, GA, is grown on over ten million acres in the USA for hay and forage. Of the bermudagrass cultivars, Tifton 85 exhibits improved digestibility because the ratio of ether- to ester-linked phenolic acids has been lowered using traditional plant breeding techniques. A previously developed pressurized batch hot water (PBHW) method was used to treat Tifton 85 bermudagrass for enzymatic hydrolysis. Native grass (untreated) and PBHW-pretreated material were compared as substrates for fungal cultivation to produce enzymes. Cellulase activity, measured via the filter paper assay, was higher for fungi cultivated on PBHW-pretreated grass, whereas the other nine enzyme assays produced higher activities for the untreated grass. Ferulic acid and vanillin levels increased significantly for the enzyme preparations produced using PBHW-pretreated grass and the release of these phenolic compounds may have contributed to the observed reduction in enzyme activities. Culture supernatant from Tifton 85 bermudagrass-grown fungi were combined with two commercial enzyme preparations and the enzyme activity profiles are reported. The amount of reducing sugar liberated by the enzyme mixture from Hypocrea jecorina (after 192 h incubation with untreated bermudagrass) individually or in combination with feruloyl esterase was 72.1 and 84.8%, respectively, of the commercial cellulase preparation analyzed under the same conditions.

Evaluation of a Hypocrea jecorina Enzyme Preparation for Hydrolysis of Tifton 85 Bermudagrass

NASA Astrophysics Data System (ADS)

Ximenes, E. A.; Brandon, S. K.; Doran-Peterson, J.

Tifton 85 bermudagrass, developed at the ARS-USDA in Tifton, GA, is grown on over ten million acres in the USA for hay and forage. Of the bermudagrass cultivars, Tifton 85 exhibits improved digestibility because the ratio of ether- to ester-linked phenolic acids has been lowered using traditional plant breeding techniques. A previously developed pressurized batch hot water (PBHW) method was used to treat Tifton 85 bermudagrass for enzymatic hydrolysis. Native grass (untreated) and PBHW-pretreated material were compared as substrates for fungal cultivation to produce enzymes. Cellulase activity, measured via the filter paper assay, was higher for fungi cultivated on PBHW-pretreated grass, whereas the other nine enzyme assays produced higher activities for the untreated grass. Ferulic acid and vanillin levels increased significantly for the enzyme preparations produced using PBHW-pretreated grass and the release of these phenolic compounds may have contributed to the observed reduction in enzyme activities. Culture supernatant from Tifton 85 bermudagrass-grown fungi were combined with two commercial enzyme preparations and the enzyme activity profiles are reported. The amount of reducing sugar liberated by the enzyme mixture from Hypocrea jecorina (after 192 h incubation with untreated bermudagrass) individually or in combination with feruloyl esterase was 72.1 and 84.8%, respectively, of the commercial cellulase preparation analyzed under the same conditions.

AlGaN/GaN heterostructures with an AlGaN layer grown directly on reactive-ion-etched GaN showing a high electron mobility (>1300 cm2 V-1 s-1)

NASA Astrophysics Data System (ADS)

Yamamoto, Akio; Makino, Shinya; Kanatani, Keito; Kuzuhara, Masaaki

2018-04-01

In this study, the metal-organic-vapor-phase-epitaxial growth behavior and electrical properties of AlGaN/GaN structures prepared by the growth of an AlGaN layer on a reactive-ion-etched (RIE) GaN surface without regrown GaN layers were investigated. The annealing of RIE-GaN surfaces in NH3 + H2 atmosphere, employed immediately before AlGaN growth, was a key process in obtaining a clean GaN surface for AlGaN growth, that is, in obtaining an electron mobility as high as 1350 cm2 V-1 s-1 in a fabricated AlGaN/RIE-GaN structure. High-electron-mobility transistors (HEMTs) were successfully fabricated with AlGaN/RIE-GaN wafers. With decreasing density of dotlike defects observed on the surfaces of AlGaN/RIE-GaN wafers, both two-dimensional electron gas properties of AlGaN/RIE-GaN structures and DC characteristics of HEMTs were markedly improved. Since dotlike defect density was markedly dependent on RIE lot, rather than on growth lot, surface contaminations of GaN during RIE were believed to be responsible for the formation of dotlike defects and, therefore, for the inferior electrical properties.

Proximity Effects of Beryllium-Doped GaN Buffer Layers on the Electronic Properties of Epitaxial AlGaN/GaN Heterostructures

DTIC Science & Technology

2010-05-17

arranged by Prof. A. Zaslavsky Keywords: Gallium nitride High electron mobility transistor Molecular beam epitaxy Homoepitaxy Doping a b s t r a c t AlGaN...GaN/Be:GaN heterostructures have been grown by rf-plasma molecular beam epitaxy on free- standing semi-insulating GaN substrates, employing...hydride vapor phase epitaxy (HVPE) grown GaN sub- strates has enabled the growth by molecular beam epitaxy (MBE) of AlGaN/GaNHEMTswith significantly

GaSbBi/GaSb quantum-well and wire laser diodes

NASA Astrophysics Data System (ADS)

Ridene, Said

2018-06-01

In this work, we present detailed theoretical studies of the optical gain spectra and the emission wavelength of GaSb1-xBix/GaSb and traditional GaAs1-xBix/GaAs dilute-bismide quantum wells and wires (QWs, QWRs) focusing on comparison between their performances. It is found that the optical gain and the emission wavelength of the GaSb-based QW and QWRs lasers would be considerably greater than that of the GaAs-based QW lasers and QWRs for the same QW-, QWR-width, Bi-content and carrier density. The theoretical results were found to be in good agreement with available experimental data, especially for the emission wavelength given by GaSb-based QW laser diodes.

Normally-off p-GaN/AlGaN/GaN high electron mobility transistors using hydrogen plasma treatment

NASA Astrophysics Data System (ADS)

Hao, Ronghui; Fu, Kai; Yu, Guohao; Li, Weiyi; Yuan, Jie; Song, Liang; Zhang, Zhili; Sun, Shichuang; Li, Xiajun; Cai, Yong; Zhang, Xinping; Zhang, Baoshun

2016-10-01

In this letter, we report a method by introducing hydrogen plasma treatment to realize normally-off p-GaN/AlGaN/GaN HEMT devices. Instead of using etching technology, hydrogen plasma was adopted to compensate holes in the p-GaN above the two dimensional electron gas (2DEG) channel to release electrons in the 2DEG channel and form high-resistivity area to reduce leakage current and increase gate control capability. The fabricated p-GaN/AlGaN/GaN HEMT exhibits normally-off operation with a threshold voltage of 1.75 V, a subthreshold swing of 90 mV/dec, a maximum transconductance of 73.1 mS/mm, an ON/OFF ratio of 1 × 107, a breakdown voltage of 393 V, and a maximum drain current density of 188 mA/mm at a gate bias of 6 V. The comparison of the two processes of hydrogen plasma treatment and p-GaN etching has also been made in this work.

The atomic structure of polar and non-polar InGaN quantum wells and the green gap problem.

PubMed

Humphreys, C J; Griffiths, J T; Tang, F; Oehler, F; Findlay, S D; Zheng, C; Etheridge, J; Martin, T L; Bagot, P A J; Moody, M P; Sutherland, D; Dawson, P; Schulz, S; Zhang, S; Fu, W Y; Zhu, T; Kappers, M J; Oliver, R A

2017-05-01

We have used high resolution transmission electron microscopy (HRTEM), aberration-corrected quantitative scanning transmission electron microscopy (Q-STEM), atom probe tomography (APT) and X-ray diffraction (XRD) to study the atomic structure of (0001) polar and (11-20) non-polar InGaN quantum wells (QWs). This paper provides an overview of the results. Polar (0001) InGaN in QWs is a random alloy, with In replacing Ga randomly. The InGaN QWs have atomic height interface steps, resulting in QW width fluctuations. The electrons are localised at the top QW interface by the built-in electric field and the well-width fluctuations, with a localisation energy of typically 20meV. The holes are localised near the bottom QW interface, by indium fluctuations in the random alloy, with a localisation energy of typically 60meV. On the other hand, the non-polar (11-20) InGaN QWs contain nanometre-scale indium-rich clusters which we suggest localise the carriers and produce longer wavelength (lower energy) emission than from random alloy non-polar InGaN QWs of the same average composition. The reason for the indium-rich clusters in non-polar (11-20) InGaN QWs is not yet clear, but may be connected to the lower QW growth temperature for the (11-20) InGaN QWs compared to the (0001) polar InGaN QWs. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of GA3 Treatment on Seed Development and Seed-Related Gene Expression in Grape

PubMed Central

Cheng, Chenxia; Xu, Xiaozhao; Singer, Stacy D.; Li, Jun; Zhang, Hongjing; Gao, Min; Wang, Li; Song, Junyang; Wang, Xiping

2013-01-01

Background The phytohormone gibberellic acid (GA3) is widely used in the table grape industry to induce seedlessness in seeded varieties. However, there is a paucity of information concerning the mechanisms by which GAs induce seedlessness in grapes. Methodology/Principal Findings In an effort to systematically analyze the cause of this GA3-induced seed abortion, we conducted an in depth characterization of two seeded grape cultivars (‘Kyoho’ and ‘Red Globe’), along with a seedless cultivar (‘Thompson Seedless’), following treatment with GA3. In a similar fashion to the seedless control, which exhibited GA3-induced abortion of the seeds 9 days after full bloom (DAF), both ‘Kyoho’ and ‘Red Globe’ seeded varieties exhibited complete abortion of the seeds 15 DAF when treated with GA3. Morphological analyses indicated that while fertilization appeared to occur normally following GA3 treatment, as well as in the untreated seedless control cultivar, seed growth eventually ceased. In addition, we found that GA3 application had an effect on redox homeostasis, which could potentially cause cell damage and subsequent seed abortion. Furthermore, we carried out an analysis of antioxidant enzyme activities, as well as transcript levels from various genes believed to be involved in seed development, and found several differences between GA3-treated and untreated controls. Conclusion Therefore, it seems that the mechanisms driving GA3-induced seedlessness are similar in both seeded and seedless cultivars, and that the observed abortion of seeds may result at least in part from a GA3-induced increase in cell damage caused by reactive oxygen species, a decrease in antioxidant enzymatic activities, and an alteration of the expression of genes related to seed development. PMID:24224035

Effect of an InxGa1-xAs-GaAs blocking heterocathode metal contact on the GaAs TED operation

NASA Astrophysics Data System (ADS)

Arkusha, Yu. V.; Prokhorov, E. D.; Storozhenko, I. P.

2004-09-01

The frequency dependence of the generation efficiency of an mm- -nn:In:InxGaGa1-1-xAs- As-nn:GaAs-:GaAs-nn++:GaAs TED with the 2.5-mm long active region is calculated. The optimum values - which yield the diode maximum generation efficiency - for the :GaAs TED with the 2.5-mm long active region is calculated. The optimum values - which yield the diode maximum generation efficiency - for the nn:In:InxGaGa1-1-xAs cathode length, the cathode concentration of ionized impurities, and the height of the potential barrier on metal contact are determined.As cathode length, the cathode concentration of ionized impurities, and the height of the potential barrier on metal contact are determined.

Strain-compensated (Ga,In)N/(Al,Ga)N/GaN multiple quantum wells for improved yellow/amber light emission

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lekhal, K.; Damilano, B., E-mail: bd@crhea.cnrs.fr; De Mierry, P.

2015-04-06

Yellow/amber (570–600 nm) emitting In{sub x}Ga{sub 1−x}N/Al{sub y}Ga{sub 1−y}N/GaN multiple quantum wells (QWs) have been grown by metal organic chemical vapor deposition on GaN-on- sapphire templates. When the (Al,Ga)N thickness of the barrier increases, the room temperature photoluminescence is red-shifted while its yield increases. This is attributed to an increase of the QW internal electric field and an improvement of the material quality due to the compensation of the compressive strain of the In{sub x}Ga{sub 1−x}N QWs by the Al{sub y}Ga{sub 1−y}N layers, respectively.

Titanium induced polarity inversion in ordered (In,Ga)N/GaN nanocolumns.

PubMed

Kong, X; Li, H; Albert, S; Bengoechea-Encabo, A; Sanchez-Garcia, M A; Calleja, E; Draxl, C; Trampert, A

2016-02-12

We report on the formation of polarity inversion in ordered (In,Ga)N/GaN nanocolumns grown on a Ti-masked GaN-buffered sapphire substrate by plasma assisted molecular beam epitaxy. High-resolution transmission electron microscopy and electron energy-loss spectroscopy reveal a stacking fault-like planar defect at the homoepitaxial GaN interface due to Ti incorporation, triggering the generation of N-polar domains in Ga-polar nanocolumns. Density functional theory calculations are applied to clarify the atomic configurations of a Ti monolayer occupation on the GaN (0002) plane and to prove the inversion effect. The polarity inversion leads to an enhanced indium incorporation in the subsequent (In,Ga)N segment of the nanocolumn. This study provides a deeper understanding of the effects of Ti mask in the well-controlled selective area growth of (In,Ga)N/GaN nanocolumns.

MOVPE growth of Ga(PBi) on GaP and GaP on Si with Bi fractions up to 8%

NASA Astrophysics Data System (ADS)

Nattermann, L.; Beyer, A.; Ludewig, P.; Hepp, T.; Sterzer, E.; Volz, K.

2017-04-01

Dilute bismide containing materials can play an important role in addressing the issue of finding new highly efficient lasers for telecommunications as well as sensing applications. In the last several years a growing body of literature has emerged, particularly on the growth of Ga(AsBi). However, the metal organic vapor phase epitaxy growth of Ga(AsBi) with high amounts of Bi, which are necessary to overcome Auger recombination and reach telecommunications wavelengths, still remains a challenge. Ga(PBi) could be a promising alternative, but has not been deposited with significant amounts of Bi so far. A second argument for Ga(PBi) is that it could be grown on GaP, which was already deposited on Si. A number of researchers have reported theoretical calculations on the band structure of Ga(PBi), but experimental results are still lacking. In this work we present the first Ga(PBi) structures, grown by metal organic vapor phase epitaxy on GaP and on GaP on Si. By careful characterization with high resolution X-ray diffraction, atomic force microscopy, secondary ion mass spectrometry and scanning transmission electron microscopy, we will show that we have realized high quality Ga(PBi) with Bi fractions over 8%.

A hole modulator for InGaN/GaN light-emitting diodes

NASA Astrophysics Data System (ADS)

Zhang, Zi-Hui; Kyaw, Zabu; Liu, Wei; Ji, Yun; Wang, Liancheng; Tan, Swee Tiam; Sun, Xiao Wei; Demir, Hilmi Volkan

2015-02-01

The low p-type doping efficiency of the p-GaN layer has severely limited the performance of InGaN/GaN light-emitting diodes (LEDs) due to the ineffective hole injection into the InGaN/GaN multiple quantum well (MQW) active region. The essence of improving the hole injection efficiency is to increase the hole concentration in the p-GaN layer. Therefore, in this work, we have proposed a hole modulator and studied it both theoretically and experimentally. In the hole modulator, the holes in a remote p-type doped layer are depleted by the built-in electric field and stored in the p-GaN layer. By this means, the overall hole concentration in the p-GaN layer can be enhanced. Furthermore, the hole modulator is adopted in the InGaN/GaN LEDs, which reduces the effective valance band barrier height for the p-type electron blocking layer from ˜332 meV to ˜294 meV at 80 A/cm2 and demonstrates an improved optical performance, thanks to the increased hole concentration in the p-GaN layer and thus the improved hole injection into the MQWs.

