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  1. [Fabry disease].

    Science.gov (United States)

    Boggio, Paula; Luna, Paula Carolina; Abad, María Eugenia; Larralde, Margarita

    2009-01-01

    Fabry disease is an uncommon, X-linked lysosomal storage disorder, caused by partial or complete deficiency of the enzyme a-galactosidase A. The defect leads to accumulation of uncleaved globotriaosylceramide on the vascular endothelium and visceral tissues, being the skin, heart, kidneys and central nervous system the most affected organs. We performed review of the literature related to the disease and emphasized that early recognition of angiokeratomas and hypohidrosis are key diagnostic signs of this serious disease. We also addressed the need of multidisciplinary assessment of these patients.

  2. Fabry Disease

    Science.gov (United States)

    ... Foundation National Organization for Rare Disorders (NORD) National Tay-Sachs and Allied Diseases Association See all related ... Foundation National Organization for Rare Disorders (NORD) National Tay-Sachs and Allied Diseases Association See all related ...

  3. Genetics Home Reference: Fabry disease

    Science.gov (United States)

    ... AJ, Germain DP, Goldman M, Grabowski G, Packman S, Wilcox WR. Fabry disease, an under-recognized multisystemic disorder: ... Sims K, Brodie SE, Pastores GM, Strotmann JM, Wilcox WR. Fabry disease: guidelines for the evaluation and ...

  4. Fabry disease simulating Crohn's ileitis.

    Science.gov (United States)

    Rubio, Carlos A; Villnow, Elizabeth; Sundelin, Birgitta; Eriksson, Elina; Dolapcsiev, Karoli; Björk, Jan; Befrits, Ragnar; Tengvar, Magnus; Iversen, Henrik

    2014-05-01

    Fabry disease is an inherited (X-linked) lysosomal storage disorder caused by deficiency of α-galactosidase A, leading to accumulation of globotriaosylceramide in various tissues. A 57-year-old male with a family history and laboratory findings of Fabry disease, was consulted for severe abdominal pain, undulating pyrexia, weight loss and diarrhea. The tentative clinical diagnosis of Crohn's ileitis was supported at computed tomographic examination, at laparotomy and at inspection of the resected ileal segment. Histology revealed chronic and acute inflammation, thick-walled occluded vessels, fibrosis and characteristic bi-refringent lamellar deposits of globotriaosylceramide and calcifications. Multi-nucleated giant cells contained phagocytized bi-refringent material. Transmission electron microscopy showed cells with irregular cytoplasmic bodies displaying distinctive zebra-like lamellar structures. It is submitted that the gastrointestinal phenotype of Fabry disease may concur with symptoms resembling abdominal Crohn's disease.

  5. Fabry disease in children

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Feldt-Rasmussen, U; Rasmussen, AK

    2013-01-01

    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...

  6. Neurological manifestations in Fabry's disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Jensen, Troels Staehelin

    2007-01-01

    . Neurological symptoms, such as burning sensations (occasionally accompanied by acroparesthesia) and stroke, are among the first to appear, and occur in both male and female patients. A delay in establishing the diagnosis of Fabry's disease can cause unnecessary problems, especially now that enzyme replacement...... treatment is available to prevent irreversible organ damage. Females with Fabry's disease who present with pain have often been ignored and misdiagnosed because of the disorder's X-linked inheritance. This Review will stress the importance of recognizing neurological symptoms for the diagnosis of Fabry...

  7. Cochleovestibular Manifestations in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Alberto Ciceran MD

    2016-09-01

    Full Text Available Fabry disease is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity and globotriaosylceramide accumulation throughout the body. This accumulation leads to various clinical disorders, including inner ear lesions, with sensorineural hearing loss and dizziness. Although hearing loss is recognized in these patients, its incidence and natural history have not been characterized. Hearing disorders develop mainly in adulthood, and tinnitus may be an earlier symptom in Fabry disease. A significant incidence of mid- and high-frequency sensorineural hearing loss in affected males is commonly reported, whereas in female carriers, it is much less frequent. In addition, a high incidence of vestibular disorders with dizziness and chronic instability is also observed in these patients. The few studies about the effects of enzyme replacement therapy (ERT on cochleovestibular symptoms show controversial results. Based on the model of densely stained material accumulation in the inner ear, stria vascularis cell, and organ damage, an early indication of ERT may prevent hearing loss due to the reduction in substrate accumulation.

  8. Cochleovestibular Manifestations in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Alberto Ciceran MD

    2016-09-01

    Full Text Available Fabry disease is a rare, X-linked lysosomal storage disorder resulting from deficient α-galactosidase A activity and globotriaosylceramide accumulation throughout the body. This accumulation leads to various clinical disorders, including inner ear lesions, with sensorineural hearing loss and dizziness. Although hearing loss is recognized in these patients, its incidence and natural history have not been characterized. Hearing disorders develop mainly in adulthood, and tinnitus may be an earlier symptom in Fabry disease. A significant incidence of mid- and high-frequency sensorineural hearing loss in affected males is commonly reported, whereas in female carriers, it is much less frequent. In addition, a high incidence of vestibular disorders with dizziness and chronic instability is also observed in these patients. The few studies about the effects of enzyme replacement therapy (ERT on cochleovestibular symptoms show controversial results. Based on the model of densely stained material accumulation in the inner ear, stria vascularis cell, and organ damage, an early indication of ERT may prevent hearing loss due to the reduction in substrate accumulation.

  9. Neurological manifestations in Fabry's disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Jensen, Troels Staehelin

    2007-01-01

    Fabry's disease is an X-linked lysosomal storage disorder caused by a defect in the gene that encodes the lysosomal enzyme alpha-galactosidase A. Symptoms arise because of accumulation of globotriaosylceramide in multiple organs, resulting in severely reduced quality of life and premature death....... Neurological symptoms, such as burning sensations (occasionally accompanied by acroparesthesia) and stroke, are among the first to appear, and occur in both male and female patients. A delay in establishing the diagnosis of Fabry's disease can cause unnecessary problems, especially now that enzyme replacement...

  10. Fabry disease and early stroke

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, U

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme a-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes...... in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial...... accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses...

  11. Fabry disease and early stroke

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, U

    2011-01-01

    Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes...... in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial...... accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses...

  12. Cognitive and Psychological Functioning in Fabry Disease

    Science.gov (United States)

    Sigmundsdottir, Linda; Tchan, Michel C.; Knopman, Alex A.; Menzies, Graham C.; Batchelor, Jennifer; Sillence, David O.

    2014-01-01

    Fabry disease is an X-linked lysosomal storage disorder which can result in renal, cardiac, and cerebrovascular disease. Patients are at increased risk of stroke and neuroimaging studies note cerebrovascular pathology. This study provides a cognitive profile of a cohort of individuals with Fabry disease and investigates the impact of pain, age, renal, cardiac, and cerebrovascular functioning on cognition and psychological functioning. Seventeen Fabry patients (12 males) with ages ranging 25 to 60 years (M = 46.6+11.8), and 15 age-matched healthy controls (M = 46.2+12.7) were administered a comprehensive neuropsychological battery. Fabry males demonstrated slower speed of information processing, reduced performance on measures of executive functions (verbal generation, reasoning, problem solving, perseveration), were more likely to show clinically significant reductions, and were more likely to report symptoms of anxiety and depression. Conversely, Fabry females performed at a similar level to controls. Correlational analyses indicated a link between cognitive and clinical measures of disease severity. PMID:25319043

  13. Fabry disease, respiratory symptoms, and airway limitation

    DEFF Research Database (Denmark)

    Svensson, Camilla Kara; Feldt-Rasmussen, Ulla; Backer, Vibeke

    2015-01-01

    abnormalities in patients with Fabry disease. Electron microscopy of lung biopsy and induced sputum show lamellar inclusion bodies (Zebra bodies) in the cytoplasm of cells in the airway wall. X-ray and CT scan have shown patchy ground-glass pulmonary infiltrations, fibrosis, and air trapping. Fibrosis diagnosed...

  14. Vertebrobasilar Dolichoectasia in Fabry Disease

    Directory of Open Access Journals (Sweden)

    Juan Politei

    2014-06-01

    Full Text Available Introduction: Fabry disease (FD is a lysosomal storage disorder associated with marked cerebrovascular involvement. Conventional magnetic resonance imaging (MRI shows different abnormalities, like white matter lesions that may already be present at an early stage in the disease. Aim: To present observations from a series of brain MRIs performed among a cohort of patients with FD and the relationship of imaging abnormalities with the presence of cardiovascular risk factors (CVRFs. Methods: A total of 70 patients with FD (43 women were enrolled. The cardiac, renal, ophthalmic, and peripheral nerve functioning was assessed. The MRI evaluation included assessment for evidence of ischemia, microbleeds, pulvinar sign, Arnold-Chiari type 1 malformation, and vertebrobasilar dolichoectasia (VBD. The presence or absence of CVRFs was examined for all patients. Results: Renal involvement was found in 60%, cardiac compromise in 30%, cornea verticillata in 91.4%, and acroparesthesias in 87.1% of patients. Brain MRI analysis found evidence of cerebral ischemic injury in 25.9% of men and 30.2% of women. Vertebrobasilar dolichoectasia was observed in imaging from 55.5% of men and 34.8% of women. The logistic regression analysis adjusted for cardiovascular risks factors, using ischemia or VBD as a dependent variable, showed no statistically significant results. Discussion: Our results have demonstrated cerebrovascular involvement before the third decade in many patients with FD. This study is further evidence confirming that women are not just carriers of FD and should be followed clinically and evaluated comprehensively to monitor for disease burden and progression. Although silent brain ischemias in MRI should be included as a key feature for the diagnoses of FD, VBD is an earlier and frequent sign.

  15. Neurological manifestations in Fabry disease

    Institute of Scientific and Technical Information of China (English)

    Joseph Bruno Bidin Brooks; Yara Dadalti Fragoso

    2016-01-01

    Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deifciency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The resulting effect of the deposition is generalized inlfammation and vasculopathy, which can also affect the central and peripheral nervous system. FD progresses with kidney dysfunction, angiokeratoma of the skin, cardiomyopathy, cerebrovascular events and neurological disorders. In the present review, the neurological manifestations of FD are summarized with emphasis on cerebral vasculopathy, cochlear nerve dysfunction, psychiatric and cognitive symptoms, autonomic dysfunction and peripheral neuropathy. Enzyme replacement therapy is also discussed in the light of its more prominent effects when administered early in life, which make it essential to diagnose FD as soon as possible.

  16. Dermatologic Aspects of Fabry Disease

    Directory of Open Access Journals (Sweden)

    Paula C. Luna MD

    2016-09-01

    Full Text Available Isolated angiokeratomas (AKs are common cutaneous lesions, generally deemed unworthy of further investigation. In contrast, diffuse AKs should alert the physician to a possible diagnosis of Fabry disease (FD. Angiokeratomas often do not appear until adolescence or young adulthood. The number of lesions and the extension over the body increase progressively with time, so that generalization and mucosal involvement are frequent. Although rare, FD remains an important diagnosis to consider in patients with AKs, with or without familial history. Dermatologists must have a high index of suspicion, especially when skin features are associated with other earlier symptoms such as acroparesthesia, hypohidrosis, or heat intolerance. Once the diagnosis is established, prompt screening of family members should be performed. In all cases, a multidisciplinary team is necessary for the long-term follow-up and treatment.

  17. Doença de Fabry Fabry disease

    Directory of Open Access Journals (Sweden)

    Paula Boggio

    2009-08-01

    Full Text Available A doença de Fabry é enfermidade de armazenamento lisossômico rara, ligada ao cromossomo-X, causada pela deficiência parcial ou completa da enzima alfagalactosidase A. O defeito resulta no acúmulo de globotriaosilceramida no endotélio vascular e tecidos viscerais, sendo a pele, o coração, os rins e o sistema nervoso central os mais afetados. As autoras realizam revisão da literatura relacionada a essa afecção e ressaltam que o reconhecimento precoce dos angioqueratomas e da hipoidrose constitui sinal-chave no diagnóstico dessa doença grave. Destacam também a necessidade de esses doentes serem avaliados por equipe multidisciplinar.Fabry disease is an uncommon, X-linked lysosomal storage disorder, caused by partial or complete deficiency of the enzyme a-galactosidase A. The defect leads to accumulation of uncleaved globotriaosylceramide on the vascular endothelium and visceral tissues, being the skin, heart, kidneys and central nervous system the most affected organs. We performed review of the literature related to the disease and emphasized that early recognition of angiokeratomas and hypohidrosis are key diagnostic signs of this serious disease. We also addressed the need of multidisciplinary assessment of these patients.

  18. A case of Fabry's disease with congenital agammaglobulinemia.

    Science.gov (United States)

    Lee, Ki-Yeol; Jeon, Su-Young; Hong, Jin-Woo; Kim, Sung-Eun; Song, Ki-Hoon; Kim, Young-Hun; Kim, Ki-Ho

    2011-07-01

    Fabry's disease is an X-linked lysosomal storage disorder caused by abnormalities in the α-galactosidase A (GLA) gene, which leads to a GLA deficiency and to the intracellular deposition of globotriaosylceramide (Gb3) within vascular endothelium and other tissues. It manifests as progressive multiple organ dysfunctions caused by the deposition of Gb3. On the other hand, congenital agammaglobulinemia is usually caused by mutations in Bruton's tyrosine kinase (Btk) gene with X-linked dominence, suppresses B cell maturation, and causes recurrent pyogenic infections. In former reports, the distance between the loci in the Xq22 region of the human X chromosome was found to be about 69 kilobases. A 23-yr-old man diagnosed with congenital agammaglobulinemia at age 5, showed typical clinical and laboratory and histopathological findings of Fabry's disease. The genetic basis of this combination of the two syndromes was studied in this patient. Here, we report a case of Fabry's disease with congenital agammaglobulinemia.

  19. Fabry Disease in Families With Hypertrophic Cardiomyopathy

    DEFF Research Database (Denmark)

    Adalsteinsdottir, Berglind; Palsson, Runolfur; Desnick, Robert J

    2017-01-01

    BACKGROUND: The screening of Icelandic patients clinically diagnosed with hypertrophic cardiomyopathy resulted in identification of 8 individuals from 2 families with X-linked Fabry disease (FD) caused by GLA(α-galactosidase A gene) mutations encoding p.D322E (family A) or p.I232T (family B...

  20. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry

    DEFF Research Database (Denmark)

    Wilcox, W.R.; Oliveira, J.P.; Hopkin, R.J.;

    2008-01-01

    Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A deficiency. The Fabry Registry is a global clinical effort to collect longitudinal data on FD. In the past, most "carrier" females were usually thought to be clinically unaffected. A systematic effort has ...

  1. Multiple parapelvic cysts in Fabry disease.

    Science.gov (United States)

    Azancot, María A; Vila, Josefa; Domínguez, Carmen; Serres, Xavier; Espinel, Eugenia

    2016-01-01

    Fabry disease is an inherited, X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha galactosidase A (alpha-GLA A), which leads to glycosphingolipid accumulation, mainly globotriaosylceramide, in tissues. Disease prevalence and the index of suspicion are both low, which tends to result in delayed diagnosis and treatment. We present the case of a male Fabry disease patient who manifested no angiokeratoma lesions but presented multiple parapelvic cysts and renal failure. The genetic study revealed an alpha-GLA A gene mutation that had not been recorded in the mutations registry. The de novo mutation was not found in his relatives and it was not transmitted to his offspring. The large number and peculiar appearance of the parapelvic cysts led to the diagnosis. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Magnetic resonance spectroscopy in patients with Fabry and Gaucher disease

    Energy Technology Data Exchange (ETDEWEB)

    Gruber, S., E-mail: stephan@nmr.at [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bogner, W. [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Stadlbauer, A. [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten (Austria); Krssak, M. [Department of Radiology, MR-Centre of Excellence, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Bodamer, O. [Department of Pediatrics, Medical University of Vienna (Austria)

    2011-08-15

    Objective: Fabry and Gaucher diseases are rare progressive inherited disorders of glycosphingolipid metabolism that affect multiple organ systems. The aim of this study was to investigate evidence for metabolic changes in the central nervous system involvement using proton magnetic resonance spectroscopic imaging. Methods: Seven Fabry and eight Gaucher patients were included into this study. A two-dimensional, spectroscopic imaging method with an ultra-short echo-time of 11 ms was used at a 3 T whole body magnet. Absolute metabolic values were retrieved using internal water scaling. Results were compared, with sex- and age-matched controls. Results: In contrast to previous findings, absolute and relative metabolite values of N-acetyl-aspartate (NAA) or NAA/Creatine (Cr), Cr, Choline (Cho) or Cho/Cr and myo-Inositol (mI) or mI/Cr revealed no, differences between Fabry and Gaucher Type 1 (GD1) patients and controls. Average values were, 10.22, 6.32, 2.15 and 5.39 mMol/kg wet weight for NAA, Cr, Cho and mI, respectively. In this study, we found significantly decreasing NAA/Cho with increasing age in all three groups (Fabry, GD1, patients and healthy controls) (between 5 and 8% per decade). Conclusions: There were no changes of the quantified metabolites detected by MRS in normal appearing white matter. This study shows the importance of sex- and age-matched controls.

  3. Prognostic Indicators of Renal Disease Progression in Adults with Fabry Disease: Natural History Data from the Fabry Registry

    NARCIS (Netherlands)

    C. Wanner; J.P. Oliveira; A. Ortiz; M. Mauer; D.P. Germain; G.E. Linthorst; A.L. Serra; L. Marodi; R. Mignani; B. Cianciaruso; B. Vujkovac; R. Lemay; D. Beitner-Johnson; S. Waldek; D.G. Warnock

    2010-01-01

    Background and objectives: These analyses were designed to characterize renal disease progression in untreated adults with Fabry disease. Design, setting, participants, & measurements: Data from the Fabry Registry for 462 untreated adults (121 men and 341 women) who had at least two estimated GFR (e

  4. Fabry's disease and psychosis: causality or coincidence?

    Science.gov (United States)

    Gairing, S; Wiest, R; Metzler, S; Theodoridou, A; Hoff, P

    2011-01-01

    A 21-year-old female with Fabry's disease (FD) presented acute psychotic symptoms such as delusions, auditory hallucinations and formal thought disorders. Since the age of 14, she had suffered from various psychiatric symptoms increasing in frequency and intensity. We considered the differential diagnoses of prodromal symptoms of schizophrenia and organic schizophrenia-like disorder. Routine examinations including cognitive testing, electroencephalography and structural magnetic resonance imaging revealed no pathological findings. Additional structural and functional imaging demonstrated a minor CNS involvement of FD, yet without functional limitations. In summary our examination results support the thesis that in the case of our patient a mere coincidence of FD and psychotic symptoms is more likely than a causal connection.

  5. Involvement of dorsal root ganglia in Fabry's disease.

    Science.gov (United States)

    Gadoth, N; Sandbank, U

    1983-08-01

    Bouts of shooting pain along the extremities are common in the early stages of Fabry's disease. No pathological explanation has been advanced to clarify the mechanism of such pain. In the present case neuronal storage of glycolipid was confined to dorsal root ganglia neurones only. It is suggested that this may explain the shooting pain in Fabry's disease. In hereditary sensory radicular neuropathy, familial dysautonomia, and tabes dorsalis, changes in dorsal root ganglia cells cause similar clinical signs and thus it may be concluded that shooting pains in Fabry's disease may be caused by damage to dorsal root ganglia neurones.

  6. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

    Science.gov (United States)

    Fall, Brent; Scott, C. Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A.; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value. PMID:27992580

  7. Autonomic skin responses in females with Fabry disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Bach, Flemming W.; Feldt-Rasmussen, Ulla

    2009-01-01

    dysfunction. This study examined peripheral autonomic nerve function in 19 female patients with Fabry disease and 19 sex and age-matched controls by measuring (1) sweat production following acetylcholine challenge; (2) the sympathetically mediated vasoconstrictor responses to inspiratory gasp, stress......, and the cold pressor test; and (3) cutaneous blood flow following capsaicin. The vasoconstrictor response to inspiratory gasp was increased in Fabry patients compared to controls (p = 0.03), while the response to cold and mental stress did not change. Female patients with Fabry disease had a reduced sweat...

  8. Fabry disease: recent advances in pathology, diagnosis, treatment and monitoring

    Directory of Open Access Journals (Sweden)

    Hoffmann Björn

    2009-10-01

    Full Text Available Abstract Background In Fabry disease (α-galactosidase A deficiency accumulation of Globotriaosylceramide (Gb3 leads to progressive organ failure and premature death. The introduction of enzyme replacement therapy (ERT was the beginning of a new era in this disorder, and has prompted a broad range of research activities. This review aims to summarize recent developments and progress with high impact for Fabry disease. Methods A Pubmed analysis was performed using the search terms "Fabry disease", "Anderson-Fabry disease", "alpha-galactosidase A" and "Gb3". Of the given publications by 31st January 2009 only original articles recently published in peer reviewed journals were included for this review. Case reports were included only when they comprised a new aspect. In addition we included relevant conference abstracts when the results had not already been published as original articles. Results Apart from Gb3-accumulation cellular and organ specific damages may be related also to inflammatory and immunological consequences. It will be interesting whether this may lead to new therapeutic strategies in the treatment of Fabry disease. Since newborn screening is still difficult in Fabry disease, detection of patients in populations at risk is of great importance. Undiagnosed patients with Fabry disease may still be found in cohorts of subjects with renal diseases, cardiomyopathy and TIA or stroke. Efforts should be undertaken to identify these individuals and initialise ERT in order to hault disease progression. It has also been demonstrated that Gb3-accumulation leads to pre-clinical damages and it is believed that early treatment may be the only possibility so far to prevent irreversible organ damage.

  9. Plasma globotriaosylsphingosine: diagnostic value and relation to clinical manifestations of Fabry disease.

    Science.gov (United States)

    Rombach, S M; Dekker, N; Bouwman, M G; Linthorst, G E; Zwinderman, A H; Wijburg, F A; Kuiper, S; Vd Bergh Weerman, M A; Groener, J E M; Poorthuis, B J; Hollak, C E M; Aerts, J M F G

    2010-09-01

    Fabry disease is an X-linked lysosomal storage disorder due to deficiency of alpha-Galactosidase A, causing accumulation of globotriaosylceramide and elevated plasma globotriaosylsphingosine (lysoGb3). The diagnostic value and clinical relevance of plasma lysoGb3 concentration was investigated. All male and adult female patients with classical Fabry disease could be discerned by an elevated plasma lysoGb3. In young pre-symptomatic Fabry heterozygotes, lysoGb3 levels can be normal. Individuals carrying the R112H and P60L mutations, without classical Fabry symptoms, showed no elevated plasma lysoGb3. Multiple regression analysis showed that there is no correlation of plasma lysoGb3 concentration with total disease severity score in Fabry males. However, plasma lysoGb3 concentration did correlate with white matter lesions (odds ratio: 6.1 per 100 nM lysoGb3 increase (95% CI: 1.4-25.9, p=0.015). In females, plasma lysoGb3 concentration correlated with overall disease severity. Furthermore, plasma lysoGb3 level was related to left ventricular mass (19.5+/-5.5 g increase per 10 nM lysoGb3 increase; p=0.001). In addition, it was assessed whether lifetime exposure to lysoGb3 correlates with disease manifestations. Male Fabry patients with a high lysoGb3 exposure (>10,000 U), were moderately or severely affected, only one mildly. Female patients with a low exposure (1000 U showed disease complications. Plasma lysoGb3 is useful for the diagnosis of Fabry disease. LysoGb3 is an independent risk factor for development of cerebrovascular white matter lesions in male patients and left ventricular hypertrophy in females. Disease severity correlates with exposure to plasma lysoGb3.

  10. Arterial Wall Properties and Womersley Flow in Fabry Disease

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    Dimitriadis Emilios

    2002-01-01

    Full Text Available Abstract Background Fabry disease is an X-linked recessive lysosomal storage disease resulting in the cellular accumulation of globotriaosylceramide particularly globotriaosylceramide. The disease is characterized by a dilated vasculopathy with arterial ectasia in muscular arteries and arterioles. Previous venous plethysomographic studies suggest enhanced endothelium-dependent vasodilation in Fabry disease indicating a functional abnormality of resistance vessels. Methods We examined the mechanical properties of the radial artery in Fabry disease, a typical fibro-muscular artery. Eight control subjects and seven patients with Fabry disease had a right brachial arterial line placed allowing real time recording of intra-arterial blood pressure. Real time B-mode ultrasound recordings of the right radial artery were obtained simultaneously allowing calculation of the vessel wall internal and external diameter, the incremental Young's modulus and arterial wall thickness. By simultaneously measurement of the distal index finger-pulse oximetry the pulse wave speed was calculated. From the wave speed and the internal radial artery diameter the volume flow was calculated by Womersley analysis following truncation of the late diastolic phase. Results No significant difference was found between Fabry patients and controls for internal or external arterial diameters, the incremental Young's modulus, the arterial wall thickness, the pulse wave speed and the basal radial artery blood flow. Further, no significant difference was found for the radial artery blood flow in response to intra-arterial acetylcholine or sodium nitroprusside. Both drugs however, elevated the mean arterial flow. Conclusions The current study suggests that no structural or mechanical abnormality exists in the vessel wall of fibro-muscular arteries in Fabry disease. This may indicate that a functional abnormality downstream to the conductance vessels is the dominant feature in

  11. A case of minimal change disease in a Fabry patient.

    Science.gov (United States)

    Zarate, Yuri A; Patterson, Larry; Yin, Hong; Hopkin, Robert J

    2010-03-01

    Fabry disease is an X-linked lysosomal storage disorder caused by mutations of the GLA gene and deficiency in alpha-galactosidase A activity. Glycosphingolipids accumulation causes renal injury that manifests early during childhood as tubular dysfunction and later in adulthood as proteinuria and renal insufficiency. Nephrotic syndrome as the first evidence of Fabry-related kidney damage is rare. We report the case of a teenager with known Fabry disease and normal renal function who developed acute nephrotic syndrome. He was found to have typical glycosphingolipids accumulation with no other findings suggestive of alternative causes of nephrotic syndrome on kidney biopsy. After treatment with enzyme replacement therapy and oral steroids, he went into complete remission from nephrotic syndrome, a response that is atypical for Fabry disease patients who develop heavy proteinuria as a result of longstanding disease and chronic renal injury. The nephrotic syndrome in this patient appears to have developed secondary to minimal change disease. We recommend considering immunotherapy in addition to enzyme replacement therapy in those patients with confirmed Fabry disease and acute nephrotic syndrome with clinical and microscopic findings suggestive of minimal change disease.

  12. Screening, diagnosis, and management of patients with Fabry disease

    DEFF Research Database (Denmark)

    Schiffmann, Raphael; Hughes, Derralynn A; Linthorst, Gabor E

    2017-01-01

    Patients with Fabry disease (FD) are at a high risk for developing chronic kidney disease and cardiovascular disease. The availability of specific but costly therapy has elevated the profile of this rare condition. This KDIGO conference addressed controversial areas in the diagnosis, screening, a...

  13. Cardiac device implantation in Fabry disease

    Science.gov (United States)

    Sené, Thomas; Lidove, Olivier; Sebbah, Joel; Darondel, Jean-Marc; Picard, Hervé; Aaron, Laurent; Fain, Olivier; Zenone, Thierry; Joly, Dominique; Charron, Philippe; Ziza, Jean-Marc

    2016-01-01

    Abstract The incidence and predictive factors of arrhythmias and/or conduction abnormalities (ACAs) requiring cardiac device (CD) implantation are poorly characterized in Fabry disease (FD). The aim of our retrospective study was to determine the prevalence, incidence, and factors associated with ACA requiring CD implantation in a monocentric cohort of patients with confirmed FD who were followed up in a department of internal medicine and reference center for FD. Forty-nine patients (20M, 29F) were included. Nine patients (4M, 5F; 18%) had at least one episode of ACA leading to device therapy. Six patients (4M/2F) required a pacemaker (PM) for sinus node dysfunction (n = 4) or atrioventricular disease (n = 2). One female patient required an internal cardioverter-defibrillator (ICD) to prevent sudden cardiac death because of nonsustained ventricular tachycardia (nSVT). One female patient required PM-ICD for sinus node dysfunction and nSVT. One patient underwent CD implantation before the diagnosis of FD. The annual rate of CD implantation was estimated at 1.90 per 100 person years. On univariate analysis at the end of the follow-up period, the factors associated with ACAs requiring CD implantation were as follows: delayed diagnosis of FD, delayed initiation of enzyme replacement therapy, age at the last follow-up visit, and severe multiorgan phenotype (hypertrophic cardiomyopathy, chronic kidney disease, and/or sensorineural hearing loss). On multivariate analysis, age at diagnosis of FD and age at the last follow-up visit were independently associated with an increased risk of ACAs requiring CD (P sudden death in patients with FD, regular monitoring is mandatory, especially in patients with a late diagnosis of FD and/or with a severe phenotype. Regular Holter ECGs, therapeutic education of patients, and deliverance of an emergency card including a phenotype summary are crucial in the care of FD patients. Available guidelines for device therapy and the

  14. Fabry disease - current treatment and new drug development.

    Science.gov (United States)

    Motabar, Omid; Sidransky, Ellen; Goldin, Ehud; Zheng, Wei

    2010-07-23

    Fabry disease is a rare inherited lysosomal storage disorder caused by a partial or complete deficiency of α-galactosidase A (GLA), resulting in the storage of excess cellular glycosphingolipids. Enzyme replacement therapy is available for the treatment of Fabry disease, but it is a costly, intravenous treatment. Alternative therapeutic approaches, including small molecule chaperone therapy, are currently being explored. High throughput screening (HTS) technologies can be utilized to discover other small molecule compounds, including non-inhibitory chaperones, enzyme activators, molecules that reduce GLA substrate, and molecules that activate GLA gene promoters. This review outlines the current therapeutic approaches, emerging treatment strategies, and the process of drug discovery and development for Fabry disease.

  15. Gaucher disease and Fabry disease: new markers and insights in pathophysiology for two distinct glycosphingolipidoses.

    Science.gov (United States)

    Ferraz, Maria J; Kallemeijn, Wouter W; Mirzaian, Mina; Herrera Moro, Daniela; Marques, Andre; Wisse, Patrick; Boot, Rolf G; Willems, Lianne I; Overkleeft, H S; Aerts, J M

    2014-05-01

    Gaucher disease (GD) and Fabry disease (FD) are two relatively common inherited glycosphingolipidoses caused by deficiencies in the lysosomal glycosidases glucocerebrosidase and alpha-galactosidase A, respectively. For both diseases enzyme supplementation is presently used as therapy. Cells and tissues of GD and FD patients are uniformly deficient in enzyme activity, but the two diseases markedly differ in cell types showing lysosomal accumulation of the glycosphingolipid substrates glucosylceramide and globotriaosylceramide, respectively. The clinical manifestation of Gaucher disease and Fabry disease is consequently entirely different and the response to enzyme therapy is only impressive in the case of GD patients. This review compares both glycosphingolipid storage disorders with respect to similarities and differences. Presented is an update on insights regarding pathophysiological mechanisms as well as recently available biochemical markers and diagnostic tools for both disorders. Special attention is paid to sphingoid bases of the primary storage lipids in both diseases. The value of elevated glucosylsphingosine in Gaucher disease and globotriaosylsphingosine in Fabry disease for diagnosis and monitoring of disease is discussed as well as the possible contribution of the sphingoid bases to (patho)physiology. This article is part of a Special Issue entitled New Frontiers in Sphingolipid Biology.

  16. Fabry disease, a complex pathology not easy to diagnose

    Directory of Open Access Journals (Sweden)

    Paolo Colomba

    2015-12-01

    Full Text Available Fabry disease is a multisystemic lysosomal storage disorder, inherited in an X-linked manner. It is a defect of metabolism of the glycosphingolipids, due to the reduction or absence of the activity of lysosomal enzyme α-galactosidase A. This reduction of activity causes the storage of globotriaosylceramide and derivatives in the lysosomes, triggering a cascade of cellular events, mainly in vascular endothelium. These events are the responsible for the systemic clinical manifestations and the renal, cardiac and cerebrovascular complications, or a combination of them. The symptomatology can lead to the premature death of patient between the fourth or fifth decade of life. The first symptoms can occur at different ages, generally in childhood, with different severity and course. Fabry disease is suspected on the basis of clinical and anamnestic-familial data, and it is confirmed by enzymatic and genetic assays. However, Fabry disease could be a pathology more complex than previously considered, and the diagnostic tests that are currently in use could be not always sufficient to confirm the clinical diagnosis. Probably, other factors could be also involved in the onset of symptomatology. In the last years, the knowledge of the disease is considerably increased but other studies are necessary to make a prompt and reliable diagnosis. An early diagnosis of Fabry disease is essential for the beginning of the enzyme replacement therapy, which can contribute to arrest its progression and improve the quality of life of patients.

  17. Measuring patient experiences in Fabry disease: validation of the Fabry-specific Pediatric Health and Pain Questionnaire (FPHPQ

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    Ramaswami Uma

    2012-09-01

    Full Text Available Abstract Introduction Common symptoms for children with Anderson-Fabry Disease (FD such as acroparaesthesia and gastrointestinal manifestations can only be objectively assessed in patients using a valid instrument. To date, no such instrument exists. Methods A preliminary 40-item measure of symptoms and experience with FD, the Fabry-specific Paediatric Health and Pain Questionnaire (FPHPQ was developed, but lacked a formal assessment of its measurement properties. The FPHPQ was used in the Fabry Outcome Survey (FOS, a registry for all patients with a confirmed diagnosis of FD who are receiving agalsidase alfa, or are treatment naïve and who are managed by physicians participating in FOS. After an item analysis to explore how items performed and combined into domains, a battery of psychometric analyses was performed to assess the measurement properties of this new instrument. Results Eighty-seven children (ages 4-18 years completed the questionnaire. Twenty-three items in three subscales of the questionnaire emerged: pain associated with heat or exertion, pain associated with cold, and abdominal pain and fatigue symptoms. Internal consistency reliability for all three subscales was good (Cronbach alpha ≥ 0.84. Reliability was equally high for all age groups (4-7, 8-12, and 13-18. Test-retest reliability was high for all three subscales (intraclass correlation coefficient ≥ 0.74. Construct validity was demonstrated by moderate correlation with brief pain inventory (BPI, KINDL, and EQ-5D. Known group validity showed all subscales were able to discriminate between Fabry disease severity groups as classified by above or below median of the FOS MSSI (Mainz Severity Score Index grade. The heat or exertion subscale was responsive to change in symptoms between responders and non-responders as defined by change in EQ-5D index scores between the first and second visit. Conclusions Preliminary results indicate that the measurement properties

  18. Clinical prodromes of neurodegeneration in Anderson-Fabry disease

    Science.gov (United States)

    Hughes, Derralynn; Milligan, Alan; Richfield, Linda; Reichmann, Heinz; Mehta, Atul; Schapira, Anthony H.V.

    2015-01-01

    Objective: To estimate the prevalence of prodromal clinical features of neurodegeneration in patients with Anderson-Fabry disease (AFD) in comparison to age-matched controls. Methods: This is a single-center, prospective, cross-sectional study in 167 participants (60 heterozygous females and 50 hemizygous males with genetically confirmed AFD, 57 age-matched controls) using a clinical screening program consisting of structured interview, quantitative tests of motor function, and assessments of cognition, depression, olfaction, orthostatic intolerance, pain, REM sleep behavior disorder, and daytime sleepiness. Results: In comparison to age-matched controls (mean age 48.3 years), patients with AFD (mean age 49.0 years) showed slower gait and transfer speed, poorer fine manual dexterity, and lower hand speed, which was independent of focal symptoms due to cerebrovascular disease. Patients with AFD were more severely affected by depression, pain, and daytime sleepiness and had a lower quality of life. These motor and nonmotor manifestations significantly correlated with clinical disease severity. However, patients with AFD did not reveal extrapyramidal motor features or signs of significant cognitive impairment, hyposmia, orthostatic intolerance, or REM sleep behavior disorder, which commonly precede later neurodegenerative disease. In our cohort, there were no differences in neurologic manifestations of AFD between heterozygous females and hemizygous males. Conclusions: Aside from cerebrovascular manifestations and small fiber neuropathy, AFD results in a distinct neurologic phenotype comprising poorer motor performance and specific nonmotor features. In contrast to functional loss of glucocerebrosidase in Gaucher disease, α-galactosidase deficiency in AFD is not associated with a typical cluster of clinical features prodromal for neurodegenerative diseases, such as Parkinson disease. PMID:25762709

  19. The Prevalence of Fabry Disease in Patients with Chronic Kidney Disease in Turkey: The TURKFAB Study

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    Kultigin Turkmen

    2016-12-01

    Full Text Available Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD characterized by a genetic deficiency of α-galactosidase A. European Renal Best Practice (ERBP recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed α-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males of 313 CKD patients (0.95% were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%, tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%, heat intolerance (71%, and abdominal pain (57%. The most frequent manifestations in female patients were fatigue and cornea verticillata (50%, and tinnitus, vertigo and angiokeratoma (25%. Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. Conclusions: The prevalence of Fabry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin.

  20. Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease.

    Directory of Open Access Journals (Sweden)

    John Marshall

    Full Text Available Fabry disease is an X-linked glycosphingolipid storage disorder caused by a deficiency in the activity of the lysosomal hydrolase α-galactosidase A (α-gal. This deficiency results in accumulation of the glycosphingolipid globotriaosylceramide (GL-3 in lysosomes. Endothelial cell storage of GL-3 frequently leads to kidney dysfunction, cardiac and cerebrovascular disease. The current treatment for Fabry disease is through infusions of recombinant α-gal (enzyme-replacement therapy; ERT. Although ERT can markedly reduce the lysosomal burden of GL-3 in endothelial cells, variability is seen in the clearance from several other cell types. This suggests that alternative and adjuvant therapies may be desirable. Use of glucosylceramide synthase inhibitors to abate the biosynthesis of glycosphingolipids (substrate reduction therapy, SRT has been shown to be effective at reducing substrate levels in the related glycosphingolipidosis, Gaucher disease. Here, we show that such an inhibitor (eliglustat tartrate, Genz-112638 was effective at lowering GL-3 accumulation in a mouse model of Fabry disease. Relative efficacy of SRT and ERT at reducing GL-3 levels in Fabry mouse tissues differed with SRT being more effective in the kidney, and ERT more efficacious in the heart and liver. Combination therapy with ERT and SRT provided the most complete clearance of GL-3 from all the tissues. Furthermore, treatment normalized urine volume and uromodulin levels and significantly delayed the loss of a nociceptive response. The differential efficacies of SRT and ERT in the different tissues indicate that the combination approach is both additive and complementary suggesting the possibility of an improved therapeutic paradigm in the management of Fabry disease.

  1. Agalsidase benefits renal histology in young patients with Fabry disease.

    Science.gov (United States)

    Tøndel, Camilla; Bostad, Leif; Larsen, Kristin Kampevold; Hirth, Asle; Vikse, Bjørn Egil; Houge, Gunnar; Svarstad, Einar

    2013-01-01

    The effect of early-onset enzyme replacement therapy on renal morphologic features in Fabry disease is largely unknown. Here, we evaluated the effect of 5 years of treatment with agalsidase alfa or agalsidase beta in 12 consecutive patients age 7-33 years (median age, 16.5 years). We performed renal biopsies at baseline and after 5 years of enzyme replacement therapy; 7 patients had additional biopsies after 1 and 3 years. After a median of 65 months, biopsy findings from all patients showed total clearance of glomerular endothelial and mesangial cell inclusions, and findings from 2 patients showed complete clearance of inclusions from epithelial cells of the distal tubule. The 4 patients who received the highest dose of agalsidase exhibited substantial clearance of podocyte inclusions, and the youngest patient had nearly complete clearance of these inclusions. Linear regression analysis showed a highly significant correlation between podocyte globotriaocylceramide clearance and cumulative agalsidase dose (r=0.804; P=0.002). Microalbuminuria normalized in five patients. In summary, long-term enzyme replacement therapy in young patients can result in complete globotriaocylceramide clearance of mesangial and glomerular endothelial cells across all dosage regimens, and clearance of podocyte inclusions is dose-dependent.

  2. Fabry disease presenting with sudden hearing loss and otosclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Felisati Giovanni

    2012-04-01

    Full Text Available Abstract Introduction Fabry disease is an X-linked lysosomal storage disorder resulting in a multiple-system disorder with a wide spectrum of physical signs and symptoms, predominantly affecting the central and peripheral nervous systems, skin, heart, kidneys, and eyes. Case presentation We describe the case of a 26-year-old European Caucasian man who had Fabry disease and who presented with episodic sudden unilateral hearing loss and was treated with glucocorticoids, pentoxifylline, hyperbaric oxygen, and fluoride because of concomitant audiometric evidence of otosclerosis. This case demonstrates the partial and transient beneficial effect of standard treatment for sudden hearing loss not related to Fabry disease and analyzes the possible connection between typical Fabry disease inner-ear lesions and otosclerosis. Whereas hearing loss has been described in connection with Fabry disease, otosclerosis-associated hearing loss in Fabry disease has not yet been described. Conclusions Although progressive hearing loss in patients with Fabry disease seems to be influenced by replacement therapy, few data concerning treatment of sudden hearing loss are available. The lack of literature concerning the pathogenesis of the otological involvement in Fabry disease makes it impossible to identify a connection between the latter and otosclerosis. Therefore, this report may help to reinforce the importance of a thorough evaluation of hearing in patients with Fabry disease and may be of help with therapeutic decision-making.

  3. Avascular necrosis of bilateral femoral heads in a patient with Fabry's disease.

    LENUS (Irish Health Repository)

    O'Neill, Francis

    2012-07-13

    The underlying cause of avascular necrosis (AVN) of the femoral head is often not apparent. We report the case of a 26 year old builder with a four month history of bilateral hip pain, and a diagnosis of bilateral femoral head avascular necrosis. Fabry\\'s disease was identified as the probable cause. Since 2001, enzyme replacement therapy for Fabry\\'s disease has become available, with a potential to influence the disease process, and this is of potential importance to clinicians treating AVN.

  4. Upregulation of inward rectifying currents and Fabry disease neuropathy.

    Science.gov (United States)

    Geevasinga, Nimeshan; Tchan, Michel; Sillence, David; Vucic, Steve

    2012-12-01

    Peripheral neuropathy and neuropathic pain are common clinical manifestations of Fabry disease (FD). Although the mechanisms underlying the development of sensory neuropathy remain to be fully elucidated, a chronic ischemic process was proposed. Consequently, this study utilized axonal excitability techniques to gain further insights into the pathophysiological mechanisms underlying the development of FD neuropathy. Median motor and sensory axonal excitability studies were undertaken in 13 FD patients and results were compared to 19 healthy subjects. A "fanning-in" of threshold electrotonus, suggestive of membrane depolarization, was evident only in motor axons in FD patients. In contrast, the sensory axons exhibited a lower threshold in FD (p < 0.05) and a significantly increased hyperpolarizing current/threshold (I/V) gradient (FD 0.48 ± 0.03; controls, 0.31 ± 0.02, p < 0.001), which correlated with clinical scores of disease severity (Rho = 0.65, p < 0.05), neuropathy (Rho = 0.54, p < 0.05) and neuropathic pain (Rho = 0.56, p < 0.05). These findings indicate that upregulation of I(h) , rather than ischemia, may underlie the sensory symptoms and possibly development of neuropathy in FD. Modulation of sensory I(h) may prove therapeutically useful in Fabry disease.

  5. Renal histology before and after effective enzyme replacement therapy in a patient with classical Fabry's disease.

    Science.gov (United States)

    Hirashio, S; Taguchi, T; Naito, T; Maki, K; Ogata, S; Taniyama, K; Taniguchi, Y; Yorioka, N

    2009-05-01

    A 38-year-old man underwent renal biopsy because of proteinuria. It revealed swelling and vacuolation of glomerular epithelial cells, as well as myelin-like structures characteristic of Fabry's disease. Detection of decreased plasma activity of alpha-galactosidase A confirmed the diagnosis. Enzyme replacement therapy was provided with recombinant agalsidase-beta, resulting in improvement of his symptoms. When renal biopsy was repeated, specific staining for globotriaosylceramide showed that renal deposits were decreased by enzyme therapy.

  6. Analysis of Placental Tissue in Fabry Disease With and Without Enzyme Replacement Therapy

    NARCIS (Netherlands)

    M.G. Bouwman; C.E.M. Hollak; M.A. van den Bergh Weerman; F.A. Wijburg; G.E. Linthorst

    2010-01-01

    There are only a few reports on the histology of placental tissue of pregnancies from mothers with Fabry disease. Fabry disease is a lysosomal disorder caused by alpha-galactosidase A deficiency. Extensive glycosphingolipid (GSL) accumulation in fetal and maternal placenta tissue obtained from a Fab

  7. Enfermedad de Fabry: Comunicación de ocho casos Fabry disease: Report of eight cases

    Directory of Open Access Journals (Sweden)

    M Palombo

    2011-12-01

    Full Text Available La Enfermedad de Fabry (EF constituye una alteración hereditaria del metabolismo de los glicoesfingolípidos, debida a la deficiencia parcial o completa de la enzima alfa-galactosidasa A. Es una enfermedad de transmisión genética ligada a X, que afecta universalmente a todas las etnias humanas con una incidencia comunicada de 1 cada 100.000 nacimientos, aunque es probable que esta cifra subestime la real prevalencia de la enfermedad, especialmente por el gran número de casos no diagnosticados. La EF se manifiesta en su forma más florida, en varones homocigotas que carecen completamente de actividad alfa-galactosidasa A, provocando una miríada de alteraciones, incluyendo anomalías renales (proteinuria progresiva e insuficiencia renal, cardiovasculares (cardiopatías, arritmias, accidentes cerebrovasculares, neurológicas (dolor acral y abdominal, y cocleo-vestibulares, entre las más importantes. Sin embargo, la afectación cutánea constituye la alteración más específica de la enfermedad y es en general, la que conduce a la sospecha diagnóstica. La EF no tratada reduce francamente la expectativa de vida de acuerdo a la severidad de la afectación renal y cardiovascular, si bien la terapia con reemplazo enzimático puede modificar e incluso detener el curso de la enfermedad. En 2010, una paciente de 28 años oriunda de la Provincia de Santa Fe, consultó porangioqueratomas, que condujeron al diagnóstico de enfermedad de Fabry. Desde entonces hemos estudiado y tratado a toda la familia, con ocho casos confirmados a la fecha y otros tantos en evaluación.Fabry disease (Online Mendelian Inheritance in Man No. 301500 is an X-linked inherited condition due to absence or reduction of ɑ galactosidase activity in lysosomes that results in accumulation of globotriaosylceramide and related neutral glycosphingolipids (storage disorder. It is estimated to occur in 1 in 40.000 to 117.000 live male births, although a more recent screening study in

  8. Screening for Fabry Disease in Left Ventricular Hypertrophy: Documentation of a Novel Mutation

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Ana, E-mail: baptista-ana@hotmail.com; Magalhães, Pedro; Leão, Sílvia; Carvalho, Sofia; Mateus, Pedro; Moreira, Ilídio [Centro Hospitalar de Trás-os-Montes e Alto Douro, Unidade de Vila Real (Portugal)

    2015-08-15

    Fabry disease is a lysosomal storage disease caused by enzyme α-galactosidase A deficiency as a result of mutations in the GLA gene. Cardiac involvement is characterized by progressive left ventricular hypertrophy. To estimate the prevalence of Fabry disease in a population with left ventricular hypertrophy. The patients were assessed for the presence of left ventricular hypertrophy defined as a left ventricular mass index ≥ 96 g/m{sup 2} for women or ≥ 116 g/m{sup 2} for men. Severe aortic stenosis and arterial hypertension with mild left ventricular hypertrophy were exclusion criteria. All patients included were assessed for enzyme α-galactosidase A activity using dry spot testing. Genetic study was performed whenever the enzyme activity was decreased. A total of 47 patients with a mean left ventricular mass index of 141.1 g/m{sup 2} (± 28.5; 99.2 to 228.5 g/m{sup 2}] were included. Most of the patients were females (51.1%). Nine (19.1%) showed decreased α-galactosidase A activity, but only one positive genetic test − [GLA] c.785G>T; p.W262L (exon 5), a mutation not previously described in the literature. This clinical investigation was able to establish the association between the mutation and the clinical presentation. In a population of patients with left ventricular hypertrophy, we documented a Fabry disease prevalence of 2.1%. This novel case was defined in the sequence of a mutation of unknown meaning in the GLA gene with further pathogenicity study. Thus, this study permitted the definition of a novel causal mutation for Fabry disease - [GLA] c.785G>T; p.W262L (exon 5)

  9. [Treatment of Fabry disease: Successes, failures, and expectations].

    Science.gov (United States)

    Lidove, Olivier; Barbey, Frédéric; Joly, Dominique

    2016-04-01

    Fabry disease, an X-linked lysosomal storage disease, results from α-galactosidase A deficiency. Two different recombinant enzyme treatments (algalsidase alpha agalsidase beta) have been available since 2001 to treat a disease that affects not only men but also women. Enzyme replacement therapy promotes cell clearance of susbtrate, and improves some clinical parameters (heart, kidney damage, pain, quality of life). However, there is no proven efficacy to date on central nervous system lesions, on cardiac morbidity and mortality, nor on renal damage beyond a certain stage (proteinuria>1g/day and/or estimated glomerular filtration rate<60mL/min/1.73m(2)). In this review, we discuss the potential benefit of an early intervention, the vascular protective measures to be associated with enzyme therapy and their rationale, and some alternative treatments under development, such as chaperones and substrate molecules inhibitors.

  10. The coincidence of IgA nephropathy and Fabry disease

    Directory of Open Access Journals (Sweden)

    Maixnerová Dita

    2013-01-01

    Full Text Available Abstract Background IgA nephropathy (IgAN is the most common glomerulonephritis, which may also coexist with other diseases. We present two patients with an unusual coincidence of IgAN and Fabry disease (FD. Case presentation A 26 year-old man underwent a renal biopsy in February 2001. Histopathology showed very advanced IgAN and vascular changes as a result of hypertension. Because of his progressive renal insufficiency the patient began hemodialysis in August 2001. By means of the blood spot test screening method the diagnosis of FD was suspected. Low activity of alpha-galactosidase A in the patient’s plasma and leukocytes and DNA analysis confirmed the diagnosis of FD. Enzyme replacement therapy started in July 2004. Then the patient underwent kidney transplantation in November 2005. Currently, his actual serum creatinine level is 250 μmol/l. Other organ damages included hypertrophic cardiomyopathy, neuropathic pain and febrile crisis. After enzyme replacement therapy, myocardial hypertrophy has stabilized and other symptoms have disappeared. No further progression of the disease has been noted. The other patient, a 30 year-old woman, suffered from long-term hematuria with a good renal function. Recently, proteinuria (2.6 g/day appeared and a renal biopsy was performed. Histopathology showed IgAN with remarkably enlarged podocytes. A combination of IgAN and a high suspicion of FD was diagnosed. Electron microscopy revealed dense deposits in paramesangial areas typical for IgAN and podocytes with inclusive zebra bodies and myelin figures characteristic of FD. FD was confirmed by the decreased alpha-galactosidase A activity in plasma and leukocytes and by DNA and RNA analysis. Enzyme replacement therapy and family screening were initiated. Conclusions Our results emphasize the role of complexity in the process of diagnostic evaluation of kidney biopsy samples. Electron microscopy represents an integral part of histopathology, and genetic

  11. Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors.

    Science.gov (United States)

    Bennett, Robin L; Hart, Kimberly A; O'Rourke, Erin; Barranger, John A; Johnson, Jack; MacDermot, Kay D; Pastores, Gregory M; Steiner, Robert D; Thadhani, Ravi

    2002-04-01

    The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing and interpretation of results, psychosocial considerations, and references for professional and patient resources. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a healthcare provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.