Ga originated kink-and-tail Zn diffusion profiles in InGaAsP and InGaAlAs alloys during MOVPE regrowth

NASA Astrophysics Data System (ADS)

Kitatani, T.; Okamoto, K.; Uchida, K.; Tanaka, S.

2017-12-01

We investigated the diffusion characteristics of Zn in ternary and quaternary alloys of InGaAsP and InGaAlAs, which are important materials in long-wavelength optical communication devices. The measured Zn diffusion profiles of InGaAs, InGaAsP, and InGaAlAs showed kink-and-tail shapes in which Zn concentration fell abruptly at first and then decreased slowly, whereas those of InP and InAlAs showed only abrupt decreases. Thus, only Ga-containing alloys had tail-like profiles. Since this tail was well described by the group-V vacancy related defect model, we deduced that its mechanism is closely related with group-V vacancies in Ga-related bonds such as GaP or GaAs. Furthermore, we demonstrated the possibility that many more group-V vacancies originated from GaP bonds than from GaAs bonds, indicating the difficulty in crystal growth of high quality alloys that have GaP components.

Homologous compounds of type ARO3(ZnO)m in the system Ga-Sn-Zn-O

NASA Astrophysics Data System (ADS)

Eichhorn, Simon; Schmid, Herbert; Assenmacher, Wilfried; Mader, Werner

2017-02-01

Several members of hitherto unknown homologous compounds [Sn0.5Zn0.5]GaO3(ZnO)m (m=3-7) of the general formula ARO3(ZnO)m were prepared by solid state methods from the binary oxides in sealed Pt-tubes. UV-vis measurements confirm these compounds to be transparent oxides with an optical band gap in the UV region with Eg≈3 eV. Rietveld refinements on powder samples of [Sn0.5Zn0.5]GaO3(ZnO)m proved the compounds to be isostructural with InGaO3(ZnO)m, where In3+ on octahedral sites is replaced statistically by Sn4+ and Zn2+ in equal amounts preserving an average charge of 3+. Additionally, the structure of [Sn0.5Zn0.5]GaO3(ZnO)3 has been determined from flux-grown single crystals by X-ray diffraction (R 3 ̅ m , Z=3, a=3.2387(7) Å, c=41.78(1) Å, 19 parameters, 201 independent reflections, R1=0.047, wR2=0.074). The compound [Sn0.5Zn0.5]GaO3(ZnO)3 is isostructural with InGaO3(ZnO)3. [Sn0.5Zn0.5]GaO3(ZnO)3 was furthermore analyzed by High Angle Annular Dark Field (HAADF) scanning TEM and EELS spectroscopic imaging, supporting the structure model derived from X-ray diffraction data.

Influence of partial replacement of ground wheat with whole wheat and exogenous enzyme supplementation on growth performance, nutrient digestibility and energy utilization in young broilers.

PubMed

Abdollahi, M R; Ravindran, V; Amerah, A M

2016-10-01

This study investigated the influence of pre-pelleting inclusion of whole wheat (WW) and exogenous enzyme supplementation on growth performance, coefficient of apparent ileal nutrient digestibility (CAID) and apparent metabolizable energy (AME) in broilers fed wheat-based pelleted diets. A 2 × 3 factorial arrangement of treatments was used with two methods of wheat inclusion [622 g/kg ground wheat (GW) and 250 g/kg WW replaced GW (wt/wt) pre-pelleting (PWW)] and three enzymes (xylanase, phytase and xylanase plus phytase). A total of 288, one-day-old male broilers (Ross 308) were individually weighed and allocated to 36 cages (8 broilers/cage), and the cages were randomly assigned to the six dietary treatments. Birds fed PWW diets gained more (p < 0.05) weight than those fed GW diets. There was no effect (p > 0.05) of WW inclusion on feed intake (FI). Phytase alone increased (p < 0.05) FI compared to xylanase or the combination. Whole wheat inclusion increased (p < 0.05) the gain-to-feed ratio (G:F). Feeding xylanase plus phytase and phytase-added diets resulted in the greatest and lowest G:F, respectively, with xylanase supplemented diets being intermediate. Birds fed PWW diets had greater (p < 0.05) relative gizzard weights than those fed GW diets. There was no effect (p > 0.05) of WW inclusion on the CAID of nitrogen (N), starch and fat. Combination of xylanase and phytase resulted in greater (p < 0.05) digestibility of N, starch and fat than that of individual additions. Feeding PWW diets resulted in greater (p < 0.05) AME values than GW diets. Combination of xylanase and phytase increased (p < 0.05) the AME compared to the diets with individual additions of xylanase or phytase. The current results suggest that the influence of pre-pelleting WW inclusion and exogenous enzymes on nutrient digestibility and broiler performance is not additive. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Above room temperature operation of InGaAs/AlGaAs/GaAs quantum cascade lasers

NASA Astrophysics Data System (ADS)

Pierścińska, D.; Gutowski, P.; Hałdaś, G.; Kolek, A.; Sankowska, I.; Grzonka, J.; Mizera, J.; Pierściński, K.; Bugajski, M.

2018-03-01

In this work we report on the performance of mid-infrared quantum cascade lasers (QCLs) based on strained InGaAs/AlGaAs grown by molecular beam epitaxy on GaAs substrate. Structures were grown with indium content from 1% to 6% in GaAs quantum wells (QW) and 45% of Al in AlGaAs barrier layers. The design results in strained heterostructure, however, no strain relaxation was observed as documented by x-ray diffraction measurements up to ∼3% of In content in QWs. The investigation of heterostructures and devices was performed, including structural measurements and electrooptical characterization of devices. Devices fabricated from epi wafers with 2.64% of In exhibited performance largely improved over GaAs/AlGaAs QCLs. Roughly two times reduction of the threshold current density was observed at lasing wavelength ∼9.45 μm. The lasers operated in pulsed mode up to T = 50 °C with characteristic temperature T 0 = 115 K. The decrease of the threshold current density has been mainly attributed to the reduction of interface roughness scattering and the increase of activation energy for the escape of carriers from the upper laser level to the 3D continuum. Further increase of In content in QWs resulted in the deterioration of device parameters.

Engineering Cellulase Enzymes for Bioenergy

NASA Astrophysics Data System (ADS)

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

Enzyme replacement therapy with galsulfase in 34 children younger than five years of age with MPS VI.

PubMed

Horovitz, Dafne D G; Magalhães, Tatiana S P C; Acosta, Angelina; Ribeiro, Erlane M; Giuliani, Liane R; Palhares, Durval B; Kim, Chong A; de Paula, Ana Carolina; Kerstenestzy, Marcelo; Pianovski, Mara A D; Costa, Maria Ione F; Santos, Francisca C; Martins, Ana Maria; Aranda, Carolina S; Correa Neto, Jordão; Holanda, Gervina Brady Moreira; Cardoso, Laércio; da Silva, Carlos A B; Bonatti, Renata C F; Ribeiro, Bethania F R; Rodrigues, Maria do Carmo S; Llerena, Juan C

2013-05-01

Mucopolysaccharidosis type VI (MPS VI) is a progressive, chronic and multisystem lysosomal storage disease with a wide disease spectrum. Clinical and biochemical improvements have been reported for MPS VI patients on enzyme replacement therapy (ERT) with rhASB (recombinant human arylsulfatase B; galsulfase, Naglazyme®, BioMarin Pharmaceutical Inc.), making early diagnosis and intervention imperative for optimal patient outcomes. Few studies have included children younger than five years of age. This report describes 34 MPS VI patients that started treatment with galsulfase before five years of age. Data from patients who initiated treatment at <5 years of age were collected from patients' medical records. Baseline and follow-up assessments of common symptoms that led to diagnosis and that were used to evaluate disease progression and treatment efficacy were evaluated. A significant negative correlation was seen with treatment with ERT and urinary GAG levels. Of those with baseline and follow-up growth data, 47% remained on their pre-treatment growth curve or moved to a higher percentile after treatment. Of the 9 patients with baseline and follow-up sleep studies, 5 remained unaffected and 1 patient initially with mild sleep apnea showed improvement. Data regarding cardiac, ophthalmic, central nervous system, hearing, surgical interventions and development are also reported. No patient discontinued treatment due to an adverse event and all that were treatment-emergent resolved. The prescribed dosage of 1mg/kg IV weekly with galsulfase ERT is shown to be safe and effective in slowing and/or improving certain aspects of the disease, although patients should be closely monitored for complications associated with the natural history of the disease, especially cardiac valve involvement and spinal cord compression. A long-term follow-up investigation of this group of children will provide further information on the benefits of early treatment as well as disease

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

PubMed

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.

Enhanced thermoelectric transport in modulation-doped GaN/AlGaN core/shell nanowires.

PubMed

Song, Erdong; Li, Qiming; Swartzentruber, Brian; Pan, Wei; Wang, George T; Martinez, Julio A

2016-01-08

The thermoelectric properties of unintentionally n-doped core GaN/AlGaN core/shell N-face nanowires are reported. We found that the temperature dependence of the electrical conductivity is consistent with thermally activated carriers with two distinctive donor energies. The Seebeck coefficient of GaN/AlGaN nanowires is more than twice as large as that for the GaN nanowires alone. However, an outer layer of GaN deposited onto the GaN/AlGaN core/shell nanowires decreases the Seebeck coefficient at room temperature, while the temperature dependence of the electrical conductivity remains the same. We attribute these observations to the formation of an electron gas channel within the heavily-doped GaN core of the GaN/AlGaN nanowires. The room-temperature thermoelectric power factor for the GaN/AlGaN nanowires can be four times higher than the GaN nanowires. Selective doping in bandgap engineered core/shell nanowires is proposed for enhancing the thermoelectric power.

Hip joint replacement

MedlinePlus

... Total hip replacement; Hip hemiarthroplasty; Arthritis - hip replacement; Osteoarthritis - hip replacement ... total hip replacement surgery in patients with hip osteoarthritis: a long-term follow-up of a randomised ...

AlGaN/GaN field effect transistors for power electronics—Effect of finite GaN layer thickness on thermal characteristics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodges, C., E-mail: chris.hodges@bristol.ac.uk; Anaya Calvo, J.; Kuball, M.

2013-11-11

AlGaN/GaN heterostructure field effect transistors with a 150 nm thick GaN channel within stacked Al{sub x}Ga{sub 1−x}N layers were investigated using Raman thermography. By fitting a thermal simulation to the measured temperatures, the thermal conductivity of the GaN channel was determined to be 60 W m{sup −1} K{sup −1}, over 50% less than typical GaN epilayers, causing an increased peak channel temperature. This agrees with a nanoscale model. A low thermal conductivity AlGaN buffer means the GaN spreads heat; its properties are important for device thermal characteristics. When designing power devices with thin GaN layers, as well as electrical considerations, the reducedmore » channel thermal conductivity must be considered.« less

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

PubMed

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

A hole modulator for InGaN/GaN light-emitting diodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Zi-Hui; Kyaw, Zabu; Liu, Wei

2015-02-09

The low p-type doping efficiency of the p-GaN layer has severely limited the performance of InGaN/GaN light-emitting diodes (LEDs) due to the ineffective hole injection into the InGaN/GaN multiple quantum well (MQW) active region. The essence of improving the hole injection efficiency is to increase the hole concentration in the p-GaN layer. Therefore, in this work, we have proposed a hole modulator and studied it both theoretically and experimentally. In the hole modulator, the holes in a remote p-type doped layer are depleted by the built-in electric field and stored in the p-GaN layer. By this means, the overall holemore » concentration in the p-GaN layer can be enhanced. Furthermore, the hole modulator is adopted in the InGaN/GaN LEDs, which reduces the effective valance band barrier height for the p-type electron blocking layer from ∼332 meV to ∼294 meV at 80 A/cm{sup 2} and demonstrates an improved optical performance, thanks to the increased hole concentration in the p-GaN layer and thus the improved hole injection into the MQWs.« less

Isotype InGaN/GaN heterobarrier diodes by ammonia molecular beam epitaxy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fireman, Micha N.; Browne, David A.; Speck, James S.

The design of isotype InGaN/GaN heterobarrier diode structures grown by ammonia molecular beam epitaxy is presented. On the (0001) Ga-polar plane, a structure consisting of a surface n{sup +} GaN contact layer, followed by a thin InGaN layer, followed by a thick unintentionally doped (UID) GaN layer, and atop a buried n{sup +} GaN contact layer induces a large conduction band barrier via a depleted UID GaN layer. Suppression of reverse and subthreshold current in such isotype barrier devices under applied bias depends on the quality of this composite layer polarization. Sample series were grown under fixed InGaN growth conditionsmore » that varied either the UID GaN NH{sub 3} flow rate or the UID GaN thickness, and under fixed UID GaN growth conditions that varied InGaN growth conditions. Decreases in subthreshold current and reverse bias current were measured for thicker UID GaN layers and increasing InGaN growth rates. Temperature-dependent analysis indicated that although extracted barrier heights were lower than those predicted by 1D Schrödinger Poisson simulations (0.9 eV–1.4 eV for In compositions from 10% to 15%), optimized growth conditions increased the extracted barrier height from ∼11% to nearly 85% of the simulated values. Potential subthreshold mechanisms are discussed, along with those growth factors which might affect their prevalence.« less

First Principles Electronic Structure of Mn doped GaAs, GaP, and GaN Semiconductors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulthess, Thomas C; Temmerman, Walter M; Szotek, Zdzislawa

We present first-principles electronic structure calculations of Mn doped III-V semiconductors based on the local spin-density approximation (LSDA) as well as the self-interaction corrected local spin density method (SIC-LSD). We find that it is crucial to use a self-interaction free approach to properly describe the electronic ground state. The SIC-LSD calculations predict the proper electronic ground state configuration for Mn in GaAs, GaP, and GaN. Excellent quantitative agreement with experiment is found for magnetic moment and p-d exchange in (GaMn)As. These results allow us to validate commonly used models for magnetic semiconductors. Furthermore, we discuss the delicate problem of extractingmore » binding energies of localized levels from density functional theory calculations. We propose three approaches to take into account final state effects to estimate the binding energies of the Mn-d levels in GaAs. We find good agreement between computed values and estimates from photoemisison experiments.« less

Current-induced switching in CoGa/L10 MnGa/(CoGa)/Pt structure with different thicknesses

NASA Astrophysics Data System (ADS)

Ranjbar, R.; Suzuki, K. Z.; Mizukami, S.