  12. Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study

    Directory of Open Access Journals (Sweden)

    Lidicker Jeffrey R

    2008-11-01

    Full Text Available Abstract Background We previously demonstrated improved sweating after enzyme replacement therapy (ERT in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating, has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM system. Methods We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1 moisture reading of the 100th repetitive reading, 2 rate of change, 3 average of 60–110th reading and 4 overall average of all readings. Results All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p Conclusion The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.

  13. [Atypical symptoms of Fabry's disease: sudden bilateral deafness, lymphoedema and Lown-Ganong-Levine syndrome].

    Science.gov (United States)

    Undas, Anetta; Ryś, Donata; Wegrzyn, Wojciech; Musiał, Jacek

    2002-11-01

    A 40-year-old man with Fabry disease, confirmed by decreased leukocyte alpha-galactosidase A activity in 2001, complained of sudden bilateral deafness, as evidenced by clinical history and audiometry. Magnetic resonance of the brain revealed features typical of Fabry disease. Other clinical manifestations of the disease included: angiokeratoma, mild proteinuria with normal renal function, lymphoedema of the lower limbs, pre-excitation syndrome, myocardial hypertrophy.

  14. [Fabry's disease: an example of cardiorenal syndrome type 5].

    Science.gov (United States)

    Villa, Gianluca; Romagnoli, Stefano; Sharma, Aashish; Ronco, Claudio

    2017-03-01

    Fabry's disease (FD) is a severe congenital metabolic disorder characterized by the deficient activity of lysosomal exoglycohydrolase alpha-galactosidase, characterized by glycosphingolipid deposition in several cells, such as capillary endothelial cells, renal, cardiac, and nerve cells. As a systemic disease leading to a contemporaneous myocardial and renal dysfunction, FD might be an example of cardiorenal syndrome type 5 (CRS-5). Kidney damage is commonly characterized by proteinuria, isosthenuria and altered tubular function when occurs at the second-third decade, azotemia and end-stage renal disease in third-fifth decade. Beyond the irreversible glomerular, tubular and vascular damages, the podocytes foot process effacement is the major cause of kidney dysfunction. Myocardial damage is usually observed with right and left ventricular hypertrophy, arrhythmias (due to sinus node and conduction system impairment), diastolic dysfunction, congestive heart failure, myocardial ischemia, fibrosis and cardiac death. The enzymatic replacement therapy is essential for the management of FD, as well as the control of renal (with anti-proteinuric agents such as angiotensin-converting enzyme inhibitors- and/or angiotensin II receptor blockers), brain (coated aspirin, clopidogrel and statins to prevent strokes) and heart complications (calcium channel blockers for ischemic cardiomyopathy, warfarin and amiodarone or cardioverter device for arrhythmias). Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

  15. Fabry disease in Spain. Description of Spanish patients and a comparison with other European countries using data from the Fabry Outcome Survey (FOS)

    OpenAIRE

    Barba Romero, Miguel Angel; Rivera Gallego, Alberto; Pintos Morell, Guillem

    2011-01-01

    Abstract Aims: Fabry disease (FD) is an X chromosome-linked transmitted lysosomal storage disorder due to the deficient activity of enzyme ?-galactosidase A. This leads to accumulation of neutral glycosphingolipids associated with organ involvement and premature death. We report the clinical characteristics of Spanish patients enrolled on the Fabry Outcome Survey (FOS; an international multicentre registry for the disease) and also compare these data with those from the rest of Eur...

  16. High Variability of Fabry Disease Manifestations in an Extended Italian Family

    Directory of Open Access Journals (Sweden)

    Giuseppe Cammarata

    2015-01-01

    Full Text Available Fabry disease (FD is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolase α-galactosidase A (α-GAL. The impairment of α-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences in α-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease.

  17. Time to treatment benefit for adult patients with Fabry disease receiving agalsidase β: data from the Fabry Registry

    Science.gov (United States)

    Ortiz, Alberto; Abiose, Ademola; Bichet, Daniel G; Cabrera, Gustavo; Charrow, Joel; Germain, Dominique P; Hopkin, Robert J; Jovanovic, Ana; Linhart, Aleš; Maruti, Sonia S; Mauer, Michael; Oliveira, João P; Patel, Manesh R; Politei, Juan; Waldek, Stephen; Wanner, Christoph; Yoo, Han-Wook; Warnock, David G

    2016-01-01

    Background Agalsidase β is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low α-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase β cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a ‘lag time’ to clinical benefit after initiating agalsidase β treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase β. Methods The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase β (average dose 1 mg/kg every 2 weeks) for up to 5 years. Results The incidence of all severe clinical events was 111 per 1000 person-years (95% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40–58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged ≥40 years when agalsidase β was initiated. Conclusions Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase β 1 mg/kg every 2 weeks. Trial registration number NCT00196742. PMID:26993266

  18. Neuro-Otological and Peripheral Nerve Involvement in Fabry Disease

    Science.gov (United States)

    Carmona, Sergio; Weinschelbaum, Romina; Pardal, Ana; Marchesoni, Cintia; Zuberbuhler, Paz; Acosta, Patricia; Cáceres, Guillermo; Kisinovsky, Isaac; Bayón, Luciana; Reisin, Ricardo

    2017-01-01

    Fabry disease (FD) is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain), vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%), vertigo (27.8%) or both (25%). An involvement of either cochlear or vestibular function was identified in most patients (75%). In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neuro-otological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities. PMID:28794847

  19. Positron Emission Tomography and Magnetic Resonance Imaging of the Brain in Fabry Disease

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Feldt-Rasmussen, Ulla; Granqvist, Henrik;

    2015-01-01

    risk of cerebrovascular disease at a young age in addition to heart and kidney failure. OBJECTIVE: The objective of this study was to assess brain function and structure in the Danish cohort of patients with Fabry disease in a prospective way using 18-fluoro-deoxyglucose (F-18 FDG) positron emission....... CONCLUSION: Our data indicated that, in patients with Fabry disease, MRI is the preferable clinical modality--if applicable--when monitoring cerebral status, as no additional major brain-pathology was detected with FDG-PET.......BACKGROUND: Fabry disease is a rare metabolic glycosphingolipid storage disease caused by deficiency of the lysosomal enzyme α-galactosidase A--leading to cellular accumulation of globotriasylceramide in different organs, vessels, tissues, and nerves. The disease is associated with an increased...

  20. Fabry Disease: A Turkish Case with a Novel Mutation and Dermatological Manifestations

    Directory of Open Access Journals (Sweden)

    Neslihan Onenli Mungan

    2015-03-01

    Full Text Available Fabry disease is a rare, X-linked disease, caused by the deficiency of lysosomal and #945;-galactosidase. Clinical fetaures are; acroparesthesia, unexplained fever, hypohidrosis and angiokeratomas. Untreated cases die early from cardiac complications, renal insuffiency or stroke. Currently there is no cure for Fabry disease, enzyme replacement therapy is the only choice in this progressive disease. A 9-year-old boy admitted to the Dermatology Clinic with reddish papular skin lesions, joint pain and anhydrosis. Hystological examination of the skin biopsy revealed angiokeratoma. There was no renal dysfunction or proteinuria. Biochemical confirmation of Fabry disease was made by determining the deficient leukocyte and #945;-galactosidase activity. Subsequently, the patient's molecular analysis was identified a novel nonsense mutation c. 785G>T in the GLA gene. Enzyme replacement therapy with agalsidase beta was started. He is on enzyme replacement therapy for 8 years, significant improvement was obtained in severity and frequency of pain crisis and fatigue. We report this case to emphasize the importance of early diagnosis of Fabry disease restricted to dermatological findings, especially before renal and cardiac involvement occurs, while enzyme replacement therapy is now available. Also this patient is one of the first Fabry patients under enzyme replacement therapy in Turkey. [Cukurova Med J 2015; 40(Suppl 1: 156-160

  1. Social-adaptive and psychological functioning of patients affected by Fabry disease.

    Science.gov (United States)

    Laney, Dawn Alyssia; Gruskin, Daniel J; Fernhoff, Paul M; Cubells, Joseph F; Ousley, Opal Y; Hipp, Heather; Mehta, Ami J

    2010-12-01

    Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficiency of alpha-galactosidase A. In addition to the debilitating physical symptoms of FD, there are also under-recognized and poorly characterized psychiatric features. As a first step toward characterizing psychiatric features of FD, we administered the Achenbach adult self report questionnaire to 30 FD patients and the Achenbach adult behavior checklist questionnaire to 28 partners/parents/friends of FD patients. Data from at least one of the questionnaires were available on 33 subjects. Analysis focused on social-adaptive functioning in various aspects of daily life and on criteria related to the Diagnostic and statistical manual of mental disorders IV (DSM-IV). Adaptive functioning scale values, which primarily measure social and relationship functioning and occupational success, showed that eight FD patients (six female and two male) had mean adaptive functioning deficits as compared to population norms. Greater rates of depression (P personality (P Individuals affected by Fabry disease exhibited social-adaptive functioning deficits that were significantly correlated with anxiety, depression, antisocial behavior, and AD/H problems in a sampling of our male and female patients aged between 18 years and 59 years.

  2. Copious Podocyturia without Proteinuria and with Normal Renal Function in a Young Adult with Fabry Disease

    Science.gov (United States)

    Trimarchi, H.; Canzonieri, R.; Muryan, A.; Schiel, A.; Forrester, M.; Karl, A.; Lombi, F.; Andrews, J.; Pomeranz, V.; Rengel, T.; Zotta, E.

    2015-01-01

    The time for starting a patient with Fabry disease on enzyme replacement therapy is still a matter of debate, particularly when no overt classical clinical signs or symptoms are present. With respect to Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement infusion until signs of renal disease appear as the appearance of proteinuria or an elevation in serum creatinine and the lack of validated biomarkers of early renal damage. In this regard, proteinuria is nowadays considered as an early and appropriate marker of kidney disease and of cardiovascular morbidity and mortality. However, in this report we demonstrate that podocyturia antedates the classical appearance of proteinuria and could be considered as an even earlier biomarker of kidney damage. Podocyturia may be a novel indication for the initiation of therapy in Fabry disease. PMID:26064721

  3. Copious Podocyturia without Proteinuria and with Normal Renal Function in a Young Adult with Fabry Disease

    Directory of Open Access Journals (Sweden)

    H. Trimarchi

    2015-01-01

    Full Text Available The time for starting a patient with Fabry disease on enzyme replacement therapy is still a matter of debate, particularly when no overt classical clinical signs or symptoms are present. With respect to Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement infusion until signs of renal disease appear as the appearance of proteinuria or an elevation in serum creatinine and the lack of validated biomarkers of early renal damage. In this regard, proteinuria is nowadays considered as an early and appropriate marker of kidney disease and of cardiovascular morbidity and mortality. However, in this report we demonstrate that podocyturia antedates the classical appearance of proteinuria and could be considered as an even earlier biomarker of kidney damage. Podocyturia may be a novel indication for the initiation of therapy in Fabry disease.

  4. [Globosides as key players in the pathophysiology of Shiga toxin-associated acute kidney failure and Fabry disease].

    Science.gov (United States)

    Porubsky, S

    2014-11-01

    Globosides and their isomeric counterparts isoglobosides belong to the class of neutral glycosphingolipids with an as yet undefined physiological function. In the pathogenesis of human diseases, globosides play an important role as cellular receptors for Shiga toxins which are produced by certain strains of S. dysenteriae and E. coli. In order to elucidate the pathogenesis of Shiga toxin-associated kidney failure, we studied human kidney biopsies and animal models. Our work showed that in patients suffering from Shiga toxin-elicited kidney failure, no complement activation could be demonstrated by immunohistochemical analysis of kidney biopsies. Therefore, complement activation is unlikely to play a major role in mediating thrombotic microangiopathy on exposure to Shiga toxin. Moreover, analysis of the human biopsies and of a murine model of Shiga toxin-associated disease pinpointed acute tubular damage as an important and previously neglected contributor to acute kidney failure in patients infected with Shiga toxin-producing E. coli. Furthermore, globosides play a decisive role in the pathogenesis of Fabry disease which results from a decreased or absent activity of the lysosomal enzyme α-galactosidase A. The results on transgenic mice showed that in vital organs, such as the heart, kidneys and liver, it was possible to revert the phenotype of Fabry disease by eliminating the synthesis of globosides. This implicates that substrate reduction therapy through inhibition of globosides might represent a new therapeutic option for Fabry disease, all the more so as globosides seem to be dispensable.

  5. Fabry disease mimicking hypertrophic cardiomyopathy: genetic screening needed for establishing the diagnosis in women

    DEFF Research Database (Denmark)

    Havndrup, Ole; Christiansen, Michael; Stoevring, Birgitte

    2010-01-01

    AIMS: Fabry disease, an X-linked storage disorder caused by defective lysosomal enzyme alpha-galactosidase A activity, may resemble sarcomere-gene-associated hypertrophic cardiomyopathy (HCM). The 'cardiac variant' of Fabry disease which only affects the heart may be missed unless specifically...... tested for. METHODS AND RESULTS: We evaluated 90 consecutively recruited HCM probands and their relatives. Probands without sarcomere-gene mutations were tested for alpha-galactosidase A gene (GLA) mutations. Of the 90 families, 31 (34%) had sarcomere gene mutations and were therefore excluded...... without sarcomere gene mutations. GLA mutations were found in 3/90 (3%) of HCM families and in 2/20 (10%) of females without sarcomere-gene mutations. None of the probands presented other indices of Fabry disease. This, in combination with putative reversibility of cardiac changes by enzyme replacement...

  6. Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

  7. Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Nielsen, Rikke; Larsen, Jakob Vejby;

    2011-01-01

    Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocy...

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

    Directory of Open Access Journals (Sweden)

    Majid Alfadhel

    2011-02-01

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

  9. [Fabry disease: clinic and enzymatic diagnosis of homozygous and heterozygous. New therapeutic prospects].

    Science.gov (United States)

    Peces, R; Olea, T

    2002-01-01

    Fabry disease is an X-linked recessive lysosomal storage disorder caused by a partial or complete deficiency of alpha-galactosidase A. Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and early death. Men are predominantly affected but many female carriers have similar clinical involvement, including increased risk of stroke. Physical stigmata, such as angiokeratomas in skin and mucous membranes and characteristic benign corneal abnormalities, facilitate identification of Fabry disease. The finding of a marked decreased activity of (alpha-galactosidase A in plasma, white blood cells or cultured skin fibroblasts confirms the diagnosis. Treatment thus far has been symptomatic only. Etiology-based therapies are being developed that include enzyme replacement therapy, gene therapy, and substrate deprivation. The recently completed double-blind, placebo-controlled trials of intravenous infusions of (alpha-galactosidase A in patients with Fabry disease demonstrated the safety and efficacy of this treatment. We report a family with Fabry disease composed of hemicygous and heterocygous. The propositus developed chronic renal failure and received a cadaver renal transplant, which remained with adequate renal function during 15 years.

  10. Two-dimensional speckle tracking as a non-invasive tool for identification of myocardial fibrosis in Fabry disease.

    Science.gov (United States)

    Krämer, Johannes; Niemann, Markus; Liu, Dan; Hu, Kai; Machann, Wolfram; Beer, Meinrad; Wanner, Christoph; Ertl, Georg; Weidemann, Frank

    2013-06-01

    This cross-sectional study aimed to analyse myocardial deformation in patients with Fabry disease (FD) in order to evaluate speckle tracking as a method for non-invasive determination of myocardial fibrosis. Myocardial fibrosis is common in Fabry cardiomyopathy and is associated with disease progression and severe prognosis. In 101 consecutive Fabry patients (39.8 ± 12.9 years; 42 males), the quantitative measurement of myocardial fibrosis with magnetic resonance imaging was compared with regional myocardial deformation assessed by speckle-tracking imaging. Patients were analysed in relation to per cent of late-enhancement (LE)-positive areas of left-ventricular (LV) mass. Fifty-two patients (51%) displayed LE with a mean volume of 1.2 ± 1.8% of total LV mass. Predominantly basal lateral and posterior segments were affected. Patients with LE had lower global systolic longitudinal strain than those without (LE -14.8 ± 3.5% and -18.9 ± 2.1%, respectively; P speckle tracking, was predominantly caused by basal posterior (P = 0.049) and lateral (P = 0.005) segments and global systolic strain correlated with the amount of LE (r = 0.543; P 2%, n = 22) showed the lowest deformation values (-5.9 ± 8.4%) in basal postero-lateral segments when compared with those with mild (Speckle tracking can be used as a tool for the indirect evaluation of LE in FD.

  11. Functional and structural nerve fiber findings in heterozygote patients with Fabry disease

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Bach, Flemming Winther; Feldt-Rasmussen, Ulla;

    2009-01-01

    recently disease manifestations in female carriers of Fabry disease have been questioned. To explore the frequency of symptoms and the functional and structural involvement of the nervous system in female patients we examined the presence of pain, manifestations of peripheral neuropathy and nerve density...... in skin biopsies in 19 female patients with Fabry disease and 19 sex- and age-matched controls. Diaries, quantitative sensory testing, neurophysiologic tests and skin biopsies were performed. Daily pain was present in 63% of patients, with a median VAS score of 4.0. Tactile detection threshold...... and pressure pain threshold were lower and cold detection thresholds increased in patients. Sensory nerve action potential amplitude and maximal sensory conduction velocity were not different, whereas there was a highly significant reduction in intraepidermal nerve fiber density. We found no correlation...

  12. Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease.

    Science.gov (United States)

    Labilloy, Anatália; Youker, Robert T; Bruns, Jennifer R; Kukic, Ira; Kiselyov, Kirill; Halfter, Willi; Finegold, David; do Monte, Semiramis Jamil Hadad; Weisz, Ora A

    2014-02-01

    Accumulation of globotriaosylceramide (Gb3) and other neutral glycosphingolipids with galactosyl residues is the hallmark of Fabry disease, a lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A (α-gal A). These lipids are incorporated into the plasma membrane and intracellular membranes, with a preference for lipid rafts. Disruption of raft mediated cell processes is implicated in the pathogenesis of several human diseases, but little is known about the effects of the accumulation of glycosphingolipids on raft dynamics in the context of Fabry disease. Using siRNA technology, we have generated a polarized renal epithelial cell model of Fabry disease in Madin-Darby canine kidney cells. These cells present increased levels of Gb3 and enlarged lysosomes, and progressively accumulate zebra bodies. The polarized delivery of both raft-associated and raft-independent proteins was unaffected by α-gal A knockdown, suggesting that accumulation of Gb3 does not disrupt biosynthetic trafficking pathways. To assess the effect of α-gal A silencing on lipid raft dynamics, we employed number and brightness (N&B) analysis to measure the oligomeric status and mobility of the model glycosylphosphatidylinositol (GPI)-anchored protein GFP-GPI. We observed a significant increase in the oligomeric size of antibody-induced clusters of GFP-GPI at the plasma membrane of α-gal A silenced cells compared with control cells. Our results suggest that the interaction of GFP-GPI with lipid rafts may be altered in the presence of accumulated Gb3. The implications of our results with respect to the pathogenesis of Fabry disease are discussed.

  13. Non-invasive determination of myocardial lipid content in Fabry disease by {sup 1}H-MR spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Petritsch, B.; Koestler, H.; Machann, W.; Horn, M.; Weng, A.M.; Goltz, J.P.; Hahn, D.; Beer, M. [Universitaetsklinikum Wuerzburg (Germany). Inst. fuer Roentgendiagnostik im ZOM; Niemann, M.; Weidemann, F.; Wanner, C. [Universitaetsklinikum Wuerzburg (Germany). Medizinische Klinik I

    2012-11-15

    Purpose: In Fabry disease (FD), a progressive deposition of sphingolipids is reported in different organs. The present study applied {sup 1}H magnetic resonance spectroscopy (MRS) to investigate the myocardial lipid content in FD. Materials and Methods: In patients (PTS, n = 15) with genetically proven FD, {sup 1}H MRS of the heart was acquired in the same examination as routine cardiac cine and late enhancement MR imaging. Healthy volunteers (n = 11) without history of cardiac disease served as control (CTL). Myocardial triglycerides in vivo were quantified in {sup 1}H MRS. Left ventricular (LV) ejection fraction (EF) and late enhancement were assessed for the determination of LV systolic function, and onset or absence of myocardial fibrosis. Results: All {sup 1}H MRS revealed resonances for intramyocardial triglycerides. Clinical parameters, e.g. EF (PTS 64 {+-} 2 % vs. CTL 61 {+-} 1 %) were similar in PTS and CTL or showed a non-significant trend (LV mass). Apart from a single patient with elevated myocardial triglycerides, no significant impact of Fabry disease on the triglyceride/water resonance ratio (PTS 0.47 {+-} 0.11 vs. CTL 0.52 {+-} 0.11 %) was observed in our patient cohort. Conclusion: A comprehensive cardiac evaluation of morphology, function as well as metabolism in Fabry PTS with suspected cardiac involvement is feasible in a single examination. No significant effect of myocardial triglyceride deposition could be observed in patients. The remarkably high myocardial triglyceride content in one patient with advanced FD warrants further studies in PTS with an extended history of the disease. (orig.)

  14. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina

    Directory of Open Access Journals (Sweden)

    Isaac Kisinovsky

    2013-02-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme α-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years and 36 females (mean age: 34 years. A total of 5229 infusions (mean: 59 per patient; range: 1-150 were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions. All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.

  15. Fabry disease : Baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry

    NARCIS (Netherlands)

    Eng, C. M.; Fletcher, J.; Wilcox, W. R.; Waldek, S.; Scott, C. R.; Sillence, D. O.; Breunig, F.; Charrow, J.; Germain, D. P.; Nicholls, K.; Banikazemi, M.

    2007-01-01

    The Fabry Registry is a global observational research platform established to define outcome data on the natural and treated course of this rare disorder. Participating physicians submit structured longitudinal data to a centralized, confidential database. This report describes the baseline demograp

  16. Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

    Science.gov (United States)

    Lenders, Malte; Canaan-Kühl, Sima; Krämer, Johannes; Duning, Thomas; Reiermann, Stefanie; Sommer, Claudia; Stypmann, Jörg; Blaschke, Daniela; Üçeyler, Nurcan; Hense, Hans-Werner; Brand, Stefan-Martin; Wanner, Christoph; Weidemann, Frank; Brand, Eva

    2016-03-01

    Because of the shortage of agalsidase-β supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-α. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-α. A total of 89 adult patients with Fabry disease who had received agalsidase-β (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-α (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-α (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and Pswitch or a direct switch to agalsidase-α showed a decline of renal function independent of the eGFR formula used.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    therapy (ERT), stabilises specific mutant (amenable) forms of α-Gal to facilitate normal lysosomal trafficking. METHODS: The main objective of the 18-month, randomised, active-controlled ATTRACT study was to assess the effects of migalastat on renal function in patients with Fabry disease previously...... ventricular mass index decreased significantly with migalastat treatment (-6.6 g/m(2) (-11.0 to -2.2)); there was no significant change with ERT. Predefined renal, cardiac or cerebrovascular events occurred in 29% and 44% of patients in the migalastat and ERT groups, respectively. Plasma...... globotriaosylsphingosine remained low and stable following the switch from ERT to migalastat. PROs were comparable between groups. Migalastat was generally safe and well tolerated. CONCLUSIONS: Migalastat offers promise as a first-in-class oral monotherapy alternative treatment to intravenous ERT for patients with Fabry...

  18. COMPUTER ASSISTED RETINAL VESSEL TORTUOSITY EVALUATION IN NOVEL MUTATION FABRY DISEASE: Towards New Prognostic Markers.

    Science.gov (United States)

    San Román, Irene; Rodríguez, María-Elena; Caporossi, Orsola; Zoppetti, Claudia; Sodi, Andrea; Mecocci, Alessandro; López, David; Rodríguez, Beatriz; Gimeno, Juan-Ramón

    2017-03-01

    Fabry disease is a rare lysosomal storage disorder with systemic involvement. The authors report on a large Fabry family with GLA p.M187R mutation and exhaustive ophthalmologic assessment. Comprehensive systemic evaluation and genetic diagnosis were performed. Ophthalmologic evaluation included intraocular pressure/visual acuity measurement, refractometry, slit lamp examination, retinography, and optical coherence tomography. Three parameters quantified retinal vessel tortuosity: sum of angle metrics, product of angle distance, and triangular index. Calculations were semiautomatized using dedicated software. Ten individuals (2 males and 8 females) were described. Seventy-five percent had retinal vessel tortuosity. One hundred percent had cornea verticillata. Perimacular vessels were predominantly involved. The correlation between the right and left eye tortuosity measurements was very tight. A significant correlation between retinal vessel tortuosity and systemic severity measured by general Mainz Severity Score Index (MSSI), renal MSSI, and neurological MSSI but no cardiac MSSI was observed. Right sum of angle metrics value was an independent statistical predictor of the general-MSSI score in presence of age. p.M187R mutation causes a severe systemic and ophthalmologic phenotype, in both male and female patients. Semiautomatic assessment of retinal vessel tortuosity is an objective and reproducible tool. All three parameters of tortuosity are closely associated with Fabry severity scores. Studies of larger series are being awaited to establish the role of retinal vessel tortuosity as a noninvasive marker of disease progression.

  19. Evaluación de pacientes con enfermedad de Fabry en la Argentina Evaluation of patients with Fabry disease in Argentina

    Directory of Open Access Journals (Sweden)

    2010-02-01

    Full Text Available La enfermedad de Fabry es un desorden lisosomal de transmisión ligada al cromosoma X debida al déficit de la enzima alfa galactosidasa A, con acumulación multisistémica de globotriaosilceramida y compromiso neurológico, gastrointestinal, cardíaco, renal, dermatológico y oftalmológico. Estudios recientes indican que las mujeres heterocigotas desarrollan síntomas similares a los de los varones, pero no existen en nuestro país datos comparativos respecto de la frecuencia relativa de manifestaciones clínicas, edad de inicio y gravedad entre hombres y mujeres con enfermedad de Fabry. Identificamos 59 pacientes adultos sintomáticos con enfermedad de Fabry: 32 varones (edad media: 34.8 años y 27 mujeres (edad media: 46.6 años. El diagnóstico se hizo por estudios enzimáticos en los hombres y genéticos en las mujeres. Se evaluó la frecuencia y la gravedad de las manifestaciones de la enfermedad. Las manifestaciones más frecuentes fueron acroparestesias, angioqueratomas, hipohidrosis y córnea verticilada; las tres primeras fueron estadísticamente más frecuentes en hombres, en los cuales la gravedad de estos síntomas fue significativamente mayor. Proteinuria e hipertrofia ventricular izquierda fueron hallazgos frecuentes tanto en hombres como en mujeres. Hubo una latencia prolongada entre la edad del inicio y la del diagnóstico de 14 años para varones y 30 para mujeres. La enfermedad de Fabry es una enfermedad subdiagnosticada y potencialmente letal que afecta a ambos sexos. La existencia de reemplazo enzimático obliga a identificar precozmente los síntomas y signos sugestivos de la enfermedad para realizar un diagnóstico y tratamiento precoces.Fabry disease is an X- linked lysosomal disorder due to deficient activity of the enzyme alpha galactosidase A which leads to multisystemic storage of globotriaosylceramide with neurologic, gastrointestinal, cardiac, renal, skin and ophtalmological involvement. Recent studies indicate

  20. Corpus callosum involvement: a useful clue for differentiating Fabry disease from multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Cocozza, Sirio; Olivo, Gaia; Pontillo, Giuseppe; Ugga, Lorenzo; De Rosa, Dario; Imbriaco, Massimo; Brunetti, Arturo; Tedeschi, Enrico [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Riccio, Eleonora; Migliaccio, Silvia; Pisani, Antonio [University ' ' Federico II' ' , Department of Public Health, Nephrology Unit, Naples (Italy); Russo, Camilla [University ' ' Federico II' ' , Department of Advanced Biomedical Sciences, Naples (Italy); Feriozzi, Sandro [Belcolle Hospital, Nephrology and Dialysis Department, Viterbo (Italy); Veroux, Massimiliano [University Hospital of Catania, Department of Medical and Surgical Sciences and Advanced Technologies, Catania (Italy); Battaglia, Yuri [St. Anna Hospital-University, Department of Specialized Medicine, Division of Nephrology and Dialysis, Ferrara (Italy); Concolino, Daniela [University Magna Graecia, Department of Pediatrics, Catanzaro (Italy); Pieruzzi, Federico [University of Milano-Bicocca, Nephrology Unit, Milan (Italy); Tuttolomondo, Antonino [University of Palermo, Internal Medicine, DiBiMIS, Palermo (Italy); Caronia, Aurelio [Triolo Zancia Care Home, Palermo (Italy); Russo, Cinzia Valeria; Lanzillo, Roberta; Brescia Morra, Vincenzo [University ' ' Federico II' ' , Department of Neurosciences and Reproductive and Odontostomatological Sciences, Naples (Italy)

    2017-06-15

    Multiple sclerosis (MS) has been proposed as a possible differential diagnosis for Fabry disease (FD). The aim of this work was to evaluate the involvement of corpus callosum (CC) on MR images and its possible role as a radiological sign to differentiate between FD and MS. In this multicentric study, we retrospectively evaluated the presence of white matter lesions (WMLs) on the FLAIR images of 104 patients with FD and 117 patients with MS. The incidence of CC-WML was assessed in the two groups and also in a subgroup of 37 FD patients showing neurological symptoms. WMLs were detected in 50 of 104 FD patients (48.1%) and in all MS patients. However, a lesion in the CC was detected in only 3 FD patients (2.9%) and in 106 MS patients (90.6%). In the FD subgroup with neurological symptoms, WMLs were present in 26 of 37 patients (70.3%), with two subjects (5.4%) showing a definite callosal lesion. FD patients have a very low incidence of CC involvement on conventional MR images compared to MS, independently from the clinical presentation and the overall degree of WM involvement. Evaluating the presence of CC lesions on brain MR scans can be used as a radiological sign for a differential diagnosis between MS and FD, rapidly addressing the physician toward a correct diagnosis and subsequent treatment options. (orig.)

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

    DEFF Research Database (Denmark)

    Biegstraaten, Marieke; Arngrímsson, Reynir; Barbey, Frederic;

    2015-01-01

    INTRODUCTION: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed...... to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. METHODS: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations...

  2. Anderson-Fabry, the histrionic disease: from genetics to clinical management

    Directory of Open Access Journals (Sweden)

    Franco Cecchi

    2013-02-01

    Full Text Available Anderson-Fabry disease (AFD is an Xlinked lysosomal storage disorder of glycosphingolipid catabolism, due to deficiency or absence of a galactosidase A (α-gal A enzyme. The disease may affect males and females, the latter with an average 10 years delay. Metabolites storage (mostly Gb3 and lyso-Gb3 leads to progressive cellular and multiorgan dysfunction, with either early and late onset variable clinical manifestations that usually reduce quality of life and life expectancy. Heart and kidney failure, stroke and sudden death are the most devastating complications. AFD is always been considered a very rare disease, although new epidemiologic data, based on newborn screening, showed that AFD prevalence is probably underestimated and much higher than previously reported, especially for late-onset atypical phenotypes. Currently, the diagnosis may be easier and simpler by evaluating α-gal A enzyme activity and genetic analysis for GLA gene mutations on dried blood spot. While a marked α-gal A deficiency leads to diagnosis of AFD in hemizygous males, the molecular analysis is mandatory in heterozygous females. However, referral to a center with an expert multidisciplinary team is highly advisable, in order to ensure careful management and treatment of patients, based also on accurate molecular and biochemical data interpretation. While long-term efficacy of enzyme replacement therapy (ERT in advanced stage is still debated, increasing evidence shows greater efficacy of early treatment initiation. Concomitant, organ-specific therapy is also needed. New treatment approaches, such as chemical chaperone therapy, alone or in combination with ERT, are currently under investigation. The present review illustrates the major features of the disease, focusing also on biochemical and genetic aspects.

  3. Mutational analysis of the GLA gene in Mexican families with Fabry disease

    Indian Academy of Sciences (India)

    BIANCA ETHEL GUTIÉRREZ-AMAVIZCA; ANDREAS GAL; ROCÍO ORTÍZ-OROZCO; ULRICH ORTH; ERNESTO PRADO MONTES DE OCA; JAIME PAUL GUTIÉRREZ-AMAVIZCA; LUIS E. FIGUERA

    2017-03-01

    Fabry disease (FD) is a lysosomal storage disorder, which develops due to a deficiency in the hydrolytic enzyme, α-galactosidase A (α-Gal A). Alpha-Gal A hydrolyzes glycosphingolipid globotriaosylceramide (Gb3), and an α-Gal Adeficiency leads to Gb3 accumulation in tissues and cells in the body. This pathology is likely to involve multiple systems, but it is generally considered to affect primarily vascular endothelium. In this study, we investigated mutations in the GLA gene, which encodes α-Gal A, in Mexican families with FD. We included seven probands with FD that carried known mutations. We analysed pedigrees of the probands, and performed molecular screening in 65 relatives with the potential of carrying a GLA mutation. Five mutations (P40S, IVS4+4, G328V, R363H, R404del) were detected in seven unrelated Mexican familieswith the classic FD phenotype. Of the 65 relatives examined, 42 (64.6%) had a GLA gene mutation. In summary, among seven Mexican probands with FD, 65 relatives were at risk of carrying a known GLA mutation, and molecular screening identified 42 individuals with the mutation. Thus, our findings showed that it is important to perform molecular analysis in families with FD to detect mutations and to provide accurate diagnoses for individuals that could be affected.

  4. Globotriaosylsphingosine accumulation and not alpha-galactosidase-A deficiency causes endothelial dysfunction in Fabry disease.

    Directory of Open Access Journals (Sweden)

    Mehdi Namdar

    Full Text Available BACKGROUND: Fabry disease (FD is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA resulting in the accumulation of globotriaosylsphingosine (Gb3 in a variety of tissues. While GLA deficiency was always considered as the fulcrum of the disease, recent attention shifted towards studying the mechanisms through which Gb3 accumulation in vascular cells leads to endothelial dysfunction and eventually multiorgan failure. In addition to the well-described macrovascular disease, FD is also characterized by abnormalities of microvascular function, which have been demonstrated by measurements of myocardial blood flow and coronary flow reserve. To date, the relative importance of Gb3 accumulation versus GLA deficiency in causing endothelial dysfunction is not fully understood; furthermore, its differential effects on cardiac micro- and macrovascular endothelial cells are not known. METHODS AND RESULTS: In order to assess the effects of Gb3 accumulation versus GLA deficiency, human macro- and microvascular cardiac endothelial cells (ECs were incubated with Gb3 or silenced by siRNA to GLA. Gb3 loading caused deregulation of several key endothelial pathways such as eNOS, iNOS, COX-1 and COX-2, while GLA silencing showed no effects. Cardiac microvascular ECs showed a greater susceptibility to Gb3 loading as compared to macrovascular ECs. CONCLUSIONS: Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA. Human microvascular ECs, as opposed to macrovascular ECs, seem to be affected earlier and more severely by Gb3 accumulation and this notion may prove fundamental for future progresses in early diagnosis and management of FD patients.

  5. Morphological features of iPS cells generated from Fabry disease skin fibroblasts using Sendai virus vector (SeVdp).

    Science.gov (United States)

    Kawagoe, Shiho; Higuchi, Takashi; Otaka, Manami; Shimada, Yohta; Kobayashi, Hiroshi; Ida, Hiroyuki; Ohashi, Toya; Okano, Hirotaka J; Nakanishi, Mahito; Eto, Yoshikatsu

    2013-08-01

    We generated iPS cells from human dermal fibroblasts (HDFs) of Fabry disease using a Sendai virus (SeVdp) vector; this method has been established by Nakanishi et al. for pathogenic evaluation. We received SeVdp vector from Nakanishi and loaded it simultaneously with four reprogramming factors (Klf4, Oct4, Sox2, and c-Myc) to HDFs of Fabry disease; subsequently, we observed the presence of human iPS-like cells. The Sendai virus nucleocapsid protein was not detected in the fibroblasts by RT-PCR analysis. Additionally, we confirmed an undifferentiated state, alkaline phosphatase staining, and the presence of SSEA-4, TRA-1-60, and TRA-1-81. Moreover, ultrastructural features of these iPS cells included massive membranous cytoplasmic bodies typical of HDFs of Fabry disease. Thus, we successfully generated human iPS cells from HDFs of Fabry disease that retained the genetic conditions of Fabry disease; also, these abnormal iPS cells could not be easily differentiated into mature cell types such as neuronal cells, cardiomyocytes, etc. because of a massive accumulation of membranous cytoplasmic bodies in lysosomes, possibly the persistent damages of intracellular architecture.

  6. Uric Acid as a Marker of Mortality and Morbidity in Fabry Disease.

    Science.gov (United States)

    Rob, Daniel; Marek, Josef; Dostálová, Gabriela; Goláň, Lubor; Linhart, Aleš

    2016-01-01

    Serum uric acid (UA) elevation is common in patients with cardiovascular, renal and metabolic diseases. However, no study to date has analysed the role of UA in Fabry disease (FD). To evaluate the association between serum UA levels and mortality and morbidity in FD. We conducted a post-hoc analysis of a prospectively followed-up cohort of 124 patients with genetically proven FD. Serum UA levels were acquired at baseline; clinical events and mortality were assessed during regular visits every 6 to 12 months. The primary endpoint was a composite of multiple secondary outcomes: all-cause mortality, adverse cardiovascular events, progression of renal dysfunction and stroke or transient ischaemic attack (TIA). Predictive value was assessed using the Cox proportional hazards model and the Kaplan Meyer estimator. During follow-up of 7.4 ± 3.7 years, 64 (52%) patients reached the primary combined endpoint. Overall, UA levels were significantly associated with combined outcome (p < 0.001) and remained independently associated after correcting for age, sex and estimated glomerular filtration rate (hazard ratio [HR] per 20 μmol/l increase 1.09, 95% confidence interval [95%CI] (1.00-1.19), p = 0.04). UA was associated with overall mortality in univariate analysis (p = 0.021); however, the association did not reach statistical significance after multivariate correction (HR per 20 μmol/l increase 1.07 95%CI 0.93-1.25, p = 0.32). Higher UA levels were also associated with cardiac adverse outcomes, progression of left ventricular hypertrophy and progression of renal dysfunction (ps < 0.001). No association was observed between UA levels and stroke or TIA (p = 0.323). Increased serum UA levels may represent an independent risk factor for adverse clinical outcomes in Fabry patients and are associated with all-cause mortality. UA is a widely available and cheap biomarker that may improve risk stratification of Fabry patients in clinical practice.

  7. The right ventricle in Fabry disease: natural history and impact of enzyme replacement therapy.

    Science.gov (United States)

    Niemann, Markus; Breunig, Frank; Beer, Meinrad; Herrmann, Sebastian; Strotmann, Jörg; Hu, Kai; Emmert, Andrea; Voelker, Wolfram; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2010-12-01

    Storage of globotriaosylceramides is present in the left and right ventricles of patients with Fabry disease. Improvement of left ventricular morphology and function during enzyme replacement therapy (ERT) has previously been reported. To analyse the effects of long term ERT on right ventricular morphology and function. This was a prospective follow-up of 75 genetically confirmed consecutive Fabry patients for 3.1±1.8 years. According to treatment guidelines the natural history was followed in 18 patients, whereas 57 patients received ERT. Standard echocardiography, strain rate imaging for regional deformation of the right and left ventricle, and magnetic resonance tomography with late enhancement (LE) imaging for the detection of fibrosis were all performed at yearly intervals. Right ventricular hypertrophy was evident in 53 patients (71%) at baseline. A significant positive correlation was found between left and right ventricular wall thickness (r=0.76; pright ventricle. Patients with LE in the left ventricle presented with the lowest right ventricular deformation properties. In contrast to the left ventricle, there was no change in right ventricular wall thickness (baseline 6.9±1.6 mm vs follow-up 6.7±1.5 mm; p=0.44) or systolic strain rate (2.2±0.7/s vs 2.1±0.8/s; p=0.31) during follow-up with ERT. The degree of right ventricular involvement in Fabry disease is related to the left ventricular cardiomyopathy stage. ERT seems to have no direct impact on right ventricular morphology and function.

  8. Therapy of Fabry disease with pharmacological chaperones: from in silico predictions to in vitro tests

    Directory of Open Access Journals (Sweden)

    Cammisa Marco

    2011-10-01

    Full Text Available Abstract Background Fabry disease is a rare disorder caused by a large variety of mutations in the gene encoding lysosomal alpha-galactosidase. Many of these mutations are unique to individual families. Fabry disease can be treated with enzyme replacement therapy, but a promising novel strategy relies on small molecules, so called "pharmacological chaperones", which can be administered orally. Unfortunately only 42% of genotypes respond to pharmacological chaperones. Results A procedure to predict which genotypes responsive to pharmacological chaperones in Fabry disease has been recently proposed. The method uses a position-specific substitution matrix to score the mutations. Using this method, we have screened public databases for predictable responsive cases and selected nine representative mutations as yet untested with pharmacological chaperones. Mutant lysosomal alpha galactosidases were produced by site directed mutagenesis and expressed in mammalian cells. Seven out of nine mutations responded to pharmacological chaperones. Nineteen other mutations that were tested with pharmacological chaperones, but were not included in the training of the predictive method, were gathered from literature and analyzed in silico. In this set all five mutations predicted to be positive were responsive to pharmacological chaperones, bringing the percentage of responsive mutations among those predicted to be positive and not used to train the classifier to 86% (12/14. This figure differs significantly from the percentage of responsive cases observed among all the Fabry mutants tested so far. Conclusions In this paper we provide experimental support to an "in silico" method designed to predict missense mutations in the gene encoding lysosomal alpha galactosidase responsive to pharmacological chaperones. We demonstrated that responsive mutations can be predicted with a low percentage of false positive cases. Most of the mutations tested to validate the method

  9. Long Term Treatment with Enzyme Replacement Therapy in Patients with Fabry Disease.

    Science.gov (United States)

    Oder, Daniel; Nordbeck, Peter; Wanner, Christoph

    2016-01-01

    Anderson-Fabry disease is a potentially life-threatening hereditary lysosomal storage disorder taking origin in over 1,000 known pathogenic mutations in the alpha-galactosidase A encoding gene. Over the past 15 years, intravenous replacement therapy of the deficient alpha agalsidase A enzyme has been well-established retarding the progression of a multisystemic disease and organ involvement. Despite this innovative treatment approach, premature deaths still do occur. The response to enzyme replacement therapy (ERT) varies considerably and appears to depend on gender, genotype (classic or later onset/non-classic), stage of disease or age and agalsidase inhibition by anti-agalsidase antibodies. Early ERT treatment at young age, a personalized approach, and adjunctive therapies for specific disease manifestations appear to impact on prognosis and are currently favored with the expectance of more effective intravenous and oral treatments in the short future.

  10. Accidente cerebro-vascular en la enfermedad de Fabry: Algo más que una simple estenosis Stroke in Fabry disease: More than a simple stenosis

    Directory of Open Access Journals (Sweden)

    Juan Manuel Politei

    2006-10-01

    Full Text Available Se analiza la evidencia existente a la fecha sobre los mecanismos fisiopatológicos que pueden generar accidentes cerebrovasculares en la enfermedad de Fabry. Esta entidad es el resultado de la deficiencia de a-galactosidasa A, lo que resulta en depósito patológico de glicoesfingilípidos en distintas poblaciones celulares. Asociados a la insuficiencia renal y cardíaca, los accidentes cerebrovasculares pueden derivar en la muerte de los pacientes. Durante mucho tiempo el único mecanismo generador de daño vascular informado fue la oclusión vascular por depósito lipídico a nivel endotelial. En la actualidad se describen otros mecanismos. El advenimiento de la terapia de reemplazo enzimático ha generado gran expectativa en cuanto la posibilidad de reversión de estos mecanismos. Si bien la evidencia es escasa y son necesarios más estudios a largo plazo, algunos informes demuestran que luego de meses, el tratamiento ha logrado revertir algunos de los mecanismos implicados.The objective is to analyze the updated evidence on the physiopathological mechanisms that can generate cerebrovascular damage in Fabry disease. Fabry disease is the result of the deficiency of a-galactosidasa A, which causes pathological storage of glycosphingolipids, in different cells. Associated to renal and cardiac insufficiency, cerebrovascular complications can derive in the death of the patients. During a long time the only reported mechanism was the vascular occlusion by deposit of lipids at endothelial level. At the present time, other mechanisms are postulated. The arrival of enzyme replacement therapy has generated great expectation on the possibility of reversion of these alterations. Although the evidence is scarce and more long term studies are necessary, some reports demonstrate that after months, the treatment has managed to revert some of the mechanisms involved.

  11. Expert opinion on temporary treatment recommendations for Fabry disease during the shortage of enzyme replacement therapy (ERT)

    NARCIS (Netherlands)

    G.E. Linthorst; D.P. Germain; C.E.M. Hollak; D. Hughes; A. Rolfs; C. Wanner; A. Mehta

    2011-01-01

    The shortage of enzyme for treatment of Fabry disease has caused anxiety among patients, physicians and governments. Following a request from the European Medicines Agency, consensus was reached on the temporary prioritization of patients for treatment based on disease severity and potential reversi

  12. Screening, diagnosis, and management of patients with Fabry disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.

    Science.gov (United States)

    Schiffmann, Raphael; Hughes, Derralynn A; Linthorst, Gabor E; Ortiz, Alberto; Svarstad, Einar; Warnock, David G; West, Michael L; Wanner, Christoph

    2017-02-01

    Patients with Fabry disease (FD) are at a high risk for developing chronic kidney disease and cardiovascular disease. The availability of specific but costly therapy has elevated the profile of this rare condition. This KDIGO conference addressed controversial areas in the diagnosis, screening, and management of FD, and included enzyme replacement therapy and nonspecific standard-of-care therapy for the various manifestations of FD. Despite marked advances in patient care and improved overall outlook, there is a need to better understand the pathogenesis of this glycosphingolipidosis and to determine the appropriate age to initiate therapy in all types of patients. The need to develop more effective specific therapies was also emphasized.

  13. Monitoring renal function in children with Fabry disease: comparisons of measured and creatinine-based estimated glomerular filtration rate

    NARCIS (Netherlands)

    C. Tondel; U. Ramaswami; K.M. Aakre; F. Wijburg; M. Bouwman; E. Svarstad

    2010-01-01

    Methods. Eighty-two examinations were done in 42 children (24 boys, 18 girls) with Fabry disease from three different centres. The mean age was 12.3 years. GFR was measured with iohexol, Cr-51-EDTA or iothalamate, and the mean mGFR was 108 ml/min/1.73 m(2). Results. The widely used original Schwartz

  14. Rapid preparation of (3R,4S,5R) polyhydroxylated pyrrolidine-based libraries to discover a pharmacological chaperone for treatment of Fabry disease.

    Science.gov (United States)

    Cheng, Wei-Chieh; Wang, Jen-Hon; Yun, Wen-Yi; Li, Huang-Yi; Hu, Jia-Ming

    2017-01-27

    The rapid discovery of a pharmacological chaperone toward human α-Gal A for the treatment of Fabry disease is described. Two polyhydroxylated pyrrolidines with the (3R,4S,5R) configuration pattern underwent rapid substituent diversity by conjugating the primary aminomethyl moiety of each with a variety of carboxylic acids to generate two libraries (2 × 60 members). Our bioevaluation results showed one member with the (2R,3R,4S,5R) configuration pattern and bearing a 5-cyclohexylpentanoyl group as a substituent moiety possessed sufficient chaperoning capability to rescue α-Gal A activity in the lymphocyte of the N215S Fabry patient-derived cell line and other α-Gal A mutants in COS7 cells.

  15. Recommendations for the inclusion of Fabry disease as a rare febrile condition in existing algorithms for fever of unknown origin.

    Science.gov (United States)

    Manna, Raffaele; Cauda, Roberto; Feriozzi, Sandro; Gambaro, Giovanni; Gasbarrini, Antonio; Lacombe, Didier; Livneh, Avi; Martini, Alberto; Ozdogan, Huri; Pisani, Antonio; Riccio, Eleonora; Verrecchia, Elena; Dagna, Lorenzo

    2017-07-19

    Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.

  16. One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease

    Science.gov (United States)

    Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar; Sokolovkiy, Alexey; Smith, Kelly; Mauer, Michael

    2016-01-01

    Fabry nephropathy is associated with progressive accumulation of globotriaosylceramide (GL3) in podocytes. Reducing this GL3 burden may reduce podocyte injury. Sensitive methods to quantify podocyte GL3 content may determine whether a given strategy can benefit podocytes in Fabry disease. We developed an unbiased electron microscopic stereological method to estimate the average volume of podocytes and their GL3 inclusions in 6 paired pre- and post-enzyme replacement therapy (ERT) biopsies from 5 men with Fabry disease. Podocyte GL3 content was regularly reduced (average 73%) after 11–12 months of ERT. This was not detectable using a semi-quantitative approach. Parallel to GL3 reduction, podocytes became remarkably smaller (average 63%). These reductions in podocyte GL3 content or size were not significantly correlated with changes in foot process width (FPW). However, FPW after ERT was significantly correlated with the magnitude of the decrease in podocyte GL3 content from baseline to 11–12 months of ERT. Also podocytes exocytosed GL3 inclusions, a phenomenon correlated with their reduction in their GL3 content. Demonstrable after11–12 months, reduction in podocyte GL3 content allows for early assessment of treatment efficacy and shorter clinical trials in Fabry disease. PMID:27081853

  17. Multicomponent nanoparticles as nonviral vectors for the treatment of Fabry disease by gene therapy

    Directory of Open Access Journals (Sweden)

    Ruiz de Garibay AP

    2012-10-01

    Full Text Available Aritz Pérez Ruiz de Garibay, Diego Delgado, Ana del Pozo-Rodríguez, María Ángeles Solinís, Alicia Rodríguez GascónPharmacokinetics, Nanotechnology and Gene Therapy Group, Pharmacy Faculty, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, SpainPurpose: Gene-mediated enzyme replacement is a reasonable and highly promising approach for the treatment of Fabry disease (FD. The objective of the present study was to demonstrate the potential applications of solid lipid nanoparticle (SLN-based nonviral vectors for the treatment of FD.Methods: SLNs containing the pR-M10-αGal A plasmid that encodes the α-Galactosidase A (α-Gal A enzyme were prepared and their in vitro transfection efficacy was studied in Hep G2 cells. We also studied the cellular uptake of the vectors and the intracellular disposition of the plasmid.Results: The enzymatic activity of the cells treated with the vectors increased significantly relative to the untreated cells, regardless of the formulation assayed. When the SLNs were prepared with protamine or dextran and protamine, the activity of the α-Gal A enzyme by the transfected Hep G2 cells increased up to 12-fold compared to that of untreated cells.Conclusion: With this work we have revealed in Hep G2 cells the ability of a multicomponent system based on SLNs to act as efficient nonviral vectors to potentially correct low α-Gal A activity levels in FD with gene therapy.Keywords: solid lipid nanoparticles, Fabry disease, nonviral vectors, gene therapy

  18. Impaired Left Atrial Function in Fabry Disease: A Longitudinal Speckle-Tracking Echocardiography Study.

    Science.gov (United States)

    Pichette, Maxime; Serri, Karim; Pagé, Maude; Di, Lu Zhao; Bichet, Daniel G; Poulin, Frédéric

    2017-02-01

    Fabry disease (FD) is characterized by the accumulation of sphingolipids in multiple organs, including the left atrium. It is uncertain if the left atrial (LA) reservoir, conduit, and contractile functions evaluated by speckle-tracking echocardiography are affected in Fabry cardiomyopathy and whether enzyme replacement therapy can improve LA function. In this retrospective cohort study, LA strain, strain rates, and phasic LA volumes were studied in 50 patients with FD and compared with values in 50 healthy control subjects. All three LA phasic functions were altered. Peak positive strain (reservoir function) was 38.9 ± 14.9% versus 46.5 ± 10.9% (P = .004), and late diastolic strain (contractile function) was 12.6 ± 5.9% versus 15.6 ± 5.3% (P = .010). In 15 patients who started enzyme replacement therapy during the study, most of the LA parameters improved at 1-year follow-up (peak positive strain from 32.0 ± 13.5% to 38.0 ± 13.5%, P = .006), whereas there was a trend toward deterioration in 15 patients who never received treatment (peak positive strain from 47.3 ± 10.8% to 41.3 ± 9.3%, P = .058). Nine patients with FD (21%) experienced new-onset atrial fibrillation or stroke during 4-year follow-up. By univariate analysis, peak positive strain and early diastolic strain demonstrated significant associations with clinical events, surpassing conventional echocardiographic parameters and clinical characteristics. LA reservoir, conduit, and contractile functions by speckle-tracking echocardiography were all affected in FD. Enzyme replacement therapy improved LA function. LA strain parameters were associated with atrial fibrillation and stroke. Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.

  19. Postmortem diagnosis of Fabry disease with acromegaly and a unique vasculopathy.

    Science.gov (United States)

    Takao, Masaki; Mori, Taisuke; Orikasa, Hideki; Oh, Haengphil; Suzuki, Kinuko; Koto, Atsuo; Yamazaki, Kazuto

    2007-09-01

    A 44-year-old Japanese man with elevated growth hormone levels and gradual deterioration of mental and renal function was admitted to the hospital. With his deteriorated general condition and renal failure, the patient developed pulmonary thromboembolism and died of respiratory failure. Autopsy examination was conducted, which revealed abnormal accumulation or intracytoplasmic storage of lipid-rich material in the small blood vessels, kidney, heart, and nervous system. After postmortem pathologic studies, including light-microscopic histochemistry, electron microscopy, and biochemical analysis of the stored lipid contents, a final diagnosis of Fabry disease was made. Histopathologic examination revealed a unique vasculopathy characterized by the presence of abnormal intracytoplasmic lipid inclusions and vascular remodeling. With regard to the clinical presentation of acromegaly, hyperplasia but not adenomatous transformation of the acidophils of the anterior pituitary gland with immunohistochemical detection of growth hormone within the cells was noted. In this case, the complication of acromegaly with hyperplasia of the acidophilic cells of the anterior pituitary gland and the unique vasculopathy causing significant organ failure, mainly of the kidney, heart, and central nervous systems, possibly as a result of microcirculatory failure, are considered to be not incidental findings but to be intimately involved in the pathogenesis of Farby disease.

  20. The attenuated/late onset lysosomal storage disorders: Therapeutic goals and indications for enzyme replacement treatment in Gaucher and Fabry disease.

    Science.gov (United States)

    Hollak, Carla E M; Weinreb, Neal J

    2015-03-01

    Enzyme replacement therapies have been developed and authorized for commercial use for six different lysosomal storage disorders. For Gaucher disease, Fabry disease and mucopolysaccharidosis type 1, disease-specific treatments have been available for more than a decade. Although long term follow-up data are still sparse, therapeutic goals for patients with Gaucher disease and Fabry disease have been formulated and published for both adults and children. Without adaptation or modification, these goals are often applied in clinical research and in routine patient care across the entire phenotypic spectrum of disease, although in practice, patients commonly manifest high variability in clinical presentation and course of the illness. In this context, establishing goals for the follow-up and treatment of late onset/attenuated phenotypes is particularly challenging. In this chapter, we review current therapeutic goals for Gaucher disease and Fabry disease and discuss approaches for those with attenuated disease manifestations.

  1. Fabry disease in patients with hypertrophic cardiomyopathy: a practical approach to diagnosis.

    Science.gov (United States)

    Seo, Jiwon; Kim, Minji; Hong, Geu-Ru; Kim, Dae-Seong; Son, Jang-Won; Cho, In Jeong; Shim, Chi Young; Chang, Hyuk-Jae; Ha, Jong-Won; Chung, Namsik

    2016-09-01

    This study aimed to develop a new set of screening criteria that is easily applicable and highly sensitive for the detection of patients at high risk of Fabry disease (FD) among hypertrophic cardiomyopathy (HCM) patients. We prospectively studied 273 consecutive unrelated patients who were referred to HCM clinic for unknown left ventricular hypertrophy. Among the 273 patients, we selected 65 high-risk patients who fulfilled at least one of our newly proposed screening criteria. All 273 patients were assayed for plasma α-galactosidase A (α-GAL A) activity. The new screening criteria were: (1) atypical HCM, (2) history or presence of documented arrhythmia, (3) short PR interval defined as <120 ms on electrocardiogram, and (4) symptoms of autonomic dysfunction. From this screening study, three unrelated patients (4.6%; 2 females and 1 male) were newly diagnosed with FD using α-GAL A activity and mutation analysis of the GLA gene. Using the screening method based on the newly proposed criteria, the prevalence of FD in our HCM population was 4.6% if at least one criterion was met and 18.8% if ⩾3 criteria were met. Therefore, our proposed criteria are easily applicable and highly sensitive for classifying patients at high risk of FD from HCM patients.

  2. Persistent increase in cardiac troponin I in Fabry disease: a case report

    Directory of Open Access Journals (Sweden)

    Schneider Christian

    2011-01-01

    Full Text Available Abstract Background Hypertrophic cardiomyopathy is a frequent manifestation in Fabry disease (FD - an X-linked lysosomal storage disorder caused by reduced activity of the enzyme α-galactosidase A. In FD an elevation of specific cardiac biomarkers, such as cardiac troponin I (cTNI has been reported in case of clinical manifestation suggestive of myocardial ischemia. In diagnosing acute myocardial infarction cTNI is considered the most reliable parameter. Case Presentation In the referred case we present a 59 years old female patient with the diagnosis of FD presenting with persistently increased cTNI level (lowest value 0.46 ng/ml, highest value 0.69 ng/ml; normal range Conclusions Our case report demonstrates a persistent cTNI release in FD with cardiac involvement. Proving the persistence in a symptom free interval, it might be related to a direct damage of myocytes. In FD cTNI could serve as a beneficial long term parameter providing new perspectives for screening strategies.

  3. Angiotensinogen promoter and angiotensinogen II receptor type 1 gene polymorphisms and incidence of ischemic stroke and neurologic phenotype in Fabry disease.

    Science.gov (United States)

    Altarescu, Gheona; Haim, Shimon; Elstein, Deborah

    2013-11-01

    Stroke and/or white matter lesions (WMLs) are significant in Fabry disease. Polymorphisms of angiotensinogen (AGT), AGT Promoter and angiotensinogen II receptor type 1 (AGTR1) are correlated with WMLs. We compared AGT. AGT Promoter and AGTR1 genotypes to stroke incidence, Fabry-specific [Mainz Severity Score Index (MSSI)] severity score, and neurologic sub-score (n-MSSI). Sixty-three Fabry patients and 49 matched controls plus historic controls were genotyped. Institutional Review Board approval was received. Results. C and/or CC alleles of AGT Promoter and AGTR1 were significantly correlated with stroke and n-MSSI. Findings are suggestive of role of AGT Promoter and AGTR1 genotypes in Fabry phenotypes.

  4. Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

    Directory of Open Access Journals (Sweden)

    Sommer Claudia

    2011-05-01

    Full Text Available Abstract Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with

  5. Lentivector Iterations and Pre-Clinical Scale-Up/Toxicity Testing: Targeting Mobilized CD34+ Cells for Correction of Fabry Disease

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    Ju Huang

    2017-06-01

    Full Text Available Fabry disease is a rare lysosomal storage disorder (LSD. We designed multiple recombinant lentivirus vectors (LVs and tested their ability to engineer expression of human α-galactosidase A (α-gal A in transduced Fabry patient CD34+ hematopoietic cells. We further investigated the safety and efficacy of a clinically directed vector, LV/AGA, in both ex vivo cell culture studies and animal models. Fabry mice transplanted with LV/AGA-transduced hematopoietic cells demonstrated α-gal A activity increases and lipid reductions in multiple tissues at 6 months after transplantation. Next we found that LV/AGA-transduced Fabry patient CD34+ hematopoietic cells produced even higher levels of α-gal A activity than normal CD34+ hematopoietic cells. We successfully transduced Fabry patient CD34+ hematopoietic cells with “near-clinical grade” LV/AGA in small-scale cultures and then validated a clinically directed scale-up transduction process in a GMP-compliant cell processing facility. LV-transduced Fabry patient CD34+ hematopoietic cells were subsequently infused into NOD/SCID/Fabry (NSF mice; α-gal A activity corrections and lipid reductions were observed in several tissues 12 weeks after the xenotransplantation. Additional toxicology studies employing NSF mice xenotransplanted with the therapeutic cell product demonstrated minimal untoward effects. These data supported our successful clinical trial application (CTA to Health Canada and opening of a “first-in-the-world” gene therapy trial for Fabry disease.

  6. PrEFiNe Plan: Strategic plan for Fabry diseases in Nephrology.

    Science.gov (United States)

    Del Pino, M D; Ortiz, A; Torra, R; Hernandez, D

    2016-01-01

    Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD. We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/) From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project. PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights

  7. Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant

    OpenAIRE

    Lenders, Malte; Weidemann, Frank; Kurschat, Christine; Canaan-Kühl, Sima; Duning, Thomas; Stypmann, Jörg; Schmitz, Boris; Reiermann, Stefanie; Krämer, Johannes; Blaschke, Daniela; Wanner, Christoph; Brand, Stefan-Martin; Brand, Eva

    2016-01-01

    Background Fabry disease (FD) is an X-linked multisystemic disorder with a heterogeneous phenotype. Especially atypical or late-onset type 2 phenotypes present a therapeutical dilemma. Methods To determine the clinical impact of the alpha-Galactosidase A (GLA) p.A143T/ c.427G > A variation, we retrospectively analyzed 25 p.A143T patients in comparison to 58 FD patients with other missense mutations. Results p.A143T patients suffering from stroke/ transient ischemic attacks had slightly decrea...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene. Deficiency of α-galactosidase A (α-Gal A) causes intracellular accumulations of globotriaosylceramide (GL-3) and related glycosphingolipids in all organs, including the kidney, often leading...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...

  9. Oftalmopatía fabry : nuevos marcadores pronósticos para una enfermedad sistémica= Fabry ophthalmopathy: new prognostic markers for a systemic disease

    OpenAIRE

    2016-01-01

    INTRODUCCIÓN: La enfermedad de Fabry es un raro error innato del metabolismo de los glicoesfingolípidos perteneciente al grupo más numeroso de las enfermedades por depósito lisosomal, las lipidosis. Se estima una prevalencia de 1/40000 varones. Sigue un patrón de herencia dominante ligado a X y se origina por mutaciones en el gen GLA (Xq221). Estas mutaciones resultan en una enzima lisosomal α-galactosidasa-A (AGA) con actividad deficiente. El depósito ubícuo de moléculas glicolipídicas...

  10. Parkinson's disease showing progressive conduction aphasia

    OpenAIRE

    Sakai, Kenji; Ono, Kenjiro; Harada, Hiromi; Shima, Keisuke; Notoya, Masako; Yamada, Masahito

    2012-01-01

    Patients with Parkinson's disease (PD) may develop progressive dementia late in their clinical course. Dementia in PD is mostly related to neuropathological findings of extensive Lewy bodies (LBs), with or without the coexistence of Alzheimer's disease (AD) pathology. Aphasia has been reported in patients with LB diseases with AD pathology; however, there have been no reports of typical PD patients developing progressive aphasia during their clinical course. We describe a female PD patient wh...

  11. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina Programa de infusión domiciliaria para la enfermedad de Fabry: experiencia con agalsidasa alfa en la Argentina

    Directory of Open Access Journals (Sweden)

    Isaac Kisinovsky

    2013-02-01

    Full Text Available Fabry disease is an X-linked lysosomal storage disorder caused by inherited deficiency of the enzyme α-galactosidase A. Enzyme replacement treatment using agalsidase alfa significantly reduces pain, improves cardiac function and quality of life, and slows renal deterioration. Nevertheless, it is a life-long treatment which requires regular intravenous infusions and entails a great burden for patients. Our objective was to evaluate retrospectively the safety and tolerability of the home infusion of agalsidase alfa in patients with Fabry disease in Argentina. We evaluated all the patients with Fabry disease who received home infusion with agalsidase alfa 0.2 mg/kg between January 2005 and June 2011. The program included 87 patients; 51 males (mean age: 30 years and 36 females (mean age: 34 years. A total of 5229 infusions (mean: 59 per patient; range: 1-150 were administered. A total of 5 adverse reactions were seen in 5 patients (5.7% of patients and 0.9% of the total number of infusions. All were mild in severity and resolved by reducing the rate of infusion and by using antihistaminics. All these 5 patients were positive for IgG antibodies, but none of them presented IgE antibodies and none suffered an anaphylactic shock. In our group 18 patients were switched from agalsidase beta to agalsidase alfa without complications. Home infusion with agalsidase alfa is safe, well tolerated and is associated to high compliance.La enfermedad de Fabry es un trastorno de almacenamiento lisosomal hereditario ligado al cromosoma X ocasionado por el déficit de la enzima alfa galactosidasa A. La terapia de reemplazo enzimático utilizando agalsidasa alfa reduce significativamente el dolor, mejora la función cardíaca y la calidad de vida y enlentece el deterioro renal. Sin embargo, es un tratamiento de por vida que requiere infusiones intravenosas regulares y supone una gran carga para los pacientes. Nuestro objetivo fue evaluar retrospectivamente la

  12. Right ventricular involvement in patients with Fabry's disease and the effect of enzyme replacement therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wuest, W. [Universitaetsklinikum Erlangen (Germany). Radiologisches Inst.; Machann, W.; Koestler, H.; Hahn, D.; Beer, M. [Universitaetsklinikum Wuerzburg (Germany). Inst. fuer Roentgendiagnostik; Breunig, F.; Weidemann, F.; Wanner, C. [Universitaetsklinikum Wuerzburg (Germany). Medizinische Klinik I

    2011-11-15

    According to echocardiography reports, Fabry cardiomyopathy not only affects the left ventricle (LV) but also the right ventricle (RV). Until now no MRI studies about the effect of enzyme replacement therapy (ERT) on the RV are available. We evaluated the effect of ERT on the RV. In this prospective trial 14 patients with genetically proven Fabry's disease were examined using a 1.5 T MR scanner before ERT and after 13 {+-} 1 months of ERT. All patients underwent cardiac MR imaging and the RV/LV cardiac morphology and function were analyzed. At baseline examination the values were as follows: RV mass 31 {+-} 6 g/m{sup 2}, end-diastolic volume (EDV) 88 {+-} 13 ml/m{sup 2}, end-systolic volume (ESV) 39 {+-} 9 ml/m{sup 2}, stroke volume (SV) 49 {+-} 7 ml/m{sup 2} and ejection fraction (EF) 56 {+-} 5 %. The RV mass and EDV decreased significantly after 13 {+-} 1 months on ERT (mass 27 {+-} 7 g/m{sup 2}, p < 0.05, EDV 76 {+-} 24 ml/m{sup 2}, p < 0.05), with no significant change of ESV (33 {+-} 13 ml/m{sup 2}), SV (43 {+-} 12 ml/m{sup 2}) and EF (57 {+-} 7 %). The LV mass (102 {+-} 26 g/m{sup 2} vs. 94 {+-} 27 g/m{sup 2}, p < 0.05), EDV (76 {+-} 13 ml/m{sup 2} vs. 66 {+-} 22 ml/m{sup 2}, p < 0.05) and ESV (29 {+-} 9 ml/m{sup 2} vs. 23 {+-} 9 ml/m{sup 2}, p < 0.05) decreased significantly while the EF (64 {+-} 7 % vs. 66 {+-} 5 %; p < 0.05) increased significantly. Besides the known beneficial effect on the LV, ERT improves RV mass and EDV. (orig.)

  13. Parkinson's disease showing progressive conduction aphasia.

    Science.gov (United States)

    Sakai, Kenji; Ono, Kenjiro; Harada, Hiromi; Shima, Keisuke; Notoya, Masako; Yamada, Masahito

    2012-04-01

    Patients with Parkinson's disease (PD) may develop progressive dementia late in their clinical course. Dementia in PD is mostly related to neuropathological findings of extensive Lewy bodies (LBs), with or without the coexistence of Alzheimer's disease (AD) pathology. Aphasia has been reported in patients with LB diseases with AD pathology; however, there have been no reports of typical PD patients developing progressive aphasia during their clinical course. We describe a female PD patient who later developed progressive conduction aphasia characterized by phonemic paraphasia and disturbance in repetition of short sentences without disturbance in writing or auditory comprehension. No episodes of fluctuations of attention, memory complaints, or planning errors were observed. She experienced episodes of visual hallucination. Her low scores on the Mini-Mental State Examination suggested impairment of orientation and attention, and her scores on Raven's Coloured Progressive Matrices test indicated impaired visuospatial functions. However, her cognitive deficits were not sufficiently severe to impair her daily life. Brain magnetic resonance images revealed atrophy of the left superior temporal gyrus and widening of the left sylvian fissure. [(18)F]-fluorodeoxyglucose positron emission tomography revealed glucose hypometabolism in the left cerebral hemisphere. These findings may be related to conduction aphasia. During the progression of PD lesions, the brainstem LB is assumed to take an upward course, extend to the limbic system, and then extend to the neocortex. Conduction aphasia observed in our patient may be associated with an unusual progression of the LB pathology from the brainstem to the left temporoparietal lobe.

  14. Co-existence of Phenylketonuria and Fabry disease on a 3 year-old boy: case report

    Directory of Open Access Journals (Sweden)

    Bonapace Giuseppe

    2010-05-01

    Full Text Available Abstract Background The co-existence of two genetically distinct metabolic disorders in the same patient has rarely been reported. Phenylketonuria (PKU is an inborn error of the metabolism resulting from a phenylalanine hydroxylase deficiency. Fabry disease (FD is an X-linked lysosomal storage disorder due to a deficiency of the enzyme alpha-galactosidase A. Case presentation We report a case of a 3 year- old boy affected by classic PKU and FD, both confirmed by molecular data. The FD was suspected at the age of 21 months on the presence of non-specific GI symptoms (severe abdominal pain and periodically appearance of not specific episodes of gastroenteritis apparently non related to PKU. Conclusion This is the first report of co-existence of FD and PKU, two different congenital inborn of metabolism and in consideration of the prevalence of each disease this chance association is a very unusual event. The co-existence of this diseases made very difficult the correct interpretation of clinical symptoms as lack of appetite, severe abdominal pain and non-specific gastroenteritis episodes. Furthermore, this case report helps to define the early clinical phenotype of FD.

  15. Pedigree analysis of Mexican families with Fabry disease as a powerful tool for identification of heterozygous females.

    Science.gov (United States)

    Gutiérrez-Amavizca, B E; Orozco-Castellanos, R; R Padilla-Gutiérrez, J; Valle, Y; Figuera, L E

    2014-08-28

    Fabry disease (FD) is an X-linked lysosomal storage disease caused by α-galactosidase A deficiency; in contrast to other X-linked diseases, heterozygous females can be as affected as men. The construction and analysis of a family pedigree is a powerful tool to aid clinicians in diagnosis, establishment of inheritance pattern, and early detection of potentially affected relatives. The present study highlights the importance of pedigree analysis in families with FD for identifying other possibly affected relatives and investigating the clinical manifestations. This clinical report included 12 Mexican index cases with confirmed FD diagnosis. We constructed and analyzed their pedigree, and diagnosed FD in 24 affected relatives. Clinical features were similar to those reported for other populations. Pedigree analysis further identified an additional 30 women as possible carriers. We conclude that pedigree construction and analysis is a useful tool to help physicians detect and diagnose relatives at risk for FD, particularly heterozygous females, so that they can receive genetic counseling and early treatment. Mexican families with FD were similar to other populations reported in the literature, and our findings confirmed that heterozygous females can have signs and symptoms ranging from subtle manifestations to the classical severe presentation described in males.

  16. Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease

    Science.gov (United States)

    den-Haan, Helena; Pérez-Sánchez, Horacio; Del Prete, Rosita; Liguori, Ludovica; Cimmaruta, Chiara; Lukas, Jan; Andreotti, Giuseppina

    2016-01-01

    Personalized therapies are required for Fabry disease due to its large phenotypic spectrum and numerous different genotypes. In principle, missense mutations that do not affect the active site could be rescued with pharmacological chaperones. At present pharmacological chaperones for Fabry disease bind the active site and couple a stabilizing effect, which is required, to an inhibitory effect, which is deleterious. By in silico docking we identified an allosteric hot-spot for ligand binding where a drug-like compound, 2,6-dithiopurine, binds preferentially. 2,6-dithiopurine stabilizes lysosomal alpha-galactosidase in vitro and rescues a mutant that is not responsive to a mono-therapy with previously described pharmacological chaperones, 1-deoxygalactonojirimycin and galactose in a cell based assay. PMID:27788225

  17. Fabry disease: a study of 6 hemizygous men and 5 heterozygous women with emphasis on dermatologic manifestations.

    Science.gov (United States)

    Larralde, Margarita; Boggio, Paula; Amartino, Hernán; Chamoles, Néstor

    2004-12-01

    To determine the significance of the dermatologic and systemic abnormalities found in 11 patients with Fabry disease (FD) which is an X-linked lysosomal storage disorder caused by the partial or complete deficiency of the alpha-galactosidase A enzyme. This defect leads to the accumulation of uncleaved glycosphingolipids throughout vascular endothelium and visceral tissues. Case series. Pediatric Dermatology Division, Ramos Mejia Hospital (primary care center) and Laboratory of Neurochemistry (referral center for metabolic diseases). Eleven patients with FD were studied: 6 hemizygous men (mean age, 23.0 years) and 5 heterozygous women (mean age, 49.4 years). Mucocutaneous angiokeratomas (AKs) were found in 5 (83%) of 6 hemizygotes and 4 (80%) of 5 heterozygotes. The AKs appeared at an average age of 13 years, affecting predominantly genitalia, back, elbows, and other frequently traumatized areas. All the hemizygotes and none of the heterozygotes suffered from hypohidrosis. Angiokeratomas on the trunk and oral mucosa without sweat abnormalities were detected in 80% of heterozygous women. All hemizygotic men presented with acral pain in childhood. We emphasize the value of early recognition of AKs and hypohidrosis as diagnostic clues to FD, a severe and progressive disorder.

  18. Characterization of Early Disease Status in Treatment-Naive Male Paediatric Patients with Fabry Disease Enrolled in a Randomized Clinical Trial

    Science.gov (United States)

    Wijburg, Frits A.; Bénichou, Bernard; Bichet, Daniel G.; Clarke, Lorne A.; Dostalova, Gabriela; Fainboim, Alejandro; Fellgiebel, Andreas; Forcelini, Cassiano; An Haack, Kristina; Hopkin, Robert J.; Mauer, Michael; Najafian, Behzad; Scott, C. Ronald; Shankar, Suma P.; Thurberg, Beth L.; Tøndel, Camilla; Tylki-Szymańska, Anna; Ramaswami, Uma

    2015-01-01

    Trial Design This analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial. Methods Males aged 5–18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13–17 years), renal function, and glycolipid levels (plasma, urine). Results Plasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m2 (range 90.4–161.0 mL/min/1.73 m2) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0–27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients. Conclusions These data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of

  19. Comprehensive clinical evaluation of a large Spanish family with Anderson-Fabry disease, novel GLA mutation and severe cardiac phenotype.

    Science.gov (United States)

    San Román-Monserrat, Irene; Moreno-Flores, Victoria; López-Cuenca, David; Rodríguez-González-Herrero, Elena; Guillén-Navarro, Encarna; Rodríguez-González-Herrero, Beatriz; Alegría-Fernández, Marisol; Poza-Cisneros, Gabriela; Piñero-Fernández, Juan A; Sornichero-Martínez, Javier; Gimeno-Blanes, Juan R

    2014-06-06

    Fabry disease is an X-linked multisystemic lysosomal-storage condition. We describe a large family with a novel GLA mutation: p.M187R/g7219 T>G. Anamnesis/physical-exam, blood/urine analysis, α-Gal-A activity and/or genetic study of at-risk individuals and multidisciplinary evaluation in confirmed cases. 4 males and 13 heterozygous-females displayed the mutation. Cardiac/renal/neurological disease was diagnosed at a mean age of 41/29/39 years in males and 51/56/46 years in females. Onset mean age was 20 years versus 42 years. 9/15 had cardiomyopathy. Delta wave suggestive of accessory pathway was identified in 1 male and 2 females. 1 female had cardiac arrest (ventricular fibrillation, 61 years). 2 females and 1 male died suddenly (63, 64 and 57 years). Cardiac-subscore of Mainz Severity-Score-Index was severe for males and females over 40 years. 4/15(26%) developed early renal disease. 2 males needed dialysis. 1 male died at 69 years in spite of kidney-heart transplant. We describe the largest genetically confirmed Spanish family using multidisciplinary evaluation and MSSI calculation. The novel mutation p.M187R/g7219 T>G is associated with a particularly malignant cardiac phenotype in males and females over 40 years. Severity was higher than that of the largest Spanish FOS-cohort. Short-PR with delta is being reported for the first time. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. First experience of simultaneous PET/MRI for the early detection of cardiac involvement in patients with Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Nappi, Carmela; Altiero, Michele; Imbriaco, Massimo; Giudice, Caterina Anna; Spinelli, Letizia; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Nicolai, Emanuele; Aiello, Marco; Diomiaiuti, Claudio Tommaso [IRCCS SDN, Naples (Italy); Pisani, Antonio [University Federico II, Department of Public Health, Naples (Italy)

    2015-03-26

    Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with severe multiorgan dysfunction and premature death. Early diagnosis and treatment strategies play a key role in patient outcome. We investigated the potential role of hybrid PET/MR imaging in the assessment of early cardiac involvement in AFD patients. Thirteen AFD patients without cardiac symptoms and with normal left ventricular function underwent simultaneous cardiac PET/MR imaging after administration of {sup 18}F-FDG. Cardiac FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. The coefficient of variation (COV, i.e. the standard deviation divided by the average) of the uptake of the 17 segments was calculated as an index of heterogeneity in the heart. Six patients exhibited focal late gadolinium enhancement (LGE) indicating intramyocardial fibrosis, and four of these also had positive short inversion time inversion recovery (STIR) sequences. All patients with LGE and positive STIR MR images showed focal FDG uptake in the corresponding myocardial segments indicating inflammation. Of the seven patients with negative LGE and STIR images, five showed homogeneous FDG cardiac uptake and two showed heterogeneous FDG uptake. The COV was significantly greater in patients with focal FDG uptake (0.25 ± 0.02) than in those without (0.14 ± 0.07, p < 0.01). PET/MR imaging is clinically feasible for the early detection of cardiac involvement in patients with AFD. Further studies evaluating the role of hybrid PET/MR imaging in management of the disease in larger patient populations are warranted. (orig.)

  1. Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.

    Science.gov (United States)

    Byeon, Seul Kee; Kim, Jin Yong; Lee, Jin-Sung; Moon, Myeong Hee

    2016-03-01

    A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

  2. Characterization of Fabry mice treated with recombinant adeno-associated virus 2/8-mediated gene transfer

    Directory of Open Access Journals (Sweden)

    Choi Jin-Ok

    2010-04-01

    Full Text Available Abstract Background Enzyme replacement therapy (ERT with α-galactosidase A (α-Gal A is currently the most effective therapeutic strategy for patients with Fabry disease, a lysosomal storage disease. However, ERT has limitations of a short half-life, requirement for frequent administration, and limited efficacy for patients with renal failure. Therefore, we investigated the efficacy of recombinant adeno-associated virus (rAAV vector-mediated gene therapy for a Fabry disease mouse model and compared it with that of ERT. Methods A pseudotyped rAAV2/8 vector encoding α-Gal A cDNA (rAAV2/8-hAGA was prepared and injected into 18-week-old male Fabry mice through the tail vein. The α-Gal A expression level and globotriaosylceramide (Gb3 levels in the Fabry mice were examined and compared with Fabry mice with ERT. Immunohistochemical and ultrastructural studies were conducted. Results Treatment of Fabry mice with rAAV2/8-hAGA resulted in the clearance of accumulated Gb3 in tissues such as liver, spleen, kidney, heart, and brain with concomitant elevation of α-Gal A enzyme activity. Enzyme activity was elevated for up to 60 weeks. In addition, expression of the α-Gal A protein was identified in the presence of rAAV2/8-hAGA at 6, 12, and 24 weeks after treatment. α-Gal A activity was significantly higher in the mice treated with rAAV2/8-hAGA than in Fabry mice that received ERT. Along with higher α-Gal A activity in the kidney of the Fabry mice treated with gene therapy, immunohistochemical studies showed more α-Gal A expression in the proximal tubules and glomerulus, and less Gb3 deposition in Fabry mice treated with this gene therapy than in mice given ERT. The α-gal A gene transfer significantly reduced the accumulation of Gb3 in the tubules and podocytes of the kidney. Electron microscopic analysis of the kidneys of Fabry mice also showed that gene therapy was more effective than ERT. Conclusions The rAAV2/8-hAGA mediated α-Gal A gene

  3. Relationship between left ventricular diastolic function and myocardial sympathetic denervation measured by {sup 123}I-meta-iodobenzylguanidine imaging in Anderson-Fabry disease

    Energy Technology Data Exchange (ETDEWEB)

    Spinelli, Letizia; Giudice, Caterina Anna; Imbriaco, Massimo; Trimarco, Bruno; Cuocolo, Alberto [University Federico II, Department of Advanced Biomedical Sciences, Naples (Italy); Pellegrino, Teresa [Institute of Biostructure and Bioimaging, National Council of Research, Naples (Italy); Pisani, Antonio; Riccio, Eleonora [University Federico II, Department of Public Health, Naples (Italy); Salvatore, Marco [IRCCS SDN, Naples (Italy)

    2016-04-15

    Whether cardiac sympathetic nervous function abnormalities may be present in patients with Anderson-Fabry disease (AFD) remains unexplored. We investigated the relationship between left ventricular (LV) function and cardiac sympathetic nervous function in patients with AFD. Twenty-five patients (12 men, mean age 43 ± 13 years) with genetically proved AFD and preserved LV ejection fraction and ten age and gender-matched control subjects underwent speckle tracking echocardiography and {sup 123}I-meta-iodobenzylguanidine (MIBG) imaging from which early and late heart to mediastinum (H/M) ratios and myocardial washout rate values were calculated. In AFD patients, a significant correlation between late H/M ratio and LV mass index (r = -61, p = 0.001), left atrial volume (r = -0.72, p < 0.001), systolic pulmonary artery pressure (r = -0.75, p < 0.001), and early diastolic untwisting rate (r = -0.66, p < 0.001) was found. Ten AFD patients exhibited a late H/M ratio below two fold standard deviation of control subjects (≤1.75). Patients showing late H/M ratio ≤ 1.75 had significantly higher LV mass index, relative wall thickness, left atrial volume and systolic pulmonary artery pressure, lower systolic longitudinal strain and an early diastolic untwisting rate compared to patients with late H/M ratio > 1.75. At multivariable linear regression analysis, early diastolic untwisting rate was the only independent predictor of late H/M ratio ≤ 1.75 (odds ratio 1.15, 95 % confidence interval 1.07-1.31, p < 0.05). The present findings provide the first demonstration of a cardiac sympathetic derangement in AFD patients with preserved LV ejection fraction, which is mostly related to LV diastolic dysfunction. (orig.)

  4. Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies

    Directory of Open Access Journals (Sweden)

    Germain Dominique P

    2012-11-01

    Full Text Available Abstract Background Fabry disease (FD is a genetic disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A, which leads to globotriaosylceramide (GL-3 accumulation in multiple tissues. We report on the safety and pharmacodynamics of migalastat hydrochloride, an investigational pharmacological chaperone given orally at 150 mg every-other-day. Methods Two open-label uncontrolled phase 2 studies of 12 and 24 weeks (NCT00283959 and NCT00283933 in 9 males with FD were combined. At multiple time points, α-Gal A activity and GL-3 levels were quantified in blood cells, kidney and skin. GL-3 levels were also evaluated through skin and renal histology. Results Compared to baseline, increased α-Gal A activity of at least 50% was demonstrated in blood, skin and kidney in 6 of 9 patients. Patients’ increased α-Gal A activities paralleled the α-Gal A increases observed in vitro in HEK-293 cells transfected with the corresponding mutant form of the enzyme. The same 6 patients who demonstrated increases of α-Gal A activity also had GL-3 reduction in skin, urine and/or kidney, and had α-Gal A mutations that responded in transfected cells incubated with the drug. The 3 patients who did not show a consistent response in vivo had α-Gal A mutations that did not respond to migalastat HCl in transfected cells. Migalastat HCl was well tolerated. Conclusions Migalastat HCl is a candidate pharmacological chaperone that provides a novel genotype-specific treatment for FD. It enhanced α-Gal A activity and resulted in GL-3 substrate decrease in patients with responsive GLA mutations. Phase 3 studies are ongoing. Trial registration Clinicaltrial.gov: NCT00283959 and NCT00283933

  5. Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: an investigation of twenty-two hemizygous male patients

    Directory of Open Access Journals (Sweden)

    Chassaing Augustin

    2002-10-01

    Full Text Available Abstract Background Fabry disease (FD, OMIM 301500 is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of alpha-galactosidase A, a lysosomal enzyme. While the progressive systemic deposition of uncleaved glycosphingolipids throughout the body is known to have protean clinical manifestations, few data are available regarding the cochlear involvement. Methods We non-invasively investigated cochlear functions in 22 consecutive hemizygous males (age 19–64 years, mean 39 affected with classic FD. Conventional audiometry, tympanometry, ABR audiometry, otoacoustic emissions were performed in all patients, together with medical history record and physical examination as part of an exhaustive baseline evaluation prior to enzyme replacement therapy. Results A total of 12 patients (54.5% with classic FD were found to have abnormal audition. Five patients had progressive hearing loss and seven patients (32% experienced sudden deafness. In addition, a hearing loss on high-tone frequencies was found in 7 out of the 10 remaining patients without clinical impairment, despite their young age at time of examination. The incidence of hearing loss appeared significantly increased in FD patients with kidney failure (P tinnitus aurium was also found in six patients (27%. Conclusion This is the first evidence of a high incidence of both progressive hearing loss and sudden deafness in a cohort of male patients affected with classic Fabry disease. The exact pathophysiologic mechanism(s of the cochlear involvement deserves further studies.

  6. Kidney transplantation from a mother with unrecognized Fabry disease to her son with low α-galactosidase A activity: A 14-year follow-up without enzyme replacement therapy.

    Science.gov (United States)

    Odani, Keiko; Okumi, Masayoshi; Honda, Kazuho; Ishida, Hideki; Tanabe, Kazunari

    2016-07-01

    We report a case of kidney transplantation from mother to son, both of whom were likely to have had an unrecognized renal variant phenotype of Fabry disease. The patient was a 54-year-old man, with an unknown primary cause of end stage renal disease. He had no notable past medical history, other than end stage renal disease. He underwent living-related kidney transplantation from his mother at age 40 years. Foam cells in the glomeruli were identified on histology assessment of a 0-hour allograft biopsy, with zebra bodies identified in the glomerular visceral epithelial cells by electron microscopy. These findings were indicative of Fabry disease in the donated kidney. As a definitive diagnosis of Fabry's disease could not be confirmed, enzyme replacement therapy was not initiated. Thirteen years after kidney transplantation, the patient underwent left nephrectomy for a left renal tumour, with pathological findings of clear cell carcinoma, foam cells and zebra bodies in the native kidney. Detailed examinations identified low α-galactosidase A activity and mutation of the α-Gal A gene, confirming a diagnosis of a renal variant phenotype of Fabry disease. Histology of several allograft biopsies performed over the 14 years from the time of kidney transplantation revealed only moderate interstitial fibrosis and tubular atrophy, with no evidence of disease progression on electron microscopy, despite the presence of zebra bodies in the glomerular visceral epithelial cells.

  7. Vascular Tortuosities of the Upper Eyelid: A New Clinical Finding in Fabry Patient Screening

    Directory of Open Access Journals (Sweden)

    Langis Michaud

    2013-01-01

    Full Text Available Purpose. To report a new clinical finding related to Fabry disease. Methods. Fabry subjects were enrolled in the study, matched for age and sex with healthy individuals as a control group. This is a prospective review of all upper lid pictures taken for every subject at their last visit. A 4-step grading scale is proposed to classify this new entity. Results. Group A (Fabry comprised 16 males and 22 females, aged 40 (±14 years on average. Group B (control comprised 7 males and 8 females, aged 37 (±12 Vessels tortuosity was identified on the external superior lid in 36 of the Fabry patients (94.7%, while none of the subjects in group B showed similar vessels tortuosity. In addition, microaneurysms (MAs were found in 10/38 group A subjects while none in group B presented a similar finding. The differences are highly significant. Conclusion. This paper proposes that blood vessels tortuosity on the upper eyelid be recognized as a new clinical entity for inclusion among the classic ocular manifestations of Fabry’s disease. Without evidence of any negative impact, it should be considered a benign sign contributing to evidence of suspected Fabry disease.

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

    Science.gov (United States)

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

    2017-01-01

    Anderson-Fabry disease (AFD) is an X-linked recessive inborn error of glycosphingolipid metabolism caused by a deficiency of alpha-galactosidase A. Renal failure, heart and cerebrovascular involvement reduce survival. A Cochrane review provided little evidence on the use of enzyme replacement therapy (ERT). We now complement this review through a linear regression and a pooled analysis of proportions from cohort studies. To evaluate the efficacy and safety of ERT for AFD. For the systematic review, a literature search was performed, from inception to March 2016, using Medline, EMBASE and LILACS. Inclusion criteria were cohort studies, patients with AFD on ERT or natural history, and at least one patient-important outcome (all-cause mortality, renal, cardiovascular or cerebrovascular events, and adverse events) reported. The pooled proportion and the confidence interval (CI) are shown for each outcome. Simple linear regressions for composite endpoints were performed. 77 cohort studies involving 15,305 participants proved eligible. The pooled proportions were as follows: a) for renal complications, agalsidase alfa 15.3% [95% CI 0.048, 0.303; I2 = 77.2%, p = 0.0005]; agalsidase beta 6% [95% CI 0.04, 0.07; I2 = not applicable]; and untreated patients 21.4% [95% CI 0.1522, 0.2835; I2 = 89.6%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; b) for cardiovascular complications, agalsidase alfa 28% [95% CI 0.07, 0.55; I2 = 96.7%, p<0.0001]; agalsidase beta 7% [95% CI 0.05, 0.08; I2 = not applicable]; and untreated patients 26.2% [95% CI 0.149, 0.394; I2 = 98.8%, p<0.0001]. Effect differences favored agalsidase beta compared to untreated patients; and c) for cerebrovascular complications, agalsidase alfa 11.1% [95% CI 0.058, 0.179; I2 = 70.5%, p = 0.0024]; agalsidase beta 3.5% [95% CI 0.024, 0.046; I2 = 0%, p = 0.4209]; and untreated patients 18.3% [95% CI 0.129, 0.245; I2 = 95% p < 0.0001]. Effect differences favored agalsidase beta

  9. A Novel Rapid MALDI-TOF-MS-Based Method for Measuring Urinary Globotriaosylceramide in Fabry Patients

    Science.gov (United States)

    Alharbi, Fahad J.; Geberhiwot, Tarekegn; Hughes, Derralynn A.; Ward, Douglas G.

    2016-04-01

    Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A, resulting in the accumulation of glycosphingolipids in various organs. Globotriaosylceramide (Gb3) and its isoforms and analogues have been identified and quantified as biomarkers of disease severity and treatment efficacy. The current study aimed to establish rapid methods for urinary Gb3 extraction and quantitation. Urine samples from 15 Fabry patients and 21 healthy control subjects were processed to extract Gb3 by mixing equal volumes of urine, methanol containing an internal standard, and chloroform followed by sonication and centrifugation. Thereafter, the lower phase was analyzed by MALDI-TOF MS and the relative peak areas of the internal standard and four major species of Gb3 determined. The results showed high reproducibility with intra- and inter-assay coefficients variation of 9.9% and 13.7%, respectively. The limit of detection was 0.15 ng/μL and the limit of quantitation was 0.30 ng/μL. Total urinary Gb3 levels in both genders of classic Fabry patients were significantly higher than in healthy controls (p < 0.0001). Gb3 levels in Fabry males were higher than in Fabry females (p = 0.08). We have established a novel assay for urinary total Gb3 that takes less than 15 min from start to finish.

  10. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns

    Science.gov (United States)

    Sanchez-Mut, J V; Heyn, H; Vidal, E; Moran, S; Sayols, S; Delgado-Morales, R; Schultz, M D; Ansoleaga, B; Garcia-Esparcia, P; Pons-Espinal, M; de Lagran, M M; Dopazo, J; Rabano, A; Avila, J; Dierssen, M; Lott, I; Ferrer, I; Ecker, J R; Esteller, M

    2016-01-01

    Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies. PMID:26784972

  11. Lysosome-associated protein 1 (LAMP-1) and lysosome-associated protein 2 (LAMP-2) in a larger family carrier of Fabry disease.

    Science.gov (United States)

    Pereira, Ester M; do Monte, Semiramis J H; do Nascimento, Fernando F; de Castro, Jose A F; Sousa, Jackeline L M; Filho, Henrique C S A L C; da Silva, Raimundo N; Labilloy, Anatália; Monte Neto, José T; da Silva, Adalberto S

    2014-02-15

    This study investigated the potential relationship between the expression levels of lysosome-associated membrane proteins (LAMP) 1 and 2 and responses to enzyme replacement therapy (ERT) in the members of a single family with Fabry disease (FD). LAMP levels were assessed by flow cytometry in leukocytes from 17 FD patients who received an eight-month course of ERT course and 101 healthy individuals. We found that phagocytic cells from the FD patients had higher expression levels of both LAMP-1 and LAMP-2, relative to the levels in phagocytes from the healthy controls (p=0.001). Furthermore, the LAMP-1 and LAMP-2 levels in phagocytes from the FD carriers continuously decreased with ERT administration to reach levels similar to those in healthy controls. We suggest that LAMP-1 and LAMP-2 could be used as additional markers with which to assess ERT effectiveness in FD.

  12. Reactive glia show increased immunoproteasome activity in Alzheimer's disease.

    Science.gov (United States)

    Orre, Marie; Kamphuis, Willem; Dooves, Stephanie; Kooijman, Lieneke; Chan, Elena T; Kirk, Christopher J; Dimayuga Smith, Vanessa; Koot, Sanne; Mamber, Carlyn; Jansen, Anne H; Ovaa, Huib; Hol, Elly M

    2013-05-01

    The proteasome is the major protein degradation system within the cell, comprised of different proteolytic subunits; amyloid-β is thought to impair its activity in Alzheimer's disease. Neuroinflammation is a prominent hallmark of Alzheimer's disease, which may implicate an activation of the immunoproteasome, a specific proteasome variant induced by immune signalling that holds slightly different proteolytic properties than the constitutive proteasome. Using a novel cell-permeable proteasome activity probe, we found that amyloid-β enhances proteasome activity in glial and neuronal cultures. Additionally, using a subunit-specific proteasome activity assay we showed that in the cortex of the APPswePS1dE9 plaque pathology mouse model, immunoproteasome activities were strongly increased together with increased messenger RNA and protein expression in reactive glia surrounding plaques. Importantly, this elevated activity was confirmed in human post-mortem tissue from donors with Alzheimer's disease. These findings are in contrast with earlier studies, which reported impairment of proteasome activity in human Alzheimer's disease tissue and mouse models. Targeting the increased immunoproteasome activity with a specific inhibitor resulted in a decreased expression of inflammatory markers in ex vivo microglia. This may serve as a potential novel approach to modulate sustained neuroinflammation and glial dysfunction associated with Alzheimer's disease.

  13. Neuro-Behcet's disease showing severe atrophy of the cerebrum.

    Science.gov (United States)

    Miyakawa, T; Murayama, E; Deshimaru, M; Shikai, I; Kozuma, S

    1976-03-15

    A 38-year-old female died 6 years after the onset of what was, clinically and histopathologically, consistent with neuro-Behcet's disease. Pathologically the cerebrum showed severe atrophy. The main changes were observed in the grey and white matter, the diencephalon and the basal ganglia by light microscopy. All these changes originated in softenings around blood vessels, especially small vessels or capillaries. These foci fused together to form large regions of softening. Glial or mesenchymal reactions were minimal. In the white matter there was slight perivascular-infiltration, mainly consisting of lymphocytes. In view of these findings, it is suggested that these changes were caused by an allergic vasculitis. The present case of Neuro-Behcet's disease is the first one showing general atrophy of the cerebrum. It is very important in relation to demyelinating encephalitis.

  14. Investigation of multiple organ involvement in Fabry disease%法布里病患者多器官病变的临床特点分析

    Institute of Scientific and Technical Information of China (English)

    张巍; 康曼德; 赵亚雯; 李凡; 舒俊龙; 左越焕; 刘靖; 黄一宁; 袁云

    2015-01-01

    Objective To investigate incidence and clinical features of multiple organ involvement in Chinese patients with Fabry disease.Methods We collected 151 patients of 31 families with Fabry disease,all of whom were confirmed by classic pathology,decreased α-galactosidase A activity or GLA mutation from the year of 2011 to 2014 in Department of Neurology,Peking University First Hospital.The clinical data included incidence and onset of neuralgia,renal dysfunction,heart disease,hypertension and cerebral stroke.We calculate the incidence of these symptoms and analyze their gender difference using chisquare with SPSS 17.0 software.Results Among 31 families with Fabry disease,151 patients (82 males and 69 females) were affected,including 91 patients (60.26%) with neuralgia,62 patients (41.06%) with renal disease,33 patients (21.85%) with heart disease,33 patients (21.85%) with hypertension,and 21 patients (13.91%) with cerebral stroke.The peak incidence of neuralgia was from 10 to 20 years old,followed by renal disease from 30 to 40 years old,heart disease and stroke from 40 to 50 years old.There is no peak period for hypertension.Except for males with higher incidence of renal dysfunction than females (P < 0.05),there were no gender difference in the incidence of other organ involvement.Conclusion The incidence and onset of multiple organ dysfunction in Chinese patients with Fabry disease displayed special regularity.Gender difference appeared only in renal disease.%目的 总结我国法布里病患者多器官病变的发生率和临床表现特点.方法 收集北京大学第一医院神经内科2001-2014年依据病理改变、α-半乳糖苷酶活性A测定和GLA基因突变检查确诊的31个法布里病家系发病者的临床资料,统计其神经痛、肾脏病变、心脏病变、高血压病和脑卒中的发生率和起病时间,使用SPSS 17.0统计软件对男女患者不同器官损害的发生率进行x2检验,比较男女患者上述

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

    Science.gov (United States)

    Goláň, Lubor; Goker-Alpan, Ozlem; Holida, Myrl; Kantola, Ikka; Klopotowski, Mariusz; Kuusisto, Johanna; Linhart, Aleš; Musial, Jacek; Nicholls, Kathleen; Gonzalez-Rodriguez, Derlis; Sharma, Reena; Vujkovac, Bojan; Chang, Peter; Wijatyk, Anna

    2015-01-01

    Purpose Efficacy and safety of agalsidase alfa at 0.2 mg/kg weekly were compared with 0.2 mg/kg every other week (EOW). Exploratory analyses were performed for 0.4 mg/kg weekly. Patients and methods This was a 53-week, Phase III/IV, multicenter, open-label study (NCT01124643) in treatment-naïve adults (≥18 years) with Fabry disease. Inclusion criteria were left ventricular hypertrophy at baseline, defined as left ventricular mass indexed to height >50 g/m2.7 for males and >47 g/m2.7 for females. Primary endpoint was reduction of left ventricular mass indexed to height as assessed by echocardiography. Secondary endpoints included cardiac (peak oxygen consumption, 6-minute walk test, Minnesota Living with Heart Failure Questionnaire, New York Heart Association classification), renal (Modification of Diet in Renal Disease, estimated glomerular filtration rate), and biomarker (plasma globotriaosylceramide) assessments. Safety endpoints were adverse events and anti–agalsidase alfa antibodies. Results Twenty patients were randomized to 0.2 mg/kg EOW (mean age, 50.3 years; 70% male), 19 to 0.2 mg/kg weekly (51.8 years; 53% male), and 5 to 0.4 mg/kg weekly (49.4 years; 40% male). The mean change in left ventricular mass indexed to height by Week 53 in the 0.2-mg/kg EOW and weekly groups was 3.2 g/m2.7 and 0.5 g/m2.7, with no significant difference between groups. No clinically meaningful changes by Week 53 were found within or between the 0.2-mg/kg groups for peak oxygen consumption, 6-minute walk test, or Minnesota Living with Heart Failure Questionnaire. Two patients in each group improved by ≥1 New York Heart Association classification. No significant differences were found between 0.2 mg/kg EOW and weekly for mean change in estimated glomerular filtration rate (−1.21 mL/min/1.73 m2 vs −3.32 mL/min/1.73 m2) or plasma globotriaosylceramide (−1.05 nmol/mL vs −2.13 nmol/mL), respectively. Infusion-related adverse events were experienced by 25% and 21% in the

  16. Anti-BlyS antibody reduces the immune reaction against enzyme and enhances the efficacy of enzyme replacement therapy in Fabry disease model mice.

    Science.gov (United States)

    Sato, Yohei; Ida, Hiroyuki; Ohashi, Toya

    2017-02-02

    Formation of antibodies against a therapeutic enzyme is an important complication during enzyme replacement therapy (ERT) for lysosomal storage diseases. Fabry disease (FD) is caused by a deficiency of alpha-galactosidase (GLA), which results in the accumulation of globotriaosylceramide (GL-3). We have shown immune tolerance induction (ITI) during ERT in FD model mice by using an anti-B lymphocyte stimulator (anti-BlyS) antibody (belimumab). A single dose of the anti-BlyS antibody temporarily lowered the percentage of B cells and IgG antibody titer against recombinant human GLA. Administration of a low maintenance dose of the anti-BlyS antibody suppressed the B cell population and immunotolerance was induced in 20% of mice, but antibody formation could not be prevented. We then increased the maintenance dose of the anti-BlyS antibody and immunotolerance was induced in 50% of mice. Therapeutic enzyme distribution and clearance of GL-3 were also enhanced by a high maintenance dose of the anti-BlyS antibody.

  17. The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations

    Directory of Open Access Journals (Sweden)

    Valentina Citro

    2016-12-01

    Full Text Available Fabry disease is caused by mutations in the GLA gene and is characterized by a large genotypic and phenotypic spectrum. Missense mutations pose a special problem for graduating diagnosis and choosing a cost-effective therapy. Some mutants retain enzymatic activity, but are less stable than the wild type protein. These mutants can be stabilized by small molecules which are defined as pharmacological chaperones. The first chaperone to reach clinical trial is 1-deoxygalactonojirimycin, but others have been tested in vitro. Residual activity of GLA mutants has been measured in the presence or absence of pharmacological chaperones by several authors. Data obtained from transfected cells correlate with those obtained in cells derived from patients, regardless of whether 1-deoxygalactonojirimycin was present or not. The extent to which missense mutations respond to 1-deoxygalactonojirimycin is variable and a reference table of the results obtained by independent groups that is provided with this paper can facilitate the choice of eligible patients. A review of other pharmacological chaperones is provided as well. Frequent mutations can have residual activity as low as one-fourth of normal enzyme in vitro. The reference table with residual activity of the mutants facilitates the identification of non-pathological variants.