2018-06-01

In this paper, we present the results of our study into current-induced spin-orbit torque (SOT) switching in perpendicularly magnetized CoGa/MnGa/Pt trilayers with different thicknesses of MnGa and Pt. The SOT switching was observed for all films that undergo Joule heating. We also investigate SOT switching in the bottom (CoGa)/MnGa/top(CoGa/Pt) films with different top layers. Although both the bottom and top layers contribute to the SOT, the relative magnitudes of the switching current densities JC in the top and bottom layers indicate that the SOT is dominant in the top layer. The JC as a function of thickness is discussed in terms of the magnetic properties and resistivity. Experimental data suggested that the MnGa thickness dependence of JC may originate from the perpendicular magnetic anisotropy thickness product Kueff t value. On the other hand, JC as a function of the Pt thickness shows weak dependence. This may be attributed to the slight change of spin-Hall angle θSH value with different thicknesses of Pt, when we assumed that the SOT switching is primarily due to the spin-Hall effect.

Ultrafast carrier dynamics in GaN/InGaN multiple quantum wells nanorods

NASA Astrophysics Data System (ADS)

Chen, Weijian; Wen, Xiaoming; Latzel, Michael; Yang, Jianfeng; Huang, Shujuan; Shrestha, Santosh; Patterson, Robert; Christiansen, Silke; Conibeer, Gavin

2018-01-01

GaN/InGaN multiple quantum wells (MQW) is a promising material for high-efficiency solid-state lighting. Ultrafast optical pump-probe spectroscopy is an important characterization technique for examining fundamental phenomena in semiconductor nanostructure with sub-picosecond resolution. In this study, ultrafast exciton and charge carrier dynamics in GaN/InGaN MQW planar layer and nanorod are investigated using femtosecond transient absorption (TA) techniques at room temperature. Here nanorods are fabricated by etching the GaN/InGaN MQW planar layers using nanosphere lithography and reactive ion etching. Photoluminescence efficiency of the nanorods have been proved to be much higher than that of the planar layers, but the mechanism of the nanorod structure improvement of PL efficiency is not adequately studied. By comparing the TA profile of the GaN/InGaN MQW planar layers and nanorods, the impact of surface states and nanorods lateral confinement in the ultrafast carrier dynamics of GaN/InGaN MQW is revealed. The nanorod sidewall surface states have a strong influence on the InGaN quantum well carrier dynamics. The ultrafast relaxation processes studied in this GaN/InGaN MQW nanostructure is essential for further optimization of device application.

Formation of target-specific binding sites in enzymes: solid-phase molecular imprinting of HRP.

PubMed

Czulak, J; Guerreiro, A; Metran, K; Canfarotta, F; Goddard, A; Cowan, R H; Trochimczuk, A W; Piletsky, S

2016-06-07

Here we introduce a new concept for synthesising molecularly imprinted nanoparticles by using proteins as macro-functional monomers. For a proof-of-concept, a model enzyme (HRP) was cross-linked using glutaraldehyde in the presence of glass beads (solid-phase) bearing immobilized templates such as vancomycin and ampicillin. The cross-linking process links together proteins and protein chains, which in the presence of templates leads to the formation of permanent target-specific recognition sites without adverse effects on the enzymatic activity. Unlike complex protein engineering approaches commonly employed to generate affinity proteins, the method proposed can be used to produce protein-based ligands in a short time period using native protein molecules. These affinity materials are potentially useful tools especially for assays since they combine the catalytic properties of enzymes (for signaling) and molecular recognition properties of antibodies. We demonstrate this concept in an ELISA-format assay where HRP imprinted with vancomycin and ampicillin replaced traditional enzyme-antibody conjugates for selective detection of templates at micromolar concentrations. This approach can potentially provide a fast alternative to raising antibodies for targets that do not require high assay sensitivities; it can also find uses as a biochemical research tool, as a possible replacement for immunoperoxidase-conjugates.

Pyramidal dislocation induced strain relaxation in hexagonal structured InGaN/AlGaN/GaN multilayer

NASA Astrophysics Data System (ADS)

Yan, P. F.; Du, K.; Sui, M. L.

2012-10-01

Due to the special dislocation slip systems in hexagonal lattice, dislocation dominated deformations in hexagonal structured multilayers are significantly different from that in cubic structured systems. In this work, we have studied the strain relaxation mechanism in hexagonal structured InGaN/AlGaN/GaN multilayers with transmission electron microscopy. Due to lattice mismatch, the strain relaxation was found initiated with the formation of pyramidal dislocations. Such dislocations locally lie at only one preferential slip direction in the hexagonal lattice. This preferential slip causes a shear stress along the basal planes and consequently leads to dissociation of pyramidal dislocations and operation of the basal plane slip system. The compressive InGaN layers and "weak" AlGaN/InGaN interfaces stimulate the dissociation of pyramidal dislocations at the interfaces. These results enhance the understanding of interactions between dislocations and layer interfaces and shed new lights on deformation mechanism in hexagonal-lattice multilayers.

Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study.

PubMed

Imbriaco, M; Pisani, A; Spinelli, L; Cuocolo, A; Messalli, G; Capuano, E; Marmo, M; Liuzzi, R; Visciano, B; Cianciaruso, B; Salvatore, M

2009-07-01

Anderson-Fabry disease is a multisystem X linked disorder of lipid metabolism frequently associated with cardiac symptoms, including left ventricular (LV) hypertrophy gradually impairing cardiac function. Evidence showing that enzyme-replacement therapy (ERT) can be effective in reducing LV hypertrophy and improving myocardial function in the long term is limited. This study aimed to assess the long-term effects of ERT with recombinant alpha-galactosidase A (agalsidase beta, Fabrazyme) on LV function and myocardial signal intensity in 11 patients with Anderson-Fabry disease. Eleven patients (eight males, three females) with varying stages of genetically confirmed Anderson-Fabry disease were examined by means of physical examination and magnetic resonance imaging before ERT with agalsidase beta at 1 mg/kg every other week (study 1) and after a mean treatment duration of 45 months (study 2). At 45 months of treatment, LV mass and LV wall thickness had significantly reduced: 188 (SD 60) g versus 153 (47) g, and 16 (4) mm versus 14 (4) mm, respectively. Furthermore, a significant reduction in myocardial T2 relaxation times was noted in all myocardial regions, that is, interventricular septum 80 (5) ms versus 66 (8) ms, apex 79 (10) ms versus 64 (10) ms, and lateral wall 80 (8) ms versus 65 (16) ms. Changes in LV ejection fraction were not significant. Amelioration of clinical symptoms was observed in all patients. Long-term therapy with agalsidase beta at 1 mg/kg every 2 weeks was effective in significantly reducing LV hypertrophy, improving overall cardiac performance and ameliorating clinical symptoms in patients with Anderson-Fabry disease.

Fungal Enzymes for Bio-Products from Sustainable and Waste Biomass.

PubMed

Gupta, Vijai K; Kubicek, Christian P; Berrin, Jean-Guy; Wilson, David W; Couturier, Marie; Berlin, Alex; Filho, Edivaldo X F; Ezeji, Thaddeus

2016-07-01

Lignocellulose, the most abundant renewable carbon source on earth, is the logical candidate to replace fossil carbon as the major biofuel raw material. Nevertheless, the technologies needed to convert lignocellulose into soluble products that can then be utilized by the chemical or fuel industries face several challenges. Enzymatic hydrolysis is of major importance, and we review the progress made in fungal enzyme technology over the past few years with major emphasis on (i) the enzymes needed for the conversion of polysaccharides (cellulose and hemicellulose) into soluble products, (ii) the potential uses of lignin degradation products, and (iii) current progress and bottlenecks for the use of the soluble lignocellulose derivatives in emerging biorefineries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ga metal nanoparticle-GaAs quantum molecule complexes for Terahertz generation.

PubMed

Bietti, Sergio; Basso Basset, Francesco; Scarpellini, David; Fedorov, Alexey; Ballabio, Andrea; Esposito, Luca; Elborg, Martin; Kuroda, Takashi; Nemcsics, Akos; Toth, Lajos; Manzoni, Cristian; Vozzi, Caterina; Sanguinetti, Stefano

2018-06-18

A hybrid metal-semiconductor nanosystem for the generation of THz radiation, based on the fabrication of GaAs quantum molecules-Ga metal nanoparticles complexes through a self assembly approach, is proposed. The role of the growth parameters, the substrate temperature, the Ga and As flux during the quantum dot molecule fabrication and the metal nanoparticle alignment is discussed. The tuning of the relative positioning of quantum dot molecules and metal nanoparticles is obtained through the careful control of Ga droplet nucleation sites via Ga surface diffusion. The electronic structure of a typical quantum dot molecule was evaluated on the base of the morphological characterizations performed by Atomic Force Microscopy and cross sectional Scanning Electron Microscopy, and the predicted results confirmed by micro-photoluminescence experiments, showing that the Ga metal nanoparticle-GaAs quantum molecule complexes are suitable for terahertz generation from intraband transition. . © 2018 IOP Publishing Ltd.

Enhanced thermoelectric transport in modulation-doped GaN/AlGaN core/shell nanowires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Erdong; Li, Qiming; Swartzentruber, Brian

2015-11-25

The thermoelectric properties of unintentionally n-doped core GaN/AlGaN core/shell N-face nanowires are reported. We found that the temperature dependence of the electrical conductivity is consistent with thermally activated carriers with two distinctive donor energies. The Seebeck coefficient of GaN/AlGaN nanowires is more than twice as large as that for the GaN nanowires alone. However, an outer layer of GaN deposited onto the GaN/AlGaN core/shell nanowires decreases the Seebeck coefficient at room temperature, while the temperature dependence of the electrical conductivity remains the same. We attribute these observations to the formation of an electron gas channel within the heavily-doped GaN coremore » of the GaN/AlGaN nanowires. The room-temperature thermoelectric power factor for the GaN/AlGaN nanowires can be four times higher than the GaN nanowires. As a result, selective doping in bandgap engineered core/shell nanowires is proposed for enhancing the thermoelectric power.« less

The Effects of the Addition of Dy, Nb, and Ga on Microstructure and Magnetic Properties of Nd2Fe14B/α-Fe Nanocomposite Permanent Magnetic Alloys.

PubMed

Ren, Kezhi; Tan, Xiaohua; Li, Heyun; Xu, Hui; Han, Ke

2017-04-01

We study the effects of Dy, Nb, and Ga additions on the microstructure and magnetic properties of Nd2Fe14B/α-Fe nanocomposites. Dy, Nb, and Ga additions inhibit the growth of the soft magnetic α-Fe phase. Dy and Nb additions are able to refine the microstructure, whereas Ga addition plays only a minor role in prohibiting crystal growth. The magnetic properties are sensitive to Dy, Nb, and Ga additions. The Dy-containing alloy enhances the intrinsic coercivity of 872 kA/m because Dy partially replaces Nd, forming (Nd, Dy)2Fe14B. Nb addition refines the microstructure, and consequently increases the exchange coupling between magnetic grains. The Nd9.5Fe75.4Co5Zr3B6.5Ga0.6 alloy exhibits the highest remanence (0.92 T) due to Ga addition.

Simulation and optimization performance of GaAs/GaAs0.5Sb0.5/GaSb mechanically stacked tandem solar cells

NASA Astrophysics Data System (ADS)

Tayubi, Y. R.; Suhandi, A.; Samsudin, A.; Arifin, P.; Supriyatman

2018-05-01

Different approaches have been made in order to reach higher solar cells efficiencies. Concepts for multilayer solar cells have been developed. This can be realised if multiple individual single junction solar cells with different suitably chosen band gaps are connected in series in multi-junction solar cells. In our work, we have simulated and optimized solar cells based on the system mechanically stacked using computer simulation and predict their maximum performance. The structures of solar cells are based on the single junction GaAs, GaAs0.5Sb0.5 and GaSb cells. We have simulated each cell individually and extracted their optimal parameters (layer thickness, carrier concentration, the recombination velocity, etc), also, we calculated the efficiency of each cells optimized by separation of the solar spectrum in bands where the cell is sensible for the absorption. The optimal values of conversion efficiency have obtained for the three individual solar cells and the GaAs/GaAs0.5Sb0.5/GaSb tandem solar cells, that are: η = 19,76% for GaAs solar cell, η = 8,42% for GaAs0,5Sb0,5 solar cell, η = 4, 84% for GaSb solar cell and η = 33,02% for GaAs/GaAs0.5Sb0.5/GaSb tandem solar cell.

[The switch of enzyme therapy in Fabry disease].

PubMed

Riccio, Eleonora; Pisani, Antonio

2014-01-01

Fabry disease (FD) is a multiorgan X-linked lysosomal storage disorder resulted from the deficiency of the lysosomal enzyme alpha galactosidase A. It particularly affects the heart, kidneys and cerebrovascular system. The treatment options for FD patients include long-term enzyme replacement therapy (ERT). Two recombinant enzyme formulations for the ERT of FD are available on European market: agalsidase alfa and agalsidase beta. Numerous evidences in the literature have confirmed the safety and efficacy of ERT. However, to date, there have been limited comparisons between the two agents, and no firm conclusion can be drawn regarding their specific efficacy and safety. In June 2009, a viral contamination in the manufacturing process of Fabrazyme led to a global shortage of agalsidase beta. Recommendations to shift patients to the recommended dose of Replagal were published by the European Medicines Agency (EMA) for all patients receiving Fabrazyme. This offered the unique opportunity to compare, although indirectly, the two drugs evaluating any clinical modification or adverse events that occurred after the switch. Moreover, with the increased availability of agalsidase beta in the last 3 months of 2012, some of the patients who previously switched to agalsidase alfa, were switched-back and returned to full-dose agalsidase beta. This article reviews the published evidence for the clinical efficacy of the two available enzyme preparations and compare it with the experience of our center.

Fabrication and improved photoelectrochemical properties of a transferred GaN-based thin film with InGaN/GaN layers.

PubMed

Cao, Dezhong; Xiao, Hongdi; Gao, Qingxue; Yang, Xiaokun; Luan, Caina; Mao, Hongzhi; Liu, Jianqiang; Liu, Xiangdong

2017-08-17

Herein, a lift-off mesoporous GaN-based thin film, which consisted of a strong phase-separated InGaN/GaN layer and an n-GaN layer, was fabricated via an electrochemical etching method in a hydrofluoric acid (HF) solution for the first time and then transferred onto quartz or n-Si substrates, acting as photoanodes during photoelectrochemical (PEC) water splitting in a 1 M NaCl aqueous solution. Compared to the as-grown GaN-based film, the transferred GaN-based thin films possess higher and blue-shifted light emission, presumably resulting from an increase in the surface area and stress relaxation in the InGaN/GaN layer embedded on the mesoporous n-GaN. The properties such as (i) high photoconversion efficiency, (ii) low turn-on voltage (-0.79 V versus Ag/AgCl), and (iii) outstanding stability enable the transferred films to have excellent PEC water splitting ability. Furthermore, as compared to the film transferred onto the quartz substrate, the film transferred onto the n-Si substrate exhibits higher photoconversion efficiency (2.99% at -0.10 V) due to holes (h + ) in the mesoporous n-GaN layer that originate from the n-Si substrate.