  18. The Large Phenotypic Spectrum of Fabry Disease Requires Graduated Diagnosis and Personalized Therapy: A Meta-Analysis Can Help to Differentiate Missense Mutations

    Science.gov (United States)

    Citro, Valentina; Cammisa, Marco; Liguori, Ludovica; Cimmaruta, Chiara; Lukas, Jan; Cubellis, Maria Vittoria; Andreotti, Giuseppina

    2016-01-01

    Fabry disease is caused by mutations in the GLA gene and is characterized by a large genotypic and phenotypic spectrum. Missense mutations pose a special problem for graduating diagnosis and choosing a cost-effective therapy. Some mutants retain enzymatic activity, but are less stable than the wild type protein. These mutants can be stabilized by small molecules which are defined as pharmacological chaperones. The first chaperone to reach clinical trial is 1-deoxygalactonojirimycin, but others have been tested in vitro. Residual activity of GLA mutants has been measured in the presence or absence of pharmacological chaperones by several authors. Data obtained from transfected cells correlate with those obtained in cells derived from patients, regardless of whether 1-deoxygalactonojirimycin was present or not. The extent to which missense mutations respond to 1-deoxygalactonojirimycin is variable and a reference table of the results obtained by independent groups that is provided with this paper can facilitate the choice of eligible patients. A review of other pharmacological chaperones is provided as well. Frequent mutations can have residual activity as low as one-fourth of normal enzyme in vitro. The reference table with residual activity of the mutants facilitates the identification of non-pathological variants. PMID:27916943

  19. Small-fibre neuropathy in female Fabry patients: reduced allodynia and skin blood flow after topical capsaicin

    DEFF Research Database (Denmark)

    Møller, Anette Torvin; Feldt-Rasmussen, Ulla; Rasmussen, Åse K.;

    2006-01-01

    affected. Recently, attention has been drawn to female patients whether they also show signs of nerve involvement. An early sign of the disease is painful small-fibre neuropathy. The aim of this study was to evaluate a small-fibre dysfunction in female Fabry patients by using capsaicin applied topically....... The response to capsaicin was evaluated by laser Doppler imaging. We found that the female Fabry patients had a significantly smaller increase in blood flow (p = 0.0003) after capsaicin application. The area of static mechanical allodynia and dynamic mechanical hyperalgesia was also significantly smaller (p...

  20. Fabry-Perot interferometers

    CERN Document Server

    Mora-Hernandez, G

    1988-01-01

    This book describes the Fabry-Perot interferometer and its variants as well as its use, optimisation and applications. The author begins with an historical perspective on the development of the instrument. Because of the quantitative uses of the device, the text tends to be mostly mathematical in its treatment. However, there is also much practical detail on the use and optimization of the Fabry-Perot interferometer and discussion of its classical uses (such as in metrology) and its contemporary applications (such as in lasers). In addition the book contains a comprehensive bibliography summarizing the extensive literature on the subject. This book will appeal both to high-resolution practitioners, such as spectroscopists, and to the laser community, since the Fabrv-Perot is not only an integral part of the laser but is also usea to characterize its optical and spectroscopic behaviour.

  1. Which new approaches to tackling neglected tropical diseases show promise?

    Science.gov (United States)

    Spiegel, Jerry M; Dharamsi, Shafik; Wasan, Kishor M; Yassi, Annalee; Singer, Burton; Hotez, Peter J; Hanson, Christy; Bundy, Donald A P

    2010-05-18

    This PLoS Medicine Debate examines the different approaches that can be taken to tackle neglected tropical diseases (NTDs). Some commentators, like Jerry Spiegel and colleagues from the University of British Columbia, feel there has been too much focus on the biomedical mechanisms and drug development for NTDs, at the expense of attention to the social determinants of disease. Burton Singer argues that this represents another example of the inappropriate "overmedicalization" of contemporary tropical disease control. Peter Hotez and colleagues, in contrast, argue that the best return on investment will continue to be mass drug administration for NTDs.

  2. Which new approaches to tackling neglected tropical diseases show promise?

    Directory of Open Access Journals (Sweden)

    Jerry M Spiegel

    2010-05-01

    Full Text Available This PLoS Medicine Debate examines the different approaches that can be taken to tackle neglected tropical diseases (NTDs. Some commentators, like Jerry Spiegel and colleagues from the University of British Columbia, feel there has been too much focus on the biomedical mechanisms and drug development for NTDs, at the expense of attention to the social determinants of disease. Burton Singer argues that this represents another example of the inappropriate "overmedicalization" of contemporary tropical disease control. Peter Hotez and colleagues, in contrast, argue that the best return on investment will continue to be mass drug administration for NTDs.

  3. The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

    Science.gov (United States)

    Ferreira, Susana; Ortiz, Alberto; Germain, Dominique P.; Viana-Baptista, Miguel; Gomes, António Caldeira; Camprecios, Marta; Fenollar-Cortés, Maria; Gallegos-Villalobos, Ángel; Garcia, Diego; García-Robles, José Antonio; Egido, Jesús; Gutiérrez-Rivas, Eduardo; Herrero, José Antonio; Mas, Sebastián; Oancea, Raluca; Péres, Paloma; Salazar-Martín, Luis Manuel; Solera-Garcia, Jesús; Alves, Helena; Garman, Scott C.; Oliveira, João Paulo

    2015-01-01

    Summary Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue – GLA p.(Arg118Cys) –, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands’ close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease, since the allelic frequency in stroke patients was 0.0087 (p=0.0185 vs the general population). The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for “rare” condition. PMID:25468652

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

    Directory of Open Access Journals (Sweden)

    Goláň L

    2015-07-01

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

  5. Klinefelter syndrome with fabry disease--a case of nondisjunction of the X-chromosome with sex-linked recessive mutation.

    Science.gov (United States)

    Sadick, Victoria J; Fietz, Michael J; Tchan, Michel C; Kovoor, Pramesh; Thomas, Liza; Sadick, Norman

    2014-12-01

    A 52 year-old male with Klinefelter syndrome presented with chest tightness and rapid atrial fibrillation with hypotension. His echocardiogram demonstrated symmetrical left ventricular hypertrophy with minimal diastolic dysfunction. Subsequent investigations confirmed the diagnosis of Fabry cardiomyopathy. This is the first reported case of Klinefelter syndrome with homozygous sex-linked recessive mutation presenting primarily with cardiac manifestation.

  6. Genetic Disorders with Dyshidrosis: Ectodermal Dysplasia, Incontinentia Pigmenti, Fabry Disease, and Congenital Insensitivity to Pain with Anhidrosis.

    Science.gov (United States)

    Wataya-Kaneda, Mari

    2016-01-01

    Sweating is regulated by various neurohormonal mechanisms. A disorder in any part of the sweating regulatory pathways, such as the thermal center, neurotransmitters in the central to peripheral nerve, innervation of periglandular neurotransmission, and sweat secretion in the sweat gland itself, induces dyshidrosis. Therefore, hereditary disorders with dyshidrosis result from a variety of causes. These diseases have characteristic symptoms derived from each pathogenesis besides dyshidrosis. The information in this chapter is useful for the differential diagnosis of representative genetic disorders with dyshidrosis. © 2016 S. Karger AG, Basel.

  7. Genetic Screening of Mutations Associated with Fabry Disease in a Nationwide Cohort of Juvenile Idiopathic Arthritis Patients

    Science.gov (United States)

    Gonçalves, Maria J.; Mourão, Ana F.; Martinho, António; Simões, Olívia; Melo-Gomes, José; Salgado, Manuel; Estanqueiro, Paula; Ribeiro, Célia; Brito, Iva; Fonseca, João E.; Canhão, Helena

    2017-01-01

    Fabry’s disease (FD) is a lysosomal storage disorder associated with an alpha-galactosidase A deficiency. The prevalence of FD among juvenile idiopathic arthritis (JIA) patients with established diagnosis is unknown, but as musculoskeletal pain may be an important complaint at presentation, misdiagnosed cases are anticipated. With this study, we aim to calculate the frequency of FD-associated mutations in a cohort of JIA patients. Children with JIA from a national cohort were selected. Clinical and laboratorial information was recorded in the Portuguese rheumatic diseases register (http://Reuma.pt). Molecular genetic testing to detect GLA gene mutations was performed. After the multiplex polymerase chain reactions technique for DNA amplification, direct sequencing of the complete sequence of GLA gene was completed. From a cohort of 292 patients with JIA (188 females, 104 males), mutations were identified in 5 patients (all female). Four patients had the mutation D313Y, a rare GLA variant, which is associated with low enzymatic levels in plasma, but normal lysosomal levels. One patient presented the missense mutation R118C, which was previously described in Mediterranean patients with FD. This is the first screening of FD mutations in a cohort of JIA patients. No “classic” pathogenic FD mutations were reported. The late-onset FD-associated mutation, R118C, was found in a frequency of 0.34% (1/292). PMID:28299312

  8. Clinical and magnetic resonance imaging studies of Anderson-Fabry disease: 2 cases report%表现为早发缺血性卒中的Fabry病二例

    Institute of Scientific and Technical Information of China (English)

    李小璇; 王璐; 张赟; 张巍; 洪道俊; 王朝霞; 高惠珍; 袁云

    2011-01-01

    Objective To report 2 cases of Fabry disease with early-onset ischemic stroke and investigate the clinical and image features. Methods The 2 patients developed dizziness, diplopia and progressive memory decline at 32 and 25 years of age respectively. The α-galactosidase A (GLA)activity was 4. 3 U in case 1 and 1. 0 U in case 2 ( normal range 100-500 U). Skin biopsy showed numerous membrane bounded osmiophilic laminar material in vascular smooth muscle cells and endothelial cells. GLA gene analysis revealed GLA exon 7 1033-1034 TC del in case 1 and GLA exon 3 466G > A in case 2. The 2 patients were evaluated by Mainz severity score index (MSSI) and cranial MRI. Results The general MSSI was 32 in case 1 and 16 in case 2, with the highest score of neurological score ( 11 and 14). Both cases showed multifocal infarcts in bilateral cerebellum, occipital lobe, basal ganglia, which were hypointensity on T1 WI and hyperintensity on T2WI. There were hyperintensity changes in the pulvinar and basal ganglia on T1 WI in case 2. Conclusions Cerebral ischemic stroke could appear as initial symptoms in Fabry disease,which predominantly involved the posterior circulation. There might be no dilation of basal-vertebral artery.%目的 报道以早发缺血性卒中为主要表现的2例Fabry病,分析其卒中表现规律和影像学改变特点.方法 2例Fabry病患者分别在32岁和25岁出现头晕和突发视物成双,伴随记忆力下降.α-半乳糖苷酶活性在例1为4.3 U,例2为1.0 U(正常值100~500 U).皮肤病理检查发现血管平滑肌细胞和内皮细胞内充满膜性包裹的板层样小体.α-半乳糖苷酶基因检查显示例1的7号外显子存在1033-1034 TC del突变,而例2存在3号外显子c.466G>A突变.对2例患者进行美茵滋严重度评分(MSSI)和头MRI检查.结果 例1的MSSI总分为32,其中神经系统评分最高(11分),例2的总分为16,其中神经系统评分最高(14分).MRI均表现为双侧小脑、枕叶、基

  9. Holographic Fabry-Perot spectrometer.

    Science.gov (United States)

    Martínez-Matos, O; Rodrigo, José A; Vaveliuk, P; Calvo, M L

    2011-02-15

    We propose a spectrum analyzer based on the properties of a hologram recorded with the field transmitted by a Fabry-Perot etalon. The spectral response of this holographic Fabry-Perot spectrometer (HFPS) is analytically investigated in the paraxial approximation and compared with a conventional Fabry-Perot etalon of similar characteristics. We demonstrate that the resolving power is twice increased and the free spectral range (FSR) is reduced to one-half. The proposed spectrometer could improve the operational performance of the etalon because it can exhibit high efficiency and it would be insensible to environmental conditions such as temperature and vibrations. Our analysis also extends to another variant of the HFPS based on holographic multiplexing of the transmitted field of a Fabry-Perot etalon. This device increases the FSR, keeping the same HFPS performance.

  10. Presymptomatic diagnosis of Fabry's disease

    DEFF Research Database (Denmark)

    Hasselbalch, Rasmus Bo; Madsen, Per Lav; Bundgaard, Henning;

    2016-01-01

    differential diagnoses in patients presenting with cardiac hypertrophy. In boys, onset has been reported in early childhood with complaints initially comprising neuropathic pain, reduced sweat production, and gastrointestinal symptoms. Later the cardiac, renal, and central nervous systems may become affected...

  11. 以慢性肾炎综合征为主要表现的Fabry病2例报道并文献复习%Fabry disease with chronic nephritis syndrome as the main manifestation and literature study:2 cases report

    Institute of Scientific and Technical Information of China (English)

    廖武琼; 李典耕; 谢大洋; 陈仆; 李清刚; 陈香美

    2015-01-01

    Objective To investigate the clinical manifestation and renal pathology of Fabry disease which characteri zed with chronic nephritis syndrome as the main manifestation. Methods Retrospectively review the 2 cases of Fabry disease, which characterized as chronic nephritis syndrome as the main manifestation, the clinical signs and pathology were analyzed, and review of the relevant literature to master the methods of diagnosis and treatment. Results One case was male patient, the other was female patient, and onset age was 46 years old and 44 years old, 2 cases showed proteinuria, hematuria, hyperten-sion, and no characteristic of extra-renal manifestations. Under the light microscope, glomerular sclerosis rates were 30. 8%and 32. 1% respectively, significant swelling of glomerular podocytes, visible vacuoles formed in the cytoplasm, renal tubular multifocal atrophic were found. Dense and irregular osmiophilic myelin bodies also can be found. There is no effective cure methods for Fabry disease, combined with renal damage, the treatment mainly was to protect the kidney function, reducing protein, control symptom, the main medicine are ARB, such as losartan potassium, leflunomide. Conclusion Fabry disease is a rare genetic chromosome X diseases, renal damage is one of the most common clinical manifestation, under microscopic osmiophilic myelin bodies is the pathological finding, symptomatic treatment with enzyme replacement therapy are the main treatment, and combined with the genetics of appropriate intervention to block the genetics of the disease.%目的:探讨以慢性肾炎综合征为主要表现的Fabry病临床表现和肾脏病理学特点。方法回顾性分析收治的以慢性肾炎综合征为主要表现的Fabry病2例,分析其临床体征及病理学特征,同时复习相关文献掌握其诊断及治疗方法。结果男女患者各1例,发病年龄分别为46岁和44岁,2例均表现为蛋白尿、血尿、高血压,而无特征性的肾外表现

  12. New drug treatments show neuroprotective effects in Alzheimer's and Parkinson's diseases.

    Science.gov (United States)

    Hölscher, Christian

    2014-11-01

    Type 2 diabetes is a risk factor for Alzheimer's disease and Parkinson's disease. Insulin signaling in the brains of people with Alzheimer's disease or Parkinson's disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alzheimer's disease and Parkinson's disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer's disease and Parkinson's disease. On the basis of these promising findings, several clinical trials are ongoing with the first encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer's disease and Parkinson's disease that are currently unavailable.

  13. Inhibition of Intermediate-Conductance Calcium-Activated K Channel (KCa3.1) and Fibroblast Mitogenesis by α-Linolenic Acid and Alterations of Channel Expression in the Lysosomal Storage Disorders, Fabry Disease, and Niemann Pick C

    Science.gov (United States)

    Oliván-Viguera, Aida; Lozano-Gerona, Javier; López de Frutos, Laura; Cebolla, Jorge J.; Irún, Pilar; Abarca-Lachen, Edgar; García-Malinis, Ana J.; García-Otín, Ángel Luis; Gilaberte, Yolanda; Giraldo, Pilar; Köhler, Ralf

    2017-01-01

    The calcium/calmodulin-gated KCa3.1 channel regulates normal and abnormal mitogenesis by controlling K+-efflux, cell volume, and membrane hyperpolarization-driven calcium-entry. Recent studies suggest modulation of KCa3.1 by omega-3 fatty acids as negative modulators and impaired KCa3.1 functions in the inherited lysosomal storage disorder (LSD), Fabry disease (FD). In the first part of present study, we characterize KCa3.1 in murine and human fibroblasts and test the impact of omega-3 fatty acids on fibroblast proliferation. In the second, we study whether KCa3.1 is altered in the LSDs, FD, and Niemann-Pick disease type C (NPC). Our patch-clamp and mRNA-expression studies on murine and human fibroblasts show functional expression of KCa3.1. KCa currents display the typical pharmacological fingerprint of KCa3.1: Ca2+-activation, potentiation by the positive-gating modulators, SKA-31 and SKA-121, and inhibition by TRAM-34, Senicapoc (ICA-17043), and the negative-gating modulator, 13b. Considering modulation by omega-3 fatty acids we found that α-linolenic acid (α-LA) and docosahexanenoic acid (DHA) inhibit KCa3.1 currents and strongly reduce fibroblast growth. The α-LA-rich linseed oil and γ-LA-rich borage oil at 0.5% produce channel inhibition while α-LA/γ-LA-low oils has no anti-proliferative effect. Concerning KCa3.1 in LSD, mRNA expression studies, and patch-clamp on primary fibroblasts from FD and NPC patients reveal lower KCa3.1-gene expression and membrane expression than in control fibroblasts. In conclusion, the omega-3 fatty acid, α-LA, and α-LA/γ-LA-rich plant oils, inhibit fibroblast KCa3.1 channels and mitogenesis. Reduced fibroblast KCa3.1 functions are a feature and possible biomarker of cell dysfunction in FD and NPC and supports the concept that biased lipid metabolism is capable of negatively modulating KCa3.1 expression. PMID:28197106

  14. Wide-angle spectral imaging using a Fabry-Perot interferometer

    NARCIS (Netherlands)

    Strauch, M.; Livshits, I.L.; Bociort, F.; Urbach, H.P.

    2015-01-01

    We show that wide-angle spectral imaging can be achieved with compact and cost-effective devices using Fabry-Pérot interferometers. Designs with a full field of view of 90°, in which the Fabry-Pérot interferometer is mounted either in front of an imaging lens system or behind a telecentric lens syst

  15. The prevalent deep intronic c. 639+919 G>A GLA mutation causes pseudoexon activation and Fabry disease by abolishing the binding of hnRNPA1 and hnRNP A2/B1 to a splicing silencer

    DEFF Research Database (Denmark)

    Palhais, Bruno; Dembic, Maja; Sabaratnam, Rugivan;

    2016-01-01

    with the ESS is also able to inhibit inclusion of an unrelated pseudoexon in the FGB gene, and that also in the FGB context inactivation of the ESS by the c.639+919 G>A mutation causes pseudoexon activation, underscoring the universal nature of the ESS. Finally, we demonstrate that splice switching......Fabry disease is an X-linked recessive inborn disorder of the glycosphingolipid metabolism, caused by total or partial deficiency of the lysosomal α-galactosidase A enzyme due to mutations in the GLA gene. The prevalent c.639+919 G>A mutation in GLA leads to pathogenic insertion of a 57bp...... pseudoexon sequence from intron 4, which is responsible for the cardiac variant phenotype. In this study we investigate the splicing regulatory mechanism leading to GLA pseudoexon activation. Splicing analysis of GLA minigenes revealed that pseudoexon activation is influenced by cell-type. We demonstrate...

  16. New drug treatments show neuroprotective effects in Alzheimer's and Parkinson's diseases

    OpenAIRE

    Hölscher, Christian

    2014-01-01

    Type 2 diabetes is a risk factor for Alzheimer's disease and Parkinson's disease. Insulin signaling in the brains of people with Alzheimer's disease or Parkinson's disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alzheimer's disease and Parkinson's disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synapt...

  17. New drug treatments show neuroprotective effects in Alzheimer’s and Parkinson’s diseases

    Institute of Scientific and Technical Information of China (English)

    Christian Hölscher

    2014-01-01

    Type 2 diabetes is a risk factor for Alzheimer’s disease and Parkinson’s disease. Insulin signaling in the brains of people with Alzheimer’s disease or Parkinson’s disease is impaired. Preclinical studies of growth factors showed impressive neuroprotective effects. In animal models of Alz-heimer’s disease and Parkinson’s disease, insulin, glia-derived neurotrophic factor, or analogues of the incretin glucagon-like peptide-1 prevented neurodegenerative processes and improved neuronal and synaptic functionality in Alzheimer’s disease and Parkinson’s disease. On the basis of these promising ifndings, several clinical trials are ongoing with the ifrst encouraging clinical results published. This gives hope for developing effective treatments for Alzheimer’s disease and Parkinson’s disease that are currently unavailable.

  18. Gamma irradiation of Fabry-Perot interband cascade lasers

    Energy Technology Data Exchange (ETDEWEB)

    Myers, Tanya L.; Cannon, Bret D.; Brauer, Carolyn S.; Canedy, Chadwick L.; Kim, Chul Soo; Kim, Mijin; Merritt, Charles D.; Bewley, William W.; Vurgaftman, Igor; Meyer, Jerry R.

    2017-09-20

    Two Fabry-Perot interband cascade lasers (ICLs) were exposed to Cobalt-60 gamma rays for a dosage of 500 krad(Si) each, which is higher than is typically encountered in space applications. The ICLs do not show any significant changes in threshold current or slope efficiency, suggesting the suitability of ICLs for use in radiation environments.

  19. Leukocyte-technetium-99m uptake in Crohn s disease:Does it show subclinical disease?

    Institute of Scientific and Technical Information of China (English)

    Luciene; G; Mota; Luiz; GV; Coelho; Carlos; JR; Simal; Maria; LA; Ferrari; Clodomiro; Toledo; Josep; Martin-Comin; Simone; OF; Diniz; Valbert; N; Cardoso

    2010-01-01

    AIM:To evaluate inflammatory activity in patients with Crohn's disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy.METHODS: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn's Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the Internat...

  20. Fabry-Perot Diaphragm Fiber Optic Sensor (DFOS for Acoustic Detection

    Directory of Open Access Journals (Sweden)

    Yan SUN

    2007-10-01

    Full Text Available A diaphragm fiber optic sensor (DFOS solely based on Fabry-Perot multiple beam interference has been designed and fabricated with micro-electric mechanical system (MEMS technology. The silicon diaphragm with an embossed center was designed with an interference gap width kept accurately. The DFOS was verified to be a truly and purely Fabry-Perot device via a critical test. Parallel testing with a Piezoelectric (PZT sensor showed that the DFOS had high sensitivity. The Fabry-Perot DFOS also demonstrated excellent performance in on-line monitoring of Partial Discharge (PD in power transformers.

  1. Demonstrations Using a Fabry-Perot. I. Multiple-Slit Interference

    Science.gov (United States)

    Roychoudhuri, Chandrasekhar

    1975-01-01

    Describes a demonstration technique for showing multiple-slit interference patterns with the use of a Fabry-Perot etalon and a laser beam. A simple derivation of the analytical expression for such fringes is presented. (Author/CP)

  2. Nearly All Autopsied NFL Players Show Trauma-Linked Brain Disease

    Science.gov (United States)

    ... gov/news/fullstory_167405.html Nearly All Autopsied NFL Players Show Trauma-Linked Brain Disease No position ... 2017 (HealthDay News) -- Ninety-nine percent of former NFL players who donated their brain to science turned ...

  3. Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients

    Directory of Open Access Journals (Sweden)

    Hollak Carla EM

    2011-10-01

    Full Text Available Abstract Background Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, reduced dose 0.5 mg/kg/m, or switch to agalsidase alpha (administered dose 0.2 mg/kg/eow. An assessment report from the European Medicines Agency (EMA raised serious concerns about an increase in adverse events at lower dosages of agalsidase beta. We determined the influence of the shortage on clinical event incidence and the most sensitive biochemical marker (lysoGb3 in Dutch Fabry patients. Methods The incidence of clinical events per person per year was calculated from start of agalsidase beta treatment until the shortage, and was compared to the incidence of clinical events during the shortage period. In addition, plasma lysoGb3, eGFR, quality of life (SF-36 and brief pain inventory (BPI questionnaires were analysed. Results All thirty-five Dutch Fabry patients using agalsidase beta (17 males were included. Mean clinical event incidence was unchanged: 0.15 events per person per year before versus 0.15 during the shortage (p = 0.68. In total 28 clinical events occurred in 14 patients during 4.6 treatment years, compared to 7 events in 6 patients during the 1.3 year shortage period. eGFR and BPI scores were not significantly altered. Two SF-36 subscales were significantly but minimally reduced in females. In males, lysoGb3 increased with a median of 8.1 nM (range 2.5 - 29.2 after 1 year of shortage (p = 0.001. Increases in lysoGb3 were found in both patients switching to agalsidase alpha and on a reduced agalsidase beta dose. Antibody status, treatment duration or clinical event incidence showed no clear correlation to lysoGb3 increases. Conclusions No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase

  4. Fabry-Perot resonance of water waves.

    Science.gov (United States)

    Couston, Louis-Alexandre; Guo, Qiuchen; Chamanzar, Maysamreza; Alam, Mohammad-Reza

    2015-10-01

    We show that significant water wave amplification is obtained in a water resonator consisting of two spatially separated patches of small-amplitude sinusoidal corrugations on an otherwise flat seabed. The corrugations reflect the incident waves according to the so-called Bragg reflection mechanism, and the distance between the two sets controls whether the trapped reflected waves experience constructive or destructive interference within the resonator. The resulting amplification or suppression is enhanced with increasing number of ripples and is most effective for specific resonator lengths and at the Bragg frequency, which is determined by the corrugation period. Our analysis draws on the analogous mechanism that occurs between two partially reflecting mirrors in optics, a phenomenon named after its discoverers Charles Fabry and Alfred Perot.

  5. Electrical Changes in Resting, Exercise, and Holter Electrocardiography in Fabry Cardiomyopathy.

    Science.gov (United States)

    Krämer, Johannes; Nordbeck, Peter; Störk, Stefan; Ritter, Christian; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2015-10-27

    In Fabry cardiomyopathy, little is known about the interaction between its key feature of myocardial replacement fibrosis and changes in resting, Holter, and exercise electrocardiography (-ECG). Resting ECG, 24-h Holter ECG, and exercise ECG were performed in 95 patients (50 women) with Fabry disease, staged using cardiac magnetic resonance imaging to measure left ventricular fibrosis. With resting ECG, T alterations were seen in patients with cardiac fibrosis, while time intervals and rhythm were unchanged (except for a longer QRS duration in patients with severe fibrosis). All patients with severe fibrosis showed T inversion, ST alteration, or both. With Holter ECG, maximum and minimum heart rate did not differ with fibrosis severity. Patients without fibrotic tissue showed less ventricular premature beats (VPB) (median 5/24 h) compared to those with mild (median 11/24 h) or severe fibrosis (median 115/24 h; P 10 mmHg) occurred in some patients with no (3/41) or mild fibrosis (3/34) but not in patients with severe fibrosis (0/20; P Holter ECG. During exercise ECG, advanced cardiomyopathy is characterized by chronotropic incompetence with limitations on blood pressure and heart rate increase.

  6. Curvature sensor based on a Fabry-Perot interferometer

    Science.gov (United States)

    Monteiro, Catarina; Ferreira, Marta S.; Kobelke, Jens; Schuster, Kay; Bierlich, Jörg; Frazão, Orlando

    2016-05-01

    A curvature sensor based on a Fabry-Perot interferometer is proposed. A capillary tube of silica is fusion spliced between two single mode fibers, producing a Fabry-Perot cavity. The light propagates in air, when passing through the capillary tube. Two different cavities are subjected to curvature and temperature. The cavity with shorter length shows insensitivity to both measurands. The larger cavity shows two operating regions for curvature measurement, where a linear response is shown, with a maximum sensitivity of 18.77pm/m-1 for the high curvature radius range. When subjected to temperature, the sensing head produces a similar response for different curvature radius, with a sensitivity of 0.87pm/°C.

  7. Optical power equalization using Fabry-Perot semiconductor optical amplifier

    Institute of Scientific and Technical Information of China (English)

    Yun Ling; Kun Qiu; Wei Zhang; Ying Pang

    2006-01-01

    A novel scheme of optical power equalization based on Fabry-Perot semiconductor optical amplifier (FPSOA) is proposed. Because of the gain characteristic of FP-SOA, real-time controlling mechanism according to input optical power is aborted in the scheme. The simulations show that 10-dB pulse peak power variation can be clamped in less than i dB. The influences of injecting current, pulse periods, and pulse width are discussed.

  8. Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes.

    Science.gov (United States)

    2012-08-03

    Huntington's disease (HD) is an inherited neurodegenerative disorder caused by an expanded stretch of CAG trinucleotide repeats that results in neuronal dysfunction and death. Here, The HD Consortium reports the generation and characterization of 14 induced pluripotent stem cell (iPSC) lines from HD patients and controls. Microarray profiling revealed CAG-repeat-expansion-associated gene expression patterns that distinguish patient lines from controls, and early onset versus late onset HD. Differentiated HD neural cells showed disease-associated changes in electrophysiology, metabolism, cell adhesion, and ultimately cell death for lines with both medium and longer CAG repeat expansions. The longer repeat lines were however the most vulnerable to cellular stressors and BDNF withdrawal, as assessed using a range of assays across consortium laboratories. The HD iPSC collection represents a unique and well-characterized resource to elucidate disease mechanisms in HD and provides a human stem cell platform for screening new candidate therapeutics.

  9. Distributed Fabry-Perot Measurement System

    Institute of Scientific and Technical Information of China (English)

    WENG Jian-hua

    2003-01-01

    The theoretic analysis indicates that if the lengths of the cascaded and paralleled Fabry-Perot sensors are properly selected, the crosstalk can be well restricted.And the experiment simulation results agree with that of the theoretic analysis.

  10. Reversible Lansoprazole-Induced Interstitial Lung Disease Showing Improvement after Drug Cessation

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Kyu Won; Woo, Ok Hee; Yong, Hwan Seok; Shin, Bong Kyung; Shim, Jae Jeong; Kang, Eun Young [College of Medicine, Korea University, Guro Hospital, Seoul (Korea, Republic of)

    2008-04-15

    Lansoprazole is an acid proton-pump inhibitor that is similar to omeprazole. It is used to treat duodenal or gastric ulcers, H. pylori infection, gastroesophageal reflux disease (GERD) or Zollinger-Ellison syndrome. Common adverse effects of lansoprazole are diarrhea, abdominal pain, skin rash and/or itching. Information from U.S. National Library of Medicine warns that this drug can on rare occasion cause cough or cold-like symptoms. The pathophysiological mechanisms of lansoprazole-related pulmonary symptoms are not yet understood. In particular, there are no known reports regarding lansoprazole-induced interstitial lung diseases. We report here a case of interstitial lung disease (ILD) induced by oral administration of lansoprazole, which showed a pattern of nonspecific interstitial pneumonia (NSIP) as detected from a video-assisted thoracoscopic lung biopsy. We believe that this is the first report of a case of pathologically proven lansoprazole-induced ILD for which a surgical lung biopsy was performed. To the best of our knowledge, this is the first description of DI-ILD caused by lansoprazole. The diagnosis was made by considering the radiological, histopathological and clinical findings, including the close temporal relationship between lansoprazole exposure and symptom severity. Other possible causes were excluded due to a lack of a temporal relationship between the symptoms and work history or prednisolone therapy, and no other history of specific allergen exposure. When there is diffuse interstitial lung disease with an unknown etiology, it is important to remember that drugs can be the cause of pulmonary symptoms and it is crucial to take a careful patient history. If there is a recent history of taking lansoprazole in a patient with clinical and radiological findings of diffuse interstitial lung disease, we recommend stopping the medication to see if there is clinical and radiological improvement. That way, one can avoid using invasive procedures to

  11. Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy.

    Science.gov (United States)

    de Munck, Estefanía; Palomo, Valle; Muñoz-Sáez, Emma; Perez, Daniel I; Gómez-Miguel, Begoña; Solas, M Teresa; Gil, Carmen; Martínez, Ana; Arahuetes, Rosa M

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor neuron disease animal model has been developed using β-N-methylamino-L-alanine (L-BMAA), a neurotoxic amino acid related to the appearing of ALS. In the present work, the neuroprotective role of VP2.51, a small heterocyclic GSK-3 inhibitor, is analysed in this novel murine model together with the analysis of autophagy. VP2.51 daily administration for two weeks, starting the first day after L-BMAA treatment, leads to total recovery of neurological symptoms and prevents the activation of autophagic processes in rats. These results show that the L-BMAA murine model can be used to test the efficacy of new drugs. In addition, the results confirm the therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS.

  12. Small GSK-3 Inhibitor Shows Efficacy in a Motor Neuron Disease Murine Model Modulating Autophagy

    Science.gov (United States)

    de Munck, Estefanía; Palomo, Valle; Muñoz-Sáez, Emma; Perez, Daniel I.; Gómez-Miguel, Begoña; Solas, M. Teresa; Gil, Carmen; Martínez, Ana; Arahuetes, Rosa M.

    2016-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron degenerative disease that has no effective treatment up to date. Drug discovery tasks have been hampered due to the lack of knowledge in its molecular etiology together with the limited animal models for research. Recently, a motor neuron disease animal model has been developed using β-N-methylamino-L-alanine (L-BMAA), a neurotoxic amino acid related to the appearing of ALS. In the present work, the neuroprotective role of VP2.51, a small heterocyclic GSK-3 inhibitor, is analysed in this novel murine model together with the analysis of autophagy. VP2.51 daily administration for two weeks, starting the first day after L-BMAA treatment, leads to total recovery of neurological symptoms and prevents the activation of autophagic processes in rats. These results show that the L-BMAA murine model can be used to test the efficacy of new drugs. In addition, the results confirm the therapeutic potential of GSK-3 inhibitors, and specially VP2.51, for the disease-modifying future treatment of motor neuron disorders like ALS. PMID:27631495

  13. Cooperative genome-wide analysis shows increased homozygosity in early onset Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Javier Simón-Sánchez

    Full Text Available Parkinson's disease (PD occurs in both familial and sporadic forms, and both monogenic and complex genetic factors have been identified. Early onset PD (EOPD is particularly associated with autosomal recessive (AR mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. Since mutations in these genes account for less than 10% of EOPD patients, we hypothesized that further recessive genetic factors are involved in this disorder, which may appear in extended runs of homozygosity.We carried out genome wide SNP genotyping to look for extended runs of homozygosity (ROHs in 1,445 EOPD cases and 6,987 controls. Logistic regression analyses showed an increased level of genomic homozygosity in EOPD cases compared to controls. These differences are larger for ROH of 9 Mb and above, where there is a more than three-fold increase in the proportion of cases carrying a ROH. These differences are not explained by occult recessive mutations at existing loci. Controlling for genome wide homozygosity in logistic regression analyses increased the differences between cases and controls, indicating that in EOPD cases ROHs do not simply relate to genome wide measures of inbreeding. Homozygosity at a locus on chromosome19p13.3 was identified as being more common in EOPD cases as compared to controls. Sequencing analysis of genes and predicted transcripts within this locus failed to identify a novel mutation causing EOPD in our cohort.There is an increased rate of genome wide homozygosity in EOPD, as measured by an increase in ROHs. These ROHs are a signature of inbreeding and do not necessarily harbour disease-causing genetic variants. Although there might be other regions of interest apart from chromosome 19p13.3, we lack the power to detect them with this analysis.

  14. A large outbreak of Legionnaires' disease at a flower show, the Netherlands, 1999.

    Science.gov (United States)

    Den Boer, Jeroen W; Yzerman, Ed P F; Schellekens, Joop; Lettinga, Kamilla D; Boshuizen, Hendriek C; Van Steenbergen, Jim E; Bosman, Arnold; Van den Hof, Susan; Van Vliet, Hans A; Peeters, Marcel F; Van Ketel, Ruud J; Speelman, Peter; Kool, Jacob L; Conyn-Van Spaendonck, Marina A E

    2002-01-01

    In 1999, an outbreak of Legionnaires' disease affected many visitors to a flower show in the Netherlands. To identify the source of the outbreak, we performed an environmental investigation, as well as a case-control study among visitors and a serologic cohort study among exhibitors to measure exposure to possible sources. Of 77,061 visitors, 188 became ill (133 confirmed and 55 probable cases), for an attack rate of 0.23% for visitors and 0.61% for exhibitors. Two whirlpool spas in halls 3 and 4 of the exhibition and a sprinkler in hall 8 were culture positive for Legionella pneumophila. One of three genotypes found in both whirlpool spas was identical to the isolates from 28 of 29 culture-positive patients. Persons who paused at the whirlpool spa in hall 3 were at increased risk for becoming ill. This study illustrates that whirlpool spas may be an important health hazard if disinfection fails.

  15. Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients

    NARCIS (Netherlands)

    B.E. Smid; S.M. Rombach; J.M.F.G. Aerts; S. Kuiper; M. Mirzaian; H.S. Overkleeft; B.J.H.M. Poorthuis; C.E.M. Hollak; J.E.M. Groener; G.E. Linthorst

    2011-01-01

    ABSTRACT: BACKGROUND: Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, re

  16. Kinetic assay shows that increasing red cell volume could be a treatment for sickle cell disease

    Science.gov (United States)

    Li, Quan; Henry, Eric R.; Hofrichter, James; Smith, Jeffrey F.; Cellmer, Troy; Dunkelberger, Emily B.; Metaferia, Belhu B.; Jones-Straehle, Stacy; Boutom, Sarah; Christoph, Garrott W.; Wakefield, Terri H.; Link, Mary E.; Staton, Dwayne; Vass, Erica R.; Miller, Jeffery L.; Hsieh, Matthew M.; Tisdale, John F.; Eaton, William A.

    2017-01-01

    Although it has been known for more than 60 years that the cause of sickle cell disease is polymerization of a hemoglobin mutant, hydroxyurea is the only drug approved for treatment by the US Food and Drug Administration. This drug, however, is only partially successful, and the discovery of additional drugs that inhibit fiber formation has been hampered by the lack of a sensitive and quantitative cellular assay. Here, we describe such a method in a 96-well plate format that is based on laser-induced polymerization in sickle trait cells and robust, automated image analysis to detect the precise time at which fibers distort (“sickle”) the cells. With this kinetic method, we show that small increases in cell volume to reduce the hemoglobin concentration can result in therapeutic increases in the delay time prior to fiber formation. We also show that, of the two drugs (AES103 and GBT440) in clinical trials that inhibit polymerization by increasing oxygen affinity, one of them (GBT440) also inhibits sickling in the absence of oxygen by two additional mechanisms. PMID:28096387

  17. Cybrid models of Parkinson's disease show variable mitochondrial biogenesis and genotype-respiration relationships.

    Science.gov (United States)

    Keeney, Paula M; Dunham, Lisa D; Quigley, Caitlin K; Morton, Stephanie L; Bergquist, Kristen E; Bennett, James P

    2009-12-01

    Sporadic Parkinson's disease (sPD) is a nervous system-wide disease that presents with a bradykinetic movement disorder and frequently progresses to include depression and cognitive impairment. Cybrid models of sPD are based on expression of sPD platelet mitochondrial DNA (mtDNA) in neural cells and demonstrate some similarities to sPD brains. In sPD and CTL cybrids we characterized aspects of mitochondrial biogenesis, mtDNA genomics, composition of the respirasome and the relationships among isolated mitochondrial and intact cell respiration. Cybrid mtDNA levels varied and correlated with expression of PGC-1 alpha, a transcriptional co-activator regulator of mitochondrial biogenesis. Levels of mtDNA heteroplasmic mutations were asymmetrically distributed across the mitochondrial genome; numbers of heteroplasmies were more evenly distributed. Neither levels nor numbers of heteroplasmies distinguished sPD from CTL. sPD cybrid mitochondrial ETC subunit protein levels were not altered. Isolated mitochondrial complex I respiration rates showed limited correlation with whole cell complex I respiration rates in both sPD and CTL cybrids. Intact cell respiration during the normoxic-anoxic transition yielded K(m) values for oxygen that directly related to respiration rates in CTL but not in sPD cell lines. Both sPD and CTL cybrid cells are substantially heterogeneous in mitochondrial genomic and physiologic properties. Our results suggest that mtDNA depletion may occur in sPD neurons and could reflect impairment of mitochondrial biogenesis. Cybrids remain a valuable model for some aspects of sPD but their heterogeneity mitigates against a simple designation of sPD phenotype in this cell model.

  18. Neurological aspects of Gaucher and Fabry disease

    NARCIS (Netherlands)

    Biegstraaten, M.

    2011-01-01

    Momenteel zijn er meer dan vijftig stapelingsziekten bekend, waarvan de ernst zeer uiteen loopt. Sommige aandoeningen worden gekenmerkt door ernstige mentale retardatie, neurologische problemen en overlijden op kinderleeftijd; andere vormen hebben nauwelijks een lagere levensverwachting. Ook in de l

  19. Distributed torsion sensor based on cascaded coaxial cable Fabry-Perot interferometers

    Science.gov (United States)

    Cheng, Baokai; Zhu, Wenge; Hua, Liwei; Liu, Jie; Li, Yurong; Nygaard, Runar; Xiao, Hai

    2016-07-01

    Cascaded coaxial cable Fabry-Perot interferometers (FPI) are studied and demonstrated for distributed torsion measurement. Multiple weak reflectors are implemented on a coaxial cable so that any two consecutive reflectors can form a Fabry-Perot cavity. By fixing the cable sensor in a helical form on a shaft, the distributed torsion of the shaft can be measured by the cascaded Fabry-Perot cavities. A test on a single section shows that the sensor has a linear response with a sensitivity of 1.834 MHz (rad/m)-1 in the range of twisted rate from 0 to 8.726 rad m-1. The distributed torsion sensing capability is useful in drilling process monitoring, structure health monitoring and machine failure detection.

  20. Improved spectral characteristics of 980 nm broad area slotted Fabry-Perot diode lasers

    Institute of Scientific and Technical Information of China (English)

    Gao Zhuo; Wang Jun; Xiong Cong; Liu Yuanyuan; Liu Suping; Ma Xiaoyu

    2012-01-01

    A novel broad area slotted Fabry-Perot diode laser is designed and fabricated.Using a new semianalytical method,we introduce effective refractive index perturbations in the form of etched slot features into a conventional 980 nm broad area Fabry-Perot cavity,and the spectral characteristics of the device are expected to be noticeably improved.A low density of slot features is formed by using standard optical lithography and inductively coupled plasma dry etching.The experimental results show that the full spectral width at half-maximum is less than 0.4 nm,meanwhile,the thermal shift of the emission spectrum is decreased from 0.26 to 0.07 nm/℃ over a temperature range of 10 to 60 ℃.The improved spectral characteristics of the device are proved to be attributed to such slotted Fabry-Perot laser structures.

  1. Review: Research progress on Fabry-Perot resonator antenna

    Institute of Scientific and Technical Information of China (English)

    Zhen-guo LIU; Zhi-chen GE; Xi-yuan CHEN

    2009-01-01

    The Fabry-Perot resonator (FPR) antenna has found wide applications in microwave and millimeter waves and recently attracted considerable interest, in this paper, a summary of planar and cylindrical structures, analytic models and research development is presented, and a comparison between these structures and analytic models is made, showing that such analytic models as the FP cavity mode, electromagnetic band gap (EBG) defect mode, transmission line mode, and leaky-wave mode are consistent when applied to analyze this type of resonator antenna. Some interesting topics under recent research, including dual or multi-band, improvement of gain bandwidth, low profile and beam control, are surveyed.

  2. Airway wall thickening and emphysema show independent familial aggregation in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Patel, Bipen D; Coxson, Harvey O; Pillai, Sreekumar G

    2008-01-01

    RATIONALE: It is unclear whether airway wall thickening and emphysema make independent contributions to airflow limitation in chronic obstructive pulmonary disease (COPD) and whether these phenotypes cluster within families. OBJECTIVES: To determine whether airway wall thickening and emphysema (1...

  3. High-temperature fiber-optic Fabry-Perot interferometric sensors

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Wenhui; Jiang, Yi; Gao, Ran, E-mail: bitjy@bit.edu.cn [School of Optoelectronics, Beijing Institute of Technology, Beijing 100081 (China); Liu, Yuewu [Key Laboratory for Mechanics in Fluid Solid Coupling Systems, Institute of Mechanics, Chinese Academy of Science, Beijing 100190 (China)

    2015-05-15

    A photonic crystal fiber (PCF) based high-temperature fiber-optic sensor is proposed and experimentally demonstrated. The sensor head is a Fabry-Perot cavity manufactured with a short section of endless single-mode photonic crystal fiber (ESM PCF). The interferometric spectrum of the Fabry-Perot interferometer is collected by a charge coupled device linear array based micro spectrometer. A high-resolution demodulation algorithm is used to interrogate the peak wavelengths. Experimental results show that the temperature range of 1200 °C and the temperature resolution of 1 °C are achieved.

  4. High-temperature fiber-optic Fabry-Perot interferometric sensors.

    Science.gov (United States)

    Ding, Wenhui; Jiang, Yi; Gao, Ran; Liu, Yuewu

    2015-05-01

    A photonic crystal fiber (PCF) based high-temperature fiber-optic sensor is proposed and experimentally demonstrated. The sensor head is a Fabry-Perot cavity manufactured with a short section of endless single-mode photonic crystal fiber (ESM PCF). The interferometric spectrum of the Fabry-Perot interferometer is collected by a charge coupled device linear array based micro spectrometer. A high-resolution demodulation algorithm is used to interrogate the peak wavelengths. Experimental results show that the temperature range of 1200 °C and the temperature resolution of 1 °C are achieved.

  5. Displacement-noise-free gravitational-wave detection with two Fabry-Perot cavities

    CERN Document Server

    Rakhubovsky, Andrey A

    2008-01-01

    We propose two detuned Fabry-Perot cavities, each pumped through both the mirrors, positioned in line as a toy model of the gravitational-wave (GW) detector free from displacement noise of the test masses. It is demonstrated that the noise of cavity mirrors can be completely excluded in a proper linear combination of the cavities output signals. This model is illustrated by a simplified round trip model (without Fabry-Perot cavities). We show that in low-frequency region the obtained displacement-noise-free response signal is stronger than the one of the interferometer recently proposed by S.Kawamura and Y.Chen.

  6. Patients with eating disorders showed no signs of coeliac disease before and after nutritional intervention.

    Science.gov (United States)

    Kaltsa, Maria; Garoufi, Anastasia; Tsitsika, Artemis; Tsirogianni, Alexandra; Papasteriades, Chryssa; Kossiva, Lydia

    2015-07-01

    This study assessed the presence of specific antibodies for coeliac disease in outpatients suffering from eating disorders before and after nutritional intervention. We also evaluated whether those patients should undergo regular screening for coeliac disease. The sample consisted of 154 patients with a mean age of 16.7 years - ranging from one to 19 years of age - suffering from eating disorders. Serology screening for coeliac disease and total immunoglobulin A (IgA) levels was evaluated in the 154 children before the nutritional intervention and in 104 patients after the intervention. The patients consumed an adequate amount of gluten in both phases. Postintervention evaluation revealed that 92 patients (88.5%) achieved a normal body weight, while the remaining 12 (11.5%) became obese. Postprandial abdominal discomfort and pain were resolved. The serology tests were negative in all patients, before and after intervention. None displayed IgA deficiency. To the best of our knowledge, this was the first prospective study where patients underwent a screening serology for coeliac disease before and after nutritional intervention. No indication of the coexistence of eating disorders and coeliac disease was documented, and the patients in our study were unlikely to require regular screening for coeliac disease. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  7. Ceruloplasmin gene-deficient mice with experimental autoimmune encephalomyelitis show attenuated early disease evolution.

    Science.gov (United States)

    Gresle, Melissa M; Schulz, Katrin; Jonas, Anna; Perreau, Victoria M; Cipriani, Tania; Baxter, Alan G; Miranda-Hernandez, Socorro; Field, Judith; Jokubaitis, Vilija G; Cherny, Robert; Volitakis, Irene; David, Samuel; Kilpatrick, Trevor J; Butzkueven, Helmut

    2014-06-01

    We conducted a microarray study to identify genes that are differentially regulated in the spinal cords of mice with the inflammatory disease experimental autoimmune encephalomyelitis (EAE) relative to healthy mice. In total 181 genes with at least a two-fold increase in expression were identified, and most of these genes were associated with immune function. Unexpectedly, ceruloplasmin (Cp), a ferroxidase that converts toxic ferrous iron to its nontoxic ferric form and also promotes the efflux of iron from astrocytes in the CNS, was shown to be highly upregulated (13.2-fold increase) in EAE spinal cord. Expression of Cp protein is known to be increased in several neurological conditions, but the role of Cp regulation in CNS autoimmune disease is not known. To investigate this, we induced EAE in Cp gene knockout, heterozygous, and wild-type mice. Cp knockout mice were found to have slower disease evolution than wild-type mice (EAE days 13-17; P = 0.05). Interestingly, Cp knockout mice also exhibited a significant increase in the number of astrocytes with reactive morphology in early EAE compared with wild-type mice at the same stage of disease. CNS iron levels were not increased with EAE in these mice. Based on these observations, we propose that an increase in Cp expression could contribute to tissue damage in early EAE. In addition, endogenous CP either directly or indirectly inhibits astrocyte reactivity during early disease, which could also worsen early disease evolution.

  8. Modulation of microrna in two genetically disparate chicken lines showing different necrotic enteritis disease susceptibility

    Science.gov (United States)

    Necrotic enteritis (NE) is a re-emerging disease as a result of an increased restriction on the use of antibiotics in poultry. However, the molecular mechanisms underlying the pathology of NE are unclear. Therefore, we carried out small RNA transcriptome analysis in an experimentally induced NE m...

  9. Left Ventricular Geometry and Blood Pressure as Predictors of Adverse Progression of Fabry Cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Johannes Krämer

    Full Text Available In spite of several research studies help to describe the heart in Fabry disease (FD, the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated.In 74 FD patients (mean age 36±12 years; 45 females the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE. Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT. After 51±24 months, a follow-up examination was performed.Systolic blood pressure (SBP was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001 indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg and also the highest SI (0.32±0.05 was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04. Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05.LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy.

  10. Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?

    Science.gov (United States)

    Lepesheva, Galina I.

    2013-01-01

    Introduction Endemic in Latin America, Chagas disease is now becoming a serious global health problem, and yet has no financial viability for the pharmaceutical industry and remains incurable. In 2012, two antimycotic drugs inhibitors of fungal sterol 14α-demethylase (CYP51) – posaconazole and ravuconazole – entered clinical trials. Availability of the X-ray structure of the orthologous enzyme from the causative agent of the disease, protozoan parasite Trypanosoma cruzi, determined in complexes with posaconazole as well as with several experimental protozoa-specific CYP51 inhibitors opens an excellent opportunity to improve the situation. Areas covered This article summarizes the information available in PubMed and Google on the outcomes of treatment of the chronic Chagas disease. It also outlines the major features of the T. cruzi CYP51 structure and the possible structure-based strategies for rational design of novel T. cruzi specific drugs. Expert opinion There is no doubt that screenings for alternative drug-like molecules as well as mining the T. cruzi genome for novel drug targets are of great value and might eventually lead to groundbreaking discoveries. However, all newly identified molecules must proceed through the long, expensive and low-yielding drug optimization process, and all novel potential drug targets must be validated in terms of their essentiality and druggability. CYP51 is already a well-validated and highly successful target for clinical and agricultural antifungals. With minimal investments into the final stages of their development/trials, T. cruzi-specific CYP51 inhibitors can provide an immediate treatment for Chagas disease, either on their own or in combination with the currently available drugs. PMID:24079515

  11. Autoimmune Hepatitis and Celiac Disease: Case Report Showing an Entero-Hepatic Link

    Directory of Open Access Journals (Sweden)

    Francesco Tovoli

    2010-10-01

    Full Text Available Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management.

  12. Fourier Transform Fabry-Perot Interferometer

    Science.gov (United States)

    Snell, Hilary E.; Hays, Paul B.

    1992-01-01

    We are developing a compact, rugged, high-resolution remote sensing instrument with wide spectral scanning capabilities. This relatively new type of instrument, which we have chosen to call the Fourier-Transform Fabry-Perot Interferometer (FT-FPI), is accomplished by mechanically scanning the etalon plates of a Fabry-Perot interferometer (FPI) through a large optical distance while examining the concomitant signal with a Fourier-transform analysis technique similar to that employed by the Michelson interferometer. The FT-FPI will be used initially as a ground-based instrument to study near-infrared atmospheric absorption lines of trace gases using the techniques of solar absorption spectroscopy. Future plans include modifications to allow for measurements of trace gases in the stratosphere using spectral lines at terahertz frequencies.