Control of magnetic anisotropy in (Ga,Mn)as by lithography-induced strain relaxation.

PubMed

Wenisch, J; Gould, C; Ebel, L; Storz, J; Pappert, K; Schmidt, M J; Kumpf, C; Schmidt, G; Brunner, K; Molenkamp, L W

2007-08-17

We report control of magnetic anisotropy in epitaxial (Ga,Mn)As by anisotropic strain relaxation in patterned structures. The strain in the structures is characterized using reciprocal space mapping by x-ray techniques. The magnetic anisotropy before patterning of the layer, which shows biaxial easy axes along [100] and [010], is replaced by a hard axis in the direction of large elastic strain relaxation and a uniaxial easy axis in the direction where pseudomorphic conditions are retained.

Interconversion of the Specificities of Human Lysosomal Enzymes Associated with Fabry and Schindler Diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomasic, Ivan B.; Metcalf, Matthew C.; Guce, Abigail I.

2010-09-03

The human lysosomal enzymes {alpha}-galactosidase ({alpha}-GAL, EC 3.2.1.22) and {alpha}-N-acetylgalactosaminidase ({alpha}-NAGAL, EC 3.2.1.49) share 46% amino acid sequence identity and have similar folds. The active sites of the two enzymes share 11 of 13 amino acids, differing only where they interact with the 2-position of the substrates. Using a rational protein engineering approach, we interconverted the enzymatic specificity of {alpha}-GAL and {alpha}-NAGAL. The engineered {alpha}-GAL (which we call {alpha}-GALSA) retains the antigenicity of {alpha}-GAL but has acquired the enzymatic specificity of {alpha}-NAGAL. Conversely, the engineered {alpha}-NAGAL (which we call {alpha}-NAGAL{sup EL}) retains the antigenicity of {alpha}-NAGAL but has acquired themore » enzymatic specificity of the {alpha}-GAL enzyme. Comparison of the crystal structures of the designed enzyme {alpha}-GAL{sup SA} to the wild-type enzymes shows that active sites of {alpha}-GAL{sup SA} and {alpha}-NAGAL superimpose well, indicating success of the rational design. The designed enzymes might be useful as non-immunogenic alternatives in enzyme replacement therapy for treatment of lysosomal storage disorders such as Fabry disease.« less

Investigation of gate-diode degradation in normally-off p-GaN/AlGaN/GaN high-electron-mobility transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ťapajna, M., E-mail: milan.tapajna@savba.sk; Kuzmík, J.; Hilt, O.

2015-11-09

Gate diode conduction mechanisms were analyzed in normally-off p-GaN/AlGaN/GaN high-electron mobility transistors grown on Si wafers before and after forward bias stresses. Electrical characterization of the gate diodes indicates forward current to be limited by channel electrons injected through the AlGaN/p-GaN triangular barrier promoted by traps. On the other hand, reverse current was found to be consistent with carrier generation-recombination processes in the AlGaN layer. Soft breakdown observed after ∼10{sup 5 }s during forward bias stress at gate voltage of 7 V was attributed to formation of conductive channel in p-GaN/AlGaN gate stack via trap generation and percolation mechanism, likely due tomore » coexistence of high electric field and high forward current density. Possible enhancement of localized conductive channels originating from spatial inhomogeneities is proposed to be responsible for the degradation.« less

Dry-grind processing using amylase corn and superior yeast to reduce the exogenous enzyme requirements in bioethanol production.

PubMed

Kumar, Deepak; Singh, Vijay

2016-01-01

Conventional corn dry-grind ethanol production process requires exogenous alpha and glucoamylases enzymes to breakdown starch into glucose, which is fermented to ethanol by yeast. This study evaluates the potential use of new genetically engineered corn and yeast, which can eliminate or minimize the use of these external enzymes, improve the economics and process efficiencies, and simplify the process. An approach of in situ ethanol removal during fermentation was also investigated for its potential to improve the efficiency of high-solid fermentation, which can significantly reduce the downstream ethanol and co-product recovery cost. The fermentation of amylase corn (producing endogenous α-amylase) using conventional yeast and no addition of exogenous α-amylase resulted in ethanol concentration of 4.1 % higher compared to control treatment (conventional corn using exogenous α-amylase). Conventional corn processed with exogenous α-amylase and superior yeast (producing glucoamylase or GA) with no exogenous glucoamylase addition resulted in ethanol concentration similar to control treatment (conventional yeast with exogenous glucoamylase addition). Combination of amylase corn and superior yeast required only 25 % of recommended glucoamylase dose to complete fermentation and achieve ethanol concentration and yield similar to control treatment (conventional corn with exogenous α-amylase, conventional yeast with exogenous glucoamylase). Use of superior yeast with 50 % GA addition resulted in similar increases in yield for conventional or amylase corn of approximately 7 % compared to that of control treatment. Combination of amylase corn, superior yeast, and in situ ethanol removal resulted in a process that allowed complete fermentation of 40 % slurry solids with only 50 % of exogenous GA enzyme requirements and 64.6 % higher ethanol yield compared to that of conventional process. Use of amylase corn and superior yeast in the dry-grind processing industry

A Comparative Study of AlGaN and InGaN Back-Barriers in Ultrathin-Barrier AlN/GaN Heterostructures

NASA Astrophysics Data System (ADS)

All Abbas, J. M.; Atmaca, G.; Narin, P.; Kutlu, E.; Sarikavak-Lisesivdin, B.; Lisesivdin, S. B.

2017-08-01

Investigations of the effects of back-barrier introduction on the two-dimensional electron gas (2DEG) of ultrathin-barrier AlN/GaN heterostructures with AlGaN and InGaN back-barriers are carried out using self-consistent solutions of 1-dimensional Schrödinger-Poisson equations. Inserted AlGaN and InGaN back-barriers are used to provide a good 2DEG confinement thanks to raising the conduction band edge of GaN buffer with respect to GaN channel layer. Therefore, in this paper the influence of these back-barrier layers on sheet carrier density, 2DEG confinement, and mobility are systematically and comparatively investigated. As a result of calculations, although sheet carrier density is found to decrease with InGaN back-barrier layer, it is not changed with AlGaN back-barrier layer for suggested optimise heterostructures. Obtained results can give some insights for further experimental studies.

Laser induced OMCVD growth of AlGaAs on GaAs

NASA Technical Reports Server (NTRS)

Wilt, David M.; Warner, Joseph D.; Aron, Paul R.; Pouch, John J.; Hoffman, Richard W., Jr.

1987-01-01

A major factor limiting the efficiency of the GaAs-GaAlAs solar cell is the rate of recombination at the GaAs-AlGaAs interface. Evidence has been previously reported which indicates that recombination at this interface can be greatly reduced if the AlGaAs layer is grown at lower than normal temperatures. The authors examine the epitaxial growth of AlGaAs on GaAs using a horizontal OMCVD reactor and an excimer laser operating in the UV (lambda = 193 nm) region. The growth temperatures were 450 and 500 C. The laser beam was utilized in two orientations: 75 deg angle of incidence and parallel to the substrate. Film composition and structure were determined by Auger electron spectroscopy (AES) and transmission electron microscopy (TEM). Auger analysis of epilayers grown at 500 C with the laser impinging show no carbon or oxygen contamination of the epitaxial layers or interfaces. TEM diffraction patterns of these same epilayers exhibit single crystal (100) zone axis patterns.

Crystallographic Studies of Two Bacterial AntibioticResistance Enzymes: Aminoglycoside Phosphotransferase (2')-Ic and GES-1\\beta-lactamase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brynes, Laura; /Rensselaer Poly.

2007-10-31

Guiana Extended-Spectrum-1 (GES-1) and Aminoglycoside phosphotransferase (2')-Ic (APH(2')-Ic) are two bacteria-produced enzymes that essentially perform the same task: they provide resistance to an array of antibiotics. Both enzymes are part of a growing resistance problem in the medical world. In order to overcome the ever-growing arsenal of antibiotic-resistance enzymes, it is necessary to understand the molecular basis of their action. Accurate structures of these proteins have become an invaluable tool to do this. Using protein crystallography techniques and X-ray diffraction, the protein structure of GES-1 bound to imipenem (an inhibitor) has been solved. Also, APH(2')-Ic has been successfully crystallized, butmore » its structure was unable to be solved using molecular replacement using APH(2')-Ib as a search model. The structure of GES-1, with bound imipenem was solved to a resolution of 1.89A, and though the inhibitor is bound with only moderate occupancy, the structure shows crucial interactions inside the active site that render the enzyme unable to complete the hydrolysis of the {beta}-lactam ring. The APH(2')-Ic dataset could not be matched to the model, APH(2')-Ib, with which it shares 25% sequence identity. The structural information gained from GES-1, and future studies using isomorphous replacement to solve the APH(2')-Ic structure can aid directly to the creation of novel drugs to combat both of these classes of resistance enzymes.« less

High efficiency epitaxial GaAs/GaAs and GaAs/Ge solar cell technology using OM/CVD

NASA Technical Reports Server (NTRS)

Wang, K. L.; Yeh, Y. C. M.; Stirn, R. J.; Swerdling, S.

1980-01-01

A technology for fabricating high efficiency, thin film GaAs solar cells on substrates appropriate for space and/or terrestrial applications was developed. The approach adopted utilizes organometallic chemical vapor deposition (OM-CVD) to form a GaAs layer epitaxially on a suitably prepared Ge epi-interlayer deposited on a substrate, especially a light weight silicon substrate which can lead to a 300 watt per kilogram array technology for space. The proposed cell structure is described. The GaAs epilayer growth on single crystal GaAs and Ge wafer substrates were investigated.

On the dissolution properties of GaAs in Ga

NASA Technical Reports Server (NTRS)

Davidson, M. C.; Moynahan, A. H.

1977-01-01

The dissolution of GaAs in Ga was studied to determine the nature and cause of faceting effects. Ga was allowed to dissolve single crystalline faces under isothermal conditions. Of the crystalline planes with low number indices, only the (100) surface showed a direct correlation of dissolution sites to dislocations. The type of dissolution experienced depended on temperature, and there were three distinct types of behavior.

Self-diffusion in 69Ga121Sb/71Ga123Sb isotope heterostructures

NASA Astrophysics Data System (ADS)

Bracht, H.; Nicols, S. P.; Haller, E. E.; Silveira, J. P.; Briones, F.

2001-05-01

Gallium and antimony self-diffusion experiments have been performed in undoped 69Ga121Sb/71Ga123Sb isotope heterostructures at temperatures between 571 and 708 °C under Sb- and Ga-rich ambients. Ga and Sb profiles measured with secondary ion mass spectrometry reveal that Ga diffuses faster than Sb by several orders of magnitude. This strongly suggests that the two self-atom species diffuse independently on their own sublattices. Experimental results lead us to conclude that Ga and Sb diffusion are mediated by Ga vacancies and Sb interstitials, respectively, and not by the formation of a triple defect proposed earlier by Weiler and Mehrer [Philos. Mag. A 49, 309 (1984)]. The extremely slow diffusion of Sb up to the melting temperature of GaSb is proposed to be a consequence of amphoteric transformations between native point defects which suppress the formation of those native defects which control Sb diffusion. Preliminary experiments exploring the effect of Zn indiffusion at 550 °C on Ga and Sb diffusion reveal an enhanced intermixing of the Ga isotope layers compared to undoped GaSb. However, under the same conditions the diffusion of Sb was not significantly affected.

Classical Spin Nematic Transition in LiGa0.95In0.05Cr4O8

NASA Astrophysics Data System (ADS)

Wawrzyńczak, R.; Tanaka, Y.; Yoshida, M.; Okamoto, Y.; Manuel, P.; Casati, N.; Hiroi, Z.; Takigawa, M.; Nilsen, G. J.

2017-08-01

We present the results of a combined 7Li -NMR and diffraction study on LiGa0.95In0.05Cr4O8, a member of the LiGa1 -xInxCr4O8 "breathing" pyrochlore family. Via specific heat and NMR measurements, we find that the complex sequence of first-order transitions observed for LiGaCr4O8 is replaced by a single second-order transition at Tf=11 K . Neutron and x-ray diffraction rule out both structural symmetry lowering and magnetic long-range order as the origin of this transition. Instead, reverse Monte Carlo fitting of the magnetic diffuse scattering indicates that the low-temperature phase may be described as a collinear spin nematic state, characterized by a quadrupolar order parameter. This state also shows signs of short-range order between collinear spin arrangements on tetrahedra, revealed by mapping the reverse Monte Carlo spin configurations onto a three-state color model.

Highly efficient pseudomorphic InGaAs/GaAs/AlGaAs single quantum well lasers for monolithic integration

NASA Technical Reports Server (NTRS)

Larsson, A.; Cody, J.; Forouhar, S.; Lang, R. J.

1990-01-01

Highly efficient ridge waveguide pseudomorphic single quantum well lasers, emitting at 980 nm, have been fabricated from an In(0.2)Ga(0.8)As/GaAs/AlGaAs graded-index separate confinement heterostructure grown by molecular beam epitaxy. The laterial index guiding provided by the ridge reduces the anomalously large lateral loss of optical power found in gain-guided structures, thereby reducing the internal loss by more than 50 percent. The low threshold current (7.6 mA) and high differential quantum efficiency (79 percent) obtained under continuous operation as well as the transparency of the GaAs substrate to the emitted radiation render these lasers attractive for Ga-As-based optoelectronic integration.

Characterisation of Ga-coated and Ga-brazed aluminium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferchaud, E.; Christien, F., E-mail: frederic.christien@univ-nantes.fr; Barnier, V.

This work is devoted to the brazing of aluminium using liquid gallium. Gallium was deposited on aluminium samples at {approx} 50 Degree-Sign C using a liquid gallium 'polishing' technique. Brazing was undertaken for 30 min at 500 Degree-Sign C in air. EDS (Energy Dispersive X-ray Spectroscopy) and AES (Auger Electron Spectroscopy) characterisation of Ga-coated samples has shown that the Ga surface layer thickness is of ten (or a few tens of) nanometres. Furthermore, aluminium oxide layer (Al{sub 2}O{sub 3}) was shown to be 'descaled' during Ga deposition, which ensures good conditions for further brazing. Cross-section examination of Ga-coated samples showsmore » that liquid gallium penetrates into the aluminium grain boundaries during deposition. The thickness of the grain boundary gallium film was measured using an original EDS technique and is found to be of a few tens of nanometres. The depth of gallium grain boundary penetration is about 300 {mu}m at the deposition temperature. The fracture stress of the brazed joints was measured from tensile tests and was determined to be 33 MPa. Cross-section examination of brazed joints shows that gallium has fully dissolved into the bulk and that the joint is really autogenous. - Highlights: Black-Right-Pointing-Pointer Aluminium can be brazed using liquid gallium deposited by a 'polishing' technique. Black-Right-Pointing-Pointer The aluminium oxide layer is 'descaled' during liquid Ga 'polishing' deposition. Black-Right-Pointing-Pointer EDS can be used for determination of surface and grain boundary Ga film thickness. Black-Right-Pointing-Pointer The surface and grain boundary Ga film thickness is of a few tens of nm. Black-Right-Pointing-Pointer Surface and grain boundary gallium dissolves in the bulk during brazing.« less

High-Power Single-Mode 2.65-micron InGaAsSb/AlInGaAsSb Diode Lasers

NASA Technical Reports Server (NTRS)

Frez, Clifford F.; Briggs, Ryan M.; Forouhar, Siamak; Borgentun, Carl E.; Gupta, James

2013-01-01

AsSb multi-quantum well structures. The device fabrication utilizes etched index-coupled gratings in the top AlGaAsSb cladding of the laser chip along the ridge waveguide, whereas commercial lasers that emit close to this wavelength include loss-coupled metal gratings that limit the output power of the laser. Semiconductor-laser-based spectrometers can be used to replace gas sensors currently used in industry and government. With the availability of high-power laser sources at mid-infrared wavelengths, sensors can target strong fundamental gas absorption lines to maximize instrument sensitivity.

All zinc-blende GaAs/(Ga,Mn)As core-shell nanowires with ferromagnetic ordering.

PubMed

Yu, Xuezhe; Wang, Hailong; Pan, Dong; Zhao, Jianhua; Misuraca, Jennifer; von Molnár, Stephan; Xiong, Peng

2013-04-10

Combining self-catalyzed vapor-liquid-solid growth of GaAs nanowires and low-temperature molecular-beam epitaxy of (Ga,Mn)As, we successfully synthesized all zinc-blende (ZB) GaAs/(Ga,Mn)As core-shell nanowires on Si(111) substrates. The ZB GaAs nanowire cores are first fabricated at high temperature by utilizing the Ga droplets as the catalyst and controlling the triple phase line nucleation, then the (Ga,Mn)As shells are epitaxially grown on the side facets of the GaAs core at low temperature. The growth window for the pure phase GaAs/(Ga,Mn)As core-shell nanowires is found to be very narrow. Both high-resolution transmission electron microscopy and scanning electron microscopy observations confirm that all-ZB GaAs/(Ga,Mn)As core-shell nanowires with smooth side surface are obtained when the Mn concentration is not more than 2% and the growth temperature is 245 °C or below. Magnetic measurements with different applied field directions provide strong evidence for ferromagnetic ordering in the all-ZB GaAs/(Ga,Mn)As nanowires. The hybrid nanowires offer an attractive platform to explore spin transport and device concepts in fully epitaxial all-semiconductor nanospintronic structures.

Photoluminescence and Band Alignment of Strained GaAsSb/GaAs QW Structures Grown by MBE on GaAs

PubMed Central

Sadofyev, Yuri G.; Samal, Nigamananda

2010-01-01

An in-depth optimization of growth conditions and investigation of optical properties including discussions on band alignment of GaAsSb/GaAs quantum well (QW) on GaAs by molecular beam epitaxy (MBE) are reported. Optimal MBE growth temperature of GaAsSb QW is found to be 470 ± 10 °C. GaAsSb/GaAs QW with Sb content ~0.36 has a weak type-II band alignment with valence band offset ratio QV ~1.06. A full width at half maximum (FWHM) of ~60 meV in room temperature (RT) photoluminescence (PL) indicates fluctuation in electrostatic potential to be less than 20 meV. Samples grown under optimal conditions do not exhibit any blue shift of peak in RT PL spectra under varying excitation.

Self-organized formation of GaSb/GaAs quantum rings.

PubMed

Timm, R; Eisele, H; Lenz, A; Ivanova, L; Balakrishnan, G; Huffaker, D L; Dähne, M

2008-12-19

Ring-shaped GaSb/GaAs quantum dots, grown by molecular beam epitaxy, were studied using cross-sectional scanning tunneling microscopy. These quantum rings have an outer shape of a truncated pyramid with baselengths around 15 nm and heights of about 2 nm but are characterized by a clear central opening extending over about 40% of the outer baselength. They form spontaneously during the growth and subsequent continuous capping of GaSb/GaAs quantum dots due to the large strain and substantial As-for-Sb exchange reactions leading to strong Sb segregation.

Rectifying behavior in the GaN/graded-AlxGa1‑xN/GaN double heterojunction structure

NASA Astrophysics Data System (ADS)

Wang, Caiwei; Jiang, Yang; Ma, Ziguang; Zuo, Peng; Yan, Shen; Die, Junhui; Wang, Lu; Jia, Haiqiang; Wang, Wenxin; Chen, Hong

2018-05-01

Rectifying characteristics induced by the polarization fields are achieved in the GaN/graded-AlxGa1‑xN/GaN double heterojunction structure (DHS). By grading AlxGa1‑xN from x  =  0.4(0.3) to 0.1, the DHS displays a better conductivity for smaller reverse bias than for forward bias voltages (reverse rectifying behavior) which is opposite to p–n junction rectifying characteristics. The mechanism of reverse rectifying behavior is illustrated via calculating the energy band structures of the samples. The band gap narrowing caused by decreasing Al composition could compensate the for the band tilt due to the polarization effect in AlxGa1‑xN barriers, thus lowering the barrier height for electron transport from top to bottom. The reverse rectifying behavior could be enhanced by increasing the Al content and the thickness of the multi-layer graded AlxGa1‑xN barriers. This work gives a better understanding of the mechanism of carrier transport in a DHS and makes it possible to realize novel GaN-based heterojunction transistors.

Pancreatic enzyme replacement therapy.

PubMed

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.

Energetics of Mg incorporation at GaN(0001) and GaN(0001¯) surfaces

NASA Astrophysics Data System (ADS)

Sun, Qiang; Selloni, Annabella; Myers, T. H.; Doolittle, W. Alan

2006-04-01

By using density functional calculations in the generalized gradient approximation, we investigate the energetics of Mg adsorption and incorporation at GaN(0001) and GaN(0001¯) surfaces under various Ga and Mg coverage conditions as well as in presence of light or electron beam-induced electronic excitation. We find significant differences in Mg incorporation between Ga- and N-polar surfaces. Mg incorporation is easier at the Ga-polar surface, but high Mg coverages are found to cause important distortions which locally change the polarity from Ga to N polar. At the N-rich and moderately Ga-rich GaN(0001) surface, 0.25 ML of Mg substituting Ga in the top bilayer strongly reduce the surface diffusion barriers of Ga and N adatoms, in agreement with the surfactant effect observed in experiments. As the Mg coverage exceeds 0.5 ML, partial incorporation in the subsurface region (second bilayer) becomes favorable. A surface structure with 0.5 ML of incorporated Mg in the top bilayer and 0.25 ML in the second bilayer is found to be stable over a wide range of Ga chemical potential. At the Ga bilayer-terminated GaN(0001) surface, corresponding to Ga-rich conditions, configurations where Mg is incorporated in the interface region between the metallic Ga bilayer and the underlying GaN bilayer appear to be favored. At the N-polar surface, Mg is not incorporated under N-rich or moderately Ga-rich conditions, whereas incorporation in the adlayer may take place under Ga-rich conditions. In the presence of light or electron beam induced excitation, energy differences between Mg incorporated at the surface and in deeper layers are reduced so that the tendency toward surface segregation is also reduced.

Hybrid type-I InAs/GaAs and type-II GaSb/GaAs quantum dot structure with enhanced photoluminescence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ji, Hai-Ming; Institute of Semiconductors, Chinese Academy of Sciences, Beijing 100083; Liang, Baolai, E-mail: bliang@cnsi.ucla.edu

2015-03-09

We investigate the photoluminescence (PL) properties of a hybrid type-I InAs/GaAs and type-II GaSb/GaAs quantum dot (QD) structure grown in a GaAs matrix by molecular beam epitaxy. This hybrid QD structure exhibits more intense PL with a broader spectral range, compared with control samples that contain only InAs or GaSb QDs. This enhanced PL performance is attributed to additional electron and hole injection from the type-I InAs QDs into the adjacent type-II GaSb QDs. We confirm this mechanism using time-resolved and power-dependent PL. These hybrid QD structures show potential for high efficiency QD solar cell applications.

Response of single junction GaAs/GaAs and GaAs/Ge solar cells to multiple doses of 1 MeV electrons

NASA Technical Reports Server (NTRS)

Meier, D. L.; Szedon, J. R.; Bartko, J.; Chung, M. A.

1989-01-01

A comparison of the radiation tolerance of MOCVD-grown GaAs cells and GaAs/Ge cells was undertaken using 1 MeV electrons. The GaAs/Ge cells are somewhat more tolerant of 1 MeV electron irradiation and more responsive to annealing than are the GaAs/GaAs cells examined in this study. However, both types of cells suffer a greater degradation in efficiency than has been observed in other recent studies. The reason for this is not certain, but it may be associated with an emitter thickness which appears to be greater than desired. The deep level transient spectroscopy (DLTS) spectra following irradiation are not significantly different for the GaAs/Ge and the GaAs/GaAs cells, with each having just two peaks. The annealing behavior of these peaks is also similar in the two samples examined. It appears that no penalty in radiation tolerance, and perhaps some benefit, is associated with fabricating MOCVD GaAs cells on Ge substrates rather than GaAs substrates.

Polarization-Engineered Ga-Face GaN-Based Heterostructures for Normally-Off Heterostructure Field-Effect Transistors

NASA Astrophysics Data System (ADS)

Kim, Hyeongnam; Nath, Digbijoy; Rajan, Siddharth; Lu, Wu

2013-01-01

Polarization-engineered Ga-face GaN-based heterostructures with a GaN cap layer and an AlGaN/ p-GaN back barrier have been designed for normally-off field-effect transistors (FETs). The simulation results show that an unintentionally doped GaN cap and p-GaN layer in the buffer primarily deplete electrons in the channel and the Al0.2Ga0.8N back barrier helps to pinch off the channel. Experimentally, we have demonstrated a normally-off GaN-based field-effect transistor on the designed GaN cap/Al0.3Ga0.7N/GaN channel/Al0.2Ga0.8N/ p-GaN/GaN heterostructure. A positive threshold voltage of 0.2 V and maximum transconductance of 2.6 mS/mm were achieved for 80- μm-long gate devices. The device fabrication process does not require a dry etching process for gate recessing, while highly selective etching of the GaN cap against a very thin Al0.3GaN0.7N top barrier has to be performed to create a two-dimensional electron gas for both the ohmic and access regions. A self-aligned, selective etch of the GaN cap in the access region is introduced, using the gate metal as an etch mask. The absence of gate recess etching is promising for uniform and repeatable threshold voltage control in normally-off AlGaN/GaN heterostructure FETs for power switching applications.

Medium energy proton radiation damage to (AlGa)As-GaAs solar cells

NASA Technical Reports Server (NTRS)

Loo, R. Y.; Kamath, G. S.; Knechtli, R. C.

1982-01-01

The performance of (AlGa)As-GaAs solar cells irradiated by medium energy 2, 5, and 10 MeV protons was evaluated. The Si cells without coverglass and a number of GaAs solar cells with 12 mil coverglass were irradiated simultaneously with bare GaAs cells. The cell degradation is directly related to the penetration of depth of protons with GaAs. The influence of periodic and continuous thermal annealing on the GaAs solar cells was investigated.

Dependence of Ag/Ga composition ratio in AgGaSe2 thin film

NASA Astrophysics Data System (ADS)

Matsuo, H.; Yoshino, K.; Ikari, T.

2006-09-01

AgGaSe2 thin film was deposited on glass substrates by vacuum evaporation method. The starting material was mixed Ag2Se and Ga2Se3 powders. Ag/Ga ratios of the samples were 1.5, 1.2, 1.0, 0.8, 0.7 and 0.4. The samples were annealed from 100 to 600 °C for 10 min. After these processes, single phase AgGaSe2 thin films could be obtained except Ag/Ga ratio of 0.4 at annealing temperature of 600 °C. Ag-rich samples had large grain. On the other hand, Ga-rich samples had small grain. Furthermore, Ga-rich and Ag-rich samples indicated p- and n-types because of Ag- and/or Ga-vacancy and Se-vacancy, respectively.

Comparison of as-grown and annealed GaN/InGaN : Mg samples

NASA Astrophysics Data System (ADS)

Deng, Qingwen; Wang, Xiaoliang; Xiao, Hongling; Wang, Cuimei; Yin, Haibo; Chen, Hong; Lin, Defeng; Jiang, Lijuan; Feng, Chun; Li, Jinmin; Wang, Zhanguo; Hou, Xun

2011-08-01

Mg-doped InGaN was grown on unintentionally doped GaN layer, and Mg and defect behaviours in both GaN and InGaN : Mg were investigated through photoluminescence measurement at 7 K. Mg acceptor was found in unintentionally doped GaN after thermal annealing in N2 ambient, and Mg activation energy was estimated to be 200 meV and 110 meV for GaN and InGaN, respectively. Particularly, the ultraviolet band (3.0-3.2 eV) in the GaN layer was infrequently observed in the unannealed sample but quenched in the annealed sample; this band may be associated with oxygen-substituted nitrogen defects. Moreover, the measurement errors of photoluminescence and x-ray diffraction originated from strain were taken into account.

Thermal annealing effect on the Mg-doped AlGaN/GaN superlattice

NASA Astrophysics Data System (ADS)

Wang, Baozhu; An, Shengbiao; Wen, Huanming; Wu, Ruihong; Wang, Xiaojun; Wang, Xiaoliang

2009-11-01

Mg-doped AlGaN/GaN superlattice has been grown by metalorganic chemical vapor deposition (MOCVD). Rapid thermal annealing (RTA) treament are carryied out on the samples under nitrogen as protect gas. Hall, photoluminescence (PL), high resolution x-ray diffraction (HRXRD) and atomic-force microscopy (AFM) are used to characterize the electrical, optical and structural properties of the as-grown and annealed samples, respectively. After annealing, the Hall results indicate more Mg acceptors are activated, which leads to higher hole concentration and lower p-type resistivity. The PL intensity of Mg related defect band shows a strong decrease after annealing. The annealing of the superlattice degrade the interface quality of the AlGaN/GaN from the HRXRD results. Many nanometer-grains can be observed on the surface of AlGaN/GaN superlattice from the AFM image. This maybe related with the decomposing of GaN or the separating of Mg from the AlGaN/GaN superlattice.

Atomic-scale structure and electronic properties of GaN/GaAs superlattices

NASA Astrophysics Data System (ADS)

Goldman, R. S.; Feenstra, R. M.; Briner, B. G.; O'Steen, M. L.; Hauenstein, R. J.

1996-12-01

We have investigated the atomic-scale structure and electronic properties of GaN/GaAs superlattices produced by nitridation of a molecular beam epitaxially grown GaAs surface. Using cross-sectional scanning tunneling microscopy (STM) and spectroscopy, we show that the nitrided layers are laterally inhomogeneous, consisting of groups of atomic-scale defects and larger clusters. Analysis of x-ray diffraction data in terms of fractional area of clusters (determined by STM), reveals a cluster lattice constant similar to bulk GaN. In addition, tunneling spectroscopy on the defects indicates a conduction band state associated with an acceptor level of NAs in GaAs. Therefore, we identify the clusters and defects as nearly pure GaN and NAs, respectively. Together, the results reveal phase segregation in these arsenide/nitride structures, in agreement with the large miscibility gap predicted for GaAsN.