  13. Fiber-coupled short Fabry-Perot resonators

    Energy Technology Data Exchange (ETDEWEB)

    Stone, J.; Marcuse, D. (AT and T Bell Labs., Holmdel, NJ (USA))

    1989-05-01

    Fabry-Perot resonators intended as filters in wavelength-multiplexed optical communications systems may have to be very short (on the order of 10 {mu}m) in order to increase their free spectral range. Short, yet tunable cavities can be designed as air gaps between two fibers placed in close proximity with highly reflecting mirrors deposited on their ends. However, an air-gap resonator with plane mirrors between closely spaced fiber ends may yield low throughout because of the poor match between the modes of typical single-mode fibers and the resonant mode in the air-gap cavity. The throughput can be improved by confining the resonant mode by means of a hollow dielectric tube placed inside the resonator. This paper compares short fiber-coupled Fabry-Parot resonators with and without an inserted hollow dielectric waveguide and derives expressions for their transmission losses. The authors show that the throughput of both types of resonator can be improved significantly by using a special fiber with large mode size to couple to the resonator. The special fiber is then spliced to a conventional single-mode fiber. They conclude that the resonator with an inserted hollow dielectric waveguide offers increased throughput for resonators with high finesse.

  14. Transforming Fabry-Pérot resonances into a Tamm mode

    Science.gov (United States)

    Durach, Maxim; Rusina, Anastasia

    2012-12-01

    We propose an optical structure composed of two metal nanolayers enclosing a distributed Bragg reflector (DBR) mirror. The structure is an open photonic system whose bound modes are coupled to external radiation. We apply the special theoretical treatment based on inversion symmetry of the structure to classify its resonances. We show that the structure supports resonances transitional between Fabry-Pérot modes and Tamm plasmons. When the dielectric contrast of the DBR is removed these modes are a pair of conventional Fabry-Pérot resonances. They spectrally merge into a Tamm mode at high contrast. The optical properties of the structure in the frequency range of the DBR stop band, including highly beneficial 50% transmittivity through thick structures with sub-skin-depth metal films, are determined by the hybrid quasinormal modes of the open nonconservative structure under consideration. The results can find a broad range of applications in photonics and optoelectronics, including the possibility of coherent control over optical fields in the class of structures similar to the one proposed here.

  15. An Archetype Semi-Ring Fabry-Perot (SRFP) Resonator

    Science.gov (United States)

    Taghavi-Larigani, Shervin; VanZyl, Jakob

    2009-01-01

    We introduce and demonstrate the generation of a novel resonator, termed Semi-Ring Fabry-Perot (SRFP), that exhibits unique features, such as, its use of one plane mirror, allowing the SRFP to be easily fabricated as a symmetrical device. In addition to its unique features, it exhibits advantages of ring and Fabry-Perot resonators: 1) compared to a ring resonator that only allows a transmitted intensity, the Semi-Ring Fabry-Perot (SRFP) supports standing waves, allowing both a reflected and transmitted intensity; 2) the reflected light spectrum of the SRFP resonator is much narrower than similar Fabry-Perot, implying higher finesse.

  16. A Case of Porokeratosis Showing Different Clinical Patterns of the Disease with Anogenital Involvement

    Directory of Open Access Journals (Sweden)

    Özlem Karabudak

    2008-10-01

    Full Text Available Porokeratosis (PK is a group of cutaneous entities characterized by marginate scaling lesions, histologically showing a column of parakeratotic keratinocytes (cornoid lamella. Various forms are recognized such as porokeratosis of Mibelli (PM, linear porokeratosis, disseminated superficial actinic porokeratosis, punctate parakeratosis. PM should be treated because of the possibility of developing malignant epithelial tumors. We are presenting a 21 year old male patient suffering from PM on the back of the hands, foot, scrotum, oral mucosa and anal region. The histological biopsy specimens showed the characteristic features of porokeratosis. We destroyed the lesions by cryotherapy sessions. Here, we present a case of PM since it is rarely seen as multiple lesions with oral, anal and scrotal involvements altogether. (Turkderm 2008; 42: 97-9

  17. In vitro and in vivo models of Huntington's disease show alterations in the endocannabinoid system.

    Science.gov (United States)

    Bari, Monica; Battista, Natalia; Valenza, Marta; Mastrangelo, Nicolina; Malaponti, Marinella; Catanzaro, Giuseppina; Centonze, Diego; Finazzi-Agrò, Alessandro; Cattaneo, Elena; Maccarrone, Mauro

    2013-07-01

    In this study, we analyzed the components of the endocannabinoid system (ECS) in R6/2 mice, a widely used model of Huntington's disease (HD). We measured the endogenous content of N-arachidonoylethanolamine and 2-arachidonoylglycerol and the activity of their biosynthetic enzymes (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D and diacylglycerol lipase, respectively) and hydrolytic enzymes [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively] and of their target receptors (type 1 cannabinoid receptor, type 2 cannabinoid receptor, and transient receptor potential vanilloid-1) in the brains of wild-type and R6/2 mice of different ages, as well as in the striatum and cortex of 12-week-old animals. In addition, we measured FAAH activity in lymphocytes of R6/2 mice. In the whole brains of 12-week-old R6/2 mice, we found reductions in N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D activity, diacylglycerol lipase activity and cannabinoid receptor binding, mostly associated with changes in the striatum but not in the cortex, as well as an increase in 2-arachidonoylglycerol content as compared with wild-type littermates, without any other change in ECS elements. Then, our analysis was extended to HD43 cells, an inducible cellular model of HD derived from rat ST14A cells. In both induced and noninduced conditions, we demonstrated a fully functional ECS. Overall, our data suggest that the ECS is differently affected in mouse and human HD, and that HD43 cells are suitable for high-throughput screening of FAAH-oriented drugs affecting HD progression.

  18. Surveying quality of life in patients with Fabry disease by the SF-36 scale%SF-36量表评估Fabry病患者生活质量的研究

    Institute of Scientific and Technical Information of China (English)

    欧阳彦; 潘晓霞; 王朝晖; 沈平雁; 王伟铭; 任红; 张文; 陈楠

    2014-01-01

    Objective To test the availability of the SF-36 scale for the Chinese patient with Fabry disease (FD),the quality of life(QOL) and its probable influence factors were analyzed.Methods The data were obtained from 50 healthy volunteers and 57 patients with FD enrolled in nephrology department of Ruijin hospital from Jan,2003 to Jan,2013.The SF-36 scale was used to evaluate the QOL of patients and to compare the difference between the patients and controls.Furthermore,the influencing factors were estimated by multiple linear regressions.Results Between the patients and controls,the differences of 8 dimensionalitiy's scores had statistical significance,which claimed that the reaction was sensitive.Especially,in the patient group,the Pearson correlation coefficient among each domain of the SF-36 was lower than its Cronbach's α coefficient (0.934),which indicated good internal consistency reliability.The two common factors were much the same to the theory assume,which illustrated the construct validity was available.Even the acceptability of the patient' group at 100% proved the scale was appropriate for patients with FD.In addition,in rolephysical (RP) and bodily pain (BP),the scores of the male patients were less than the females (P <0.01),declared that the QOL of the males was inferior to the females.In the physical function (PF) and the mental health (MH),the scores of the patients with angiokeratoma were less than the group without it,so the patients who had evident clinical symptoms more likely contributed to depression.Using multiple linear regression,age,gender and clinical types were chosen into regression equation by stepwise regression,and the main potential predictor was age.Conclusions The SF-36 scale applies to evaluate the QOL of patients with FD.It is critical to concern and manage the QOL of FD patients,especially in their mental health aspect.%目的 调查中国Fabry病患者生存质量(quality of life,QOL),分析其可能的影响因

  19. Lectin staining shows no evidence of involvement of glycocalyx/mucous layer carbohydrate structures in development of celiac disease

    DEFF Research Database (Denmark)

    Toft-Hansen, Henrik; Nielsen, Christian; Biagini, Matteo

    2013-01-01

    The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD) by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases...... with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD) and type 1 diabetes (T1D); 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls). Patients with both CD and T1D...... showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3)-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates....

  20. Millimeter-long fiber Fabry-Perot cavities.

    Science.gov (United States)

    Ott, Konstantin; Garcia, Sebastien; Kohlhaas, Ralf; Schüppert, Klemens; Rosenbusch, Peter; Long, Romain; Reichel, Jakob

    2016-05-01

    We demonstrate fiber Fabry-Perot (FFP) cavities with concave mirrors that can be operated at cavity lengths as large as 1.5 mm without significant deterioration of the finesse. This is achieved by using a laser dot machining technique to shape spherical mirrors with ultralow roughness and employing single-mode fibers with large mode area for good mode matching to the cavity. Additionally, in contrast to previous FFPs, these cavities can be used over an octave-spanning frequency range with adequate coatings. We also show directly that shape deviations caused by the fiber's index profile lead to a finesse decrease as observed in earlier attempts to build long FFP cavities, and show a way to overcome this problem.

  1. Millimeter-long Fiber Fabry-Perot cavities

    CERN Document Server

    Ott, Konstantin; Kohlhaas, Ralf; Schüppert, Klemens; Rosenbusch, Peter; Long, Romain; Reichel, Jakob

    2016-01-01

    We demonstrate fiber Fabry-Perot (FFP) cavities with concave mirrors that can be operated at cavity lengths as large as 1.5mm without significant deterioration of the finesse. This is achieved by using a laser dot machining technique to shape spherical mirrors with ultralow roughness and employing single-mode fibers with large mode area for good mode matching to the cavity. Additionally, in contrast to previous FFPs, these cavities can be used over an octave-spanning frequency range with adequate coatings. We also show directly that shape deviations caused by the fiber's index profile lead to a finesse decrease as observed in earlier attempts to build long FFP cavities, and show a way to overcome this problem.

  2. A high resolution scanning fabry-perot for OSIRIS

    Directory of Open Access Journals (Sweden)

    A. Bernal

    2007-01-01

    Full Text Available Following the directives of the workshop on the interferometric mode of OSIRIS, the Mexican team has received support to ac- quire a scanning Fabry-Perot interferometer for OSIRIS. In this presentation we will try to define which Fabry-Perot will be selected as well as which filters need to be acquired. We will also discuss the acquisition software

  3. Immunohistochemical diagnosis of Fabry nephropathy and localisation of globotriaosylceramide deposits in paraffin-embedded kidney tissue sections.

    Science.gov (United States)

    Valbuena, Carmen; Leitão, Dina; Carneiro, Fátima; Oliveira, João Paulo

    2012-02-01

    Fabry disease (FD) is a rare X-linked lysosomal storage disorder of glycosphingolipids, mostly globotriaosylceramide (Gb3). Proteinuric chronic kidney disease develops frequently, and recognition of Fabry nephropathy on a kidney biopsy may be the first clue to the underlying diagnosis. Since the accumulated glycosphingolipids are largely extracted by the paraffin-embedding procedure, the most characteristic feature of Fabry nephropathy on routine light microscopy (LM) is nonspecific cell vacuolization. To test whether residual Gb3 in kidney tissue might be exploited for the specific diagnosis of Fabry nephropathy, paraffin-embedded kidney biopsies of nine FD patients (one boy, four men, four women) and of a female carrier of a mild genetic mutation, with no evidence of Fabry nephropathy, were immunostained with an anti-Gb3 antibody. The adult biopsies were additionally co-stained with a lysosomal marker (anti-lysosomal-associated membrane protein 2 (anti-LAMP2) antibody). The distribution of Gb3 deposits was scored per cell type and compared to the histological scorings of glycosphingolipid inclusions on semi-thin sections. FD patients had residual Gb3 in all types of glomerular, tubular, interstitial and vascular kidney cells. The highest expression of LAMP2 was seen in tubular cells, but there were no meaningful associations between LAMP2 expression and prevalence of Gb3 deposits on different kidney cell types. The histological scorings of glycosphingolipid inclusions were relatively higher than the corresponding immunohistochemical scorings of Gb3 deposits. In the mildly affected female, Gb3 expression was limited to tubular cells, a pattern similar to controls. Gb3 immunostaining allows the specific diagnosis of Fabry nephropathy even in kidney biopsies routinely processed for LM.

  4. Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement

    DEFF Research Database (Denmark)

    Fledelius, Hans C.; Sandfeld, Lisbeth; Rasmussen, Åse Krogh

    2015-01-01

    PURPOSE: Enzyme replacement therapy (ERT) was offered from year 2001 to patients with Fabry disease. The ophthalmic experience was analysed, as part of a general 10-year status. METHODS: A retrospective observational series comprising 39 patients (25 females, 14 males) closely followed by the end...

  5. Cervical flexion myelopathy in a patient showing apparent long tract signs: a severe form of Hirayama disease.

    Science.gov (United States)

    Sakai, Kenji; Ono, Kenjiro; Okamoto, Yoshiyuki; Murakami, Hideki; Yamada, Masahito

    2011-05-01

    We describe an 18-year-old male with cervical flexion myelopathy with Hirayama disease-like features who showed apparent long tract signs. He first experienced insidious-onset hand muscle weakness and atrophy at the age of 15. Subsequently, he developed sensory disturbance in his lower limb. Neurological examination revealed atrophy and weakness in the right hand and forearm, pyramidal signs in the right lower extremity, and disturbance of superficial sensation in the lower left half of the body. Cervical magnetic resonance images and computed tomographic myelography revealed anterior displacement with compression of the cervical cord in flexion that was more apparent in the right side. The right side of the cervical cord showed severe atrophy. The mechanisms of myelopathy in our patient appeared to be same as that of "tight dural canal in flexion," which has been reported to be the mechanism of juvenile muscular atrophy of the unilateral upper extremity (Hirayama disease). Patients with Hirayama disease generally show minimal sensory signs and no pyramidal signs. An autopsy case of Hirayama disease revealed confined necrosis of the cervical anterior horn without obvious changes in the white matter. Our patient's disease progression suggests that cervical flexion myelopathy patients with severe cervical cord compression in flexion may develop extensive cervical cord injury beyond the anterior horn.

  6. An economic Fabry-Perot wavelength reference

    Science.gov (United States)

    Fżrész, Gábor; Glenday, Alex; Latham, Christian

    2014-07-01

    Precision radial velocity (PRV) measurements are key in studying exoplanets, and so are wavelength calibrators in PRV instruments. ThAr lamps offer an affordable but somewhat limited solution for the visible passband. Laser frequency combs are ideal calibrators, except the (still) narrow wavelength coverage and large price tag. White light Fabry-Perot (FP) calibrators offer frequency-comb like properties in a more affordable and less complicated package1. Using a commercial solid FP etalon and off-the shelf components we have constructed an economic FP calibrator suitable for observatories on a smaller budget.

  7. Fiber Fabry-Perot interferometer for curvature sensing

    Science.gov (United States)

    Monteiro, Catarina S.; Ferreira, Marta S.; Silva, Susana O.; Kobelke, Jens; Schuster, Kay; Bierlich, Jörg; Frazão, Orlando

    2016-07-01

    A curvature sensor based on an Fabry-Perot (FP) interferometer was proposed. A capillary silica tube was fusion spliced between two single mode fibers, producing an FP cavity. Two FP sensors with different cavity lengths were developed and subjected to curvature and temperature. The FP sensor with longer cavity showed three distinct operating regions for the curvature measurement. Namely, a linear response was shown for an intermediate curvature radius range, presenting a maximum sensitivity of 68.52 pm/m-1. When subjected to temperature, the sensing head produced a similar response for different curvature radii, with a sensitivity varying from 0.84 pm/°C to 0.89 pm/°C, which resulted in a small cross-sensitivity to temperature when the FP sensor was subjected to curvature. The FP cavity with shorter length presented low sensitivity to curvature.

  8. Fiber Fabry-Perot interferometer for curvature sensing

    Science.gov (United States)

    Monteiro, Catarina S.; Ferreira, Marta S.; Silva, Susana O.; Kobelke, Jens; Schuster, Kay; Bierlich, Jörg; Frazão, Orlando

    2016-12-01

    A curvature sensor based on an Fabry-Perot (FP) interferometer was proposed. A capillary silica tube was fusion spliced between two single mode fibers, producing an FP cavity. Two FP sensors with different cavity lengths were developed and subjected to curvature and temperature. The FP sensor with longer cavity showed three distinct operating regions for the curvature measurement. Namely, a linear response was shown for an intermediate curvature radius range, presenting a maximum sensitivity of 68.52 pm/m-1. When subjected to temperature, the sensing head produced a similar response for different curvature radii, with a sensitivity varying from 0.84 pm/°C to 0.89 pm/°C, which resulted in a small cross-sensitivity to temperature when the FP sensor was subjected to curvature. The FP cavity with shorter length presented low sensitivity to curvature.

  9. Silicon-based on-chip electrically tunable sidewall Bragg grating Fabry-Perot filter.

    Science.gov (United States)

    Zhang, Weifeng; Ehteshami, Nasrin; Liu, Weilin; Yao, Jianping

    2015-07-01

    We report the design, fabrication, and testing of a silicon-based on-chip electrically tunable sidewall Bragg grating Fabry-Perot filter. Spectral measurement shows that the filter has a narrow notch in reflection of approximately 46 pm, a Q-factor of 33,500, and an extinction ratio of 16.4 dB. DC measurement shows that the average central wavelength shift rates with forward and reverse bias are -1.15  nm/V and 4.2  pm/V, respectively. Due to strong light confinement in the Fabry-Perot cavity, the electro-optic frequency response shows that the filter has a 3-dB modulation bandwidth of ∼5.6  GHz. The performance of using the filter to perform modulation of a 3.5  Gb/s2(7)-1 nonreturn-to-zero pseudorandom binary sequence is evaluated.

  10. Dynamic model and stability analysis of a laser using a nonlinear Fabry-Perot etalon as a cavity mirror

    Energy Technology Data Exchange (ETDEWEB)

    Li, S.; Pons, R. (Autonoma de Barcelona (Spain). Dept. of Fisica); Zhang, Y. (Chongqing Inst. of Posts and Telecommunications, Sichuan (China). Telecommunications Engineering Dept.)

    1994-08-01

    In this paper, the authors study a laser using a nonlinear Fabry-Perot etalon as a cavity mirror. First, using the semiclassical laser theory and the differential equation for the lossy nonlinear Fabry-Perot etalon, they develop dynamic equations describing this system for single-mode operation. In this model, the frequency-pulling effect, a finite response time of the nonlinear medium, and a finite-cavity round-trip time of the Fabry-Perot etalon are included. Second, based on this model, they analyze the stability of this laser and give some numerical results. The results show that (1) this system can exist in the stable state and in the unstable state; (2) there are not only saddle-node bifurcations but also Hopf bifurcations; (3) the detuning parameter will effect the characteristics of the bistability and the number and distribution of Hopf bifurcation points.

  11. An arc tangent function demodulation method of fiber-optic Fabry-Perot high-temperature pressure sensor

    Science.gov (United States)

    Ren, Qianyu; Li, Junhong; Hong, Yingping; Jia, Pinggang; Xiong, Jijun

    2017-09-01

    A new demodulation algorithm of the fiber-optic Fabry-Perot cavity length based on the phase generated carrier (PGC) is proposed in this paper, which can be applied in the high-temperature pressure sensor. This new algorithm based on arc tangent function outputs two orthogonal signals by utilizing an optical system, which is designed based on the field-programmable gate array (FPGA) to overcome the range limit of the original PGC arc tangent function demodulation algorithm. The simulation and analysis are also carried on. According to the analysis of demodulation speed and precision, the simulation of different numbers of sampling points, and measurement results of the pressure sensor, the arc tangent function demodulation method has good demodulation results: 1 MHz processing speed of single data and less than 1% error showing practical feasibility in the fiber-optic Fabry-Perot cavity length demodulation of the Fabry-Perot high-temperature pressure sensor.

  12. Protocol and methodology of the Stroke in Young Fabry Patients (sifap1) study: a prospective multicenter European study of 5,024 young stroke patients aged 18-55 years.

    LENUS (Irish Health Repository)

    Rolfs, Arndt

    2011-01-01

    Stroke in the young has not been thoroughly investigated with most previous studies based on a small number of patients from single centers. Furthermore, recent reports indicate that Fabry disease may be a significant cause for young stroke. The primary aim of our study was to determine the prevalence of Fabry disease in young stroke patients, while the secondary aim was to describe patterns of stroke in young patients.

  13. Cervical flexion myelopathy in a patient showing apparent long tract signs: A severe form of Hirayama disease

    OpenAIRE

    Sakai, Kenji; Ono, Kenjiro; Okamoto, Yoshiyuki; MURAKAMI, Hideki; Yamada, Masahito

    2011-01-01

    We describe an 18-year-old male with cervical flexion myelopathy with Hirayama disease-like features who showed apparent long tract signs. He first experienced insidious-onset hand muscle weakness and atrophy at the age of 15. Subsequently, he developed sensory disturbance in his lower limb. Neurological examination revealed atrophy and weakness in the right hand and forearm, pyramidal signs in the right lower extremity, and disturbance of superficial sensation in the lower left half of the b...

  14. Interleukin-18 deteriorates Fabry cardiomyopathy and contributes to the development of left ventricular hypertrophy in Fabry patients with GLA IVS4+919 G>A mutation

    Science.gov (United States)

    Huang, Wei-Lin; Chou, Shih-Jie; Chang, Wei-Chao; Chang, Yuh-Lih; Leu, Hsin-Bang; Chen, Kuan-Hsuan; Wang, Kang-Ling; Lai, Ying-Hsiu; Liu, Yung-Yang; Lu, Kai-Hsi; Li, Hsin-Yang; Sung, Yen-Jen; Jong, Yuh-Jyh; Chen, Yann-Jang; Chen, Chung-Hsuan; Yu, Wen-Chung

    2016-01-01

    Rationale A high incidence of GLA IVS4+919 G>A mutation in patients with Fabry disease of the later-onset cardiac phenotype, has been reported in Taiwan. However, suitable biomarkers or potential therapeutic surrogates for Fabry cardiomyopathy (FC) in such patients under enzyme replacement treatment (ERT) remain unknown. Objective Using FC patients carrying IVS4+919 G>A mutation, we constructed an induced pluripotent stem cell (iPSC)-based disease model to investigate the pathogenetic biomarkers and potential therapeutic targets in ERT-treated FC. Results and methods The iPSC-differentiated cardiomyocytes derived from FC-patients (FC-iPSC-CMs) carried IVS4+919 G>A mutation recapitulating FC characteristics, including low α-galactosidase A enzyme activity, cellular hypertrophy, and massive globotriaosylceramide accumulation. Microarray analysis revealed that interleukin-18 (IL-18), a pleiotropic cytokine involved in various myocardial diseases, was the most highly upregulated marker in FC-iPSC-CMs. Meanwhile, IL-18 levels were found to be significantly elevated in the culture media of FC-iPSC-CMs and patients’ sera. Notably, the serum IL-18 levels were highly paralleled with the progression of left ventricular hypertrophy in Fabry patients receiving ERT. Finally, using FC-iPSC-CMs as in vitro FC model, neutralization of IL-18 with specific antibodies combined with ERT synergistically reduced the secretion of IL-18 and the progression of cardiomyocyte hypertrophy in FC-iPSC-CMs. Conclusion Our data demonstrated that cardiac IL-18 and circulating IL-18 are involved in the pathogenesis of FC and LVH. IL-18 may be a novel marker for evaluating ERT efficacy, and targeting IL-18 might be a potential adjunctive therapy combined with ERT for the treatment of advanced cardiomyopathy in FC patients with IVS4+919 G>A mutation. PMID:27888626

  15. Graves' Disease Patients with Persistent Hyperthyroidism and Diffuse Lymphoplasmacytic Infiltration in the Thyroid Show No Histopathological Compatibility with IgG4-Related Disease.

    Directory of Open Access Journals (Sweden)

    Eijun Nishihara

    Full Text Available IgG4-related disease is a novel disease entity characterized by diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells and fibrosis into multiple organs. There is still controversy over whether some thyroid diseases are actually IgG4-related disease. The objective of this study was to elucidate the clinicopathological features of Graves' disease with diffuse lymphoplasmacytic infiltration in the thyroid.Among 1,484 Graves' disease patients who underwent thyroidectomy, we examined their histopathological findings including the degree of lymphoplasmacytic and fibrotic infiltration and levels of IgG4-positive plasma cells in the thyroid. Their clinical pictures were defined by laboratory and ultrasonographic evaluation.A total of 11 patients (0.74% showed diffuse lymphoplasmacytic infiltration in the stroma of the thyroid gland. Meanwhile, other patients showed variable lymphoid infiltration ranging from absent to focally dense but no aggregation of plasma cells in the thyroid gland. Based on the diagnostic criteria of IgG4-related disease, 5 of the 11 subjects had specifically increased levels of IgG4-positive plasma cells in the thyroid. Fibrotic infiltration was present in only 1 patient developing hypothyroidism after anti-thyroid drug treatment for 4 years, but not in the other 10 patients with persistent hyperthyroidism. Obliterative phlebitis was not identified in any of the 11 subjects. Thyroid ultrasound examination showed 1 patient developing hypothyroidism who had diffuse hypoechogenicity, but the other hyperthyroid patients had a coarse echo texture.In our study, Graves' disease patients with persistent hyperthyroidism who had diffuse lymphoplasmacytic infiltration rich in IgG4-positive plasma cells in the thyroid showed no concomitant fibrosis or obliterative phlebitis.

  16. Sensing Properties of a Fabry-Perot Dielectric Structure and Dimer Nanoparticles

    Directory of Open Access Journals (Sweden)

    A. Polemi

    2012-01-01

    Full Text Available We investigate the use of a Fabry-Perot dielectric structure combined with differently shaped nanoparticles for Surface Enhanced Raman Scattering. In particular, we show how an ideal two-layer Fabry-Perot configuration enhances the local surface field of silver nanoparticles positioned on the surface of the structure. We develop the concept using disc dimers and then extend the discussion to bowtie nanoparticles. The structure is excited by a single emitter, which couples to the nanoparticles through the dielectric layers, producing a wide aperture field that can be used to excite multiple dimers. We show how an array of nanoparticles can be properly arranged in order to increase the total scattering signal generated from the structure. The layered geometry produces robust field properties in between nanoparticles, making the overall sensing characteristics less sensitive to the interparticle seperation distance and incident polarization.

  17. Reflectivity enhanced refractive index sensor based on a fiber-integrated Fabry-Perot microresonator.

    Science.gov (United States)

    Wieduwilt, T; Dellith, J; Talkenberg, F; Bartelt, H; Schmidt, M A

    2014-10-20

    We discuss a fiber-integrated refractive index sensor with strongly improved detection performance. The resonator has been implemented by means of focused-ion beam milling of a step index fiber and shows a sensitivity of about 1.15µm/RIU. Coating the resonator walls led to a strongly improved mirror reflectivity by a factor of about 26. Design rules for device optimization and a detailed mathematical analysis are discussed, revealing that the sensor operates as an optimized Fabry-Perot resonator. We also show that the performance of such kind of Fabry-Perot sensors is, in general, limited by the detection limit function - a quantity depending on the cavitiy's finesse and on the measurement capabilities used.

  18. Clinical and Biomarker Changes in Premanifest Huntington Disease Show Trial Feasibility: A Decade of the PREDICT-HD Study

    Science.gov (United States)

    Paulsen, Jane S.; Long, Jeffrey D.; Johnson, Hans J.; Aylward, Elizabeth H.; Ross, Christopher A.; Williams, Janet K.; Nance, Martha A.; Erwin, Cheryl J.; Westervelt, Holly J.; Harrington, Deborah L.; Bockholt, H. Jeremy; Zhang, Ying; McCusker, Elizabeth A.; Chiu, Edmond M.; Panegyres, Peter K.

    2014-01-01

    There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. Neurobiological predictors of Huntington’s disease is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest HD and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease 7–12 years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease. PMID:24795630

  19. Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: a decade of the PREDICT-HD study

    Directory of Open Access Journals (Sweden)

    Jane S Paulsen

    2014-04-01

    Full Text Available There is growing consensus that intervention and treatment of Huntington disease (HD should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. PREDICT-HD is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest Huntington disease and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease seven to twelve years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease.

  20. Lectin Staining Shows no Evidence of Involvement of Glycocalyx/Mucous Layer Carbohydrate Structures in Development of Celiac Disease

    Directory of Open Access Journals (Sweden)

    Henrik Toft-Hansen

    2013-11-01

    Full Text Available The presence of unique carbohydrate structures in the glycocalyx/mucous layer of the intestine may be involved in a susceptibility to celiac disease (CD by serving as attachment sites for bacteria. This host-microbiota interaction may influence the development of CD and possibly other diseases with autoimmune components. We examined duodenal biopsies from a total of 30 children, of which 10 had both celiac disease (CD and type 1 diabetes (T1D; 10 had CD alone; and 10 were suspected of having gastrointestinal disease, but had normal duodenal histology (non-CD controls. Patients with both CD and T1D were examined before and after remission following a gluten-free diet. We performed lectin histochemistry using peanut agglutinin (PNA and Ulex europaeus agglutinin (UEA staining for Gal-β(1,3-GalNAc and Fucα1-2Gal-R, respectively, of the glycocalyx/mucous layer. The staining was scored based on dissemination of stained structures on a scale from 0 to 3. Evaluation of the scores revealed no difference between biopsies obtained before and after remission in the group of children with both CD and T1D. A comparison of this pre-remission group with the children who had CD alone or the non-CD controls also showed no significant differences. Based on our material, we found no indication that the presence of Gal-β(1,3-GalNAc or Fucα1-2Gal-R is involved in the susceptibility to CD, or that the disease process affects the expression of these carbohydrates.

  1. MRI of the SI joints commonly shows non-inflammatory disease in patients clinically suspected of sacroiliitis

    Energy Technology Data Exchange (ETDEWEB)

    Jans, L., E-mail: lennartjans@hotmail.com [Department of Radiology and Medical Imaging, Ghent University Hospital, De Pintelaan 185, 9000 Gent (Belgium); Van Praet, L.; Elewaut, D.; Van den Bosch, F.; Carron, P. [Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, 9000 Gent (Belgium); Jaremko, J.L. [Department of Radiology, University of Alberta Hospital, 8440-112 Street, Edmonton T6G 2B7, Alberta (Canada); Behaeghe, M.; Denis, A.; Huysse, W.; Lambrecht, V.; Verstraete, K. [Department of Radiology and Medical Imaging, Ghent University Hospital, De Pintelaan 185, 9000 Gent (Belgium)

    2014-01-15

    Purpose: To determine the prevalence of clinically relevant non-inflammatory disease on MRI of the sacroiliac (SI) joints in patients suspected of sacroiliitis. To assess the added value of axial imaging of the pelvis in these patients. Methods: In a retrospective study of 691 patients undergoing MRI of the SI joints from January 2006 to December 2012 for inflammatory back pain the prevalence of sacroiliitis and non-inflammatory disease was recorded. Results: In 285 (41%) patients MRI did not show any abnormal findings. In 36% of patients MRI features of sacroiliitis were present. Spinal degenerative changes were the most common non-inflammatory finding in 305 patients (44.1%) and consisted of disc degeneration in 222 (32%) patients, facet joint arthrosis in 58 (8.4%) patients and disc herniation in 25 (3.6%) patients. Hip joint disease in 44 (6.4%) patients, lumbosacral transitional anomaly in 41 (5.9%) patients, SI joint degenerative changes in 25 (3.6%) patients and diffuse idiopathic skeletal hyperostosis in 24 (3.5%) patients were also common. Osteitis condensans ilii in 17 (2.5%) patients, tumour in 11 (1.6%) patients, fracture in 8 (1.2%) patients, infection in 4 (0.6%) patients and acute spondylolysis in 2 patients (0.3%) were less frequently seen. Conclusion: Our study shows that non-inflammatory disease is more common than true sacroiliitis on MRI of the SI joints in patients with inflammatory type back pain. Axial pulse sequences may demonstrate unexpected findings that remain undetected if only coronal images are obtained. Clinical relevance statement:, MRI of the SI joints may demonstrate conditions that clinically mimic sacroiliitis. Axial imaging of the pelvis may help detect these unexpected findings.

  2. Line-imaging Fabry-Perot interferometer

    Energy Technology Data Exchange (ETDEWEB)

    Mathews, A.R.; Warnes, R.H.; Hemsing, W.F.; Whittemore, G.R.

    1990-01-01

    A method for measuring the velocity history of a line element on a shock-loaded solid has been demonstrated. Light from single-frequency laser is focused through a cylindrical lens to a line on a moving target. The return Doppler-shifted image is passed through a Fabry-Perot interferometer. Because only specific combinations of incident light angle and frequency can pass through the interferometer the output is an incomplete image of the moving target appearing as a set of fringes. This image is focused onto an electronic streak camera and swept in time. The fringe pattern changes with time as the target surface moves, allowing determination of velocity for each point on the target that forms a fringe. Because the velocity can only be measured at the fringe positions, it is necessary to use an interpolating polynomial to obtain a continuous function of time and velocity along the sampled lien. 9 refs., 7 figs.

  3. The many facets of the Fabry-Perot

    CERN Document Server

    Sanchez-Soto, Luis L; Leuchs, Gerd

    2016-01-01

    We address the response, both in amplitude and intensity, of a Fabry-Perot from a variety of viewpoints. These complementary pictures conspire to achieve a comprehensive and consistent theory of the operation of this system.

  4. Photonic crystal fibre Brillouin laser based on Bragg grating Fabry-Perot cavity

    Institute of Scientific and Technical Information of China (English)

    Geng Dan; Yang Dong-Xiao; Shen Guo-Feng; Zhang Xian-Min

    2008-01-01

    A photonic crystal fibre Brillouin laser based on fibre Bragg grating Fabry-Perot cavity is presented. A highly nonlinear photonic crystal fibre 25 m in length is used as Brillouin gain medium and fibre Bragg grating Fabry-Perot cavity is chosen in order to enhance the laser conversion efficiency and suppress the higher-order Stokes waves. The laser reaches the threshold at input power of 35 mW, and the experimental laser conversion efficiency achieves 18% of the input power of 140 mW and does not show higher-order Stokes waves. A photonic crystal fibre BriUouin laser withshorter fibre length and lower threshold is experimentally realized.

  5. Design and Fabrication of Integrated Fabry-Perot Type Color Reflector for Reflective Displays.

    Science.gov (United States)

    Cho, Seong M; Cheon, Sang Hoon; Kim, Tae-Youb; Ah, Chil Seong; Song, Juhee; Ryu, Hojun; Chu, Hye Yong

    2016-05-01

    A Fabry-Perot type integrated color reflector, with red/blue/green colors as subpixels, was designed and fabricated with Si substrate. Ag films were used as reflective mirror layers, SiO2 films were used as Fabry-Perot cavity layers and W films were used as partially reflective layers for the cavity. To minimize the effects of the thickness variation of the oxide cavity layers, the structure of the color reflector was optimized, and the differential deposition scheme was devised and applied in the fabrication process. The integrated color reflector was successfully fabricated with the proposed fabrication scheme. The measured white reflectance was > 45% in the visible spectrum range and -49% at 550 nm wavelength. The fabricated reflector had moderate color gamut of 17% of the National Television System Committee (NTSC) standard and it showed very high white reflectivity. The fabricated color reflector is expected to be applicable to reflective displays.

  6. High Gain Slot Array with Fabry-Perot Cavity Feeding Circuit

    Directory of Open Access Journals (Sweden)

    Halim Boutayeb

    2016-01-01

    Full Text Available A new approach for designing slot arrays using a Fabry-Perot cavity for the feeding circuit is presented. The proposed array has simpler and smaller feeding circuit compared to conventional feeding networks that have multiple dividers or combiners. The dividers and combiners are usually sources of losses. In addition, the profile of the proposed array is not limited by the half-wavelength resonance condition that exists for Fabry-Perot resonator antennas based on partially reflecting surfaces. The operating frequency is not sensitive to the profile of the antenna. A small profile can be achieved without the utilization of an artificial magnetic conductor or a substrate with high dielectric constant. To validate the proposed approach, full-wave numerical results are presented at 5.8 GHz showing good impedance matching, a high gain of about 22 dB, and an efficiency of 76%.

  7. Epididymal Cystadenomas in von Hippel-Lindau Disease Showing Increased Activity on 68Ga DOTATATE PET/CT.

    Science.gov (United States)

    Papadakis, Georgios Z; Millo, Corina; Sadowski, Samira M; Bagci, Ulas; Patronas, Nicholas J

    2016-10-01

    von Hippel-Lindau (VHL) disease is a familial cancer syndrome characterized by the development of a variety of malignant and benign tumors, including epididymal cystadenomas. We report a case of a VHL patient with bilateral epididymal cystadenomas who was evaluated with Ga DOTATATE PET/CT, showing intensely increased activity (SUVmax, 21.6) associated with the epididymal cystadenomas, indicating cell-surface overexpression of somatostatin receptors. The presented case supports the usefulness of somatostatin receptor imaging using Ga DOTA-conjugated peptides for detection and follow-up of VHL manifestations, as well as surveillance of asymptomatic gene carriers.

  8. Newcastle Disease Viruses Causing Recent Outbreaks Worldwide Show Unexpectedly High Genetic Similarity to Historical Virulent Isolates from the 1940s.

    Science.gov (United States)

    Dimitrov, Kiril M; Lee, Dong-Hun; Williams-Coplin, Dawn; Olivier, Timothy L; Miller, Patti J; Afonso, Claudio L

    2016-05-01

    Virulent strains of Newcastle disease virus (NDV) cause Newcastle disease (ND), a devastating disease of poultry and wild birds. Phylogenetic analyses clearly distinguish historical isolates (obtained prior to 1960) from currently circulating viruses of class II genotypes V, VI, VII, and XII through XVIII. Here, partial and complete genomic sequences of recent virulent isolates of genotypes II and IX from China, Egypt, and India were found to be nearly identical to those of historical viruses isolated in the 1940s. Phylogenetic analysis, nucleotide distances, and rates of change demonstrate that these recent isolates have not evolved significantly from the most closely related ancestors from the 1940s. The low rates of change for these virulent viruses (7.05 × 10(-5) and 2.05 × 10(-5) per year, respectively) and the minimal genetic distances existing between these and historical viruses (0.3 to 1.2%) of the same genotypes indicate an unnatural origin. As with any other RNA virus, Newcastle disease virus is expected to evolve naturally; thus, these findings suggest that some recent field isolates should be excluded from evolutionary studies. Furthermore, phylogenetic analyses show that these recent virulent isolates are more closely related to virulent strains isolated during the 1940s, which have been and continue to be used in laboratory and experimental challenge studies. Since the preservation of viable viruses in the environment for over 6 decades is highly unlikely, it is possible that the source of some of the recent virulent viruses isolated from poultry and wild birds might be laboratory viruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  9. Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

    Directory of Open Access Journals (Sweden)

    McGhee Timothy

    2009-02-01

    Full Text Available Abstract Background While standard reductionist approaches have provided some insights into specific gene polymorphisms and molecular pathways involved in disease pathogenesis, our understanding of complex traits such as atherosclerosis or type 2 diabetes remains incomplete. Gene expression profiling provides an unprecedented opportunity to understand complex human diseases by providing a global view of the multiple interactions across the genome that are likely to contribute to disease pathogenesis. Thus, the goal of gene expression profiling is not to generate lists of differentially expressed genes, but to identify the physiologic or pathogenic processes and structures represented in the expression profile. Methods RNA was separately extracted from peripheral blood neutrophils and mononuclear leukocytes, labeled, and hybridized to genome level microarrays to generate expression profiles of children with polyarticular juvenile idiopathic arthritis, juvenile dermatomyositis relative to childhood controls. Statistically significantly differentially expressed genes were identified from samples of each disease relative to controls. Functional network analysis identified interactions between products of these differentially expressed genes. Results In silico models of both diseases demonstrated similar features with properties of scale-free networks previously described in physiologic systems. These networks were observable in both cells of the innate immune system (neutrophils and cells of the adaptive immune system (peripheral blood mononuclear cells. Conclusion Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant

  10. Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.

    Directory of Open Access Journals (Sweden)

    Gordan Lauc

    Full Text Available Glycosylation of immunoglobulin G (IgG influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS results identified 9 genome-wide significant loci (P<2.27 × 10(-9 in the discovery analysis and two of the same loci (B4GALT1 and MGAT3 in the replication cohort. Four loci contained genes encoding glycosyltransferases (ST6GAL1, B4GALT1, FUT8, and MGAT3, while the remaining 5 contained genes that have not been previously implicated in protein glycosylation (IKZF1, IL6ST-ANKRD55, ABCF2-SMARCD3, SUV420H1, and SMARCB1-DERL3. However, most of them have been strongly associated with autoimmune and inflammatory conditions (e.g., systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, Crohn's disease, diabetes type 1, multiple sclerosis, Graves' disease, celiac disease, nodular sclerosis and/or haematological cancers (acute lymphoblastic leukaemia, Hodgkin lymphoma, and multiple myeloma. Follow-up functional experiments in haplodeficient Ikzf1 knock-out mice showed the same general pattern of changes in IgG glycosylation as identified in the meta-analysis. As IKZF1 was associated with multiple IgG N-glycan traits, we explored biomarker potential of affected N-glycans in 101 cases with SLE and 183 matched controls and demonstrated substantial discriminative power in a ROC-curve analysis (area under the curve = 0.842. Our study shows that it is possible to identify new loci that control glycosylation of a single plasma protein

  11. Individuals at risk for Alzheimer’s disease show differential patterns of ERP brain activation during odor identification

    Directory of Open Access Journals (Sweden)

    Morgan Charlie D

    2012-07-01

    Full Text Available Abstract Background Studies suggest that older adults at risk of developing Alzheimer’s disease may show olfactory processing deficits before other signs of dementia appear. Methods We studied 60 healthy non-demented individuals, half of whom were positive for the genetic risk factor the Apolipoprotein E ɛ4 allele, in three different age groups. Event-related potentials to visual and olfactory identification tasks were recorded and analyzed for latency and amplitude differences, and plotted via topographical maps. Results Varying patterns of brain activation were observed over the post-stimulus epoch for ɛ4- versus ɛ4+ individuals on topographical maps. Individuals with the ɛ4 allele demonstrated different ERP peak latencies during identification of olfactory but not visual stimuli. High correct ApoE classification rates were obtained utilizing the olfactory ERP. Conclusions Olfactory ERPs demonstrate functional decline in individuals at risk for Alzheimer’s disease at much earlier ages than previously observed, suggesting the potential for pre-clinical detection of AD at very early stages.

  12. Tongue Epithelium Cells from shRNA Mediated Transgenic Goat Show High Resistance to Foot and Mouth Disease Virus.

    Science.gov (United States)

    Li, Wenting; Wang, Kejun; Kang, Shimeng; Deng, Shoulong; Han, Hongbing; Lian, Ling; Lian, Zhengxing

    2015-12-16

    Foot and mouth disease induced by foot and mouth disease virus (FMDV) is severe threat to cloven-hoofed domestic animals. The gene 3Dpol in FMDV genome encodes the viral RNA polymerase, a vital element for FMDV replication. In this study, a conserved 3D-7414shRNA targeting FMDV-3Dpol gene was designed and injected into pronuclear embryos to produce the transgenic goats. Sixty-one goats were produced, of which, seven goats positively integrated 3D-7414shRNA. Loss of function assay demonstrated that siRNA effectively knockdown 3Dpol gene in skin epithelium cells of transgenic goats. Subsequently, the tongue epithelium cells from transgenic and non-transgenic goats were infected with FMDV O/YS/CHA/05 strain. A significant decrease of virus titres and virus copy number was observed in cells of transgenic goats compared with that of non-transgenic goats, which indicated that 3D-7414siRNA inhibited FMDV replication by interfering FMDV-3Dpol gene. Furthermore, we found that expression of TLR7, RIG-I and TRAF6 was lower in FMDV infected cells from transgenic goats compared to that from non-transgenic goats, which might result from lower virus copy number in transgenic goats' cells. In conclusion, we successfully produced transgenic goats highly expressing 3D-7414siRNA targeting 3Dpol gene, and the tongue epithelium cells from the transgenic goats showed effective resistance to FMDV.

  13. Apollo Lunar Astronauts Show Higher Cardiovascular Disease Mortality: Possible Deep Space Radiation Effects on the Vascular Endothelium.

    Science.gov (United States)

    Delp, Michael D; Charvat, Jacqueline M; Limoli, Charles L; Globus, Ruth K; Ghosh, Payal

    2016-07-28

    As multiple spacefaring nations contemplate extended manned missions to Mars and the Moon, health risks could be elevated as travel goes beyond the Earth's protective magnetosphere into the more intense deep space radiation environment. The primary purpose of this study was to determine whether mortality rates due to cardiovascular disease (CVD), cancer, accidents and all other causes of death differ in (1) astronauts who never flew orbital missions in space, (2) astronauts who flew only in low Earth orbit (LEO), and (3) Apollo lunar astronauts, the only humans to have traveled beyond Earth's magnetosphere. Results show there were no differences in CVD mortality rate between non-flight (9%) and LEO (11%) astronauts. However, the CVD mortality rate among Apollo lunar astronauts (43%) was 4-5 times higher than in non-flight and LEO astronauts. To test a possible mechanistic basis for these findings, a secondary purpose was to determine the long-term effects of simulated weightlessness and space-relevant total-body irradiation on vascular responsiveness in mice. The results demonstrate that space-relevant irradiation induces a sustained vascular endothelial cell dysfunction. Such impairment is known to lead to occlusive artery disease, and may be an important risk factor for CVD among astronauts exposed to deep space radiation.

  14. Newcastle disease viruses causing recent outbreaks worldwide show unexpectedly high genetic similarity with historical virulent isolates from the 1940s

    Science.gov (United States)

    Virulent strains of Newcastle disease virus (NDV) cause Newcastle disease (ND), a devastating disease of poultry and wild birds. Phylogenetic analyses clearly distinguish historical isolates (obtained prior to 1960) from currently circulating viruses of class II genotypes V, VI, VII, and XII throug...

  15. The GREGOR Fabry-P\\'erot Interferometer

    CERN Document Server

    Puschmann, K G; Kneer, F; Erdogan, N Al; Balthasar, H; Bauer, S M; Beck, C; González, N Bello; Collados, M; Hahn, T; Hirzberger, J; Hofmann, A; Louis, R E; Nicklas, H; Okunev, O; Pillet, V Martínez; Popow, E; Seelemann, T; Volkmer, R; Wittmann, A D; Woche, M

    2012-01-01

    The GREGOR Fabry-P\\'erot Interferometer (GFPI) is one of three first-light instruments of the German 1.5-meter GREGOR solar telescope at the Observatorio del Teide, Tenerife, Spain. The GFPI uses two tunable etalons in collimated mounting. Thanks to its large-format, high-cadence CCD detectors with sophisticated computer hard- and software it is capable of scanning spectral lines with a cadence that is sufficient to capture the dynamic evolution of the solar atmosphere. The field-of-view (FOV) of 50" x 38" is well suited for quiet Sun and sunspot observations. However, in the vector spectropolarimetric mode the FOV reduces to 25" x 38". The spectral coverage in the spectroscopic mode extends from 530-860 nm with a theoretical spectral resolution R of about 250,000, whereas in the vector spectropolarimetric mode the wavelength range is at present limited to 580-660 nm. The combination of fast narrow-band imaging and post-factum image restoration has the potential for discovery science concerning the dynamic Su...

  16. Optical fiber Fabry-Perot interferometer for microorganism growth detection

    Science.gov (United States)

    Liu, Xiaohui; Jiang, Mingshun; Sui, Qingmei; Luo, Shuyang; Geng, Xiangyi

    2016-07-01

    An optical fiber Fabry-Perot interferometer (FPI) based on hollow-core photonic crystal fiber (HCPCF) for microorganism growth detection is proposed and demonstrated. The FPI is formed by splicing both ends of a short section of HCPCF to SMFs and cleaving the SMF pigtail to a proper length. By measuring the fringe contrast of interference pattern, the refractive index (RI) changes of analyte during microorganism growth can be obtained. RI response of the sensor was investigated theoretically and experimentally. It shows linear response with sensitivity of -136 dB/RIU and good repeatability. Temperature response was also tested and the result confirms the low temperature cross-sensitivity of the sensor. Detection of yeast growth in liquid medium by the FPI sensor was conducted and the result shows the characteristic of typical yeast growth curve. With its advantages of high RI sensitivity, low temperature cross-sensitivity, capability for real-time measurement and so on, this FPI sensor has great potential in biosensing.

  17. Whole blood DNA aberrant methylation in pancreatic adenocarcinoma shows association with the course of the disease: a pilot study.

    Directory of Open Access Journals (Sweden)

    Albertas Dauksa

    Full Text Available Pancreatic tumors are usually diagnosed at an advanced stage in the progression of the disease, thus reducing the survival chances of the patients. Non-invasive early detection would greatly enhance therapy and survival rates. Toward this aim, we investigated in a pilot study the power of methylation changes in whole blood as predictive markers for the detection of pancreatic tumors. We investigated methylation levels at selected CpG sites in the CpG rich regions at the promoter regions of p16, RARbeta, TNFRSF10C, APC, ACIN1, DAPK1, 3OST2, BCL2 and CD44 in the blood of 30 pancreatic tumor patients and in the blood of 49 matching controls. In addition, we studied LINE-1 and Alu repeats using degenerate amplification approach as a surrogate marker for genome-wide methylation. The site-specific methylation measurements at selected CpG sites were done by the SIRPH method. Our results show that in the patient's blood, tumor suppressor genes were slightly but significantly higher methylated at several CpG sites, while repeats were slightly less methylated compared to control blood. This was found to be significantly associated with higher risk for pancreatic ductal adenocarcinoma. Additionally, high methylation levels at TNFRSCF10C were associated with positive perineural spread of tumor cells, while higher methylation levels of TNFRSF10C and ACIN1 were significantly associated with shorter survival. This pilot study shows that methylation changes in blood could provide a promising method for early detection of pancreatic tumors. However, larger studies must be carried out to explore the clinical usefulness of a whole blood methylation based test for non-invasive early detection of pancreatic tumors.

  18. Early onset APOE E4-negative Alzheimer's disease patients show faster cognitive decline on non-memory domains.

    Science.gov (United States)

    Smits, Lieke L; Pijnenburg, Yolande A L; van der Vlies, Annelies E; Koedam, Esther L G E; Bouwman, Femke H; Reuling, Ilona E W; Scheltens, Philip; van der Flier, Wiesje M

    2015-07-01

    Age at onset and APOE E4-genotype have been shown to influence clinical manifestation of Alzheimer's disease (AD). We investigated rate of decline in specific cognitive domains according to age at onset and APOE E4-genotype in patients with AD. 199 patients with probable AD underwent at least two annual neuropsychological assessments. Patients were classified according to age-at-onset (≤ 65 years vs >65 years) and APOE genotype (positive vs negative). The neuropsychological test battery compromised tests for memory, language, attention, executive and visuo-spatial functioning. For each domain compound z-scores were calculated, based on the baseline performance of patients. Average duration of follow-up was 1.5 ± 1 years. We used linear mixed models (LMM) to estimate effects of age, APOE and age⁎APOE on cognitive decline over time. At baseline, patients were 65 ± 8 years, 98(49%) were female and MMSE was 22 ± 4. LMM showed that early onset patients declined faster on executive functioning (β ± SE:-0.09 ± 0.06) than late onset patients, but age was not related to decline in the other cognitive domains. APOE E4 negative patients declined faster on language than APOE E4 positive patients (β ± SE:-0.1 ± 0.06). When we took age and APOE genotype into account simultaneously, we found that compared to late onset-E4 positive patients, early onset-E4 negative patients declined faster on language (β ± SE:-0.36 ± 0.1), attention (β ± SE:-0.42 ± 0.1), executive (β ± SE:-0.41 ± 0.1) and visuo-spatial functioning (β ± SE:-0.43 ± 0.1). Late onset-E4 negative and early onset-E4 positive patients showed intermediate rates of decline. We found no differences in decline on memory. We found that patients who develop AD despite absence of the two most important risk factors, show steepest cognitive decline on non-memory cognitive domains. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  19. Calibrating echelle spectrographs with Fabry-Perot etalons

    CERN Document Server

    Bauer, Florian F; Reiners, Ansgar

    2015-01-01

    Over the past decades hollow-cathode lamps have been calibration standards for spectroscopic measurements. Advancing to cm/s radial velocity precisions with the next generation of instruments requires more suitable calibration sources with more lines and less dynamic range problems. Fabry-Perot interferometers provide a regular and dense grid of lines and homogeneous amplitudes making them good candidates for next generation calibrators. We investigate the usefulness of Fabry-Perot etalons in wavelength calibration, present an algorithm to incorporate the etalon spectrum in the wavelength solution and examine potential problems. The quasi periodic pattern of Fabry-Perot lines is used along with a hollow-cathode lamp to anchor the numerous spectral features on an absolute scale. We test our method with the HARPS spectrograph and compare our wavelength solution to the one derived from a laser frequency comb. The combined hollow-cathode lamp/etalon calibration overcomes large distortion (50 m/s) in the wavelengt...