Shoulder replacement - discharge

MedlinePlus

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Periodic Two-Dimensional GaAs and InGaAs Quantum Rings Grown on GaAs (001) by Droplet Epitaxy.

PubMed

Tung, Kar Hoo Patrick; Huang, Jian; Danner, Aaron

2016-06-01

Growth of ordered GaAs and InGaAs quantum rings (QRs) in a patterned SiO2 nanohole template by molecular beam epitaxy (MBE) using droplet epitaxy (DE) process is demonstrated. DE is an MBE growth technique used to fabricate quantum nanostructures of high crystal quality by supplying group III and group V elements in separate phases. In this work, ordered QRs grown on an ordered nanohole template are compared to self-assembled QRs grown with the same DE technique without the nanohole template. This study allows us to understand and compare the surface kinetics of Ga and InGa droplets when a template is present. It is found that template-grown GaAs QRs form clustered rings which can be attributed to low mobility of Ga droplets resulting in multiple nucleation sites for QR formation when As is supplied. However, the case of template-grown InGaAs QRs only one ring is formed per nanohole; no clustering is observed. The outer QR diameter is a close match to the nanohole template diameter. This can be attributed to more mobile InGa droplets, which coalesce from an Ostwald ripening to form a single large droplet before As is supplied. Thus, well-patterned InGaAs QRs are demonstrated and the kinetics of their growth are better understood which could potentially lead to improvements in the future devices that require the unique properties of patterned QRs.

Synthesis of GaN:ZnO solid solution by solution combustion method and characterization for photocatalytic application

NASA Astrophysics Data System (ADS)

Menon, Sumithra Sivadas; Anitha, R.; Gupta, Bhavana; Baskar, K.; Singh, Shubra

2016-05-01

GaN-ZnO solid solution has emerged as a successful and reproducible photocatalyst for overall water splitting by one-step photoexcitation, with a bandgap in visible region. When the solid solution is formed, some of the Zn and O ions are replaced by Ga and N ions respectively and there is a narrowing of bandgap which is hypothesized as due to Zn3d-N2p repulsion. The traditional method of synthesis of GaN-ZnO solid solution is by nitridation of the starting oxides under constant ammonia flow. Here we report a solution combustion technique for the synthesis of the solid solution at a temperature about 500 ° C in a muffle furnace with metal nitrates as precursors and urea as the fuel. The as prepared samples showed change in color with the increased concentration of ZnO in the solution. The structural, microstructural, morphological and optical properties of the samples were realized by Powder X ray diffraction, Scanning electron microscopy, Energy dispersive X ray analysis, Transmission electron microscopy and Photoluminescence. Finally the hydrogen production efficiency of the GaN-ZnO nanopowders by water splitting was found, using methanol as a scavenger. The apparent quantum yield (AQY) of 0.048% is obtained for GaN-ZnO solid solution.

Efficacy and safety of enzyme-replacement-therapy with agalsidase alfa in 36 treatment-naïve Fabry disease patients.

PubMed

Tsuboi, Kazuya; Yamamoto, Hiroshi

2017-06-07

Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from the α-galactosidase A gene mutations. Enzyme-replacement-therapy (ERT) products for FD currently used include agalsidase alfa and agalsidase beta. There are many reports on efficacy and safety of ERT. However, most of the previous studies are done as a retrospective medical records analysis. The Japan Fabry Research - 002 (JFR-002) was a prospective observational clinical study of 36 ERT-naïve FD patients (14 men and 22 women) at baseline (BL) and after initiation of ERT with agalsidase alfa 0.2 mg/kg every two weeks, a median period 62.5 months. The parameters measured included globotriaosylceramide (Gb3), globotriaosylsphingosine (Lyso-Gb3), left ventricular mass index (LVMI), brain natriuretic peptide (BNP), high-sensitivity troponin I (hs-Trop I), estimated glomerular filtration rate (eGFR), and anti-agalsidase alfa IgG antibody formation. All parameters remained steady during ERT treatment period. BNP levels in 14 patients whose BL levels were within the normal range (<19.5 pg/mL) remained within the same range, while 22 patients whose BL levels were abnormally high (≥19.5 pg/mL) gradually showed decreased levels after start of ERT. Gb3 and Lyso-Gb3 levels remarkably decreased after the initiation of ERT and remained low. The JFR-002 suggests that agalsidase alfa is effective in maintaining organ function in FD patients, and that the incidence of infusion reactions related to the treatment with agalsidase alfa is low, indicating the good tolerability to this ERT. The JFR-002 was retrospectively registered at Japan Medical Association Center for Clinical Trials (Registration number: JMA-IIA00291 ) on May 19th, 2017.

Photocurrent characteristics of metal–AlGaN/GaN Schottky-on-heterojunction diodes induced by GaN interband excitation

NASA Astrophysics Data System (ADS)

Tang, Xi; Li, Baikui; Chen, Kevin J.; Wang, Jiannong

2018-05-01

The photocurrent characteristics of metal–AlGaN/GaN Schottky-on-heterojunction diodes were investigated. When the photon energy of incident light was larger than the bandgap of GaN but smaller than that of AlGaN, the alternating-current (ac) photocurrent measured using lock-in techniques increased with the chopper frequency. Analyzing the generation and flow processes of photocarriers revealed that the photocurrent induced by GaN interband excitation featured a transient behavior, and its direction reversed when the light excitation was removed. The abnormal dependence of the measured ac photocurrent magnitude on the chopper frequency was explained considering the detection principles of a lock-in amplifier.

Control of Ga-oxide interlayer growth and Ga diffusion in SiO2/GaN stacks for high-quality GaN-based metal-oxide-semiconductor devices with improved gate dielectric reliability

NASA Astrophysics Data System (ADS)

Yamada, Takahiro; Watanabe, Kenta; Nozaki, Mikito; Yamada, Hisashi; Takahashi, Tokio; Shimizu, Mitsuaki; Yoshigoe, Akitaka; Hosoi, Takuji; Shimura, Takayoshi; Watanabe, Heiji

2018-01-01

A simple and feasible method for fabricating high-quality and highly reliable GaN-based metal-oxide-semiconductor (MOS) devices was developed. The direct chemical vapor deposition of SiO2 films on GaN substrates forming Ga-oxide interlayers was carried out to fabricate SiO2/GaO x /GaN stacked structures. Although well-behaved hysteresis-free GaN-MOS capacitors with extremely low interface state densities below 1010 cm-2 eV-1 were obtained by postdeposition annealing, Ga diffusion into overlying SiO2 layers severely degraded the dielectric breakdown characteristics. However, this problem was found to be solved by rapid thermal processing, leading to the superior performance of the GaN-MOS devices in terms of interface quality, insulating property, and gate dielectric reliability.

Effects of GaN/AlGaN/Sputtered AlN nucleation layers on performance of GaN-based ultraviolet light-emitting diodes

PubMed Central

Hu, Hongpo; Zhou, Shengjun; Liu, Xingtong; Gao, Yilin; Gui, Chengqun; Liu, Sheng

2017-01-01

We report on the demonstration of GaN-based ultraviolet light-emitting diodes (UV LEDs) emitting at 375 nm grown on patterned sapphire substrate (PSS) with in-situ low temperature GaN/AlGaN nucleation layers (NLs) and ex-situ sputtered AlN NL. The threading dislocation (TD) densities in GaN-based UV LEDs with GaN/AlGaN/sputtered AlN NLs were determined by high-resolution X-ray diffraction (XRD) and cross-sectional transmission electron microscopy (TEM), which revealed that the TD density in UV LED with AlGaN NL was the highest, whereas that in UV LED with sputtered AlN NL was the lowest. The light output power (LOP) of UV LED with AlGaN NL was 18.2% higher than that of UV LED with GaN NL owing to a decrease in the absorption of 375 nm UV light in the AlGaN NL with a larger bandgap. Using a sputtered AlN NL instead of the AlGaN NL, the LOP of UV LED was further enhanced by 11.3%, which is attributed to reduced TD density in InGaN/AlInGaN active region. In the sputtered AlN thickness range of 10–25 nm, the LOP of UV LED with 15-nm-thick sputtered AlN NL was the highest, revealing that optimum thickness of the sputtered AlN NL is around 15 nm. PMID:28294166

Hydrogenation of GaSb/GaAs quantum rings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodgson, P. D., E-mail: pdhodgson@hotmail.co.uk; Hayne, M.; Zhuang, Q. D.

2014-08-25

We present the results of photoluminescence measurements on hydrogenated type-II GaSb/GaAs quantum dot/ring (QD/QR) samples at temperatures ranging from 4.2 K to 400 K. Hydrogenation is found to suppress optically induced charge depletion (associated with the presence of carbon acceptors in this system). A redshift of the QD\\QR emission energy of a few tens of meV is observed at temperatures ≥300 K, consistent with a reduction in average occupancy by ∼1 hole. These effects are accompanied by a reduction in PL intensity post-hydrogenation. We conclude that although hydrogenation may have neutralized the carbon acceptors, multiple hole occupancy of type-II GaSb/GaAs QD/QRs is verymore » likely a precondition for intense emission, which would make extending the wavelength significantly beyond 1300 nm at room temperature difficult.« less

46 CFR 7.80 - Tybee Island, GA to St. Simons Island, GA.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Tybee Island south of the entrance to Buck Hammock Creek. (b) A line drawn from the southernmost... 46 Shipping 1 2011-10-01 2011-10-01 false Tybee Island, GA to St. Simons Island, GA. 7.80 Section... BOUNDARY LINES Atlantic Coast § 7.80 Tybee Island, GA to St. Simons Island, GA. (a) A line drawn from the...

46 CFR 7.80 - Tybee Island, GA to St. Simons Island, GA.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Tybee Island south of the entrance to Buck Hammock Creek. (b) A line drawn from the southernmost... 46 Shipping 1 2012-10-01 2012-10-01 false Tybee Island, GA to St. Simons Island, GA. 7.80 Section... BOUNDARY LINES Atlantic Coast § 7.80 Tybee Island, GA to St. Simons Island, GA. (a) A line drawn from the...

46 CFR 7.80 - Tybee Island, GA to St. Simons Island, GA.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Tybee Island south of the entrance to Buck Hammock Creek. (b) A line drawn from the southernmost... 46 Shipping 1 2014-10-01 2014-10-01 false Tybee Island, GA to St. Simons Island, GA. 7.80 Section... BOUNDARY LINES Atlantic Coast § 7.80 Tybee Island, GA to St. Simons Island, GA. (a) A line drawn from the...

46 CFR 7.80 - Tybee Island, GA to St. Simons Island, GA.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Tybee Island south of the entrance to Buck Hammock Creek. (b) A line drawn from the southernmost... 46 Shipping 1 2013-10-01 2013-10-01 false Tybee Island, GA to St. Simons Island, GA. 7.80 Section... BOUNDARY LINES Atlantic Coast § 7.80 Tybee Island, GA to St. Simons Island, GA. (a) A line drawn from the...

Hybrid UV Imager Containing Face-Up AlGaN/GaN Photodiodes

NASA Technical Reports Server (NTRS)

Zheng, Xinyu; Pain, Bedabrata

2005-01-01

A proposed hybrid ultraviolet (UV) image sensor would comprise a planar membrane array of face-up AlGaN/GaN photodiodes integrated with a complementary metal oxide/semiconductor (CMOS) readout-circuit chip. Each pixel in the hybrid image sensor would contain a UV photodiode on the AlGaN/GaN membrane, metal oxide/semiconductor field-effect transistor (MOSFET) readout circuitry on the CMOS chip underneath the photodiode, and a metal via connection between the photodiode and the readout circuitry (see figure). The proposed sensor design would offer all the advantages of comparable prior CMOS active-pixel sensors and AlGaN UV detectors while overcoming some of the limitations of prior (AlGaN/sapphire)/CMOS hybrid image sensors that have been designed and fabricated according to the methodology of flip-chip integration. AlGaN is a nearly ideal UV-detector material because its bandgap is wide and adjustable and it offers the potential to attain extremely low dark current. Integration of AlGaN with CMOS is necessary because at present there are no practical means of realizing readout circuitry in the AlGaN/GaN material system, whereas the means of realizing readout circuitry in CMOS are well established. In one variant of the flip-chip approach to integration, an AlGaN chip on a sapphire substrate is inverted (flipped) and then bump-bonded to a CMOS readout circuit chip; this variant results in poor quantum efficiency. In another variant of the flip-chip approach, an AlGaN chip on a crystalline AlN substrate would be bonded to a CMOS readout circuit chip; this variant is expected to result in narrow spectral response, which would be undesirable in many applications. Two other major disadvantages of flip-chip integration are large pixel size (a consequence of the need to devote sufficient area to each bump bond) and severe restriction on the photodetector structure. The membrane array of AlGaN/GaN photodiodes and the CMOS readout circuit for the proposed image sensor would

Optical properties of two-dimensional GaS and GaSe monolayers

NASA Astrophysics Data System (ADS)

Jappor, Hamad Rahman; Habeeb, Majeed Ali

2018-07-01

Optical properties of GaS and GaSe monolayers are investigated using first-principles calculations. The optical properties are studied up to 35 eV. Precisely, our results demonstrated that the optical properties appearance of GaS monolayer is comparative with GaSe monolayer with few informations contrasts. Moreover, the absorption begins in the visible region, although the peaks in the ultraviolet (UV) region. The refractive index values are 1.644 (GaS monolayer) and 2.01 (GaSe monolayer) at zero photon energy limit and increase to 2.092 and 2.698 respectively and both located in the visible region. Furthermore, we notice that the optical properties of both monolayers are obtained in the ultraviolet range and the results are significant. Accordingly, it can be used as a highly promising material in the solar cell, ultraviolet optical nanodevices, nanoelectronics, optoelectronic, and photocatalytic applications.

Atomic structure and stoichiometry of In(Ga)As/GaAs quantum dots grown on an exact-oriented GaP/Si(001) substrate

NASA Astrophysics Data System (ADS)

Schulze, C. S.; Huang, X.; Prohl, C.; Füllert, V.; Rybank, S.; Maddox, S. J.; March, S. D.; Bank, S. R.; Lee, M. L.; Lenz, A.

2016-04-01

The atomic structure and stoichiometry of InAs/InGaAs quantum-dot-in-a-well structures grown on exactly oriented GaP/Si(001) are revealed by cross-sectional scanning tunneling microscopy. An averaged lateral size of 20 nm, heights up to 8 nm, and an In concentration of up to 100% are determined, being quite similar compared with the well-known quantum dots grown on GaAs substrates. Photoluminescence spectra taken from nanostructures of side-by-side grown samples on GaP/Si(001) and GaAs(001) show slightly blue shifted ground-state emission wavelength for growth on GaP/Si(001) with an even higher peak intensity compared with those on GaAs(001). This demonstrates the high potential of GaP/Si(001) templates for integration of III-V optoelectronic components into silicon-based technology.

Immunophenotypic and genetic characteristics of diffuse large B-cell lymphoma in Taiwan.

PubMed

Chang, Sheng-Tsung; Chen, Shang-Wen; Ho, Chung-Han; Kuo, Chun-Chi; Sakata, Seiji; Takeuchi, Kengo; Chuang, Shih-Sung

2016-11-01

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma type. The immunophenotypic and genetic features of DLBCL in Taiwan have not been characterized. In this study, we performed immunohistochemical analysis and interphase fluorescence in situ hybridization (FISH) using tissue microarray sections to investigate a cohort of unselected DLBCL cases in a single institution in Taiwan from 1990 to 2010. Of the 153 cases investigated, CD10, bcl-6, and MUM1 were expressed in 16.3%, 71.2%, and 71.9% cases, respectively, with 27.5% (n = 42) of cases being classified as having a germinal center B-cell (GCB) origin by the Hans algorithm. By FISH analysis, 19.6%, 4.6%, 26.1%, and 3.9% cases showed rearrangement at IGH, BCL2, BCL6, and MYC loci, respectively, including three (2.0%) cases of double-hit lymphoma. As compared with the non-GCB tumors, GCB tumors more frequently expressed CD10 (p < 0.001) and bcl-6 (p = 0.001) with less frequent expression of MUM1 (p = 0.007). Moreover, GCB tumors more frequently exhibited rearrangement at the BCL2 (p = 0.024) and MYC (p = 0.038) loci than non-GCB tumors. However, there was no survival difference between these two groups. In this first series of DLBCL evaluation from Taiwan, we found that the relative frequency of GCB tumors among DLBCL was low in most East Asian countries. There is a wide range of BCL2 rearrangement rates, higher in the West and lower in East Asia. A larger and/or national study is warranted to better understand the immunophenotypic and molecular features of DLBCL in Taiwan and their respective impact on patient survival. Copyright © 2016. Published by Elsevier B.V.

Laser diode bars based on strain-compensated AlGaPAs/GaAs heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marmalyuk, Aleksandr A; Ladugin, M A; Yarotskaya, I V

2012-01-31

Traditional (in the AlGaAs/GaAs system) and phosphorus-compensated (in the AlGaAs/AlGaPAs/GaAs system) laser heterostructures emitting at a wavelength of 850 nm are grown by MOVPE and studied. Laser diode bars are fabricated and their output characteristics are studied. The method used to grow heterolayers allowed us to control (minimise) mechanical stresses in the AlGaPAs/GaAs laser heterostructure, which made it possible to keep its curvature at the level of the initial curvature of the substrate. It is shown that the use of a compensated AlGaPAs/GaAs heterostructure improves the linear distribution of emitting elements in the near field of laser diode arrays andmore » allows the power - current characteristic to retain its slope at high pump currents owing to a uniform contact of all emitting elements with the heat sink. The radius of curvature of the grown compensated heterostructures turns out to be smaller than that of traditional heterostructures.« less

Flexible all-solid-state supercapacitors based on graphene/carbon black nanoparticle film electrodes and cross-linked poly(vinyl alcohol)-H2SO4 porous gel electrolytes

NASA Astrophysics Data System (ADS)

Fei, Haojie; Yang, Chongyang; Bao, Hua; Wang, Gengchao

2014-11-01

Flexible all-solid-state supercapacitors (SCs) are fabricated using graphene/carbon black nanoparticle (GCB) film electrodes and cross-linked poly(vinyl alcohol)-H2SO4 porous gel electrolytes (gPVAP-H2SO4). The GCB composite films, with carbon black (CB) nanoparticles uniformly distributed in the graphene nanosheets, greatly improve the active surface areas and ion transportation of pristine graphene film. The porous structure of as-prepared gPVAP-H2SO4 membrane improves the equilibrium swelling ratio in electrolyte and provides interconnected ion transport channels. The chemical crosslinking solves the fluidity problem of PVA-H2SO4 gel electrolyte at high temperature. As-fabricated GCB//gPVAP(20)-H2SO4//GCB flexible SC displays an increased specific capacitance (144.5 F g-1 at 0.5 A g-1) and a higher specific capacitance retention (67.9% from 0.2 to 4 A g-1). More importantly, the flexible SC possesses good electrochemical performance at high temperature (capacitance retention of 78.3% after 1000 cycles at 70 °C).

Photoluminescence emission from GaAs nanodisks in GaAs/AlGaAs nanopillar arrays fabricated by neutral beam etching

NASA Astrophysics Data System (ADS)

Ohori, Daisuke; Fukuyama, Atsuhiko; Sakai, Kentaro; Higo, Akio; Thomas, Cedric; Samukawa, Seiji; Ikari, Tetsuo

2017-05-01

GaAs quantum nanodisks (QNDs) in nanopillar (NP) arrays are considered to be an attractive candidate for photonic device applications. We report a damageless fabrication technique that can be used to produce large-area lattice-matched GaAs/AlGaAs heterostructure NP arrays through the use of a bio-template and neutral beam etching. We have successfully realized GaAs QNDs in NPs owing to nanoscale iron oxide masks included in poly(ethylene glycol)-decorated ferritin protein shells. We observed for first time the photoluminescence emission from as-etched GaAs QNDs and confirmed quantum confinement by quantum mechanical calculation. Our methodology is vital for high-efficiency pillar-based optoelectronic devices such as NP laser diodes.

Surface States in the AlxGa1-xN Barrier in AlxGa1-xN/GaN Heterostructures

NASA Astrophysics Data System (ADS)

Liu, Jie; Shen, Bo; Wang, Mao-Jun; Zhou, Yu-Gang; Chen, Dun-Jun; Zhang, Rong; Shi, Yi; Zheng, You-Dou

2004-01-01

Frequency-dependent capacitance-voltage (C-V) measurements have been performed on modulation-doped Al0.22 Ga0.78N/GaN heterostructures to investigate the characteristics of the surface states in the AlxGa1-xN barrier. Numerical fittings based on the experimental data indicate that there are surface states with high density locating on the AlxGa1-xN barrier. The density of the surface states is about 1012 cm-2eV-1, and the time constant is about 1 mus. It is found that an insulating layer (Si3N4) between the metal contact and the surface of AlxGa1-xN can passivate the surface states effectively.

Multilayer self-organization of InGaAs quantum wires on GaAs surfaces

NASA Astrophysics Data System (ADS)

Wang, Zhiming M.; Kunets, Vasyl P.; Xie, Yanze Z.; Schmidbauer, Martin; Dorogan, Vitaliy G.; Mazur, Yuriy I.; Salamo, Gregory J.

2010-12-01

Molecular-Beam Epitaxy growth of multiple In 0.4Ga 0.6As layers on GaAs (311)A and GaAs (331)A has been investigated by Atomic Force Microscopy and Photoluminescence. On GaAs (311)A, uniformly distributed In 0.4Ga 0.6As quantum wires (QWRs) with wider lateral separation were achieved, presenting a significant improvement in comparison with the result on single layer [H. Wen, Z.M. Wang, G.J. Salamo, Appl. Phys. Lett. 84 (2004) 1756]. On GaAs (331)A, In 0.4Ga 0.6As QWRs were revealed to be much straighter than in the previous report on multilayer growth [Z. Gong, Z. Niu, Z. Fang, Nanotechnology 17 (2006) 1140]. These observations are discussed in terms of the strain-field interaction among multilayers, enhancement of surface mobility at high temperature, and surface stability of GaAs (311)A and (331)A surfaces.

Epitaxial nanowire formation in metamorphic GaAs/GaPAs short-period superlattices

NASA Astrophysics Data System (ADS)

Zheng, Nan; Ahrenkiel, S. Phillip

2017-07-01

Metamorphic growth presents routes to novel nanomaterials with unique properties that may be suitable for a range of applications. We discuss self-assembled, epitaxial nanowires formed during metalorganic chemical vapor deposition of metamorphic GaAs/GaPAs short-period superlattices. The heterostructures incorporate strain-engineered GaPAs compositional grades on 6°-<111>B miscut GaAs substrates. Lateral diffusion within the SPS into vertically aligned, three-dimensional columns results in nanowires extending along <110>A directions with a lateral period of 70-90 nm. The microstructure is probed by transmission electron microscopy to confirm the presence of coherent GaAs nanowires within GaPAs barriers. The compositional profile is inferred from analysis of {200} dark-field image contrast and <210> lattice images.

Atmospheric pressure-MOVPE growth of GaSb/GaAs quantum dots

NASA Astrophysics Data System (ADS)

Tile, Ngcali; Ahia, Chinedu C.; Olivier, Jaco; Botha, Johannes Reinhardt

2018-04-01

This study focuses on the growth of GaSb/GaAs quantum dots (QD) using an atmospheric pressure MOVPE system. For the best uncapped dots, the average dot height, base diameter and density are 5 nm, 45 nm and 4.5×1010 cm-2, respectively. Capping of GaSb QDs at high temperatures caused flattening and formation of thin inhomogeneous GaSb layer inside GaAs resulting in no obvious QD PL peak. Capping at low temperatures lead to the formation of dot-like features and a wetting layer (WL) with distinct PL peaks for QD and WL at 1097 nm and 983 nm respectively. Some of the dot-like features had voids. An increase in excitation power caused the QD and WL peaks to shift to higher energies. This is attributed to electrostatic band bending leading to triangular potential wells, typical of type-II alignment between GaAs and strained GaSb. Variable temperature PL measurements of the QD sample showed the decrease in the intensity of the WL peak to be faster than that of the QD peak as the temperature increased.

Cryogenic operation of pseudomorphic AlGaAs/InGaAs single-quantum-well MODFETs

NASA Technical Reports Server (NTRS)

Masselink, W. T.; Ketterson, A.; Klem, J.; Kopp, W.; Morkoc, H.

1985-01-01

The 77 K operation of AlGaAs/InGaAs MODFETs has been investigated. The structures, grown by MBE, make use of a 200 A undoped In(0.15)Ga(0.85)As quantum well for electron confinement and an Si-doped Al(0.15)Ga(0.85)As top barrier. The MODFETs with 1 micron gate lengths exhibit extrinsic transconductances of 360 mS/mm and maximum currents of 310 mA/mm at 77 K. The use of a low Al mole fraction AlGaAs/InGaAs heterojunction makes it possible to avoid the persistent trapping effects encountered in AlGaAs/GaAs MODFETs without sacrificing device performance.

InGaN/GaN tunnel junctions for hole injection in GaN light emitting diodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krishnamoorthy, Sriram, E-mail: krishnamoorthy.13@osu.edu, E-mail: rajan@ece.osu.edu; Akyol, Fatih; Rajan, Siddharth, E-mail: krishnamoorthy.13@osu.edu, E-mail: rajan@ece.osu.edu

InGaN/GaN tunnel junction contacts were grown using plasma assisted molecular beam epitaxy (MBE) on top of a metal-organic chemical vapor deposition (MOCVD)-grown InGaN/GaN blue (450 nm) light emitting diode. A voltage drop of 5.3 V at 100 mA, forward resistance of 2 × 10{sup −2} Ω cm{sup 2}, and a higher light output power compared to the reference light emitting diodes (LED) with semi-transparent p-contacts were measured in the tunnel junction LED (TJLED). A forward resistance of 5 × 10{sup −4} Ω cm{sup 2} was measured in a GaN PN junction with the identical tunnel junction contact as the TJLED, grown completely by MBE. Themore » depletion region due to the impurities at the regrowth interface between the MBE tunnel junction and the MOCVD-grown LED was hence found to limit the forward resistance measured in the TJLED.« less

Atomic structure and stoichiometry of In(Ga)As/GaAs quantum dots grown on an exact-oriented GaP/Si(001) substrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulze, C. S.; Prohl, C.; Füllert, V.

2016-04-04

The atomic structure and stoichiometry of InAs/InGaAs quantum-dot-in-a-well structures grown on exactly oriented GaP/Si(001) are revealed by cross-sectional scanning tunneling microscopy. An averaged lateral size of 20 nm, heights up to 8 nm, and an In concentration of up to 100% are determined, being quite similar compared with the well-known quantum dots grown on GaAs substrates. Photoluminescence spectra taken from nanostructures of side-by-side grown samples on GaP/Si(001) and GaAs(001) show slightly blue shifted ground-state emission wavelength for growth on GaP/Si(001) with an even higher peak intensity compared with those on GaAs(001). This demonstrates the high potential of GaP/Si(001) templates for integration ofmore » III-V optoelectronic components into silicon-based technology.« less

Botulinum toxin detection using AlGaN /GaN high electron mobility transistors

NASA Astrophysics Data System (ADS)

Wang, Yu-Lin; Chu, B. H.; Chen, K. H.; Chang, C. Y.; Lele, T. P.; Tseng, Y.; Pearton, S. J.; Ramage, J.; Hooten, D.; Dabiran, A.; Chow, P. P.; Ren, F.

2008-12-01

Antibody-functionalized, Au-gated AlGaN /GaN high electron mobility transistors (HEMTs) were used to detect botulinum toxin. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN /GaN HEMT drain-source current showed a rapid response of less than 5s when the target toxin in a buffer was added to the antibody-immobilized surface. We could detect a range of concentrations from 1to10ng/ml. These results clearly demonstrate the promise of field-deployable electronic biological sensors based on AlGaN /GaN HEMTs for botulinum toxin detection.

Growth and characterization of GaAs/Al/GaAs heterostructures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, P.; Oh, J.E.; Singh, J.

Theoretical and experimental aspects of the growth of GaAs/Al/GaAs heterostructures have been investigated. In these heterostructures the GaAs on top of the buried metal layer is grown by migration-enhanced epitaxy (MEE) at low temperatures (200 and 400 {degree}C) to provide a kinetic barrier to the outdiffusion of Al during superlayer growth. The crystallinity and orientation of the Al film itself deposited on (100) GaAs at {approx}0 {degree}C was studied by transmission electron diffraction, dark-field imaging, and x-ray diffraction measurements. It is found that the Al growth is polycrystalline with a grain size {approx}60 A and the preferred growth orientation ismore » (111), which may be textured in plane but oriented out of plane. The quality of the GaAs superlayer grown on top of Al by MEE is very sensitive to the growth temperature. The layer grown at 400 {degree}C has good structural and optical quality, but is accompanied by considerable outdiffusion of Al at the Al-GaAs heterointerface. At 200 {degree}C, where the interface has good structural integrity, the superlayer exhibits twinning and no luminescence is observed.« less

Isolation and Role of PmRGL2 in GA-mediated Floral Bud Dormancy Release in Japanese Apricot (Prunus mume Siebold et Zucc.)