  20. The Isothiocyanate Isolated from Moringa oleifera Shows Potent Anti-Inflammatory Activity in the Treatment of Murine Subacute Parkinson's Disease.

    Science.gov (United States)

    Giacoppo, Sabrina; Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2017-02-01

    The present study was aimed at estimating a possible neuroprotective effect of glucomoringin (GMG) [4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate] bioactivated with the enzyme myrosinase to form the corresponding isothiocyanate [4-(α-L-rhamnopyranosyloxy)benzyl C; moringin] in the treatment or prevention of Parkinson's disease (PD). In this study, the beneficial effects of moringin were compared with those of pure GMG, not enzymatically activated, in an in vivo experimental mouse model of subacute PD. Subacute PD was induced in C57BL/6 mice by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were pretreated daily for 1 week with moringin (10 mg/kg +5 μL myrosinase/mouse) and with GMG (10 mg/kg). Behavioral evaluations were also performed to assess motor deficits and bradykinesia in MPTP mice. Besides, assuming that pretreatment with moringin could modulate the triggering of inflammatory cascade with a correlated response, we tested its in vitro anti-inflammatory activity by using a model of RAW 264.7 macrophages stimulated with lipopolysaccharide. Achieved results in vivo showed a higher efficacy of moringin compared with GMG not only to modulate the inflammatory pathway but also oxidative stress and apoptotic pathways. In addition, the greater effectiveness of moringin in countering mainly the inflammatory pathway has been corroborated by the results obtained in vitro. The relevance and innovation of the present study lie in the possible use of a safe formulation of a bioactive compound, resulting from exogenous myrosinase hydrolysis of the natural phytochemical GMG, which can be used in clinical practice as a useful drug for the treatment or prevention of PD.

  1. Cardioembolic and small vessel disease stroke show differences in associations between systemic C3 levels and outcome.

    Directory of Open Access Journals (Sweden)

    Anna Stokowska

    Full Text Available BACKGROUND: Activation of the complement system has been proposed to play a role in the pathophysiology of stroke. As the specific involvement of the complement proteins may be influenced by stroke etiology, we compared plasma C3 and C3a levels in patients with cardioembolic (CE and small vessel disease (SVD subtypes of ischemic stroke and control subjects and evaluated their association to outcome at three months and two years. METHODOLOGY/PRINCIPAL FINDINGS: Plasma C3 and C3a levels in 79 CE and 79 SVD stroke patients, sampled within 10 days and at three months after stroke, and age- and sex-matched control subjects from The Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assesed with modified Rankin Scale. In the CE group, plasma C3 levels were elevated only in the acute phase, whereas C3a was elevated at both time points. The follow-up phase plasma C3 levels in the upper third were associated with an increased risk of unfavorable outcome at three months (OR 7.12, CI 1.72-29.46, P = 0.007 as well as after two years (OR 8.25, CI 1.61-42.28, P = 0.011 after stroke. These associations withstand adjustment for age and sex. Conversely, three-month follow-up plasma C3a/C3 level ratios in the middle third were associated with favorable outcome after two years both in the univariate analysis (OR 0.19, CI 0.05-0.82, P = 0.026 and after adjustment for age and sex (OR 0.19, CI 0.04-0.88, P = 0.033. In the SVD group, plasma C3 and C3a levels were elevated at both time points but showed no significant associations with outcome. CONCLUSIONS: Plasma C3 and C3a levels are elevated after CE and SVD stroke but show associations with outcome only in CE stroke.

  2. Time Delay Properties of a Fabry-Perot Interferometer

    Institute of Scientific and Technical Information of China (English)

    YUAN Shi; MAN Wei-Ning; YU Jin; GAO Jin-Yue

    2001-01-01

    The time delay properties of a Fabry-Perot interferometer are investigated. We found that the group velocity of light through a Fabry-Perot interferometer can be reduced to 10-4 of the light speed in vacuum and the time delay is 210ns, when the reflectivity is 0.999 and the distance between two mirrors is 1 cm. The system is analogous to the recently proposed one-dimensional photonic band-gap structures with a defect [Zhu et al. Opt.Commun. 174(2000)139].

  3. Familial Parkinson's disease iPSCs show cellular deficits in mitochondrial responses that can be pharmacologically rescued

    Science.gov (United States)

    Cooper, Oliver; Seo, Hyemyung; Andrabi, Shaida; Guardia-Laguarta, Cristina; Graziotto, John; Sundberg, Maria; McLean, Jesse R.; Carrillo-Reid, Luis; Xie, Zhong; Osborn, Teresia; Hargus, Gunnar; Deleidi, Michela; Lawson, Tristan; Bogetofte, Helle; Perez-Torres, Eduardo; Clark, Lorraine; Moskowitz, Carol; Mazzulli, Joseph; Chen, Li; Volpicelli-Daley, Laura; Romero, Norma; Jiang, Houbo; Uitti, Ryan J.; Huang, Zhigao; Opala, Grzegorz; Scarffe, Leslie A.; Dawson, Valina L.; Klein, Christine; Feng, Jian; Ross, Owen A.; Trojanowski, John Q.; Lee, Virginia M.-Y.; Marder, Karen; Surmeier, D. James; Wszolek, Zbigniew K.; Przedborski, Serge; Krainc, Dimitri; Dawson, Ted M.; Isacson, Ole

    2012-01-01

    Parkinson's disease (PD) is a common neurodegenerative disease caused by genetic and environmental factors. We analyzed induced pluripotent stem cell (iPSC)-derived neural cells from PD patients and presymptomatic individuals carrying mutations in the PINK1 and LRRK2 genes, and healthy control subjects. We measured several aspects of mitochondrial responses in the iPSC-derived neural cells including production of reactive oxygen species, mitochondrial respiration, proton leakage and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial function in iPSC-derived neural cells from PD patients and at-risk individuals could be rescued with coenzyme Q10, rapamycin or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insights into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in PD. PMID:22764206

  4. Mathematical model of Fabry-Perot cavity filter%WDM设计中的Fabry-Perot腔传递函数模型

    Institute of Scientific and Technical Information of China (English)

    孙雅东; 武良春

    2003-01-01

    作为WDM(Wave Division Multiplexing)一个重要的器件,Fabry-Perot腔的相关设计和算法不断更新.笔者提出一种新的数学模型:把Fabry-Perot作为系统的一个参数对待,将信号与系统的知识纳入Fabry-Perot腔中,用系统的方法(梅森公式)求解Fabry-Perot腔的传递函数,避免了繁琐的矩阵运算,这样易于理解和优化设计.

  5. Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases

    DEFF Research Database (Denmark)

    Nexo, Mette Andersen; Watt, Torquil; Bonnema, Steen Joop;

    2015-01-01

    , and other thyroid diseases), 391 of which had participated in a study 5 years previously. Responses to select items were compared to general population data. We used confirmatory factor analyses for categorical data, logistic regression analyses and tests of differential item function, and head...

  6. Risk of death in heart disease is associated with elevated urinary globotriaosylceramide.

    Science.gov (United States)

    Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A; Taylor, Matthew R G; Lowes, Brian D; Fuller, Maria; Benjamin, Elfrida R; Sweetman, Lawrence

    2014-02-04

    Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X-linked lysosomal disorder that is a risk factor for most types of heart disease. We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α-galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow-up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near-term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. clinicaltrials.gov. Unique Identifier: NCT01019629.

  7. Characterization of miniature fiber-optic Fabry-Perot interferometric sensors based on hollow silica tube

    Science.gov (United States)

    Jia, Pinggang; Fang, Guocheng; Wang, Daihua

    2016-09-01

    A miniature fiber-optic Fabry-Perot interferometer (MOFPI) fabricated by splicing a hollow silica tube (HST) with inner diameter of 4 µm to the end of a single-mode fiber is investigated and experimentally demonstrated. The theoretical relationship between the free spectrum range and the length of HST is verified by fabricating several MOFPIs with different lengths. We characterize the MOFPIs for temperature, liquid refractive index, and strain. Experimental results show that the sensitivities of the temperature, liquid refractive index, and strain are 16.42 pm/°C,-118.56 dB/RIU, and 1.21 pm/µɛ, respectively.

  8. Mode-resolved Fabry-Perot experiment in low-loss Bragg-reflection waveguides.

    Science.gov (United States)

    Pressl, B; Günthner, T; Laiho, K; Geßler, J; Kamp, M; Höfling, S; Schneider, C; Weihs, G

    2015-12-28

    Based on the interaction between different spatial modes, semiconductor Bragg-reflection waveguides (BRWs) provide a highly functional platform for non-linear optics. For achieving any desired quantum optical functionality, we must control and engineer the properties of each spatial mode. To reach this purpose we extend the Fabry-Perot technique and achieve a detailed linear optical characterization of dispersive multimode semiconductor waveguides. With this efficient broadband spectral method we gain direct experimental access to the relevant modes of our BRWs and determine their group velocities. Furthermore, we show that our waveguides have lower than expected loss coefficients. This renders them suitable for integrated quantum optics applications.

  9. A Fabry-Perot interferometer with quantum mirrors: nonlinear light transport and rectification

    CERN Document Server

    Fratini, F; Safari, L; Poizat, J-Ph; Valente, D; Auffèves, A; Gerace, D; Santos, M F

    2014-01-01

    Optical transport represents a natural route towards fast communications, and it is currently used in large scale data transfer. The progressive miniaturization of devices for information processing calls for the microscopic tailoring of light transport and confinement at length scales appropriate for the upcoming technologies. With this goal in mind, we present a theoretical analysis of a one-dimensional Fabry-Perot interferometer built with two highly saturable nonlinear mirrors: a pair of two-level systems. Our approach captures non-linear and non-reciprocal effects of light transport that were not reported previously. Remarkably, we show that such an elementary device can operate as a microscopic integrated optical rectifier.

  10. An optical fiber Fabry-Perot pressure sensor using corrugated diaphragm and angle polished fiber

    Science.gov (United States)

    Zhu, Jiali; Wang, Ming; Chen, Lu; Ni, Xiaoqi; Ni, Haibin

    2017-03-01

    In this paper, a Fabry-Perot pressure sensor using a corrugated diaphragm and angle polished fiber is proposed. A SU-8 structure using two step of lithography is formed to fix the polished fiber, which helps control the cavity length precisely. The fabrication process is described. The characteristics of both pressure and temperature are tested. Also the temperature compensation is realized. Experimental results show that the sensor has high sensitivity and good linearity over the pressure range of 0-0.1 MPa. The sensitivity (change in cavity/loaded pressure) is 705.64 μm/MPa.

  11. Scanning Gate Microscopy of Kondo Dots: Fabry-P\\'erot Interferences and Thermally Induced Rings

    OpenAIRE

    Kleshchonok, Andrii; Fleury, Geneviève; Pichard, Jean-Louis

    2013-01-01

    We study the conductance of an electron interferometer formed in a two dimensional electron gas between a nanostructured quantum contact and the charged tip of a scanning gate microscope. Measuring the conductance as a function of the tip position, thermally induced rings may be observed in addition to Fabry-P\\'erot interference fringes spaced by half the Fermi wavelength. If the contact is made of a quantum dot opened in the middle of a Kondo valley, we show how the location of the rings all...

  12. Scanning Gate Microscopy of Kondo Dots: Fabry-Pérot Interferences and Thermally Induced Rings

    OpenAIRE

    Kleshchonok, Andrii; Fleury, Geneviève; Pichard, Jean-Louis

    2013-01-01

    5 pages, 4 figures; We study the conductance of an electron interferometer formed in a two dimensional electron gas between a nanostructured quantum contact and the charged tip of a scanning gate microscope. Measuring the conductance as a function of the tip position, thermally induced rings may be observed in addition to Fabry-Pérot interference fringes spaced by half the Fermi wavelength. If the contact is made of a quantum dot opened in the middle of a Kondo valley, we show how the locatio...

  13. High precision optical fiber Fabry-Perot sensor for gas pressure detection

    Science.gov (United States)

    Mao, Yan; Tong, Xing-lin

    2013-09-01

    An optical fiber Fabry-Perot (F-P) sensor with quartz diaphragm for gas pressure testing was designed and fabricated. It consisted of single-mode fiber, hollow glass tube and quartz diaphragm. It uses the double peak demodulation to obtain the initialized cavity length. The variety of cavity length can be calcultated by the single peak demodulation after changing the gas pressure. The results show that the sensor is small in size, whose sensitivity is 19 pm/kPa in the range of the 10 ~ 260 kPa gas pressure. And it has good linearity and repeatability.

  14. A Fabry-Perot Solid Etalon for Teaching.

    Science.gov (United States)

    Bruce, P. J.; And Others

    1986-01-01

    Describes a solid etalon Fabry-Perot interferometer, discussing free spectral range, instrumental finesse, and temperature effects. Provides schematic of temperature control/display circuit. Explains use of 100 millimeter camera lens and 10 power micrometer eyepiece for resolving rings and measure diameters. (JM)

  15. A Coaxial Cable Fabry-Perot Interferometer for Sensing Applications

    Directory of Open Access Journals (Sweden)

    Ming Luo

    2013-11-01

    Full Text Available This paper reports a novel coaxial cable Fabry-Perot interferometer for sensing applications. The sensor is fabricated by drilling two holes half-way into a coaxial cable. The device physics was described. The temperature and strain responses of the sensor were tested. The measurement error was calculated and analyzed.

  16. Development of the Fabry-Perot Spectrometer Application

    Science.gov (United States)

    Browne, Kathryn

    2015-01-01

    Methane is a greenhouse gas with global warming effects 20 times more detrimental than carbon dioxide. Currently, only aircraft missions measure methane and do not provide continuous monitoring, This presentation will cover the Fabry-Perot spectrometer which will provide continuous monitoring of methane. It will also cover the development of the software used to extract and process the data the spectrometer collects.

  17. Silicon Carbide Mounts for Fabry-Perot Interferometers

    Science.gov (United States)

    Lindemann, Scott

    2011-01-01

    Etalon mounts for tunable Fabry- Perot interferometers can now be fabricated from reaction-bonded silicon carbide structural components. These mounts are rigid, lightweight, and thermally stable. The fabrication of these mounts involves the exploitation of post-casting capabilities that (1) enable creation of monolithic structures having reduced (in comparison with prior such structures) degrees of material inhomogeneity and (2) reduce the need for fastening hardware and accommodations. Such silicon carbide mounts could be used to make lightweight Fabry-Perot interferometers or could be modified for use as general lightweight optical mounts. Heretofore, tunable Fabry-Perot interferometer structures, including mounting hardware, have been made from the low-thermal-expansion material Invar (a nickel/iron alloy) in order to obtain the thermal stability required for spectroscopic applications for which such interferometers are typically designed. However, the high mass density of Invar structures is disadvantageous in applications in which there are requirements to minimize mass. Silicon carbide etalon mounts have been incorporated into a tunable Fabry-Perot interferometer of a prior design that originally called for Invar structural components. The strength, thermal stability, and survivability of the interferometer as thus modified are similar to those of the interferometer as originally designed, but the mass of the modified interferometer is significantly less than the mass of the original version.

  18. Variable Free Spectral Range Spherical Mirror Fabry-Perot Interferometer

    CERN Document Server

    Kerner, K; Yashchuk, V V; Budker, D; Kerner, Katherine; Rochester, Simon M.; Yashchuk, Valeriy V.

    2003-01-01

    A spherical Fabry-Perot interferometer with adjustable mirror spacing is used to produce interference fringes with frequency separation (c/2L)/N, N=2-15. The conditions for observation of these fringes are derived from the consideration of the eigenmodes of the cavity with high transverse indices.

  19. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model.

    Science.gov (United States)

    Squitieri, Ferdinando; Di Pardo, Alba; Favellato, Mariagrazia; Amico, Enrico; Maglione, Vittorio; Frati, Luigi

    2015-11-01

    Huntington disease (HD) is a neurodegenerative disorder for which new treatments are urgently needed. Pridopidine is a new dopaminergic stabilizer, recently developed for the treatment of motor symptoms associated with HD. The therapeutic effect of pridopidine in patients with HD has been determined in two double-blind randomized clinical trials, however, whether pridopidine exerts neuroprotection remains to be addressed. The main goal of this study was to define the potential neuroprotective effect of pridopidine, in HD in vivo and in vitro models, thus providing evidence that might support a potential disease-modifying action of the drug and possibly clarifying other aspects of pridopidine mode-of-action. Our data corroborated the hypothesis of neuroprotective action of pridopidine in HD experimental models. Administration of pridopidine protected cells from apoptosis, and resulted in highly improved motor performance in R6/2 mice. The anti-apoptotic effect observed in the in vitro system highlighted neuroprotective properties of the drug, and advanced the idea of sigma-1-receptor as an additional molecular target implicated in the mechanism of action of pridopidine. Coherent with protective effects, pridopidine-mediated beneficial effects in R6/2 mice were associated with an increased expression of pro-survival and neurostimulatory molecules, such as brain derived neurotrophic factor and DARPP32, and with a reduction in the size of mHtt aggregates in striatal tissues. Taken together, these findings support the theory of pridopidine as molecule with disease-modifying properties in HD and advance the idea of a valuable therapeutic strategy for effectively treating the disease. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  20. [Triglycerides--a long known risk factor for cardiovascular disease. Subgroup analysis shows the importance after acute coronary syndrome].

    Science.gov (United States)

    Olsson, Anders

    2015-09-09

    An increased blood concentration of triglycerides (TG) has long been recognized as an important risk factor for cardiovascular disease. Through competition from HDL cholesterol and the arrival of statin treatment for high LDL cholesterol the importance of TG as risk factor was largely forgotten. A high concentration of TG indicates high blood levels of TG-rich lipoproteins including cholesterol rich remnant particles. Studies using Mendelian randomizations have demonstrated that a low HDL cholesterol does not carry a direct atherogenic function and that remnant particles do so. New efforts should be exercised in order to diminish residual cardiovascular risk during statin treatment through decreasing TG rich lipoproteins.

  1. AUTOIMMUNE DISEASE. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy.

    Science.gov (United States)

    Lo, Bernice; Zhang, Kejian; Lu, Wei; Zheng, Lixin; Zhang, Qian; Kanellopoulou, Chrysi; Zhang, Yu; Liu, Zhiduo; Fritz, Jill M; Marsh, Rebecca; Husami, Ammar; Kissell, Diane; Nortman, Shannon; Chaturvedi, Vijaya; Haines, Hilary; Young, Lisa R; Mo, Jun; Filipovich, Alexandra H; Bleesing, Jack J; Mustillo, Peter; Stephens, Michael; Rueda, Cesar M; Chougnet, Claire A; Hoebe, Kasper; McElwee, Joshua; Hughes, Jason D; Karakoc-Aydiner, Elif; Matthews, Helen F; Price, Susan; Su, Helen C; Rao, V Koneti; Lenardo, Michael J; Jordan, Michael B

    2015-07-24

    Mutations in the LRBA gene (encoding the lipopolysaccharide-responsive and beige-like anchor protein) cause a syndrome of autoimmunity, lymphoproliferation, and humoral immune deficiency. The biological role of LRBA in immunologic disease is unknown. We found that patients with LRBA deficiency manifested a dramatic and sustained improvement in response to abatacept, a CTLA4 (cytotoxic T lymphocyte antigen-4)-immunoglobulin fusion drug. Clinical responses and homology of LRBA to proteins controlling intracellular trafficking led us to hypothesize that it regulates CTLA4, a potent inhibitory immune receptor. We found that LRBA colocalized with CTLA4 in endosomal vesicles and that LRBA deficiency or knockdown increased CTLA4 turnover, which resulted in reduced levels of CTLA4 protein in FoxP3(+) regulatory and activated conventional T cells. In LRBA-deficient cells, inhibition of lysosome degradation with chloroquine prevented CTLA4 loss. These findings elucidate a mechanism for CTLA4 trafficking and control of immune responses and suggest therapies for diseases involving the CTLA4 pathway. Copyright © 2015, American Association for the Advancement of Science.

  2. Modulators of cytoskeletal reorganization in CA1 hippocampal neurons show increased expression in patients at mid-stage Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Patricia F Kao

    Full Text Available During the progression of Alzheimer's disease (AD, hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF receptor tyrosine kinase B (TrkB, mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression.

  3. Two cases of pediatric bone disease (eosinophilic granuloma and Brodie's abscess) showing similar scintigraphic and radiographic findings.

    Science.gov (United States)

    Yoshikawa, M; Sugawara, Y; Kikuchi, T; Nakata, S; Mochizuki, T; Ikezoe, J; Sakayama, K

    2000-12-01

    Two 9-year-old patients with femoral bone lesions were referred to the authors' institution within a few days of each other. Both showed similar radiographic, magnetic resonance imaging, and scintigraphic findings. The radiographs showed osteolytic lesions in the right femoral diaphyses, and gadolinium-DTPA-enhanced magnetic resonance imaging revealed inhomogeneous enhancement. Tc-99m HMDP showed marked linear accumulation with relatively low central uptake in the right femoral shafts, and TI-201 scintigraphy showed considerable uptake corresponding to the area seen with Tc-99m HMDP. Histologic analysis confirmed eosinophilic granuloma in the first patient and Brodie's abscess in the second. The radiographic and scintigraphic findings in Brodie's abscess may be similar to those in eosinophilic granuloma.

  4. Evidence showing the relationship between sagittal balance and clinical outcomes in surgical treatment of degenerative spinal diseases: a literature review.

    Science.gov (United States)

    Le Huec, Jean-Charles; Faundez, Antonio; Dominguez, Dennis; Hoffmeyer, Pierre; Aunoble, Stéphane

    2015-01-01

    The measure of radiographic pelvic and spinal parameters for sagittal balance analysis has gained importance in reconstructive surgery of the spine and particularly in degenerative spinal diseases (DSD). Fusion in the lumbar spine may result in loss of lumbar lordosis (LL), with possible compensatory mechanisms: decreased sacral slope (SS), increased pelvic tilt (PT) and decreased thoracic kyphosis (TK). An increase in PT after surgery is correlated with postoperative back pain. A decreased SS and/or abnormal sagittal vertical axis (SVA) after fusion have a higher risk of adjacent segment degeneration. High pelvic incidence (PI) increases the risk of sagittal imbalance after spine fusion and is a predictive factor for degenerative spondylolisthesis. Restoration of a normal PT after surgery is correlated with good clinical outcome. Therefore, there is a need for comparative prospective studies that include pre- and postoperative spinopelvic parameters and compare complication rate, degree of disability, pain and quality of life.

  5. A switchable fiber laser based on an all-fiber Fabry-Perot filter

    Science.gov (United States)

    Lopez-Dieguez, Y.; Jauregui-Vázquez, D.; Estudillo-Ayala, J. M.; Herrera-Piad, L. A.; Rojas-Laguna, R.; Sierra-Hernandez, J. M.; Hernandez-Garcia, J. C.; Harush-Negari, A. B.

    2017-02-01

    In this experimental manuscript, a switchable Erbium-doped fiber ring laser based on an all-fiber Fabry-Perot filter was demonstrated. The filter is composed by several air micro-cavities formed into a section of a single-mode fiber splice joints with special hollow-core photonic crystal fiber. These micro-cavities are formed by air and silica, which produces several reflections generated at each silica-air-silica interfaces. Using this experimental setup we obtain a very high stable triple-laser emission at 1529.450nm, 1549.100nm and 1555.350nm with a linewidth of 0.2nm and a side-mode suppression ratio of 32dB, 37dB and 29dB respectively. These laser emission show a maximal peak power fluctuation around 0.4dB, 1.5dB and 2.6dB, with 0.025nm of wavelength oscillations. These results were observed after monitoring the laser cavity during an hour by recording the data each three minutes. By appropriately adjusting of transversal load applied over the Fabry-Perot filter between 0g and 550g, the ring laser cavity can be operated in double- wavelength, triple- wavelength, or quadruple- wavelength states. For this analysis, the all-fiber Fabry-Perot filter was set between a metal layer (below) and a thin glass layer (above) where transversal load was applied, here uniform load distribution over all the Fabry-Perot filter structure is achieved, as a result, the air intra-cavities that conform the filter are affected and the gain-losses profile is modified into the laser arrangement. The lasing emissions obtained in this work have a side-mode suppression ratio greater than 30dB. This ring laser cavity design offers a compact, simple and low-cost implementation and can be used in different applications where a very stable double, triple or quadruple laser lines are required.

  6. Fiber Optic Fabry-Perot Current Sensor Integrated with Magnetic Fluid Using a Fiber Bragg Grating Demodulation.

    Science.gov (United States)

    Xia, Ji; Wang, Qi; Liu, Xu; Luo, Hong

    2015-07-09

    An optical fiber current sensor based on Fabry-Perot interferometer using a fiber Bragg grating demodulation is proposed. Magnetic fluid is used as a sensitive medium in fiber optical Fabry-Perot (F-P) cavity for the optical characteristic of magnetic-controlled refractive index. A Fiber Bragg grating (FBG) is connected after the F-P interferometer which is used to reflect the optical power at the Bragg wavelength of the interference transmission spectrum. The corresponding reflective power of the FBG will change with different external current intensity, due to the shift on the interference spectrum of the F-P interferometer. The sensing probe has the advantages of convenient measurement for its demodulation, low cost and high current measurement accuracy on account of its sensing structure. Experimental results show that an optimal sensitivity of 0.8522 nw/A and measurement resolution of 0.001 A is obtained with a FBG at 1550 nm with 99% reflectivity.

  7. Effect of Fabry-Perot resonances in disordered one-dimensional array of alternating dielectric bi-layers

    Energy Technology Data Exchange (ETDEWEB)

    Luna-Acosta, G.A. [Instituto de Fisica, Universidad Autonoma de Puebla, Apartado Postal J-48, Puebla, Pue., 72570 (Mexico); Makarov, N.M. [Instituto de Ciencias, Universidad Autonoma de Puebla, Priv. 17 Norte No 3417, Col. San Miguel Hueyotlipan, Puebla, Pue., 72050 (Mexico)

    2009-12-15

    We study numerically and analytically the role of Fabry-Perot resonances in the transmission through a one-dimensional finite array formed by two alternating dielectric slabs. The disorder consists in varying randomly the width of one type of layers while keeping constant the width of the other type. Our numerical simulations show that localization is strongly inhibited in a wide neighborhood of the Fabry-Perot resonances. Comparison of our numerical results with an analytical expression for the average transmission, derived for weak disorder and finite number of cells, reveals that such expression works well even for medium disorder up to a certain frequency. Our results are valid for photonic and phononic one-dimensional disordered crystals, as well as for semiconductor superlattices. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  8. Show Time

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    <正> Story: Show Time!The whole class presents the story"Under the Sea".Everyone is so excited and happy.Both Leo and Kathy show their parentsthe characters of the play."Who’s he?"asks Kathy’s mom."He’s the prince."Kathy replies."Who’s she?"asks Leo’s dad."She’s the queen."Leo replieswith a smile.

  9. Snobbish Show

    Institute of Scientific and Technical Information of China (English)

    YIN PUMIN

    2010-01-01

    @@ The State Administration of Radio,Film and Television (SARFT),China's media watchdog,issued a new set of mles on June 9 that strictly regulate TV match-making shows,which have been sweeping the country's primetime programming. "Improper social and love values such as money worship should not be presented in these shows.Humiliation,verbal attacks and sex-implied vulgar content are not allowed" the new roles said.

  10. Assessment of the risks of communicable disease transmission through the movement of poultry exhibited at agricultural shows in New South Wales.

    Science.gov (United States)

    Dusan, F; Toribio, J-A; East, I J

    2010-09-01

    To assess biosecurity practices in the fancy poultry show sector that would influence the establishment and spread of exotic diseases in poultry in New South Wales. A cross-sectional survey of 105 fancy poultry exhibitors at seven agricultural shows. Exhibitors were interviewed about biosecurity practices on their farms and their knowledge of exotic diseases. Poultry stewards at 18 shows were interviewed about biosecurity practices at their shows. Although many exhibitors travelled only short distances to attend shows, some exhibitors attended up to 30 shows per year and travelled interstate to exhibit poultry. A network diagram revealed extensive connections and interactions of poultry throughout the eastern half of NSW. Five of 18 shows included cash sales without any record of purchasers; 46% of exhibitors reintroduced exhibited birds back into their flocks without a quarantine period; and 16% failed to wash cages used to transport the birds. There was a general awareness that exhibition of birds posed a risk to flock health, but knowledge of avian influenza and practices that could be adopted to minimise the risk of disease introduction was limited. The factors that could assist the establishment and spread of exotic diseases in poultry in NSW include the mixing of birds at shows, inadequate recording of exhibitor details at shows, inadequate biosecurity practices when reintroducing exhibited poultry back into flocks, cash sales associated with shows that did not include the collection of purchaser details, and inadequate identification of birds.

  11. Type II kinase inhibitors show an unexpected inhibition mode against Parkinson's disease-linked LRRK2 mutant G2019S.

    Science.gov (United States)

    Liu, Min; Bender, Samantha A; Cuny, Gregory D; Sherman, Woody; Glicksman, Marcie; Ray, Soumya S

    2013-03-12

    A number of well-known type II inhibitors (ATP-noncompetitive) that bind kinases in their DFG-out conformation were tested against wild-type LRRK2 and the most common Parkinson's disease-linked mutation, G2019S. We found that traditional type II inhibitors exhibit surprising variability in their inhibition mechanism between the wild type (WT) and the G2019S mutant of LRRK2. The type II kinase inhibitors were found to work in an ATP-competitive fashion against the G2019S mutant, whereas they appear to follow the expected noncompetitive mechanism against WT. Because the G2019S mutation lies in the DXG motif (DYG in LRRK2 but DFG in most other kinases) of the activation loop, we explored the structural consequence of the mutation on loop dynamics using an enhanced sampling method called metadynamics. The simulations suggest that the G2019S mutation stabilizes the DYG-in state of LRRK2 through a series of hydrogen bonds, leading to an increase in the conformational barrier between the active and inactive forms of the enzyme and a relative stabilization of the active form. The conformational bias toward the active form of LRRK2 mutants has two primary consequences. (1) The mutant enzyme becomes hyperactive, a known contributor to the Parkinsonian phenotype, as a consequence of being "locked" into the activated state, and (2) the mutation creates an unusual allosteric pocket that can bind type II inhibitors but in an ATP-competitive fashion. Our results suggest that developing type II inhibitors, which are generally considered superior to type I inhibitors because of desirable selectivity profiles, might be especially challenging for the G2019S LRRK2 mutant.

  12. Identification of putative TAL effector targets of the citrus canker pathogens shows functional convergence underlying disease development and defense response.

    Science.gov (United States)

    Pereira, Andre L A; Carazzolle, Marcelo F; Abe, Valeria Y; de Oliveira, Maria L P; Domingues, Mariane N; Silva, Jaqueline C; Cernadas, Raul A; Benedetti, Celso E

    2014-02-25

    Transcriptional activator-like (TAL) effectors, formerly known as the AvrBs3/PthA protein family, are DNA-binding effectors broadly found in Xanthomonas spp. that transactivate host genes upon injection via the bacterial type three-secretion system. Biologically relevant targets of TAL effectors, i.e. host genes whose induction is vital to establish a compatible interaction, have been reported for xanthomonads that colonize rice and pepper; however, citrus genes modulated by the TAL effectors PthA"s" and PthC"s" of the citrus canker bacteria Xanthomonas citri (Xc) and Xanthomonas aurantifolii pathotype C (XaC), respectively, are poorly characterized. Of particular interest, XaC causes canker disease in its host lemon (Citrus aurantifolia), but triggers a defense response in sweet orange. Based on, 1) the TAL effector-DNA binding code, 2) gene expression data of Xc and XaC-infiltrated sweet orange leaves, and 3) citrus hypocotyls transformed with PthA2, PthA4 or PthC1, we have identified a collection of Citrus sinensis genes potentially targeted by Xc and XaC TAL effectors. Our results suggest that similar with other strains of Xanthomonas TAL effectors, PthA2 and PthA4, and PthC1 to some extent, functionally converge. In particular, towards induction of genes involved in the auxin and gibberellin synthesis and response, cell division, and defense response. We also present evidence indicating that the TAL effectors act as transcriptional repressors and that the best scoring predicted DNA targets of PthA"s" and PthC"s" in citrus promoters predominantly overlap with or localize near to TATA boxes of core promoters, supporting the idea that TAL effectors interact with the host basal transcriptional machinery to recruit the RNA pol II and start transcription. The identification of PthA"s" and PthC"s" targets, such as the LOB (lateral organ boundary) and CCNBS genes that we report here, is key for the understanding of the canker symptoms development during host

  13. EROBATIC SHOW

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Visitors look at plane models of the Commercial Aircraft Corp. of China, developer of the count,s first homegrown large passenger jet C919, during the Singapore Airshow on February 16. The biennial event is the largest airshow in Asia and one of the most important aviation and defense shows worldwide. A number of Chinese companies took part in the event during which Okay Airways, the first privately owned aidine in China, signed a deal to acquire 12 Boeing 737 jets.

  14. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Science.gov (United States)

    Zeng, Yixuan; Guo, Wenyuan; Xu, Guangqing; Wang, Qinmei; Feng, Luyang; Long, Simei; Liang, Fengyin; Huang, Yi; Lu, Xilin; Li, Shichang; Zhou, Jiebin; Burgunder, Jean-Marc; Pang, Jiyan; Pei, Zhong

    2016-01-01

    Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt). Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a stable trimeric complex that can prevent the formation of mutant Htt aggregates. Taken together, we conclude that xyloketal derivatives could be novel drug candidates for treating Huntington’s disease. Molecular target analysis is a good method to simulate the interaction between proteins and drug compounds. Further, protective candidate drugs could be designed in future using the guidance of molecular docking results. PMID:27110099

  15. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington's disease.

    Science.gov (United States)

    Zeng, Yixuan; Guo, Wenyuan; Xu, Guangqing; Wang, Qinmei; Feng, Luyang; Long, Simei; Liang, Fengyin; Huang, Yi; Lu, Xilin; Li, Shichang; Zhou, Jiebin; Burgunder, Jean-Marc; Pang, Jiyan; Pei, Zhong

    2016-01-01

    Huntington's disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt). Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington's disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson's and Alzheimer's diseases. To identify potential neuroprotective molecules for Huntington's disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington's disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a stable trimeric complex that can prevent the formation of mutant Htt aggregates. Taken together, we conclude that xyloketal derivatives could be novel drug candidates for treating Huntington's disease. Molecular target analysis is a good method to simulate the interaction between proteins and drug compounds. Further, protective candidate drugs could be designed in future using the guidance of molecular docking results.

  16. Micromechanical tunable Fabry-Perot filter for IR gas analysis; Mikromechanisches durchstimmbares Fabry-Perot-Filter fuer die IR-Gasanalytik

    Energy Technology Data Exchange (ETDEWEB)

    Neumann, N.; Heinze, M.; Stegbauer, H.J. [InfraTec GmbH, Dresden (Germany); Hiller, K. [Technische Univ. Chemnitz (Germany). Zentrum fuer Mikrotechnologien; Kurth, S. [FhG-Inst. fuer Zuverlaessigkeit und Mikrointegration, Chemnitz (Germany). Aussenstelle Micro Devices and Equipment

    2005-01-01

    This contribution deals with design, fabrication and test of a micro-machined first order Fabry-Perot interferometer (FPI) intended for use as a tunable infrared (IR) filter in the (3-5) {mu}m band. The technical approach minimizes mirror curvature by using 300 {mu}m thick silicon (Si) mirror carriers for the coplanar fixed and movable mirrors of the FPI. Dielectric quarter-wave reflectance stacks consisting of alternating layers of silicon dioxide (SiO{sub 2}) and polycrystalline silicon are used as mirrors. The moveable mirror consists of two parts to form a parallel spring suspension which provides the necessary vertical movement and minimizes any tilting of the movable mirror carrier. The cavity spacing is electrostatically driven and controlled. Tunable filters with a centre wavelength (CWL) of (4.5..3.0) {mu}m and a spectral bandwith (FWHM) of about 60 nm were tested and showed a peak transmittance of about 50%. (orig.)

  17. Single-SectionFabry-Perot Mode-Locked Semiconductor Lasers

    Directory of Open Access Journals (Sweden)

    Weiguo Yang

    2011-01-01

    Full Text Available We present a review of the theoretical models and experimental verification of the single-section Fabry-Perot mode-locked semiconductor lasers based on multiple-spatial-mode (MSM coupling. The mode-locked operation at the repetition rates of 40 GHz and higher and the pulse width of a few picoseconds are confirmed by the intensity autocorrelation, the fast photo detection and RF spectrum, and the optical spectral interference measurement of ultrafast pulse. The spatial mode coupling theory of single-section Fabry-Perot mode-locked semiconductor lasers is also reviewed, and the results are compared with the experimental observations. The small signal modulation response of these lasers, which exhibits high-frequency responses well beyond the relaxation oscillation resonance limit, is also modeled theoretically, and the simulation is verified by the experimental measurements.

  18. Transforming Fabry-Perot resonances into a Tamm mode

    CERN Document Server

    Durach, Maxim

    2012-01-01

    We propose a novel photonic structure composed of metal nanolayer, Bragg mirror and metal nanolayer. The structure supports resonances that are transitional between Fabry-Perot and Tamm modes. When the dielectric contrast of the DBR is removed these modes are a pair of conventional Fabry-Perot resonances. They spectrally merge into a Tamm mode at high contrast. Such behavior differs from the results for structures supporting Tamm modes reported earlier. The optical properties of the structure in the frequency range of the DBR stop band, including highly beneficial 50% transmittivity through thick structures, are determined by the introduced in the paper hybrid resonances. The results can find a wide range of photonic applications.

  19. Human papillomavirus type 16 L1/L2 DNA methylation shows weak association with cervical disease grade in young women.

    Science.gov (United States)

    Bryant, Dean; Hibbitts, Samantha; Almonte, Maribel; Tristram, Amanda; Fiander, Alison; Powell, Ned

    2015-05-01

    Persistent infection with human papillomavirus (HPV) type 16 causes the majority of cervical cancers. Genital HPV infection is very common, but neoplastic progression is uncommon. There is an urgent need for biomarkers associated with cervical neoplasia, to enable triage of women who test positive for HPV. To assess the ability of quantitative measurement of HPV16 DNA methylation to separate samples of different cytological and histological grades from young women, among whom rates of HPV infection are high. DNA methylation was quantified by pyrosequencing of bisulphite converted DNA from liquid based cytology samples from 234 women (mean age 20.6 years) who tested positive for HPV16 and showed varying degrees of neoplasia. Methylation was assessed at CpGs in the HPV E2 and L1/L2 regions. The performance of methylation-based classifiers was assessed by ROC curve analyses. The best combination of CpGs (5600 and 5609) achieved AUCs of 0.656 (95% CI=0.520-0.792) for separation of cytologically normal and severely dyskaryotic samples, and 0.639 (95% CI=0.547-0.731) for separation of samples with or without high-grade neoplasia (CIN2+/-). The data are consistent with HPV L1/L2 methylation being a marker of the duration of infection in a specific host. Assessment of HPV DNA methylation is hence a promising biomarker to triage HPV-positive cytology samples, but may have limited utility in young women. Future studies assessing the likely utility of HPV DNA methylation as a potential triage biomarker must take account of women's age. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Nonlinear regression method for estimating neutral wind and temperature from Fabry-Perot interferometer data.

    Science.gov (United States)

    Harding, Brian J; Gehrels, Thomas W; Makela, Jonathan J

    2014-02-01

    The Earth's thermosphere plays a critical role in driving electrodynamic processes in the ionosphere and in transferring solar energy to the atmosphere, yet measurements of thermospheric state parameters, such as wind and temperature, are sparse. One of the most popular techniques for measuring these parameters is to use a Fabry-Perot interferometer to monitor the Doppler width and breadth of naturally occurring airglow emissions in the thermosphere. In this work, we present a technique for estimating upper-atmospheric winds and temperatures from images of Fabry-Perot fringes captured by a CCD detector. We estimate instrument parameters from fringe patterns of a frequency-stabilized laser, and we use these parameters to estimate winds and temperatures from airglow fringe patterns. A unique feature of this technique is the model used for the laser and airglow fringe patterns, which fits all fringes simultaneously and attempts to model the effects of optical defects. This technique yields accurate estimates for winds, temperatures, and the associated uncertainties in these parameters, as we show with a Monte Carlo simulation.

  1. Fabry-Perot Temperature Sensor for Quasi-Distributed Measurement Utilizing OTDR

    Institute of Scientific and Technical Information of China (English)

    Ping Xu; Fu-Fei Pang; Na Chen; Zhen-Yi Chen; Ting-Yun Wang

    2008-01-01

    A quasi-distributed Fabry-Perot fiber optic temperature sensor array using optical time domain reflectometry (OTDR) technique is presented. The F-P sensor is made by two face to face single-mode optical fibers and their surfaces have been polished. Due to the low reflectivity of the fiber surfaces, the sensor is described as low Fresnel Fabry-Perot interferometer (FPI). The working principle is analyzed using two-beam optical interference approximation. To measure the temperature, a certain temperature sensitive material is filled in the cavity. The slight changes of the reflective intensity which is induced by the refractive index of the material was eaught by OTDR. The length of the cavity is obtained by monitoring the interference spectrum which is used for the setting of the sensor static characteristics within the quasi-linear range. Based on our design, a three point sensor array are fabricated and characterized. The experimental results show that with the temperature increasing from -30℃ to 80℃, the reflectivity increase in a good linear manner. The sensitivity was approximate 0.074 dB℃. For the low transmission loss, more sensors can be integrated.

  2. Formation of super-resolution spot through nonlinear Fabry-Perot cavity structures: theory and simulation.

    Science.gov (United States)

    Wei, Jingsong; Wang, Rui; Yan, Hui; Fan, Yongtao

    2014-04-07

    This study explores how interference manipulation breaks through the diffraction limit and induces super-resolution nano-optical hot spots through the nonlinear Fabry-Perot cavity structure. The theoretical analytical model is established, and the numerical simulation results show that when the thickness of the nonlinear thin film inside the nonlinear Fabry-Perot cavity structure is adjusted to centain value, the constructive interference effect can be formed in the central point of the spot, which causes the nanoscale optical hot spot in the central region to be produced. The simulation results also tell us that the hot spot size is sensitive to nonlinear thin film thickness, and the accuracy is required to be up to nanometer or even subnanometer scale, which is very large challenging for thin film deposition technique, however, slightly changing the incident laser power can compensate for drawbacks of low thickness accuracy of nonlinear thin films. Taking As(2)S(3) as the nonlinear thin film, the central hot spot with a size of 40nm is obtained at suitable nonlinear thin film thickness and incident laser power. The central hot spot size is only about λ/16, which is very useful in super-high density optical recording, nanolithography, and high-resolving optical surface imaging.

  3. Voltage adjusting characteristics in terahertz transmission through Fabry-Pérot-based metamaterials

    Directory of Open Access Journals (Sweden)

    Jun Luo

    2015-10-01

    Full Text Available Metallic electric split-ring resonators (SRRs with featured size in micrometer scale, which are connected by thin metal wires, are patterned to form a periodically distributed planar array. The arrayed metallic SRRs are fabricated on an n-doped gallium arsenide (n-GaAs layer grown directly over a semi-insulating gallium arsenide (SI-GaAs wafer. The patterned metal microstructures and n-GaAs layer construct a Schottky diode, which can support an external voltage applied to modify the device properties. The developed architectures present typical functional metamaterial characters, and thus is proposed to reveal voltage adjusting characteristics in the transmission of terahertz waves at normal incidence. We also demonstrate the terahertz transmission characteristics of the voltage controlled Fabry-Pérot-based metamaterial device, which is composed of arrayed metallic SRRs. To date, many metamaterials developed in earlier works have been used to regulate the transmission amplitude or phase at specific frequencies in terahertz wavelength range, which are mainly dominated by the inductance-capacitance (LC resonance mechanism. However, in our work, the external voltage controlled metamaterial device is developed, and the extraordinary transmission regulation characteristics based on both the Fabry-Pérot (FP resonance and relatively weak surface plasmon polariton (SPP resonance in 0.025-1.5 THz range, are presented. Our research therefore shows a potential application of the dual-mode-resonance-based metamaterial for improving terahertz transmission regulation.

  4. Huntington’s disease blood and brain show a common gene expression pattern and share an immune signature with Alzheimer’s disease

    Science.gov (United States)

    Hensman Moss, Davina J.; Flower, Michael D.; Lo, Kitty K.; Miller, James R. C.; van Ommen, Gert-Jan B.; ’t Hoen, Peter A. C.; Stone, Timothy C.; Guinee, Amelia; Langbehn, Douglas R.; Jones, Lesley; Plagnol, Vincent; van Roon-Mom, Willeke M. C.; Holmans, Peter; Tabrizi, Sarah J.

    2017-01-01

    There is widespread transcriptional dysregulation in Huntington’s disease (HD) brain, but analysis is inevitably limited by advanced disease and postmortem changes. However, mutant HTT is ubiquitously expressed and acts systemically, meaning blood, which is readily available and contains cells that are dysfunctional in HD, could act as a surrogate for brain tissue. We conducted an RNA-Seq transcriptomic analysis using whole blood from two HD cohorts, and performed gene set enrichment analysis using public databases and weighted correlation network analysis modules from HD and control brain datasets. We identified dysregulated gene sets in blood that replicated in the independent cohorts, correlated with disease severity, corresponded to the most significantly dysregulated modules in the HD caudate, the most prominently affected brain region, and significantly overlapped with the transcriptional signature of HD myeloid cells. High-throughput sequencing technologies and use of gene sets likely surmounted the limitations of previously inconsistent HD blood expression studies. Our results suggest transcription is disrupted in peripheral cells in HD through mechanisms that parallel those in brain. Immune upregulation in HD overlapped with Alzheimer’s disease, suggesting a common pathogenic mechanism involving macrophage phagocytosis and microglial synaptic pruning, and raises the potential for shared therapeutic approaches. PMID:28322270

  5. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat

    DEFF Research Database (Denmark)

    Germain, Dominique P; Hughes, Derralynn A; Nicholls, Kathleen

    2016-01-01

    a significant treatment effect: 13 of 32 patients (41%) who received migalastat and 9 of 32 patients (28%) who received placebo had a response at 6 months (P=0.30). Among patients with suitable mutant α-galactosidase who received migalastat for up to 24 months, the annualized changes from baseline...

  6. Fabry's Disease: Case Series and Review of Literature

    African Journals Online (AJOL)

    case series of five patient's along with the review of literature is presented here. Keywords: ... underwent a renal transplant biopsy to ascertain the cause of ... A 16-year-old male presented in March 2002 with a fever of unknown origin and splenomegaly. ... There was no evidence of tuft necrosis/crescent formation or.

  7. Fabry-Perot腔滤波器的数学模型%The Mathematical Model of the Fabry-Perot Filter

    Institute of Scientific and Technical Information of China (English)

    齐永兴; 陈树强; 刘元安; 钱宗珏; 赵国谦

    2004-01-01

    将信号与系统的知识应用于Fabry-Perot(FP)腔滤波器的分析和设计中,避免了繁琐的矩阵运算,而且FP腔滤波器同整个系统紧密地联系在一起,使其成为一个以传递函数为特征的器件,更易于理解和优化设计.

  8. Xyloketal-derived small molecules show protective effect by decreasing mutant Huntingtin protein aggregates in Caenorhabditis elegans model of Huntington’s disease

    Directory of Open Access Journals (Sweden)

    Zeng YX

    2016-04-01

    Full Text Available Yixuan Zeng,1,2,* Wenyuan Guo,1,* Guangqing Xu,3 Qinmei Wang,4 Luyang Feng,1,2 Simei Long,1 Fengyin Liang,1 Yi Huang,1 Xilin Lu,1 Shichang Li,5 Jiebin Zhou,5 Jean-Marc Burgunder,6 Jiyan Pang,5 Zhong Pei1,2 1Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Disease, The First Affiliated Hospital, Sun Yat-sen University, 2Guangzhou Center, Chinese Huntington’s Disease Network, 3Department of Rehabilitation, The First Affiliated Hospital, 4Key laboratory on Assisted Circulation, Ministry of Health, Department of Cardiovascular Medicine of the First Affiliated Hospital, 5School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 6Swiss Huntington’s Disease Center, Department of Neurology, University of Bern, Bern, Switzerland *These authors contributed equally to this work Abstract: Huntington’s disease is an autosomal-dominant neurodegenerative disorder, with chorea as the most prominent manifestation. The disease is caused by abnormal expansion of CAG codon repeats in the IT15 gene, which leads to the expression of a glutamine-rich protein named mutant Huntingtin (Htt. Because of its devastating disease burden and lack of valid treatment, development of more effective therapeutics for Huntington’s disease is urgently required. Xyloketal B, a natural product from mangrove fungus, has shown protective effects against toxicity in other neurodegenerative disease models such as Parkinson’s and Alzheimer’s diseases. To identify potential neuroprotective molecules for Huntington’s disease, six derivatives of xyloketal B were screened in a Caenorhabditis elegans Huntington’s disease model; all six compounds showed a protective effect. Molecular docking studies indicated that compound 1 could bind to residues GLN369 and GLN393 of the mutant Htt protein, forming a

  9. Phase Space of Tristability in Dual Injection-Locked Fabry-Perot Laser Diodes

    Directory of Open Access Journals (Sweden)

    R. V. Pajković

    2015-06-01

    Full Text Available We investigate theoretically the case of dual injection-locking, in which the two light signals are simultaneously externally injected into the cavity of a slave Fabry-Perot laser diode. We show that dual injection-locking leads to formation of new stationary points, and potentially to optical tristability of the slave laser. We show that a region in which the slave laser exhibits three stable steady-states occurs only for sufficiently different frequency detunings of the two injection signals. Moreover, the slave laser tunability depends on the choice of injection modes, and strongly depends on the slave laser bias current, with an optimal value around 2 times threshold current.

  10. BUBBLY: A method for detecting and characterizing interstellar bubbles using Fabry-Perot spectroscopy

    CERN Document Server

    Camps-Fariña, Artemi; Beckman, John E; Font, Joan; García-Lorenzo, Begoña; Erroz-Ferrer, Santiago; Amram, Philippe

    2014-01-01

    We present a new method for the detection and characterization of expansion in galaxy discs based on H{\\alpha} Fabry-Perot spectroscopy, taking advantage of the high spatial and velocity resolution of our instrument (GH{\\alpha}FaS). The method analyses multi-peaked emission line profiles to find expansion along the line of sight on a point-by-point basis. At this stage we have centred our attention on the large scale structures of expanding gas associated with HII regions which show a characteristic pattern of expansion velocities, of order 100 km/s, as a result of both bubble shape and projection effects. We show an example of the expansion map obtained with our method from a superbubble detected in the Antennae galaxies. We use the information obtained from the method to measure the relevant physical parameters of the superbubbles, including their ages which can be used to date young star clusters.