PubMed Central

Lv, Lin; Huo, Ximei; Wen, Luhua; Gao, Zhihong; Khalil-ur-Rehman, Muhammad

2018-01-01

Bud dormancy release is regulated by gibberellins (GAs). DELLA proteins are highly conserved and act as negative regulators in GA signaling pathway. The present study established a relationship between PmRGL2 in Japanese apricot and GA4 levels during dormancy release of floral buds. Overexpression of PmRGL2 in poplar delayed the onset of bud dormancy and resulted in dwarf plants, relative to wild-type trees. PmRGL2 exhibited higher expression during ecodormancy and relatively lower expression during endodormancy. The relative level of GA4 exhibited an increasing trend at the transition from endodormancy to ecodormancy and displayed a similar expression pattern of genes related to GA metabolism, PmGA20ox2, PmGA3ox1, PmGID1b, in both Japanese apricot and transgenic poplar. These results suggests that PmRGL2 acts as an integrator and negative regulator of dormancy via a GA-signaling pathway. Moreover, an interaction between RGL2 and SLY1 in a yeast two hybrid (Y2H) system further suggests that SCF E3 ubiquitin ligases, such as SLY1, may be a critical factor in the regulation of RGL2 through an SCFSLY1-proteasome pathway. Our study demonstrated that PmRGL2 plays a negative role in bud dormancy release by regulating the GA biosynthetic enzymes, GA20ox and GA3ox1 and the GA receptor, GID1b. PMID:29434610

Ultrathin type-II GaSb/GaAs quantum wells grown by OMVPE

NASA Astrophysics Data System (ADS)

Pitts, O. J.; Watkins, S. P.; Wang, C. X.; Stotz, J. A. H.; Meyer, T. A.; Thewalt, M. L. W.

2004-09-01

Heterostructures containing monolayer (ML) and submonolayer GaSb insertions in GaAs were grown using organometallic vapour phase epitaxy. At the GaAs-on-GaSb interface, strong intermixing occurs due to the surface segregation of Sb. To form structures with relatively abrupt interfaces, a flashoff growth sequence, in which growth interruptions are employed to desorb Sb from the surface, was introduced. Reflectance-difference spectroscopy and high-resolution X-ray diffraction data demonstrate that interfacial grading is strongly reduced by this procedure. For layer structures grown with the flashoff sequence, a GaSb coverage up to 1 ML can be obtained in the two-dimensional (2D) growth mode. For uncapped GaSb layers, on the other hand, atomic force microscope images show that the 2D-3D growth mode transition occurs at a submonolayer coverage between 0.3 and 0.5 ML. Low-temperature photoluminescence spectra of multiple quantum well samples grown using the flashoff sequence show a strong quantum well-related peak which shifts to lower energies as the amount of Sb incorporated increases. The PL peak energies are consistent with a type-II band lineup at the GaAs/GaSb interface.

MOVPE of GaSb/InGaAsSb Multilayers and Fabrication of Dual Band Photodetectors

NASA Technical Reports Server (NTRS)

Xiao, Ye-Gao; Bhat, Ishwara; Refaat, Tamer F.; Abedin, M. Nurul; Shao, Qing-Hui

2005-01-01

Metalorganic vapor phase epitaxy (MOVPE) of GaSb/InGaAsSb multilayer thin films and fabrication of bias-selectable dual band photodetectors are reported. For the dual band photodetectors the short wavelength detector, or the upper p- GaSb/n-GaSb junction photodiode, is placed optically ahead of the long wavelength one, or the lower photodiode. The latter is based on latticed-matched In0.13Ga0.87As0.11Sb0.89 with bandgap near 0.6 eV. Specifically, high quality multilayer thin films are grown sequentially from top to bottom as p+-GaSb/p-GaSb/n-GaSb/n-InGaAsSb/p-InGaAsSb/p-GaSb on undoped p-type GaSb substrate, and as n-GaSb/p-GaSb/p-InGaAsSb/n-InGaAsSb/n-GaSb on Te-doped n-type GaSb substrate respectively. The multilayer thin films are characterized by optical microscope, atomic force microscope (AFM), electron microprobe analyses etc. The photodiode mesa steps are patterned by photolithography with wet chemical etching and the front metallization is carried out by e-beam evaporation with Pd/Ge/Au/Ti/Au to give ohmic contact on both n- and p-type Sb based layer surfaces. Dark I-V measurements show typical diode behavior for both the upper and lower photodiodes. The photoresponsivity measurements indicate that both the upper and lower photodiodes can sense the infrared illumination corresponding to their cutoff wavelengths respectively, comparable with the simulation results. More work is underway to bring the long wavelength band to the medium infrared wavelength region near 4 micrometers.

Characterizations of substrate and enzyme specificity of glucoamylase assays of mucosal starch digestion with determinations of group and single biopsy reference values

USDA-ARS?s Scientific Manuscript database

Carbohydrate digesting enzyme activities are measured in duodenal biopsies to detect deficiencies of lactase and sucrase activities, however glucoamylase (GA) assays for starch digestion are not included. Because food starch represents half of energy intake in the human diet, assays for starch diges...

Terrestrial Biomarkers for Early Life on Earth as Analogs for Possible Martian Life Forms: Examples of Minerally Replaced Bacteria and Biofilms From the 3.5 - 3.3-Ga Barberton Greenstone Belt, South Africa

NASA Technical Reports Server (NTRS)

Westall, F.; McKay, D. S.; Gibson, E. K.; deWit, M. J.; Dann, J.; Gerneke, D.; deRonde, C. E. J.

1998-01-01

The search for extraterrestrial life and especially martian life hinges on a variety of methods used to identify vestiges of what we could recognize as life, including chemical signatures, morphological fossils, and biogenic precipitates. Although the possibility of extant life on Mars (subsurface) is being considered, most exploration efforts may be directed toward the search for fossil life. Geomorphological evidence points to a warmer and wetter Mars early on in its history, a scenario that encourages comparison with the early Earth. For this reason, study of the early terrestrial life forms and environment in which they lived may provide clues as to how to search for extinct martian life. As a contribution to the early Archean database of terrestrial microfossils, we present new data on morphological fossils from the 3.5-3.3-Ga Barberton greenstone belt (BGB), South Africa. This study underlines the variety of fossil types already present in some of the oldest, best-preserved terrestrial sediments, ranging from minerally replaced bacteria and bacteria molds of vaRious morphologies (coccoid, coccobacillus, bacillus) to minerally replaced biofilm. Biofilm or extracellular polymeric substance (EPS) is produced by bacteria and appears to be more readily fossilisable than bacteria themselves. The BGB fossils occur in shallow water to subaerial sediments interbedded with volcanic lavas, the whole being deposited on oceanic crust. Penecontemporaneous silicification of sediments and volcanics resulted in the chertification of the rocks, which were later subjected to low-grade metamorphism (lower greenschist).

GaAsP on GaP top solar cells

NASA Technical Reports Server (NTRS)

Mcneely, J. B.; Negley, G. H.; Barnett, A. M.

1985-01-01

GaAsP on GaP top solar cells as an attachment to silicon bottom solar cells are being developed. The GaAsP on GaP system offers several advantages for this top solar cell. The most important is that the gallium phosphide substrate provides a rugged, transparent mechanical substrate which does not have to be removed or thinned during processing. Additional advantages are that: (1) gallium phosphide is more oxidation resistant than the III-V aluminum compounds, (2) a range of energy band gaps higher than 1.75 eV is readily available for system efficiency optimization, (3) reliable ohmic contact technology is available from the light-emitting diode industry, and (4) the system readily lends itself to graded band gap structures for additional increases in efficiency.

III-V Ultra-Thin-Body InGaAs/InAs MOSFETs for Low Standby Power Logic Applications

NASA Astrophysics Data System (ADS)

Huang, Cheng-Ying

As device scaling continues to sub-10-nm regime, III-V InGaAs/InAs metal- oxide-semiconductor ?eld-e?ect transistors (MOSFETs) are promising candidates for replacing Si-based MOSFETs for future very-large-scale integration (VLSI) logic applications. III-V InGaAs materials have low electron effective mass and high electron velocity, allowing higher on-state current at lower VDD and reducing the switching power consumption. However, III-V InGaAs materials have a narrower band gap and higher permittivity, leading to large band-to-band tunneling (BTBT) leakage or gate-induced drain leakage (GIDL) at the drain end of the channel, and large subthreshold leakage due to worse electrostatic integrity. To utilize III-V MOSFETs in future logic circuits, III-V MOSFETs must have high on-state performance over Si MOSFETs as well as very low leakage current and low standby power consumption. In this dissertation, we will report InGaAs/InAs ultra-thin-body MOSFETs. Three techniques for reducing the leakage currents in InGaAs/InAs MOSFETs are reported as described below. 1) Wide band-gap barriers: We developed AlAs0.44Sb0.56 barriers lattice-match to InP by molecular beam epitaxy (MBE), and studied the electron transport in In0.53Ga0.47As/AlAs 0.44Sb0.56 heterostructures. The InGaAs channel MOSFETs using AlAs0.44Sb0.56 bottom barriers or p-doped In0.52 Al0.48As barriers were demonstrated, showing significant suppression on the back barrier leakage. 2) Ultra-thin channels: We investigated the electron transport in InGaAs and InAs ultra-thin quantum wells and ultra-thin body MOSFETs (t ch ~ 2-4 nm). For high performance logic, InAs channels enable higher on-state current, while for low power logic, InGaAs channels allow lower BTBT leakage current. 3) Source/Drain engineering: We developed raised InGaAs and recessed InP source/drain spacers. The raised InGaAs source/drain spacers improve electrostatics, reducing subthreshold leakage, and smooth the electric field near drain, reducing

Nanoair-bridged lateral overgrowth of GaN on ordered nanoporous GaN template

NASA Astrophysics Data System (ADS)

Wang, Y. D.; Zang, K. Y.; Chua, S. J.; Tripathy, S.; Chen, P.; Fonstad, C. G.

2005-12-01

We report the growth of high-quality GaN epilayers on an ordered nanoporous GaN template by metalorganic chemical vapor deposition. The nanopores in GaN template were created by inductively coupled plasma etching using anodic aluminum oxide film as an etch mask. The average pore diameter and interpore distance is about 65 and 110nm, respectively. Subsequent overgrowth of GaN first begins at the GaN crystallite surface between the pores, and then air-bridge-mediated lateral overgrowth leads to the formation of the continuous layer. Microphotoluminescence and micro-Raman measurements show improved optical properties and significant strain relaxation in the overgrown layer when compared to GaN layer of same thickness simultaneously grown on sapphire without any template. Similar to conventional epitaxial lateral overgrown GaN, such overgrown GaN on a nanopatterned surface would also serve as a template for the growth of ultraviolet-visible light-emitting III-nitride devices.

Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates

PubMed Central

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

Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates.

PubMed

Huang, Ruiqi; Hippauf, Frank; Rohrbeck, Diana; Haustein, Maria; Wenke, Katrin; Feike, Janie; Sorrelle, Noah; Piechulla, Birgit; Barkman, Todd J

2012-02-21

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 (k(cat)/K(M)) for competing substrates, even though adaptive substitutions may affect K(M) and k(cat) 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.

Surface Morphology Evolution Mechanisms of InGaN/GaN Multiple Quantum Wells with Mixture N2/H2-Grown GaN Barrier.

PubMed

Zhou, Xiaorun; Lu, Taiping; Zhu, Yadan; Zhao, Guangzhou; Dong, Hailiang; Jia, Zhigang; Yang, Yongzhen; Chen, Yongkang; Xu, Bingshe

2017-12-01

Surface morphology evolution mechanisms of InGaN/GaN multiple quantum wells (MQWs) during GaN barrier growth with different hydrogen (H 2 ) percentages have been systematically studied. Ga surface-diffusion rate, stress relaxation, and H 2 etching effect are found to be the main affecting factors of the surface evolution. As the percentage of H 2 increases from 0 to 6.25%, Ga surface-diffusion rate and the etch effect are gradually enhanced, which is beneficial to obtaining a smooth surface with low pits density. As the H 2 proportion further increases, stress relaxation and H 2 over- etching effect begin to be the dominant factors, which degrade surface quality. Furthermore, the effects of surface evolution on the interface and optical properties of InGaN/GaN MQWs are also profoundly discussed. The comprehensive study on the surface evolution mechanisms herein provides both technical and theoretical support for the fabrication of high-quality InGaN/GaN heterostructures.

GaSb and GaSb/AlSb Superlattice Buffer Layers for High-Quality Photodiodes Grown on Commercial GaAs and Si Substrates

NASA Astrophysics Data System (ADS)

Gutiérrez, M.; Lloret, F.; Jurczak, P.; Wu, J.; Liu, H. Y.; Araújo, D.

2018-05-01

The objective of this work is the integration of InGaAs/GaSb/GaAs heterostructures, with high indium content, on GaAs and Si commercial wafers. The design of an interfacial misfit dislocation array, either on GaAs or Si substrates, allowed growth of strain-free devices. The growth of purposely designed superlattices with their active region free of extended defects on both GaAs and Si substrates is demonstrated. Transmission electron microscopy technique is used for the structural characterization and plastic relaxation study. In the first case, on GaAs substrates, the presence of dopants was demonstrated to reduce several times the threading dislocation density through a strain-hardening mechanism avoiding dislocation interactions, while in the second case, on Si substrates, similar reduction of dislocation interactions is obtained using an AlSb/GaSb superlattice. The latter is shown to redistribute spatially the interfacial misfit dislocation array to reduce dislocation interactions.

On the AlGaInP-bulk and AlGaInP/GaAs-superlattice confinement effects for heterostructure-emitter bipolar transistors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, Jung-Hui, E-mail: jhtsai@nknucc.nknu.edu.tw

2015-02-09

The confinement effect and electrical characteristics of heterostructure-emitter bipolar transistors with an AlGaInP bulk-confinement layer and an AlGaInP/GaAs superlattice-confinement layer are first demonstrated and compared by experimentally results. In the two devices, the relatively large valence band discontinuity at AlGaInP/GaAs heterojunction provides excellent confinement effect for holes to enhance current gain. As to the AlGaInP/GaAs superlattice-confinement device, part of thermionic-emission electrons will be trapped in the GaAs quantum wells of the superlattice. This will result in lower collector current and current gain as compared with the bulk-confinement device. Nevertheless, the superlattice-confinement device exhibits a larger current-gain cutoff frequency, which canmore » be attributed that the tunneling behavior is included in the carrier transportation and transporting time across the emitter region could be substantially reduced.« less

InGaN stress compensation layers in InGaN/GaN blue LEDs with step graded electron injectors

NASA Astrophysics Data System (ADS)

Sheremet, V.; Gheshlaghi, N.; Sözen, M.; Elçi, M.; Sheremet, N.; Aydınlı, A.; Altuntaş, I.; Ding, K.; Avrutin, V.; Özgür, Ü.; Morkoç, H.

2018-04-01

We investigate the effect of InGaN stress compensation layer on the properties of light emitting diodes based on InGaN/GaN multiple quantum well (MQW) structures with step-graded electron injectors. Insertion of an InGaN stress compensation layer between n-GaN and the step graded electron injector provides, among others, strain reduction in the MQW region and as a result improves epitaxial quality that can be observed by 15-fold decrease of V-pit density. We observed more uniform distribution of In between quantum wells in MQW region from results of electro- and photoluminescence measurement. These structural improvements lead to increasing of radiant intensity by a factor of 1.7-2.0 and enhancement of LED efficiency by 40%.