  11. Sibling cases of moyamoya disease having homozygous and heterozygous c.14576G>A variant in RNF213 showed varying clinical course and severity.

    Science.gov (United States)

    Miyatake, Satoko; Touho, Hajime; Miyake, Noriko; Ohba, Chihiro; Doi, Hiroshi; Saitsu, Hirotomo; Taguri, Masataka; Morita, Satoshi; Matsumoto, Naomichi

    2012-12-01

    Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive occlusion of the terminal portion of the internal carotid arteries and their branches. A genetic background was under speculation, because of the high incidence of familial occurrence. Sibling cases usually exhibit a similar clinical course. Recently, RNF213 was identified as the first MMD susceptibility gene. The c.14576G>A variant of RNF213 significantly increases the MMD risk, with an odds ratio of 190.8. Furthermore, there is a strong association between clinical phenotype and the dosage of this variant. The present study described sibling MMD cases having homozygous and heterozygous c.14576G>A variant in RNF213, as well as different clinical course and disease severity. The homozygote of c.14576G>A variant showed an early onset age and rapid disease progress, which resulted in significant neurological deficits with severe and wide distribution of vasculopathy. In contrast, the heterozygote of the variant showed a relatively late-onset age and mild clinical course without irreversible brain lesions with limited distribution of vasculopathy. This is the first report of sibling MMD cases with different doses of the RNF213 variant, showing its genetic impact on clinical phenotype even in members with similar genetic background.

  12. A Fabry-Perot interferometer system for high-speed velocity measurement

    NARCIS (Netherlands)

    Cheng, L.K.; Bruinsma, A.J.A.; Prinse, W.C.; Smorenburg, C.

    1997-01-01

    The Fabry-Perot Velocity Interferometer System (F-PVIS) is designed and built for measuring the Doppler shift of light by recording positional changes in the interferometric pattern behind the Fabry-Perot interferometer. The velocity of a surface can be deduced from the Doppler shift which is caused

  13. A Fabry-Perot interferometer system for high-speed velocity measurement

    NARCIS (Netherlands)

    Cheng, L.K.; Bruinsma, A.J.A.; Prinse, W.C.; Smorenburg, C.

    1997-01-01

    The Fabry-Perot Velocity Interferometer System (F-PVIS) is designed and built for measuring the Doppler shift of light by recording positional changes in the interferometric pattern behind the Fabry-Perot interferometer. The velocity of a surface can be deduced from the Doppler shift which is caused

  14. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory

    Science.gov (United States)

    Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

    2017-01-01

    The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients. PMID:28045968

  15. The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

    Science.gov (United States)

    Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

    2017-01-01

    The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

  16. Holographic liquid crystal polarization grating with Fabry-Perot structure.

    Science.gov (United States)

    Sakamoto, Moritsugu; Yamaguchi, Haruki; Noda, Kohei; Sasaki, Tomoyuki; Kawatsuki, Nobuhiro; Ono, Hiroshi

    2016-03-15

    A holographic liquid crystal polarization grating with a Fabry-Perot structure was developed. Because of its resonant structure, the device offers high levels of control of the diffraction properties of incident-polarized light beams, depending on the resonance conditions. The diffracted light beams are emitted in both the reflection and transmission directions, and the device thus works as a multibranch polarization grating with double optical paths, unlike a conventional polarization grating. These device features were experimentally demonstrated and were also explained theoretically.

  17. A stable fiber-based Fabry-Perot cavity

    CERN Document Server

    Steinmetz, T; Colombe, Y; Hunger, D; Hänsch, T W; Warburton, R J; Reichel, J

    2006-01-01

    We report the development of a fiber-based, tunable optical cavity with open access. The cavity is of the Fabry-Perot type and is formed with miniature spherical mirrors positioned on the end of single- or multi-mode optical fibers by a transfer technique which involves lifting a high-quality mirror from a smooth convex substrate, either a ball lens or micro-lens. The cavities typically have a finesse of $\\sim 1,000$ and a mode volume of 600 $\\mu$m$^3$. We demonstrate the detection of small ensembles of cold Rb atoms guided through such a cavity on an atom chip.

  18. Experimental measurement of photothermal effect in Fabry-Perot cavities

    CERN Document Server

    De Rosa, M L; Cerdonio, M; Pinard, M; Marin, F

    2002-01-01

    We report the experimental observation of the photothermal effect. The measurements are performed by modulating the laser power absorbed by the mirrors of two high-finesse Fabry-Perot cavities. The results are very well described by a recently proposed theoretical model [M. Cerdonio, L. Conti, A. Heidmann and M. Pinard, Phys. Rev. D 63 (2001) 082003], confirming the correctness of such calculations. Our observations and quantitative characterization of the photothermal effect demonstrate its critical importance for high sensitivity interferometric displacement measurements, as those necessary for gravitational wave detection.

  19. A compact LWIR Fourier transform imaging spectrometer employing a variable gap Fabry-Perot interferometer

    Science.gov (United States)

    Zhang, Fang; Gao, Jiaobo; Liu, Fang; Zhao, Yujie; Zheng, Yawei; Zhang, Lei

    2016-10-01

    With unique working principle and spectral characteristic, the long wave infrared (LWIR) interferometric spectral imaging is a popular technology with wide application in many fields. In order to miniaturize and light the instrument, a new method of LWIR spectral imaging system based on a variable gap Fabry-Perot (FP) interferometer is researched. With the system working principle analyzed, theoretically, it is researched that how to make certain the primary parameter, such as, the reflectivity of the two interferometric cavity surfaces and the wedge angle of interferometric cavity. A prototype is developed and good experimental results of blackbody and polypropylene film are obtained. The research shows that besides high throughput and high spectral resolution, the advantage of miniaturization is also simultaneously achieved in this method.

  20. Nonlinear response of an ultracompact waveguide Fabry-Pérot resonator

    Science.gov (United States)

    Sederberg, S.; Elezzabi, A. Y.

    2013-01-01

    We experimentally demonstrate active tuning of an ultracompact silicon-on-insulator trapezoid Fabry-Pérot resonator having a volume of 5.31 μm3. We show that the ultrafast nonlinear dynamics arising from two-photon and free-carrier absorption can be used to achieve a signal attenuation of 66% in the device, and the changes in the steady-state resonant properties of the device resulting from the thermo-optic effect induce a large red-shift in its resonance of Δλ = 7.57 nm. It is envisaged that the insight gained from this class of device will be valuable in the integrated optics community as ultrafast modulators, and switches are designed to occupy smaller volumes.

  1. Light trapping in an ensemble of pointlike impurity centers in a Fabry-Perot cavity

    Science.gov (United States)

    Kuraptsev, A. S.; Sokolov, I. M.

    2016-08-01

    We report the development of quantum microscopic theory of quasiresonant dipole-dipole interaction in the ensembles of impurity atoms imbedded into transparent dielectric and located in a Fabry-Perot cavity. On the basis of the general approach we study the simultaneous influence of the cavity and resonant dipole-dipole interaction on the shape of the line of atomic transition as well as on light trapping in dense impurity ensembles. We analyze this influence depending on the size of the ensemble, its density, as well as on rms deviation of the transition frequency shifts caused by the symmetry disturbance of the internal fields of the dielectric medium. Obtained results are compared with the case when the cavity is absent. We show that the cavity can essentially modify cooperative polyatomic effects.

  2. Light trapping in an ensemble of point-like impurity centers in Fabry-Perot cavity

    CERN Document Server

    Kuraptsev, A S

    2016-01-01

    We report the development of quantum microscopic theory of quasi-resonant dipole-dipole interaction in the ensembles of impurity atoms imbedded into transparent dielectric and located into Fabry-Perot cavity. On the basis of the general approach we study the simultaneous influence of the cavity and resonant dipole-dipole interaction on the shape of the line of atomic transition as well as on light trapping in dense impurity ensembles. We analyze this influence depending on the size of the ensemble, its density, as well as on r.m.s. deviation of the transition frequency shifts caused by the symmetry disturbance of the internal fields of the dielectric medium. Obtained results are compared with the case when the cavity is absent. We show that the cavity can essentially modify cooperative polyatomic effects.

  3. Micro-ring resonator quality factor enhancement via an integrated Fabry-Perot cavity

    Directory of Open Access Journals (Sweden)

    Jiayang Wu

    2017-05-01

    Full Text Available We propose and experimentally demonstrate the enhancement in the filtering quality (Q factor of an integrated micro-ring resonator (MRR by embedding it in an integrated Fabry-Perot (FP cavity formed by cascaded Sagnac loop reflectors. By utilizing coherent interference within the FP cavity to reshape the transmission spectrum of the MRR, both the Q factor and the extinction ratio (ER can be significantly improved. The device is theoretically analyzed and practically fabricated on a silicon-on-insulator wafer. Experimental results show that up to 11-times improvement in the Q factor, together with an 8-dB increase in the ER, can be achieved via our proposed method. The impact of varying structural parameters on the device performance is also investigated and verified by the measured spectra of the fabricated devices with different structural parameters.

  4. Displacement- and laser-noise-free gravitational-wave detection with two Fabry-Perot cavities

    CERN Document Server

    Rakhubovsky, Andrey A

    2008-01-01

    We propose two Fabry-Perot cavities, each pumped through both the mirrors, positioned in line as a toy model of the gravitational-wave (GW) detector free from displacement noise of the test masses. It is demonstrated that the displacement noise of cavity mirrors as well as laser noise can be completely excluded in a proper linear combination of the cavities output signals. We show that in low-frequency approximation (gravitational wave length $\\lambda-\\text{gw}$ is much greater than distance $L$ between mirrors $\\lambda_\\text{gw}\\gg L$) the decrease of response signal is about $(L/\\lambda_\\text{gw})^2$, i.e. signal is stronger than the one of the interferometer recently proposed by S. Kawamura and Y. Chen.

  5. Frequency splitting of polarization eigenmodes in microscopic Fabry-Perot cavities

    CERN Document Server

    Uphoff, Manuel; Rempe, Gerhard; Ritter, Stephan

    2014-01-01

    We study the frequency splitting of the polarization eigenmodes of the fundamental transverse mode in CO2 laser-machined, high-finesse optical Fabry-Perot cavities and investigate the influence of the geometry of the cavity mirrors. Their highly reflective surfaces are typically not rotationally symmetric, but have slightly different radii of curvature along two principal axes. We observe that the eccentricity of such elliptical mirrors lifts the degeneracy of the polarization eigenmodes. The impact of the eccentricity increases for smaller radii of curvature. A model derived from corrections to the paraxial resonator theory is in excellent agreement with measurements, showing that geometric effects are the main source of the frequency splitting of polarization modes for the studied type of microscopic cavity. By rotation of one of the mirrors around the cavity axis, the splitting can be tuned. In the case of an identical differential phase shift per mirror it can even be eliminated, despite a nonvanishing ec...

  6. Highly accurate spectral retardance characterization of a liquid crystal retarder including Fabry-Perot interference effects

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Asticio [Departamento de Ciencias Físicas, Universidad de La Frontera, Temuco (Chile); Center for Optics and Photonics, Universidad de Concepción, Casilla 4016, Concepción (Chile); Mar Sánchez-López, María del [Instituto de Bioingeniería, Universidad Miguel Hernández, 03202 Elche (Spain); García-Martínez, Pascuala [Departament d' Òptica, Universitat de València, 45100 Burjassot (Spain); Arias, Julia; Moreno, Ignacio [Departamento de Ciencia de Materiales, Óptica y Tecnología Electrónica, Universidad Miguel Hernández, 03202 Elche (Spain)

    2014-01-21

    Multiple-beam Fabry-Perot (FP) interferences occur in liquid crystal retarders (LCR) devoid of an antireflective coating. In this work, a highly accurate method to obtain the spectral retardance of such devices is presented. On the basis of a simple model of the LCR that includes FP effects and by using a voltage transfer function, we show how the FP features in the transmission spectrum can be used to accurately retrieve the ordinary and extraordinary spectral phase delays, and the voltage dependence of the latter. As a consequence, the modulation characteristics of the device are fully determined with high accuracy by means of a few off-state physical parameters which are wavelength-dependent, and a single voltage transfer function that is valid within the spectral range of characterization.

  7. 可调Fabry-Perot腔滤波器结构%On the Structure of Fabry-Perot Tunable Optical Filter

    Institute of Scientific and Technical Information of China (English)

    于多多

    2006-01-01

    设计了C波段可调光纤Fabry-Perot腔光滤波器,并对其进行了参数特性及影响因素的分析.器件在较宽的自由光谱区内有良好的滤光特性,可调谐范围广,优于绝大部分其他类型的光滤波器,并且具有较高的精细度特性.

  8. 光纤Fabry-Perot腔振动传感器%Fiber Optical Fabry-Perot Vibration Sensor

    Institute of Scientific and Technical Information of China (English)

    江毅; 刘莉

    2003-01-01

    用频谱分析的方法对光纤Fabry-Perot腔传感器的输出信号进行解调.在正弦振动条件下,用干涉信号的3次谐波与基次波的功率比直接计算出振动幅度,可以简单地解调出信号.这一技术能够满足工程中精度要求不是很高的场合应用.

  9. Error analysis of Fabry-Perot Filter%Fabry-Perot滤光器的误差分析

    Institute of Scientific and Technical Information of China (English)

    常亮; 刘忠

    2007-01-01

    本文介绍了影响Fabry-Perot滤光器性能的几个重要因素,并对其产生的误差进行了分析,主要有相位误差,温度变化对系统产生的误差,光线入射角度偏移所带来的误差以及平板平行度误差和平板面形精度对系统的影响等.

  10. LITAF mutations associated with Charcot-Marie-Tooth disease 1C show mislocalization from the late endosome/lysosome to the mitochondria.

    Directory of Open Access Journals (Sweden)

    Andressa Ferreira Lacerda

    Full Text Available Charcot-Marie-Tooth (CMT disease is one of the most common heritable neuromuscular disorders, affecting 1 in every 2500 people. Mutations in LITAF have been shown to be causative for CMT type 1C disease. In this paper we explore the subcellular localization of wild type LITAF and mutant forms of LITAF known to cause CMT1C (T49M, A111G, G112S, T115N, W116G, L122V and P135T. The results show that LITAF mutants A111G, G112S, W116G, and T115N mislocalize from the late endosome/lysosome to the mitochondria while the mutants T49M, L122V, and P135T show partial mislocalization with a portion of the total protein present in the late endosome/lysosome and the remainder of the protein localized to the mitochondria. This suggests that different mutants of LITAF will produce differing severity of disease. We also explored the effect of the presence of mutant LITAF on wild-type LITAF localization. We showed that in cells heterozygous for LITAF, CMT1C mutants T49M and G112S are dominant since wild-type LITAF localized to the mitochondria when co-transfected with a LITAF mutant. Finally, we demonstrated how LITAF transits to the endosome and mitochondria compartments of the cell. Using Brefeldin A to block ER to Golgi transport we demonstrated that wild type LITAF traffics through the secretory pathway to the late endosome/lysosome while the LITAF mutants transit to the mitochondria independent of the secretory pathway. In addition, we demonstrated that the C-terminus of LITAF is necessary and sufficient for targeting of wild-type LITAF to the late endosome/lysosome and the mutants to the mitochondria. Together these data provide insight into how mutations in LITAF cause CMT1C disease.

  11. Hydrocarbon gas detection with microelectromechanical Fabry-Perot interferometer

    Science.gov (United States)

    Mannila, Rami; Tuohiniemi, Mikko; Mäkynen, Jussi; Näkki, Ismo; Antila, Jarkko

    2013-05-01

    VTT Technical Research Centre of Finland has developed microelectromechanical (MEMS) Fabry-Perot interferometer (FPI) for hydrocarbon measurements. Fabry-Perot interferometer is a structure where is two highly reflective surfaces separated by a tunable air gap. The MEMS FPI is a monolithic device, i.e. it is made entirely on one substrate in a batch process, without assembling separate pieces together. The gap is adjusted by moving the upper mirror with electrostatic force, so there are no actual moving parts. The manufactured MEMS FPIs have been characterized. The tuning wavelength range of the MEMS FPI is 2.8-3.5 μm and its spectral resolution is 50-60 nm. VTT has designed and manufactured a handheld size demonstrator device based on the technology presented in this abstract. This device demonstrates gas detecting by measuring cigarette lighter gas and various plastic materials transmission spectra. The demonstrator contains light source, gas cell, MEMS FPI, detector and control electronics. It is connected to a laptop by USB connection, additional power supply or connection is not needed.

  12. Streamwater chemistry and flow dynamics along vegetation-soil gradient in a subalpine Abies fabri forest watershed,China

    Institute of Scientific and Technical Information of China (English)

    SHAN Bao-qing; WANG Wei-dong; YIN Cheng-qing

    2004-01-01

    Streamwater chemistry and spatial flow dynamics from a subalpine Abies fabri forest in an experimental watershed located in the east slope of Gongga Mountain were analyzed to gain insights into the gradient effect of primary community succession on the stream biogeochemical process. Results showed that high sand content(exceeding 80%) and porosity in the soil(exceeding 20% in A horizon and 35% in B horizon), as well as a thick humus layer on the soil surface, made the water exchange quickly in the Huangbengliu(HBL) watershed. Consequently, no surface runoff was observed, and the stream discharge changed rapidly with the daily precipitation. The flow trends of base ions in the stream water were influenced by the Abies fabri succession gradient. Ca2+, HCO3- and SO42- were the dominant anions in the streamwater in this region. A significant difference of Ca2+, HCO3- and SO42- concentration exported between the succession stages in the watershed can be found. But they had the similar temporal change in the stream flow. Ca2+, HCO3- and SO42- showed significantly negative correlations with the daily precipitation and the stream discharge. Concentrations of Cl-, Na+, K+, and Mg2+ were low in all streamwaters monitored and we observed no differences along the Abies fabri succession gradient. Low ratios of Na:(Na+Ca) (range from 0.1 to 0.2) implied cations were from bedrock weathering(internal source process in the soil system) in this region. But, a variance analysis showed there were almost no differences between rainwater and streamwaters for Mg2+, Na+, K+, and Cl- concentrations. This indicated that they might be come from rainfall inputs (external source). We suggest that the highly mobile capacity, rapid water exchange between precipitation and discharge, and long-term export lead to this observed pattern.

  13. 3,5-Diarylpyrazole Derivatives Obtained by Ammonolysis of the Total Flavonoids from Chrysanthemum indicum Extract Show Potential for the Treatment of Alzheimer's Disease.

    Science.gov (United States)

    Wu, Taizong; Jiang, Cheng; Wang, Ling; Morris-Natschke, Susan L; Miao, Hui; Gu, Lianquan; Xu, Jun; Lee, Kuo-Hsiung; Gu, Qiong

    2015-07-24

    Four new 3,5-diarylpyrazole analogues (1-4) were isolated from an extract of the flowers of Chrysanthemun indicum using a combination of ammonolysis of the total flavonoid extract and an Aβ aggregation inhibitory activity guided purification procedure. All four compounds (1-4) showed moderate to potent activity against Aβ aggregation with EC50 values of 4.3, 15.8, 1.3, and 2.9 μM, respectively. Moreover, compound 3 showed low cytotoxicity and significant neuroprotective activity against Aβ-induced cytotoxicity in the SH-SY5Y cell line. This report is the first to show that 3,5-diarylpyrazole analogues can inhibit Aβ aggregation and exhibit neuroprotective activity with potential for the treatment of Alzheimer's disease. Taken together, the method presented here offers an alternative approach to yield bioactive compounds.

  14. Extensive proteomic screening identifies the obesity-related NYGGF4 protein as a novel LRP1-interactor, showing reduced expression in early Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Taddei Kevin

    2010-01-01

    Full Text Available Abstract Background The low-density lipoprotein receptor related protein 1 (LRP1 has been implicated in Alzheimer's disease (AD but its signalling has not been fully evaluated. There is good evidence that the cytoplasmic domain of LRP1 is involved in protein-protein interactions, important in the cell biology of LRP1. Results We carried out three yeast two-hybrid screens to identify proteins that interact with the cytoplasmic domain of LRP1. The screens included both conventional screens as well as a novel, split-ubiquitin-based screen in which an LRP1 construct was expressed and screened as a transmembrane protein. The split-ubiquitin screen was validated in a screen using full-length amyloid protein precursor (APP, which successfully identified FE65 and FE65L2, as well as novel interactors (Rab3a, Napg, and ubiquitin b. Using both a conventional screen as well as the split-ubiquitin screen, we identified NYGGF4 as a novel LRP1 interactor. The interaction between LRP1 and NYGGF4 was validated using two-hybrid assays, coprecipitation and colocalization in mammalian cells. Mutation analysis demonstrated a specific interaction of NYGGF4 with an NPXY motif that required an intact tyrosine residue. Interestingly, while we confirmed that other LRP1 interactors we identified, including JIP1B and EB-1, were also able to bind to APP, NYGGF4 was unique in that it showed specific binding with LRP1. Expression of NYGGF4 decreased significantly in patients with AD as compared to age-matched controls, and showed decreasing expression with AD disease progression. Examination of Nyggf4 expression in mice with different alleles of the human APOE4 gene showed significant differences in Nyggf4 expression. Conclusions These results implicate NYGGF4 as a novel and specific interactor of LRP1. Decreased expression of LRP1 and NYGGF4 over disease, evident with the presence of even moderate numbers of neuritic plaques, suggests that LRP1-NYGGF4 is a system altered

  15. Fiber Current Sensor Based on Fabry-Perot%基于光纤Fabry-Perot的电流传感器

    Institute of Scientific and Technical Information of China (English)

    刘京诚; 姚小芳; 陈小强; 刘俊

    2007-01-01

    利用光纤抗电磁干扰、绝缘性好, 体积小等特性,提出一种新型的光纤电流传感器. 该传感器将悬臂梁结构和光纤Fabry-Perot相结合,基于材料力学理论和电磁感应原理,利用Fabry-Perot干涉仪原理来实现对电流的测量. 在解调方式上采用了相位解调法,分析了该传感器的工作原理及光纤F-P的测量原理,建立了光纤F-P腔的数学模型,推导出电流检测理论公式,并进行了相关实验,证明该电流传感器具有绝缘性好、结构简单、灵敏度高等优点.

  16. Focused ion beam post-processing of optical fiber Fabry-Perot cavities for sensing applications.

    Science.gov (United States)

    André, Ricardo M; Pevec, Simon; Becker, Martin; Dellith, Jan; Rothhardt, Manfred; Marques, Manuel B; Donlagic, Denis; Bartelt, Hartmut; Frazão, Orlando

    2014-06-01

    Focused ion beam technology is combined with chemical etching of specifically designed fibers to create Fabry-Perot interferometers. Hydrofluoric acid is used to etch special fibers and create microwires with diameters of 15 μm. These microwires are then milled with a focused ion beam to create two different structures: an indented Fabry-Perot structure and a cantilever Fabry-Perot structure that are characterized in terms of temperature. The cantilever structure is also sensitive to vibrations and is capable of measuring frequencies in the range 1 Hz - 40 kHz.

  17. A novel Michelson Fabry-Perot hybrid interference sensor based on the micro-structured fiber

    Science.gov (United States)

    Zhang, Yaxun; Zhang, Yu; Wang, Zhenzhen; Liu, Zhihai; Wei, Yong; Zhao, Enming; Yang, Xinghua; Zhang, Jianzhong; Yang, Jun; Yuan, Libo

    2016-09-01

    We propose and demonstrate a novel Michelson Fabry-Perot hybrid fiber interference sensor. By integrating a Michelson interferometer in a two-core fiber and a Fabry-Perot interferometer in a micro silica-capillary, we produce the Michelson Fabry-Perot hybrid interference sensor. Owing to the structure characteristic of the micro-structured fiber, this hybrid fiber interference sensor can achieve the measurement of the axial strain and radial bending simultaneously. The measurement sensitivity of the axial train is 0.015 nm/με and the measurement sensitivity of the radial bending is 1.393 nm/m-1.

  18. Two-Color Fabry-Perot Laser Diode with THz Primary Mode Spacing

    CERN Document Server

    O'Brien, S; Buckley, K; Fehse, R; Amann, A; O'Reilly, E P; Barry, L P; Anandarajah, P; Patchell, J; O'Gorman, J

    2006-01-01

    A class of multiwavelength Fabry-Perot lasers is introduced where the spectrum is tailored through a non-periodic patterning of the cavity effective index. The cavity geometry is obtained using an inverse scattering approach and can be designed such that the spacing of discrete Fabry-Perot lasing modes is limited only by the bandwidth of the inverted gain medium. A specific two-color semiconductor laser with a mode spacing in the THz regime is designed, and measurements are presented demonstrating the simultaneous oscillation of the two wavelengths. The extension of the Fabry-Perot laser concept described presents significant new possibilities in laser cavity design.

  19. Fabry-perot multilayers for enhancing the diffraction efficiency of ion-implanted gratings.

    Science.gov (United States)

    Escoubas, L; Flory, F O; Lemarchand, F; Drouard, E; Roux, L; Tisserand, S; Albrand, G

    2001-04-01

    Enhancement of the free-space diffraction efficiency of gratings made by titanium-ion implantation is demonstrated both theoretically and experimentally. Indeed, by insertion of a grating into a multilayer dielectric Fabry-Perot cavity, the diffraction efficiency can be increased to as much as 24 times that of a single grating. The sensitivity of the diffraction efficiency to the optogeometrical parameters of the grating or of the Fabry-Perot cavity is discussed. Moreover, a process for performance of a phase grating inside a Fabry-Perot cavity is described, and experimental results concerning efficiency measurements are compared with computed values for various grating periods.

  20. Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.

    Science.gov (United States)

    Grealish, Shane; Diguet, Elsa; Kirkeby, Agnete; Mattsson, Bengt; Heuer, Andreas; Bramoulle, Yann; Van Camp, Nadja; Perrier, Anselme L; Hantraye, Philippe; Björklund, Anders; Parmar, Malin

    2014-11-06

    Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson's disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Human ESC-Derived Dopamine Neurons Show Similar Preclinical Efficacy and Potency to Fetal Neurons when Grafted in a Rat Model of Parkinson’s Disease

    Science.gov (United States)

    Grealish, Shane; Diguet, Elsa; Kirkeby, Agnete; Mattsson, Bengt; Heuer, Andreas; Bramoulle, Yann; Van Camp, Nadja; Perrier, Anselme L.; Hantraye, Philippe; Björklund, Anders; Parmar, Malin

    2014-01-01

    Summary Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson’s disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson’s disease. PMID:25517469

  2. Fabry-Perot Observations of HH 1/2

    Directory of Open Access Journals (Sweden)

    A. Riera

    2005-01-01

    Full Text Available Presentamos nuevas observaciones Fabry-Perot del sistema HH1/2 en la l nea de H. Se han obtenidos los perfiles de las l neas, y los mapas de velocidad radial y de dispersi n de velocidades a partir de los canales de velocidad de los objetos HH 1 y HH 2. La distribuci on espacial de la velocidad radial de ambos objetos (HH 1, HH 2 presenta material desplazado al rojo hacia la fuente, y material desplazado al azul alej ndose de la fuente. Un modelo que contempla la presencia de emisi n directa+dispersada con tres condensaciones emisoras reproduce cualitativamente la distribuci n espacial de la velocidad radial y de la dispersi n de velocidades de HH 2.

  3. Fourier transform spectrometer based on Fabry-Perot interferometer.

    Science.gov (United States)

    Al-Saeed, Tarek A; Khalil, Diaa A

    2016-07-10

    We analyze the Fourier transform spectrometer based on a symmetric/asymmetric Fabry-Perot interferometer. In this spectrometer, the interferogram is obtained by recording the intensity as a function of the interferometer length. Then, we recover the spectrum by applying the discrete Fourier transform (DFT) directly on the interferogram. This technique results in spectral harmonic overlap and fictitious wavenumber components outside the original spectral range. For this purpose, in this work, we propose a second method to recover the spectrum. This method is based on expanding the DFT of the interferogram and the spectrum by a Haar or box function. By this second method, we recovered the spectrum and got rid of the fictitious spectral components and spectral harmonic overlap.

  4. A Fabry-Perot Microcavity for Diamond-Based Photonics

    CERN Document Server

    Janitz, Erika; Dimock, Mark; Bourassa, Alexandre; Sankey, Jack; Childress, Lilian

    2015-01-01

    Open Fabry-Perot microcavities represent a promising route for achieving a quantum electrodynamics (cavity-QED) platform with diamond-based emitters. In particular, they offer the opportunity to introduce high purity, minimally fabricated material into a tunable, high quality factor optical resonator. Here, we demonstrate a fiber-based microcavity incorporating a thick (> 10 {\\mu}m) diamond membrane with a finesse of 17,000, corresponding to a quality factor Q ~ $10^6$. Such minimally fabricated, thick samples can contain optically stable emitters similar to those found in bulk diamond. We observe modified microcavity spectra in the presence of the membrane, and develop analytic and numerical models to describe the effect of the membrane on cavity modes, including loss and coupling to higher-order transverse modes. We estimate that a Purcell enhancement of approximately 20 should be possible for emitters within the diamond in this device, and provide evidence that better diamond surface treatments and mirror ...

  5. Intrinsic Fabry-Perot optical fiber sensors and their multiplexing

    Science.gov (United States)

    Wang, Anbo

    2007-12-11

    An intrinsic Fabry-Perot optical sensor includes a thin film sandwiched between two fiber ends. When light is launched into the fiber, two reflections are generated at the two fiber/thin film interfaces due to a difference in refractive indices between the fibers and the film, giving rise to the sensor output. In another embodiment, a portion of the cladding of a fiber is removed, creating two parallel surfaces. Part of the evanescent fields of light propagating in the fiber is reflected at each of the surfaces, giving rise to the sensor output. In a third embodiment, the refractive index of a small portion of a fiber is changed through exposure to a laser beam or other radiation. Interference between reflections at the ends of the small portion give rise to the sensor output. Multiple sensors along a single fiber are multiplexed using an optical time domain reflectometry method.

  6. Photoacoustic imaging using an 8-beam Fabry-Perot scanner

    Science.gov (United States)

    Huynh, Nam; Ogunlade, Olumide; Zhang, Edward; Cox, Ben; Beard, Paul

    2016-03-01

    The planar Fabry Perot (FP) photoacoustic scanner has been shown to provide exquisite high resolution 3D images of soft tissue structures in vivo to depths up to approximately 10mm. However a significant limitation of current embodiments of the concept is low image acquisition speed. To increase acquisition speed, a novel multi-beam scanner architecture has been developed. This enables a line of equally spaced 8 interrogation beams to be scanned simultaneously across the FP sensor and the photoacoustic signals detected in parallel. In addition, an excitation laser operating at 200Hz was used. The combination of parallelising the detection and the high pulse repetition frequency (PRF) of the excitation laser has enabled dramatic reductions in image acquisition time to be achieved. A 3D image can now be acquired in 10 seconds and 2D images at video rates are now possible.

  7. Diffractively coupled Fabry-Perot resonator with power-recycling

    CERN Document Server

    Britzger, Michael; Kroker, Stefanie; Brückner, Frank; Burmeister, Oliver; Kley, Ernst-Bernhard; Tünnermann, Andreas; Danzmann, Karsten; Schnabel, Roman

    2011-01-01

    We demonstrate the optical coupling of two cavities without light transmission through a substrate. Compared to a conventional coupling component, that is a partially transmissive mirror, an all-reflective coupler avoids light absorption in the substrate and therefore associated thermal problems, and even allows the use of opaque materials with possibly favourable mechanical and thermal properties. Recently, the all-reflective coupling of two cavities with a low-efficiency 3-port diffraction grating was theoretically investigated. Such a grating has an additional (a third) port. However, it was shown that the additional port does not necessarily decrease the bandwidth of the coupled cavities. Such an all-reflective scheme for cavity coupling is of interest in the field of gravitational wave detection. In such detectors light that is resonantly enhanced inside the so-called power-recycling cavity is coupled to (kilometre-scale) Fabry-Perot resonators representing the arms of a Michelson interferometer. In orde...

  8. Fiber Fabry-Perot cavity with high finesse

    CERN Document Server

    Hunger, David; Colombe, Yves; Deutsch, Christian; Hänsch, Theodor W; Reichel, Jakob

    2010-01-01

    We have realized a fiber-based Fabry-Perot cavity with CO2 laser-machined mirrors. It combines very small size, high finesse F>=130000, small waist and mode volume, and good mode matching between the fiber and cavity modes. This combination of features is a major advance for cavity quantum electrodynamics (CQED), as shown in recent CQED experiments with Bose-Einstein condensates enabled by this cavity [Y. Colombe et al., Nature 450, 272 (2007)]. It should also be suitable for a wide range of other applications, including coupling to solid-state emitters, gas detection at the single-particle level, fiber-coupled single-photon sources and high-resolution optical filters with large stopband.

  9. Fabry-Perot enhanced Faraday rotation in graphene.

    Science.gov (United States)

    Ubrig, Nicolas; Crassee, Iris; Levallois, Julien; Nedoliuk, Ievgeniia O; Fromm, Felix; Kaiser, Michl; Seyller, Thomas; Kuzmenko, Alexey B

    2013-10-21

    We demonstrate that giant Faraday rotation in graphene in the terahertz range due to the cyclotron resonance is further increased by constructive Fabry-Perot interference in the supporting substrate. Simultaneously, an enhanced total transmission is achieved, making this effect doubly advantageous for graphene-based magneto-optical applications. As an example, we present far-infrared spectra of epitaxial multilayer graphene grown on the C-face of 6H-SiC, where the interference fringes are spectrally resolved and a Faraday rotation up to 0.15 radians (9°) is attained. Further, we discuss and compare other ways to increase the Faraday rotation using the principle of an optical cavity.

  10. Experimental Chagas disease in Balb/c mice previously vaccinated with T. rangeli. II. The innate immune response shows immunological memory: reality or fiction?

    Science.gov (United States)

    Basso, B; Marini, V

    2015-03-01

    Trypanosoma cruzi is a real challenge to the host's immune system, because it requires strong humoral and cellular immune response to remove circulating trypomastigote forms, and to prevent the replication of amastigote forms in tissues, involving many regulator and effector components. This protozoan is responsible for Chagas disease, a major public health problem in Latinamerica. We have developed a model of vaccination with Trypanosoma rangeli, a parasite closely related to T. cruzi, but nonpathogenic to humans, which reduces the infectiousness in three different species of animals, mice, dogs and guinea pigs, against challenge with T. cruzi. In a previous work, we demonstrated that mice vaccinated with T. rangeli showed important soluble mediators that stimulate phagocytic activity versus only infected groups. The aim of this work was to study the innate immune response in mice vaccinated or not with T. rangeli. Different population cells and some soluble mediators (cytokines) in peritoneal fluid and plasma in mice vaccinated-infected and only infected with T. cruzi were studied. In the first hours of challenge vaccinated mice showed an increase of macrophages, NK, granulocytes, and regulation of IL6, IFNγ, TNFα and IL10, with an increase of IL12, with respect to only infected mice. Furthermore an increase was observed of Li T, Li B responsible for adaptative response. Finally the findings showed that the innate immune response plays an important role in vaccinated mice for the early elimination of the parasites, complementary with the adaptative immune response, suggesting that vaccination with T. rangeli modulates the innate response, which develops some kind of immunological memory, recognizing shared antigens with T. cruzi. These results could contribute to the knowledge of new mechanisms which would have an important role in the immune response to Chagas disease. Copyright © 2014 Elsevier GmbH. All rights reserved.

  11. Experimental Chagas disease. Innate immune response in Balb/c mice previously vaccinated with Trypanosoma rangeli. I. The macrophage shows immunological memory: Reality or fiction?

    Science.gov (United States)

    Basso, B; Marini, V

    2014-04-01

    Chagas' disease, caused by Trypanosoma cruzi, is a major vector borne health problem in Latin America and an emerging or re-emerging infectious disease in several countries. Immune response to T. cruzi infection is highly complex and involves many components, both regulators and effectors. Although different parasites have been shown to activate different mechanisms of innate immunity, T. cruzi is often able to survive and replicate in its host because they are well adapted to resisting host defences. An experimental model for vaccinating mice with Trypanosoma rangeli, a parasite closely related to T. cruzi, but nonpathogenic to humans, has been designed in our laboratory, showing protection against challenge with T. cruzi infection. The aim of this work was to analyze some mechanisms of the early innate immune response in T. rangeli vaccinated mice challenged with T. cruzi. For this purpose, some interactions were studied between T. cruzi and peritoneal macrophages of mice vaccinated with T. rangeli, infected or not with T. cruzi and the levels of some molecules or soluble mediators which could modify these interactions. The results in vaccinated animals showed a strong innate immune response, where the adherent cells of the vaccinated mice revealed important phagocytic activity, and some soluble mediator (Respiratory Burst: significantly increase, p ≤ 0.03; NO: the levels of vaccinated animals were lower than those of the control group; Arginasa: significantly increase, p ≤ 0.04). The results showed an important role in the early elimination of the parasites and their close relation with the absence of histological lesions that these animals present with regard to the only infected mice. This behaviour reveals that the macrophages act with some type of memory, recognizing the antigens to which they have previously been exposed, in mice were vaccinated with T. rangeli, which shares epitopes with T. cruzi. Copyright © 2013 Elsevier GmbH. All rights reserved.

  12. Micromachined fiber optic Fabry-Perot underwater acoustic probe

    Science.gov (United States)

    Wang, Fuyin; Shao, Zhengzheng; Hu, Zhengliang; Luo, Hong; Xie, Jiehui; Hu, Yongming

    2014-08-01

    One of the most important branches in the development trend of the traditional fiber optic physical sensor is the miniaturization of sensor structure. Miniature fiber optic sensor can realize point measurement, and then to develop sensor networks to achieve quasi-distributed or distributed sensing as well as line measurement to area monitoring, which will greatly extend the application area of fiber optic sensors. The development of MEMS technology brings a light path to address the problems brought by the procedure of sensor miniaturization. Sensors manufactured by MEMS technology possess the advantages of small volume, light weight, easy fabricated and low cost. In this paper, a fiber optic extrinsic Fabry-Perot interferometric underwater acoustic probe utilizing micromachined diaphragm collaborated with fiber optic technology and MEMS technology has been designed and implemented to actualize underwater acoustic sensing. Diaphragm with central embossment, where the embossment is used to anti-hydrostatic pressure which would largely deflect the diaphragm that induce interferometric fringe fading, has been made by double-sided etching of silicon on insulator. By bonding the acoustic-sensitive diaphragm as well as a cleaved fiber end in ferrule with an outer sleeve, an extrinsic Fabry-Perot interferometer has been constructed. The sensor has been interrogated by quadrature-point control method and tested in field-stable acoustic standing wave tube. Results have been shown that the recovered signal detected by the sensor coincided well with the corresponding transmitted signal and the sensitivity response was flat in frequency range from 10 Hz to 2kHz with the value about -154.6 dB re. 1/μPa. It has been manifest that the designed sensor could be used as an underwater acoustic probe.

  13. Fabry-Perot Based Ranging Interferometer Receiver for High Spectral Resolution Lidar Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Michigan Aerospace Corporation (MAC) is pleased to present the following Phase II proposal for a Fabry-Perot Based Interferometer Receiver for the High Spectral...

  14. A Novel Technique to Measure Gain Spectrum for Fabry-Pérot Semiconductor Lasers

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A novel gain measurement technique based on the integration of the measured amplified spontaneous emission spectrum multiplying a phase function over one longitudinal mode interval is proposed for Fabry-Perot semiconductor lasers.

  15. Sinusoidal Phase-Modulating Fabry-Perot Interferometer for Angular Displacement Measurement

    Institute of Scientific and Technical Information of China (English)

    Caini Zhang; Xiangzhao Wang

    2003-01-01

    In this paper, a sinusoidal phase-modulating Fabry-Perot interferometer is proposed to measure angular displacement.The usefulness of the interferometer is demonstrated by simulations and experiments.

  16. Compact High-Resolution Broad-Band Terahertz Fabry-Perot Spectrometer Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Our objective is to develop a compact scanning Fabry-Perot spectrometer, for satellite far-infrared astronomy and Earth remote sensing, that operates at wavelengths...

  17. Sinusoidal Phase-Modulating Fabry-Perot Interferometer for Angular Displacement Measurement

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    In this paper, a sinusoidal phase-modulating Fabry-Perot interferometer is proposed to measure angular displacement. The usefulness of the interferometer is demonstrated by simulations and experiments.

  18. Rugged Low Temperature Actuators for Tunable Fabry Perot Optical Filters Project

    Data.gov (United States)

    National Aeronautics and Space Administration — During our Phase I SBIR research, we propose to integrate a novel low-temperature large-strain actuator technology into Fabry-Perot optical filters. The resulting...

  19. GATA2 mutations in patients with acute myeloid leukemia-paired samples analyses show that the mutation is unstable during disease evolution.

    Science.gov (United States)

    Hou, Hsin-An; Lin, Yun-Chu; Kuo, Yuan-Yeh; Chou, Wen-Chien; Lin, Chien-Chin; Liu, Chieh-Yu; Chen, Chien-Yuan; Lin, Liang-In; Tseng, Mei-Hsuan; Huang, Chi-Fei; Chiang, Ying-Chieh; Liu, Ming-Chih; Liu, Chia-Wen; Tang, Jih-Luh; Yao, Ming; Huang, Shang-Yi; Ko, Bor-Sheng; Hsu, Szu-Chun; Wu, Shang-Ju; Tsay, Woei; Chen, Yao-Chang; Tien, Hwei-Fang

    2015-02-01

    Recently, mutations of the GATA binding protein 2 (GATA2) gene were identified in acute myeloid leukemia (AML) patients with CEBPA double mutations (CEBPA (double-mut)), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, 14 different missense GATA2 mutations, which were all clustered in the highly conserved N-terminal zinc finger 1 domain, were identified in 27.4, 6.7, and 1 % of patients with CEBPA (double-mut), CEBPA (single-mut), and CEBPA wild type, respectively. All but one patient with GATA2 mutation had concurrent CEBPA mutation. GATA2 mutations were closely associated with younger age, FAB M1 subtype, intermediate-risk cytogenetics, expression of HLA-DR, CD7, CD15, or CD34 on leukemic cells, and CEBPA mutation, but negatively associated with FAB M4 subtype, favorable-risk cytogenetics, and NPM1 mutation. Patients with GATA2 mutation had significantly better overall survival and relapse-free survival than those without GATA2 mutation. Sequential analysis showed that the original GATA2 mutations might be lost during disease progression in GATA2-mutated patients, while novel GATA2 mutations might be acquired at relapse in GATA2-wild patients. In conclusion, AML patients with GATA2 mutations had distinct clinic-biological features and a favorable prognosis. GATA2 mutations might be lost or acquired at disease progression, implying that it was a second hit in the leukemogenesis of AML, especially those with CEBPA mutation.

  20. TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution.

    Science.gov (United States)

    Hou, H-A; Chou, W-C; Kuo, Y-Y; Liu, C-Y; Lin, L-I; Tseng, M-H; Chiang, Y-C; Liu, M-C; Liu, C-W; Tang, J-L; Yao, M; Li, C-C; Huang, S-Y; Ko, B-S; Hsu, S-C; Chen, C-Y; Lin, C-T; Wu, S-J; Tsay, W; Chen, Y-C; Tien, H-F

    2015-07-31

    The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

  1. Field vaccinated chickens with low antibody titres show equally insufficient protection against matching and non-matching genotypes of virulent Newcastle disease virus.

    Science.gov (United States)

    Dortmans, J C F M; Venema-Kemper, S; Peeters, B P H; Koch, G

    2014-08-06

    Newcastle disease (ND) is a severe threat to the poultry industry and is caused by virulent strains of Newcastle disease virus (NDV). Many countries maintain a vaccination policy, but NDV is rapidly evolving as shown by the discovery of several new genotypes in the last decades. We tested the efficacy of the currently used classical commercial ND vaccine based on the genotype II strain VG/GA, applied under standard field conditions, against outbreak strains. Field vaccinated broilers were challenged with four different viruses belonging to genotype II, V or VII. A large proportion of field vaccinated broilers showed suboptimal immunity and the protection level against early and recent NDV isolates was dramatically low. Furthermore, there were no significant differences in protection afforded by a genotype II vaccine against a genotype II virus challenge compared to a challenge with viruses belonging to the other genotypes. This study suggests that the susceptibility of vaccinated poultry to NDV infection is not the result of vaccine mismatch, but rather of poor vaccination practices.

  2. Engineering-reflected phase in Fabry-Perot sensors with resonant mirrors.

    Science.gov (United States)

    Gellineau, Antonio; Wong, Yu-Po; Solgaard, Olav

    2013-12-01

    Fabry-Perot cavities made with photonic crystal (PC) mirrors and other resonant structures exhibit nontraditional characteristics due to the strong wavelength dependence of their reflected phase. This Letter describes how engineering the phase of PC mirrors enables sensors that are tolerant to variations in laser center frequency and line width. Reflection spectra measurements of Fabry-Perot cavities made with PC mirrors were collected as a function of wavelength and cavity length, providing experimental verification of theory and simulations.

  3. Compact imaging spectrometer combining Fourier transform spectroscopy with a Fabry-Perot interferometer.

    Science.gov (United States)

    Pisani, Marco; Zucco, Massimo

    2009-05-11

    An imaging spectrometer based on a Fabry-Perot interferometer is presented. The Fabry-Perot interferometer scans the mirror distance up to contact and the intensity modulated light signal is transformed using a Fourier Transform based algorithm, as the Michelson based Fourier Transform Spectrometers does. The resulting instrument has the advantage of a compact, high numerical aperture, high luminosity hyperspectral imaging device. Theory of operation is described along with one experimental realization and preliminary results.

  4. A Study of the Chaos of Non-linear Fabry-Perot Resonator%含非线性介质Fabry-Perot腔混沌研究

    Institute of Scientific and Technical Information of China (English)

    袁圣付; 姜宗福

    2000-01-01

    根据混沌动力学的基本理论,计算了含非线性介质Fabry-Perot腔动力学方程在其参数下的Lyapunov指数分布图.利用Lyapunov指数和动力学特性的对应关系,分析出非线性Fabry-Perot腔在各种参数下的动力学特性、稳态参数区域面积和混沌转换机制.

  5. Influence of intensity loss in the cavity of a folded Fabry-Perot interferometer on interferometric signals.

    Science.gov (United States)

    Shyu, Lih-Horng; Chang, Chung-Ping; Wang, Yung-Cheng

    2011-06-01

    Fabry-Perot interferometer is often used for the micro-displacement, because of its common optical path structure being insensitive to the environmental disturbances. Recently, the folded Fabry-Perot interferometer has been investigated for displacement measurements in large ranges. The advantages of a folded Fabry-Perot interferometer are insensitive to the tilt angle and higher optical resolution. But the design of the optical cavity has become more and more complicated. For this reason, the intensity loss in the cavity will be an important parameter for the distribution of the interferometric intensity. To obtain a more accurate result of such interferometer utilized for displacement measurements, the intensity loss of the cavity in the fabricated folded Fabry-Perot interferometer and the modified equation of the folded Fabry-Perot interferometer will be described. According to the theoretical and experimental results, the presented model is available for the analysis of displacement measurements by a folded Fabry-Perot interferometer.

  6. Fiber Optic Fabry-Perot Current Sensor Integrated with Magnetic Fluid Using a Fiber Bragg Grating Demodulation

    Directory of Open Access Journals (Sweden)

    Ji Xia

    2015-07-01

    Full Text Available An optical fiber current sensor based on Fabry-Perot interferometer using a fiber Bragg grating demodulation is proposed. Magnetic fluid is used as a sensitive medium in fiber optical Fabry-Perot (F-P cavity for the optical characteristic of magnetic-controlled refractive index. A Fiber Bragg grating (FBG is connected after the F-P interferometer which is used to reflect the optical power at the Bragg wavelength of the interference transmission spectrum. The corresponding reflective power of the FBG will change with different external current intensity, due to the shift on the interference spectrum of the F-P interferometer. The sensing probe has the advantages of convenient measurement for its demodulation, low cost and high current measurement accuracy on account of its sensing structure. Experimental results show that an optimal sensitivity of 0.8522 nw/A and measurement resolution of 0.001 A is obtained with a FBG at 1550 nm with 99% reflectivity.

  7. Airborne Doppler lidar at 532nm based on a tunable dual-channel Fabry-Perot interferometer

    Science.gov (United States)

    Feng, Jian-mei; Xing, Ting-wen; Lin, Wi-mei

    2009-07-01

    The aim of this paper is to explore a high-precision, a wide range of a frequency discrimination technique, and to study the application of this technique in the optical air data system (MOADS). To overcome the traditional equipment's shortcomings of short velocity detecting range such as pilot static tubes and wind wane, this technique can provide precision aviation data for various aerocrafts , without influencing pneumatic shape and performance of aerocraft. A tunable dual channel Fabry-Perot interferometer is used as a frequency discriminator in an airborne wind lidar system. This new frequency discriminator has been proposed to overcome the exiting frequency discriminator shortcoming. By adjusting the cavity length of interferometer, the speed of aerocraft can be detected and cut into several dynamic range. By this way, the Doppler wind lidar system can detect atmospheric parameters at the meantime, such as speed of aerocraft and temperature of atmosphere around the aerocraft, by analyzing the information of Rayleigh backscattering light. There are three main contribution in this paper: the first is discussing the basic theory of MOADS, calculational method and mathematic model of relative wind velocity between aircraft and wind are put forward.; the second is the parameter optimization of the dual-channel Fabry-Perot interferometer and the structure design of the interferometer; the third is the simulation of the performance and the accuracy of this system. Theory analysis and simulation results show this method is reasonable and practical.

  8. [A case of Charcot-Marie-Tooth disease 1 B with Val 146Phe mutation of myelin protein zero showing a severe clinical phenotype].

    Science.gov (United States)

    Ohnishi, A; Aoki, A; Yamamoto, T; Tsuji, S

    2000-03-01

    A 15-year-old boy had complaints of progressive gait disturbance and foot deformity. He started to walk at the age of 18 months. Since two years of age, he had noticed unstable gait. He showed evident scoliosis and enlarged great auricular nerves. Moderate to slight degrees of muscular atrophy and weakness of distal upper, and proximal and distal lower limbs were observed. Pes equinovarus deformity of both feet was obvious. Muscle stretch reflexes were absent in both limbs except decreased triceps brachii reflex. Vibratory sensation was decreased severely in the toes and mildly in the fingers. In cerebrospinal fluid, protein was mildly elevated. Median nerve motor conduction velocity was 5.0 m/sec. On sural nerve biopsy, both demyelinated and remyelinated axons and onion-bulbs without hypomyelination were observed. Therefore, the diagnosis of Charcot-Marie-Tooth disease 1 was made. The direct sequencing of the genomic DNA encoding the Po gene revealed a mutant allele, a guanine to thymine substitution of nucleotide position 436, which caused a substitution of phenylalanine for valine at amino acid position 146. This type of Po mutation is different from any type of Po mutation reported in the literature.

  9. α-Synuclein Shows High Affinity Interaction with Voltage-dependent Anion Channel, Suggesting Mechanisms of Mitochondrial Regulation and Toxicity in Parkinson Disease.

    Science.gov (United States)

    Rostovtseva, Tatiana K; Gurnev, Philip A; Protchenko, Olga; Hoogerheide, David P; Yap, Thai Leong; Philpott, Caroline C; Lee, Jennifer C; Bezrukov, Sergey M

    2015-07-24

    Participation of the small, intrinsically disordered protein α-synuclein (α-syn) in Parkinson disease (PD) pathogenesis has been well documented. Although recent research demonstrates the involvement of α-syn in mitochondrial dysfunction in neurodegeneration and suggests direct interaction of α-syn with mitochondria, the molecular mechanism(s) of α-syn toxicity and its effect on neuronal mitochondria remain vague. Here we report that at nanomolar concentrations, α-syn reversibly blocks the voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane that controls most of the metabolite fluxes in and out of the mitochondria. Detailed analysis of the blockage kinetics of VDAC reconstituted into planar lipid membranes suggests that α-syn is able to translocate through the channel and thus target complexes of the mitochondrial respiratory chain in the inner mitochondrial membrane. Supporting our in vitro experiments, a yeast model of PD shows that α-syn toxicity in yeast depends on VDAC. The functional interactions between VDAC and α-syn, revealed by the present study, point toward the long sought after physiological and pathophysiological roles for monomeric α-syn in PD and in other α-synucleinopathies.

  10. Oral Migalastat HCl Leads to Greater Systemic Exposure and Tissue Levels of Active α-Galactosidase A in Fabry Patients when Co-Administered with Infused Agalsidase.

    Directory of Open Access Journals (Sweden)

    David G Warnock

    Full Text Available Migalastat HCl (AT1001, 1-Deoxygalactonojirimycin is an investigational pharmacological chaperone for the treatment of α-galactosidase A (α-Gal A deficiency, which leads to Fabry disease, an X-linked, lysosomal storage disorder. The currently approved, biologics-based therapy for Fabry disease is enzyme replacement therapy (ERT with either agalsidase alfa (Replagal or agalsidase beta (Fabrazyme. Based on preclinical data, migalastat HCl in combination with agalsidase is expected to result in the pharmacokinetic (PK enhancement of agalsidase in plasma by increasing the systemic exposure of active agalsidase, thereby leading to increased cellular levels in disease-relevant tissues. This Phase 2a study design consisted of an open-label, fixed-treatment sequence that evaluated the effects of single oral doses of 150 mg or 450 mg migalastat HCl on the PK and tissue levels of intravenously infused agalsidase (0.2, 0.5, or 1.0 mg/kg in male Fabry patients. As expected, intravenous administration of agalsidase alone resulted in increased α-Gal A activity in plasma, skin, and peripheral blood mononuclear cells (PBMCs compared to baseline. Following co-administration of migalastat HCl and agalsidase, α-Gal A activity in plasma was further significantly increased 1.2- to 5.1-fold compared to agalsidase administration alone, in 22 of 23 patients (95.6%. Importantly, similar increases in skin and PBMC α-Gal A activity were seen following co-administration of migalastat HCl and agalsidase. The effects were not related to the administered migalastat HCl dose, as the 150 mg dose of migalastat HCl increased α-Gal A activity to the same extent as the 450 mg dose. Conversely, agalsidase had no effect on the plasma PK of migalastat. No migalastat HCl-related adverse events or drug-related tolerability issues were identified.ClinicalTrials.gov NCT01196871.

  11. Blood RNA biomarkers in prodromal PARK4 and rapid eye movement sleep behavior disorder show role of complexin 1 loss for risk of Parkinson's disease

    NARCIS (Netherlands)

    Lahut, Suna; Gispert, Suzana; Oemur, Oezgur; Depboylu, Candan; Seidel, Kay; Dominguez-Bautista, Jorge Antolio; Brehm, Nadine; Tireli, Hulya; Hackmann, Karl; Pirkevi, Caroline; Leube, Barbara; Ries, Vincent; Reim, Kerstin; Brose, Nils; den Dunnen, Wilfred F.; Johnson, Madrid; Wolf, Zsuzsanna; Schindewolf, Marc; Schrempf, Wiebke; Reetz, Kathrin; Young, Peter; Vadasz, David; Frangakis, Achilleas S.; Schroeck, Evelin; Steinmetz, Helmuth; Jendrach, Marina; Rueb, Udo; Basak, Ayse Nazli; Oertel, Wolfgang; Auburger, Georg

    2017-01-01

    Parkinson's disease (PD) is a frequent neurodegenerative process in old age. Accumulation and aggregation of the lipid-binding SNARE complex component alpha-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA

  12. [A Case of Crohn's Disease Showing Favorable Response to Induction and Maintenance Therapy with Methotrexate after Failure of Anti-tumor Necrosis Factor Therapy].

    Science.gov (United States)

    Choi, Jung Ran; Yun, Gak Won; Park, Yoo Mi; Kim, Jie Hyun; Youn, Young Hoon; Park, Hyo Jin; Park, Jae Jun

    2015-10-01

    Thanks to the introduction of immumomodulators and biologics, therapeutic approaches in Crohn's disease have changed significantly during the past decade. Although new biologic therapy has dramatically improved the treatment of Crohn's disease, a substantial number of patients are refractory to these therapies or lose their initial response. Methotrexate (MTX) is a structural analogue of folic acid that can competitively inhibit the binding of dihydrofolic acid to the enzyme dihydrofolate reductase and has been widely used as immunomodulator in rheumatology area for patients with rheumatoid arthritis and psoriasis. Although MTX has also been shown to be an effective agent for remission induction and maintenance of remission in Crohn's disease, the use of MTX in Crohn's disease has not yet been reported in Korea. Herein, we report a case of Crohn's disease patient who was successfully treated with MTX after treatment failure with thiopurine and anti-tumor necrosis factor.

  13. Modified Fabry-Perot interferometric method for waveguide loss measurement.

    Science.gov (United States)

    Taebi, Sareh; Khorasaninejad, Mohammadreza; Saini, Simarjeet Singh

    2008-12-10

    An extension to the Fabry-Perot interferometric method is demonstrated to calculate the optical loss and the reflectivity for optical waveguides simultaneously. The method uses an excitation of the waveguide with a broadband amplified spontaneous emission source (a superluminescent diode in our case) and curve fitting to account for the change of input power, thereby simplifying the measurement procedure. The use of a broadband source as opposed to tunable lasers allows for simultaneous measurements over multiple wavelengths and decreased sensitivity to reflections in the cavity. Further, waveguides of different lengths are measured to calculate the optical loss and the reflectivity simultaneously. It is shown that, if the value for reflectivity is assumed, there could be a large error in the measurement of loss especially for short waveguides. Optical loss for ridge waveguides is measured and compared by using a tunable laser as the input source. The method can be used for a generic case where it is suspected that the input power changes during the measurement.

  14. Active Sensing with Fabry-Perot Infrared Interferometers

    Science.gov (United States)

    Huang, Jin; Gosangi, Rakesh; Gutierrez-Osuna, Ricardo

    2011-09-01

    In this article, we describe an active-sensing framework for infrared (IR) spectroscopy. The goal is to generate a sequence of wavelengths that best discriminates among chemicals. Unlike feature-selection strategies, the sequence is selected on-the-fly as the device acquires data. The framework models the problem as a Partially Observable Markov Decision Process (POMDP), which is solved by a greedy myopic algorithm. In previous work [1], we had applied this framework to temperature-modulated metal oxide sensor. Here, we adapt the framework to a tunable IR sensor based on Fabry-Perot interferometers (FPI). FPIs provide a low-cost alternative to traditional Fourier Transform Infrared Spectroscopy (FTIR), though at the expense of a narrower effective range and lower spectral resolution. Here, we first test whether the framework can scale up to large problems consisting 27 chemicals with 60 dimensions; our previous work on metal oxide sensors employed three chemicals and 7 dimensions. For this purpose, FPI spectra are simulated from FTIR. Then we validate the framework experimentally on 3 chemicals using a prototype instrument based on FPIs. These preliminary results are encouraging and indicate that the framework is able to solve classification problems of reasonable size.

  15. Dielectric Fabry-Perot mirror coatings for infrared astronomy

    Science.gov (United States)

    Trauger, J.

    1984-01-01

    A number of Fabry-Perot (FP) coating designs have been developed specifically for IR astronomy. These have been optimized for uniform reflectance over five contiguous spectral ranges of particular astronomical interest between 1 and 5 microns. Wavelength coverage in individual designs is given by (maximum wavelength/minimum wavelength) greater than 1.4, over which reflective finesse is maintained near 35. Consideration has been made for the peculiar requirements of FP coatings. Visual alignment and testing of the FP has been made convenient by bringing the reflective finesse of the coating at 632.8 nm to the same value as the main IR reflection band. For example, a calcium fluoride FP can be aligned and tested at 632.8-nm He-Ne laser line, with the assurance of a corresponding finesse and spectral resolving power over its IR (3.6-5.1-micron) range. In addition, the FP can be used for IR spectroscopy while being simultaneously monitored and/or actively controlled at the laser wavelength. The potential for the coating itself to degrade the effective surface flatness of the FP through either mechanical stress or thickness nonuniformities is minimized by reducing to a minimum the number and thickness of coating layers. Several of these coatings have been fabricated and are actively in use at a number of observatories.

  16. Fabry-Perot Interferometer for Column CO2

    Science.gov (United States)

    Heaps, William S.; Kawa, Randolph; Bhartia, P. K. (Technical Monitor)

    2002-01-01

    Global atmospheric CO2 measurements are essential to resolving significant discrepancies in our understanding of the global carbon budget and, hence, humankind's role in global climate change. The science measurement requirements for CO2 are extremely demanding (precision approx. 0.3%). No atmospheric chemical species has ever been measured from space with this precision. We are developing a novel application of a Fabry-Perot interferometer to detect spectral absorption of reflected sunlight by CO2 and O2 in the atmosphere. Preliminary design studies indicate that the method will be able to achieve the sensitivity and signal-to-noise detection required to measure column CO2 at the target specification. The objective of this program is to construct a prototype instrument for deployment on an aircraft to test the instrument performance and our ability to retrieve the data in the real atmosphere. To date we have assembled a laboratory bench system to begin testing the optical and electronic components. We are also measuring signal and noise levels in actual sunlight to evaluate component performance.

  17. Fabry-Perot Interferometer for Column CO2: Airborne

    Science.gov (United States)

    Kawa, S. R.; Heaps, W. S.; Mao, J.; Andrews, A. E.; Burris, J. F.; Miodek, M.; Georgieva, E.

    2002-01-01

    Global atmospheric CO2 measurements are essential to resolving significant discrepancies in our understanding of the global carbon budget and, hence, humankind's role in global climate change. The science measurement requirements for CO2 are, however, extremely demanding (precision approximately 0.3%). We are developing a novel application of a Fabry-Perot interferometer to detect spectral absorption of reflected sunlight by CO2 and O2 in the atmosphere that should be able to achieve sufficient sensitivity and signal-to-noise to measure column CO2 at the target specification. We are currently constructing a prototype instrument for deployment on aircraft. The aircraft version will measure total column CO2 and CO2 below the aircraft as well as O2, which allows normalization of CO2 column amounts for varying surface height and pressure. This instrument will be a valuable asset in carbon budget field studies as well as a useful tool for evaluating existing and future space-based CO2 measurements. We will present the instrument concept, sensitivity calculations, and the results of testing a bench system in the laboratory and outdoors on the ground. We will also discuss our plan for deployment on the aircraft and potential flight applications to the CO2 budget problem.

  18. Demonstration of Fabry-Perot interferometric spectrometry technology

    Science.gov (United States)

    Petersen, T. V.; Makel, D. B.; Thurman, C.

    1993-06-01

    As rocket engine components experience wear or failure, anomalous materials may be entrained in the plume. Historically, visible plume anomalies have preceded many rocket engine failures, some of which have been catastrophic. Development of a small, rugged, high-speed, high resolution Fabry-Perot interferometer (FPI) based spectrometer capable of detecting the spectral signatures of eroding engine components during rocket engine test and/or flight operations is described. An operational plume spectrometer fabricated with miniaturized optics has been successfully tested. An extensive test series was conducted to define the limits of the spectrometer with respect to time-response and resolution. The data collected during testing were correlated with measurements obtained using sensitive ground equipment in order to benchmark the spectrometer's performance against a known device. The FPI demonstrated the reliability required for a flight instrument by functioning satisfactorily at or near the rocket engine test stand environment. Several of the optical components are interchangeable, allowing collection of a greater variety of plume signals. Also, the FPI's high resolution capabilities suggest it is suitable for application to both absorption and emission spectroscopy.

  19. Performance of a dual Fabry-Perot cavity refractometer.

    Science.gov (United States)

    Egan, Patrick F; Stone, Jack A; Hendricks, Jay H; Ricker, Jacob E; Scace, Gregory E; Strouse, Gregory F

    2015-09-01

    We have built and characterized a refractometer that utilizes two Fabry-Perot cavities formed on a dimensionally stable spacer. In the typical mode of operation, one cavity is held at vacuum, and the other cavity is filled with nitrogen gas. The differential change in length between the cavities is measured as the difference in frequency between two helium-neon lasers, one locked to the resonance of each cavity. This differential change in optical length is a measure of the gas refractivity. Using the known values for the molar refractivity and virial coefficients of nitrogen, and accounting for cavity length distortions, the device can be used as a high-resolution, multi-decade pressure sensor. We define a reference value for nitrogen refractivity as n-1=(26485.28±0.3)×10(-8) at p=100.0000  kPa, T=302.9190  K, and λ(vac)=632.9908  nm. We compare pressure determinations via the refractometer and the reference value to a mercury manometer.

  20. Equation of state measurements using single Fabry-Perot velocimeter

    Science.gov (United States)

    Saxena, A. K.; Kaushik, T. C.; Rawool, A. M.; Gupta, Satish C.

    2012-07-01

    Accurate measurement of projectile and free surface velocity of target is a crucial part of any high pressure physics experiments involving hyper velocity impact. Fabry Perot velocimeter (FPV) is a widely accepted technique for single surface velocity measurements. In the present work a possibility of using single FPV for two surface velocity measurements is experimentally explored. The laser light is launched in such a way that it illuminates both the surfaces under study and reflected light coming from the flyer as well as from the target is used to generate interference fringes. Therefore by recording fringe displacements due to Doppler shift in reflected light corresponding to movement of both the surfaces at different time instants, velocity profile of both target and projectile can be computed. This technique has been utilized for equation of state measurements of polyurethane based retro-reflective tape at 12 GPa and aluminum at 15 GPa. Measured peak particle velocities at the target-glass interface have been found in good agreement with the reported equation of state data.

  1. Whole genome association analysis shows that ACE is a risk factor for Alzheimer's disease and fails to replicate most candidates from Meta-analysis.

    Science.gov (United States)

    Webster, Jennifer; Reiman, Eric M; Zismann, Victoria L; Joshipura, Keta D; Pearson, John V; Hu-Lince, Diane; Huentelman, Matthew J; Craig, David W; Coon, Keith D; Beach, Thomas; Rohrer, Kristen C; Zhao, Alice S; Leung, Doris; Bryden, Leslie; Marlowe, Lauren; Kaleem, Mona; Mastroeni, Diego; Grover, Andrew; Rogers, Joseph; Heun, Reinhard; Jessen, Frank; Kölsch, Heike; Heward, Christopher B; Ravid, Rivka; Hutton, Michael L; Melquist, Stacey; Petersen, Ron C; Caselli, Richard J; Papassotiropoulos, Andreas; Stephan, Dietrich A; Hardy, John; Myers, Amanda

    2010-01-01

    For late onset Alzheimer's disease (LOAD), the only confirmed, genetic association is with the apolipoprotein E (APOE) locus on chromosome 19. Meta-analysis is often employed to sort the true associations from the false positives. LOAD research has the advantage of a continuously updated meta-analysis of candidate gene association studies in the web-based AlzGene database. The top 30 AlzGene loci on May 1(st), 2007 were investigated in our whole genome association data set consisting of 1411 LOAD cases and neuropathoiogicaiiy verified controls genotyped at 312,316 SNPs using the Affymetrix 500K Mapping Platform. Of the 30 "top AlzGenes", 32 SNPs in 24 genes had odds ratios (OR) whose 95% confidence intervals that did not include 1. Of these 32 SNPs, six were part of the Affymetrix 500K Mapping panel and another ten had proxies on the Affymetrix array that had >80% power to detect an association with α=0.001. Two of these 16 SNPs showed significant association with LOAD in our sample series. One was rs4420638 at the APOE locus (uncorrected p-value=4.58E-37) and the other was rs4293, located in the angiotensin converting enzyme (ACE) locus (uncorrected p-value=0.014). Since this result was nominally significant, but did not survive multiple testing correction for 16 independent tests, this association at rs4293 was verified in a geographically distinct German cohort (p-value=0.03). We present the results of our ACE replication aiongwith a discussion of the statistical limitations of multiple test corrections in whole genome studies.

  2. Fabry-Perot干涉腔型光纤声发射传感器%Fiber-optic acoustic emission sensors with dual Fabry-Perot interferometric cavities

    Institute of Scientific and Technical Information of China (English)

    赵江海; 章小建

    2015-01-01

    设计了一种新型的双Fabry-Perot腔光纤传感器用于材料损伤引起的声发射信号检测.基于低细度Fabry-Perot腔多光束干涉原理,建立了光纤Fabry-Perot传感器检测声发射信号的数学模型.分析双Fabry-Perot腔正交点稳定工作机制,设计并制作了具有双Fabry-Perot腔结构的光纤声发射传感器来保持传感器正交点的稳定性.通过模拟AE信号检测与热应力干扰实验对设计的传感器进行了实验验证.实验一通过冲击振动与折断铅笔芯产生两类模拟声发射信号,使用商用的压电传感器和光纤传感器进行对比实验,结果表明光纤传感器能够成功检测到两类模拟声发射信号,灵敏度为12.9 nm,带宽达到30 kHz.实验二对传感器进行工作点稳定测试,结果表明双F-P腔的控制机制能够保证传感器工作在正交点,解决了传感器输出信号衰减的问题.

  3. An optical fiber Fabry-Perot flow measurement technology based on partial bend structure

    Science.gov (United States)

    Yang, Huijia; Jiang, Junfeng; Zhang, Xuezhi; Pan, Yuheng; Zhu, Wanshan; Zhou, Xiang; Liu, Tiegen

    2016-08-01

    An optical fiber Fabry-Perot (F-P) flow measurement technology is presented, which is based on partial bend structure. A 90° partial bend structure is designed to achieve the non-probe flow measurement with a pressure difference. The fluid simulation results of partial bend structure show that the error of the pressure difference is below 0.05 kPa during steady flow. The optical fiber F-P sensor mounted on the elbow with pressure test accuracy of 1% full scale is used to measure the fluid flow. Flow test results show that when the flow varies from 1 m3/h to 6.5 m3/h at ambient temperature of 25 °C, the response time is 1 s and the flow test accuracy is 4.5% of the F-P flow test system, proving that the F-P flow test method based on partial bend structure can be used in fluid flow measurement.

  4. Optical fibre Fabry-Perot relative humidity sensor based on HCPCF and chitosan film

    Science.gov (United States)

    Liu, Xiaohui; Jiang, Mingshun; Sui, Qingmei; Geng, Xiangyi

    2016-09-01

    An optical fibre Fabry-Perot interferometer (FPI) sensor for relative humidity (RH) measurement is proposed. The FPI is formed by splicing a short section of hollow-core photonic crystal fibre(HCPCF) to single mode fibre and covering a chitosan film at the end of HCPCF. The refractive index of chitosan and film thickness will change with ambient RH, leading to the change in the reflected interference spectrum of FPI. RH response of the FPI sensor is analysed theoretically and demonstrated experimentally. It shows nonlinear response to RH values from 35 to 95%RH. The interference fringe shifts to shorter wavelength as RH increases with a maximum sensitivity of 0.28 nm/%RH at high RH level. And the fringe contrast also decreases as RH increases with an available maximum sensitivity of 0.5 dB/%RH. The sensor shows good stability and fast response time less than 1 min. With its advantages of compact structure, good performance, simple and safe fabrication, the proposed optical fibre FPI sensor has great potential for RH sensing.

  5. Fabry-Perot interferometer based on etched side-hole fiber for microfluidic refractive index sensing

    Science.gov (United States)

    Wu, Shengnan; Yan, Guofeng; Zhou, Bin; He, Sailing

    2015-08-01

    In this paper, we present a novel fiber-optic open-cavity Fabry-Perot interferometer (FPI), which is specially designed for microfluidic refractive index (RI) sensing. An etching Side-hole fiber (SHF) was sandwiched between in two single-mode-fibers (SMF) and then a cavity was opened up by chemical etching method in the SHF. The minute order of the etching process endow such FPIs with low cost and ease of fabrication. For further microfluidic sensing test, the FPI was integrated with a cross microfluidic slit that was fabricated through photolithography. The refractive index response of the FPI was characterized using sodium hydroxide solution with RI range from 1.3400 to 1.3470. Experimental results show that FPIs with different length of open-cavity have the similar liner RI response with different RI sensitivities. The optimal RI sensitivity of more than 1138 nm/RI can be achieved with open-cavity length of 56 μm. The temperature response was also investigated, which shows that FPIs exhibit a very low temperature cross-sensitivities of 4.00 pm/ °C and 1.95 pm/ °C corresponding FPIs with cavity length of 123 μm and 56 μm, respectively. Such good performance renders the FPI a promising in-line microfluidic sensor for temperature-insensitive RI sensing.

  6. A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation

    Directory of Open Access Journals (Sweden)

    Perkins Andy D

    2009-02-01

    Full Text Available Abstract Background The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a found and validated in allergic disease and b used to find and validate one ore more novel disease-associated genes. Results To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4+ cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, IL7R, was selected for further validation. The expression levels of IL7R in allergen challenged CD4+ cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies. Conclusion We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.

  7. A module-based analytical strategy to identify novel disease-associated genes shows an inhibitory role for interleukin 7 Receptor in allergic inflammation.

    Science.gov (United States)

    Mobini, Reza; Andersson, Bengt A; Erjefält, Jonas; Hahn-Zoric, Mirjana; Langston, Michael A; Perkins, Andy D; Cardell, Lars Olaf; Benson, Mikael

    2009-02-12

    The identification of novel genes by high-throughput studies of complex diseases is complicated by the large number of potential genes. However, since disease-associated genes tend to interact, one solution is to arrange them in modules based on co-expression data and known gene interactions. The hypothesis of this study was that such a module could be a) found and validated in allergic disease and b) used to find and validate one ore more novel disease-associated genes. To test these hypotheses integrated analysis of a large number of gene expression microarray experiments from different forms of allergy was performed. This led to the identification of an experimentally validated reference gene that was used to construct a module of co-expressed and interacting genes. This module was validated in an independent material, by replicating the expression changes in allergen-challenged CD4+ cells. Moreover, the changes were reversed following treatment with corticosteroids. The module contained several novel disease-associated genes, of which the one with the highest number of interactions with known disease genes, IL7R, was selected for further validation. The expression levels of IL7R in allergen challenged CD4+ cells decreased following challenge but increased after treatment. This suggested an inhibitory role, which was confirmed by functional studies. We propose that a module-based analytical strategy is generally applicable to find novel genes in complex diseases.

  8. Host biomarkers detected in saliva show promise as markers for the diagnosis of pulmonary tuberculosis disease and monitoring of the response to tuberculosis treatment.

    Science.gov (United States)

    Jacobs, Ruschca; Tshehla, Enock; Malherbe, Stephanus; Kriel, Magdalena; Loxton, Andre G; Stanley, Kim; van der Spuy, Gian; Walzl, Gerhard; Chegou, Novel N

    2016-05-01

    There is an urgent need for new tools for the rapid diagnosis of tuberculosis (TB) disease in resource-constrained settings. Tests based on host immunological biomarkers maybe useful, especially if based on easily available samples. We investigated host biomarkers detected in saliva samples from individuals with suspected pulmonary TB disease, as tools for the diagnosis of TB disease and monitoring of the response to treatment. We collected saliva samples from 104 individuals that presented with symptoms requiring investigation for TB disease at a primary health care clinic in the outskirts of Cape Town, South Africa, prior to assessment for TB disease. We evaluated the concentrations of 33 host markers in stored saliva samples using a multiplex cytokine platform. Using a combination of clinical, radiological and laboratory results and a pre-established diagnostic algorithm, participants were later classified as having TB disease or other respiratory diseases (ORD). The diagnostic potentials of individual analytes were analysed by the receiver operator characteristics curve approach while the predictive abilities of combinations of analytes for TB disease were analysed by general discriminant analysis, with leave-one-out cross validation. Of the 104 individuals enrolled, 32 were pulmonary TB cases. There were significant differences in the levels of 10 of the markers investigated between the patients with TB disease and those with ORDs. However, the optimal diagnostic biosignature was a seven-marker combination of salivary CRP, ferritin, serum amyloid P, MCP-1, alpha-2-macroglobulin, fibrinogen and tissue plasminogen activator. This biosignature diagnosed TB disease with a sensitivity of 78.1% (95% CI, 59.6-90.1%) and specificity of 83.3% (95% CI, 72.3-90.7%) after leave-one-out cross validation. When compared to baseline levels, the concentrations of 9 markers including granzyme A, MCP-1, IL-1β, IL-9, IL-10, IL-15, MIP-1β, ferritin and serum amyloid A changed

  9. High-precision, accurate optical frequency reference using a Fabry-Perót diode laser.

    Science.gov (United States)

    Chang, Hongrok; Myneni, Krishna; Smith, David D; Liaghati-Mobarhan, Hassan R

    2017-06-01

    We show that the optical output of a temperature and current-tuned Fabry-Perót diode laser system, with no external optical feedback and in which the frequency is locked to Doppler-free hyperfine resonances of the (87)Rb D2 line, can achieve high frequency stability and accuracy. Experimental results are presented for the spectral linewidth, frequency stability, and frequency accuracy of the source. Although our optical source is limited by a short-term spectral linewidth greater than 2 MHz, beat signal measurements from two such sources demonstrate a frequency stability of 1.1 kHz, or minimum Allan deviation of 4×10(-12), at an integration time τ=15 s and with a frequency accuracy of 60 kHz at τ=300 s. We demonstrate the use of the optical source for the precision measurement of hyperfine level frequency spacings in the 5P3∕2 excited state of (87)Rb and provide an accurate frequency scale for optical spectroscopy.

  10. Fabry-Perot Microcavity Modes in Single GaP/GaNP Core/Shell Nanowires.

    Science.gov (United States)

    Dobrovolsky, Alexander; Stehr, Jan E; Sukrittanon, Supanee; Kuang, Yanjin; Tu, Charles W; Chen, Weimin M; Buyanova, Irina A

    2015-12-16

    Semiconductor nanowires (NWs) are attracting increasing interest as nanobuilding blocks for optoelectronics and photonics. A novel material system that is highly suitable for these applications are GaNP NWs. In this article, we show that individual GaP/GaNP core/shell nanowires (NWs) grown by molecular beam epitaxy on Si substrates can act as Fabry-Perot (FP) microcavities. This conclusion is based on results of microphotoluminescence (μ-PL) measurements performed on individual NWs, which reveal periodic undulations of the PL intensity that follow an expected pattern of FP cavity modes. The cavity is concluded to be formed along the NW axis with the end facets acting as reflecting mirrors. The formation of the FP modes is shown to be facilitated by an increasing index contrast with the surrounding media. Spectral dependence of the group refractive index is also determined for the studied NWs. The observation of the FP microcavity modes in the GaP/GaNP core/shell NWs can be considered as a first step toward achieving lasing in this quasidirect bandgap semiconductor in the NW geometry.

  11. Fabry-Perot observations of the ionized gas in NGC 3938

    CERN Document Server

    Jiménez-Vicente, J; Rozas, M; Castaneda, H O; Porcel, C

    1999-01-01

    The nearly face-on spiral galaxy NGC 3938 has been observed in the $H_\\alpha$ line with the TAURUS II Fabry-Perot interferometer at the William Herschel Telescope in order to study the kinematics of the ionized gas. We are able to construct intensity, velocity and velocity dispersion maps for this galaxy. The rotation curve of the galaxy is calculated up to 4.5 radial scale lengths from the galactic centre. The residual velocity field shows very small values with no systematic pattern. The mean velocity dispersion is approximately constant with radius at about 11 km/s as previously reported for the neutral and molecular gas. We have also studied the relation between intensity and velocity dispersion for the ionized gas. We have found that this distribution is compatible with a turbulent gas relaxing to a Kolmogorov type turbulence as the stationary regime. The average dispersion varies with intensity as $\\sigma which the dispersion is kept almost constant at a value of about 19 km/s.

  12. Millimeter Wave Fabry-Perot Resonator Antenna Fed by CPW with High Gain and Broadband

    Directory of Open Access Journals (Sweden)

    Xue-Xia Yang

    2016-01-01

    Full Text Available A novel millimeter wave coplanar waveguide (CPW fed Fabry-Perot (F-P antenna with high gain, broad bandwidth, and low profile is reported. The partially reflective surface (PRS and the ground form the F-P resonator cavity, which is filled with the same dielectric substrate. A dual rhombic slot loop on the ground acts as the primary feeding antenna, which is fed by the CPW and has broad bandwidth. In order to improve the antenna gain, metal vias are inserted surrounding the F-P cavity. A CPW-to-microstrip transition is designed to measure the performances of the antenna and extend the applications. The measured impedance bandwidth of S11 less than −10 dB is from 34 to 37.7 GHz (10.5%, and the gain is 15.4 dBi at the center frequency of 35 GHz with a 3 dB gain bandwidth of 7.1%. This performance of the antenna shows a tradeoff among gain, bandwidth, and profile.

  13. MEMS fiber-optic Fabry-Perot pressure sensor for high temperature application

    Science.gov (United States)

    Fang, G. C.; Jia, P. G.; Cao, Q.; Xiong, J. J.

    2016-10-01

    We design and demonstrate a fiber-optic Fabry-Perot pressure sensor (FOFPPS) for high-temperature sensing by employing micro-electro-mechanical system (MEMS) technology. The FOFPPS is fabricated by anodically bonding the silicon wafer and the Pyrex glass together and fixing the facet of the optical fiber in parallel with the silicon surface by glass frit and organic adhesive. The silicon wafer can be reduced through dry etching technology to construct the sensitive diaphragm. The length of the cavity changes with the deformation of the diaphragm due to the loaded pressure, which leads to a wavelength shift of the interference spectrum. The pressure can be gauged by measuring the wavelength shift. The pressure experimental results show that the sensor has linear pressure sensitivities ranging from 0 kPa to 600 kPa at temperature range between 20°C to 300°C. The pressure sensitivity at 300°C is approximately 27.63 pm/kPa. The pressure sensitivities gradually decrease with increasing the temperature. The sensor also has a linear thermal drift when temperature changes from 20°C - 300°C.

  14. All-fiber upconversion high spectral resolution wind lidar using a Fabry-Perot interferometer.

    Science.gov (United States)

    Shangguan, Mingjia; Xia, Haiyun; Wang, Chong; Qiu, Jiawei; Shentu, Guoliang; Zhang, Qiang; Dou, Xiankang; Pan, Jian-Wei

    2016-08-22

    An all-fiber, micro-pulse and eye-safe high spectral resolution wind lidar (HSRWL) at 1.5 μm is proposed and demonstrated by using a pair of upconversion single-photon detectors and a fiber Fabry-Perot scanning interferometer (FFP-SI). In order to improve the optical detection efficiency, both the transmission spectrum and the reflection spectrum of the FFP-SI are used for spectral analyses of the aerosol backscatter and the reference laser pulse. Taking advantages of high signal-to-noise ratio of the detectors and high spectral resolution of the FFP-SI, the center frequencies and the bandwidths of spectra of the aerosol backscatter are obtained simultaneously. Continuous LOS wind observations are carried out on two days at Hefei (31.843 °N, 117.265 °E), China. The horizontal detection range of 4 km is realized with temporal resolution of 1 minute. The spatial resolution is switched from 30 m to 60 m at distance of 1.8 km. In a comparison experiment, LOS wind measurements from the HSRWL show good agreement with the results from an ultrasonic wind sensor (Vaisala windcap WMT52). An empirical method is adopted to evaluate the precision of the measurements. The standard deviation of the wind speed is 0.76 m/s at 1.8 km. The standard deviation of bandwidth variation is 2.07 MHz at 1.8 km.

  15. Statistical parametric mapping with 18F-dopa PET shows bilaterally reduced striatal and nigral dopaminergic function in early Parkinson's disease

    OpenAIRE

    Ito, K.; Morrish, P; Rakshi, J; Uema, T; Ashburner, J.; Bailey, D.; Friston, K.; Brooks, D

    1999-01-01

    OBJECTIVE—To apply statistical parametric mapping to 18F-dopa PET data sets, to examine the regional distribution of changes in dopaminergic metabolism in early asymmetric Parkinson's disease.
METHODS—Thirteen normal volunteers (age 57.7 (SD 16.5) years; four women, nine men ) and six patients (age 50.3 (SD 13.5) years; three women, three men) with asymmetric (right sided) Parkinson's disease were studied. Images from each dynamic dopa PET dataset were aligned and parametric...

  16. Two-dimensional photonic-crystal-based Fabry-Perot etalon.

    Science.gov (United States)

    Ho, Chong Pei; Pitchappa, Prakash; Kropelnicki, Piotr; Wang, Jian; Cai, Hong; Gu, Yuandong; Lee, Chengkuo

    2015-06-15

    We demonstrate the design, fabrication, and characterization of a polycrystalline-silicon-based photonic crystal Fabry-Perot etalon, which is aimed to work in the mid-infrared wavelengths. The highly reflective mirrors required in a Fabry-Perot etalon are realized by freestanding polycrystalline-silicon-based photonic crystal membranes with etched circular air holes. A peak reflection of 96.4% is observed at 3.60 μm. We propose a monolithic CMOS-compatible fabrication process to configure two such photonic crystal mirrors to be in parallel to form a Fabry-Perot etalon; a filtered transmission centered at 3.51 μm is observed. The quality factor measured is around 300, which is significantly higher than in existing works. This creates the possibility of using such devices for high-resolution applications such as gas sensing and hyperspectral imaging.

  17. Enhanced random lasing in ZnO nanocombs assisted by Fabry-Perot resonance.

    Science.gov (United States)

    Chen, Yungting; Chen, Yangfang

    2011-04-25

    The ultraviolet random lasing behavior of an ensemble of ZnO nanocombs has been demonstrated. It is found that the Fabry-Perot resonance induced by nanocomb geometry can greatly enhance random lasing action with a low threshold condition. Besides, the emission spectra exhibit few sharp lasing peaks with a full width at half maximum (FWHM) of less than 0.3 nm and a narrow background emission with a FWHM of about 5 nm. Cathodoluminescence mapping images are utilized to analyze the Fabry-Perot resonance phenomenon. The resonant effect on the lasing system is further confirmed by nanocombs with different resonant cavity lengths. The unique lasing behavior induced by the simultaneous occurrence of Fabry-Perot resonance and random laser action shown here may open up a new possibility for the creation of highly efficient light emitting devices.

  18. High Finesse Fiber Fabry-Perot Cavities: Stabilization and Mode Matching Analysis

    CERN Document Server

    Gallego, Jose; Alavi, Seyed Khalil; Alt, Wolfgang; Martinez-Dorantes, Miguel; Meschede, Dieter; Ratschbacher, Lothar

    2015-01-01

    Fiber Fabry-Perot cavities, formed by micro-machined mirrors on the end-facets of optical fibers, are used in an increasing number of technical and scientific applications, where they typically require precise stabilization of their optical resonances. Here, we study two different approaches to construct fiber Fabry-Perot resonators and stabilize their length for experiments in cavity quantum electrodynamics with neutral atoms. A piezo-mechanically actuated cavity with feedback based on the Pound-Drever-Hall locking technique is compared to a novel rigid cavity design that makes use of the high passive stability of a monolithic cavity spacer and employs thermal self-locking and external temperature tuning. Furthermore, we present a general analysis of the mode matching problem in fiber Fabry-Perot cavities, which explains the asymmetry in their reflective line shapes and has important implications for the optimal alignment of the fiber resonators. Finally, we discuss the issue of fiber-generated background ph...

  19. A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

    DEFF Research Database (Denmark)

    Holmes, Michael V; Frikke-Schmidt, Ruth; Melis, Daniela

    2014-01-01

    BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking statu...

  20. Molecular and Phylogenetic Analyses of Bovine Rhinovirus Type 2 Shows it is Closely Related to Foot-and-Mouth Disease Virus

    Science.gov (United States)

    Bovine rhinovirus 2 (BRV2), a causative agent of respiratory disease in cattle, is currently an unclassified species tentatively assigned to the genus rhinovirus in the family Picornaviridae. A nearly full-length cDNA of the BRV2 genome was cloned and the nucleotide sequence from the poly(C) to the ...

  1. Fiber Fabry-Perot interferometer with controllable temperature sensitivity.

    Science.gov (United States)

    Zhang, Xinpu; Peng, Wei; Zhang, Yang

    2015-12-01

    We proposed a fiber taper based on the Fabry-Perot (FP) interferometer structure with controllable temperature sensitivity. The FP interferometer is formed by inserting a segment of tapered fiber tip into the capillary and subsequently splicing the other end of the capillary to a single-mode fiber (SMF), the tapered fiber endface, and the spliced face form the FP cavity. Through controlling the inserted tapered fiber length, a series of FP interferometers were made. Because the inserted taper tip has the degree of freedom along the fiber axial, when the FP interferometer is subjected to temperature variation, the thermal expansion of the fiber taper tip will resist the FP cavity length change caused by the evolution of capillary length, and we can control the temperature sensitivity by adjusting the inserted taper length. In this structure, the equivalent thermal expansion coefficient of the FP interferometer can be defined; it was used to evaluate the temperature sensitivity of the FP interferometer, which provides an effective method to eliminate the temperature effect and to enhance other measurement accuracy. We fabricated the FP interferometers and calibrated their temperature characters by measuring the wavelength shift of the resonance dips in the reflection spectrum. In a temperature range of 50°C to 150°C, the corresponding temperature sensitivities can be controlled between 0 and 1.97 pm/°C when the inserted taper is between 75 and 160 μm. Because of its controllable temperature sensitivity, ease of fabrication, and low cost, this FP interferometer can meet different temperature sensitivity requirements in various application areas, especially in the fields which need temperature insensitivity.

  2. Negative Goos-H(a)nchen Effect in Thin-Film Fabry-Perot Filter

    Institute of Scientific and Technical Information of China (English)

    LI Ming-Yu; LIU Xu; MA Xin; LI Yi-Yu; GU Pei-Fu

    2007-01-01

    We investigate the Goos-Hanchen effect of a Gaussian light beam reflected by the thin-film Fabry-Perot filter. It is shown that the Goos-Hanchen shift can be either negative or positive. The Gaussian-beam analysis and stationary phase method are introduced to calculate the lateral shift between the incident beam and the reflected beam at different wavelengths and to analyse the Goos-Hanchen effect in the thin-film Fabry-Perot filter. The effect of the incident beam diameter is also discussed.

  3. The Three-Arm Michelson-Fabry-Pérot Detector for Gravitational Waves

    Institute of Scientific and Technical Information of China (English)

    Chao-Guang Huang; Yong-Gui Li; Ning Zhu

    2016-01-01

    A three-arm Michelson-Fabry-Pérot detector for gravitational waves is designed.It consists of three Michelson Fabry-Pérot interferometers,one for each pair of arms.The new detector can be used to confirm whether the gravitational waves are in general relativity polarization states and to set the strong constraints on non-GR gravitational wave polarization states.By the new detectors,the angular resolution of sources can be improved significantly.With the new detector,it is easier to search for and confirm a gravitational wave signal in the observation data.

  4. Period Doubling in a Fabry-Perot Laser Diode Subject to Optical Pulse Injection

    Institute of Scientific and Technical Information of China (English)

    ZHAO Yue-Peng; WANG Yun-Cai; ZHANG Ming-Jiang; AN Yi; WANG Ji-Long

    2007-01-01

    Experimental study and numerical simulations of the period doubling of injected optical pulses in Fabry-Perot laser diodes are presented. In our experiments, the period doubling is achieved within a wide input frequency range and the period doubling of the injected optical pulses with 6.32 GHz repetition rate is investigated in detail. The obtained experimental results indicate that period doubling occurs at an appropriate injected optical power level when the bias current of the Fabry-Perot laser diode is located in lower ranges. Moreover, the experimental observed features have been numerically demonstrated by using a coupled rate-equation model. Numerical simulations are consistent with the experimental results.

  5. Model of Fabry-Pérot-type electromagnetic modes of a cylindrical nanowire

    DEFF Research Database (Denmark)

    Bordo, Vladimir

    2010-01-01

    The rigorous theory of normal electromagnetic modes of a cylindrical nanowire of finite length is developed. The exact integral equation which determines the solution of Maxwell's equations obeying the boundary conditions at the whole nanowire surface is derived. The nanowire normal (Fabry......-Pérot) modes are defined as non-trivial solutions of the source-free equation. The approach is considered in more detail for elongated nanowires whose length is much larger than their diameter. The resonance condition obtained for a single-mode nanowire resembles the formula for the Fabry-Pérot resonator...

  6. Fiber-Optic Anemometer Based on Silicon Fabry-Perot Interferometer

    Science.gov (United States)

    2015-11-05

    f, oo •• " • ~ OII Ct’ THIS f’ORM CANCELS AND SUPERSEOES All. P~EVIOUS \\I!:RSI Fiber-optic anemometer based on silicon Fabry-Pérot...monitoring, etc. In this paper, we propose a new anemometer which consists of a Fabry-Pérot interferometer (FPI) implemented using a thin silicon mounted...on the tip of an optical fiber. The anemometer takes advantage of the superior thermal and optical properties of silicon. Silicon is transparent to

  7. Decreased vibrational susceptibility of Fabry-Perot cavities via designs of geometry and structural support

    Institute of Scientific and Technical Information of China (English)

    Yang Tao; Li Wen-Bo; Zang Er-Jun; Chen Li-Sheng

    2007-01-01

    Ultra-stable optical cavities are widely used for laser frequency stabilization. In these experiments the laser performance relies on the length stability of the Fabry-Perot cavities. Vibration-induced deformation is one of the dominant factors that affect the stability of ultra-stable optical cavities. We have quantitatively analysed the elastic deformation of Fabry-Perot cavities with various shapes and mounting configurations. Our numerical result facilitates a novel approach for the design of ultra-stable cavities that are insensitive to vibrational perturbations. This approach can be applied to many experiments such as laser frequency stabilization, high-precision laser spectroscopy, and optical frequency standards.

  8. Genome-wide analysis of primary CD4+ and CD8+ T cell transcriptomes shows evidence for a network of enriched pathways associated with HIV disease

    Directory of Open Access Journals (Sweden)

    Wang Bin

    2011-03-01

    Full Text Available Abstract Background HIV preferentially infects CD4+ T cells, and the functional impairment and numerical decline of CD4+ and CD8+ T cells characterize HIV disease. The numerical decline of CD4+ and CD8+ T cells affects the optimal ratio between the two cell types necessary for immune regulation. Therefore, this work aimed to define the genomic basis of HIV interactions with the cellular transcriptome of both CD4+ and CD8+ T cells. Results Genome-wide transcriptomes of primary CD4+ and CD8+ T cells from HIV+ patients were analyzed at different stages of HIV disease using Illumina microarray. For each cell subset, pairwise comparisons were performed and differentially expressed (DE genes were identified (fold change >2 and B-statistic >0 followed by quantitative PCR validation. Gene ontology (GO analysis of DE genes revealed enriched categories of complement activation, actin filament, proteasome core and proton-transporting ATPase complex. By gene set enrichment analysis (GSEA, a network of enriched pathways functionally connected by mitochondria was identified in both T cell subsets as a transcriptional signature of HIV disease progression. These pathways ranged from metabolism and energy production (TCA cycle and OXPHOS to mitochondria meditated cell apoptosis and cell cycle dysregulation. The most unique and significant feature of our work was that the non-progressing status in HIV+ long-term non-progressors was associated with MAPK, WNT, and AKT pathways contributing to cell survival and anti-viral responses. Conclusions These data offer new comparative insights into HIV disease progression from the aspect of HIV-host interactions at the transcriptomic level, which will facilitate the understanding of the genetic basis of transcriptomic interaction of HIV in vivo and how HIV subverts the human gene machinery at the individual cell type level.

  9. Transgenic wheat expressing Thinopyrum intermedium MYB transcription factor TiMYB2R-1 shows enhanced resistance to the take-all disease.

    Science.gov (United States)

    Liu, Xin; Yang, Lihua; Zhou, Xianyao; Zhou, Miaoping; Lu, Yan; Ma, Lingjian; Ma, Hongxiang; Zhang, Zengyan

    2013-05-01

    The disease take-all, caused by the fungus Gaeumannomyces graminis, is one of the most destructive root diseases of wheat worldwide. Breeding resistant cultivars is an effective way to protect wheat from take-all. However, little progress has been made in improving the disease resistance level in commercial wheat cultivars. MYB transcription factors play important roles in plant responses to environmental stresses. In this study, an R2R3-MYB gene in Thinopyrum intermedium, TiMYB2R-1, was cloned and characterized. The gene sequence includes two exons and an intron. The expression of TiMYB2R-1 was significantly induced following G. graminis infection. An in vitro DNA binding assay proved that TiMYB2R-1 protein could bind to the MYB-binding site cis-element ACI. Subcellular localization assays revealed that TiMYB2R-1 was localized in the nucleus. TiMYB2R-1 transgenic wheat plants were generated, characterized molecularly, and evaluated for take-all resistance. PCR and Southern blot analyses confirmed that TiMYB2R-1 was integrated into the genomes of three independent transgenic wheat lines by distinct patterns and the transgene was heritable. Reverse transcription-PCR and western blot analyses revealed that TiMYB2R-1 was highly expressed in the transgenic wheat lines. Based on disease response assessments for three successive generations, the significantly enhanced resistance to take-all was observed in the three TiMYB2R-1-overexpressing transgenic wheat lines. Furthermore, the transcript levels of at least six wheat defence-related genes were significantly elevated in the TiMYB2R-1 transgenic wheat lines. These results suggest that engineering and overexpression of TiMYB2R-1 may be used for improving take-all resistance of wheat and other cereal crops.

  10. Blood RNA biomarkers in prodromal PARK4 and REM sleep behavior disorder show role of complexin-1 loss for risk of Parkinson's disease.

    Science.gov (United States)

    Lahut, Suna; Gispert, Suzana; Ömür, Özgür; Depboylu, Candan; Seidel, Kay; Domínguez-Bautista, Jorge Antolio; Brehm, Nadine; Tireli, Hülya; Hackmann, Karl; Pirkevi, Caroline; Leube, Barbara; Ries, Vincent; Reim, Kerstin; Brose, Nils; den Dunnen, Wilfred F; Johnson, Madrid; Wolf, Zsuzsanna; Schindewolf, Marc; Schrempf, Wiebke; Reetz, Kathrin; Young, Peter; Vadasz, David; Frangakis, Achilleas S; Schröck, Evelin; Steinmetz, Helmuth; Jendrach, Marina; Rüb, Udo; Başak, Ayşe Nazlı; Oertel, Wolfgang; Auburger, Georg

    2017-01-20

    Parkinson's disease (PD) is a frequent neurodegenerative process at old age. Accumulation and aggregation of the lipid-binding SNARE complex component alpha-synuclein (SNCA) underlies this vulnerability and defines stages of disease progression. Determinants of SNCA levels and mechanisms of SNCA neurotoxicity are intensely investigated. In view of physiological SNCA roles in blood to modulate vesicle release, we studied blood samples from a new large pedigree with SNCA gene duplication (PARK4 mutation), to identify effects of SNCA gain-of-function as potential disease biomarkers. The expression of other Parkinson's disease gene was not, but complexin-1 (CPLX1) mRNA downregulation was correlated with genotype. In global RNAseq profiling of blood from presymptomatic PARK4, bioinformatics detected significant upregulations for platelet activation, hemostasis, lipoproteins, endocytosis, lysosome, cytokine, toll like receptor signalling and extracellular pathways. In PARK4 platelets, stimulus-triggered degranulation was impaired. Strong SPP1, GZMH, and PLTP mRNA upregulations were validated in PARK4. When analysing cases with REM sleep behaviour disorder (RBD), the most specific known prodromal stage of general PD, only blood CPLX1 levels were altered. Validation experiments confirmed an inverse mutual regulation of SNCA and CPLX1 mRNA levels. In the 3'-UTR of the CPLX1 gene we identified a SNP that is significantly associated with PD risk. In summary, our data define CPLX1 as PD risk factor and provide functional insights into the role and regulation of blood alpha-synuclein levels. The novel blood biomarkers of PARK4 in this Turkish family may become useful for PD prediction.

  11. The Multi-Target Drug M30 Shows Pro-Cognitive and Anti-Inflammatory Effects in a Rat Model of Alzheimer's Disease.

    Science.gov (United States)

    Pimentel, Luisa S; Allard, Simon; Do Carmo, Sonia; Weinreb, Orly; Danik, Marc; Hanzel, Cecilia E; Youdim, Moussa B; Cuello, A Claudio

    2015-01-01

    Current therapies for Alzheimer's disease (AD) offer partial symptomatic relief and do not modify disease progression. There is substantial evidence indicating a disease onset years before clinical diagnosis, at which point no effective therapy has been found. In this study, we investigated the efficacy of a new multi-target drug, M30, at relatively early stages of the AD-like amyloid pathology in a robust rat transgenic model. McGill-R-Thy1-APP transgenic rats develop the full AD-like amyloid pathology in a progressive fashion, and have a minimal genetic burden. McGill rats were given 5 mg/kg M30 or vehicle per os, every 2 days for 4 months, starting at a stage where the transgenic animals suffer detectable cognitive impairments. At the completion of the treatment, cognitive functions were assessed with Novel Object Location and Novel Object Recognition tests. The brains were then analyzed to assess amyloid-β (Aβ) burden and the levels of key inflammatory markers. Long-term treatment with M30 was associated with both the prevention and the reversal of transgene-related cognitive decline. The effects on cognition were accompanied by a shift of the Aβ-immunoreactive material toward an amyloid plaque aggregated molecular form, diminished molecular signs of CNS inflammation and a change in microglia morphology toward a surveying phenotype. This study is the first to demonstrate the therapeutic potential of M30 in a rat model of the AD amyloid pathology. It provides a rationale for further investigations with M30 and with potential multi-target approaches to delay, prevent or reverse the progression the AD pathology at early disease-stages.

  12. Large field enhancement obtained by combining Fabry-Perot resonance and Rayleigh anomaly in photonic crystal slabs

    CERN Document Server

    Dossou, Kokou B

    2016-01-01

    By applying the properties of Fabry-Perot resonance and Rayleigh anomaly, we have showed that a photonic crystal slab can scatter the light from an incident plane wave into a diffracted light with a very large reflection or transmission coefficient. The enhanced field is either a propagating diffraction order (with a grazing angle of diffraction) or a weakly evanescent order, so it can be particularly useful for applications requiring an enhanced propagating field (or an enhanced field with a low attenuation). An efficient effective medium technique is developed for the design of the resonant photonic crystal slabs. Numerical simulations have shown that photonic crystal slabs with low index contrast, such as the ones found in the cell wall of diatoms, can enhance the intensity of the incident light by four orders of magnitude.

  13. High temperature microstructured fiber sensor based on a partial-reflection-enabled intrinsic Fabry-Perot interferometer.

    Science.gov (United States)

    Tan, Xiaoling; Geng, Youfu; Li, Xuejin; Gao, Rong; Yin, Zhen

    2013-12-01

    A compact fiber Fabry-Perot interferometer (FPI) sensor for high temperature measurements is proposed and demonstrated. The FPI consists of a small core microstructured fiber and single mode fiber, and it is enabled by partial Fresnel reflection at the interface of the two fibers and the end surface Fresnel reflection of the microstructured fiber. Simple splicing and cleaving techniques are used to construct such an interferometer, and the fringe contrast can reach 20 dB. Response to high temperature up to 1000°C is tested and a sensitivity of 17.7  pm/°C at 1570 nm is obtained. This proposed sensor is compact, and fabricated only with splicing and cleaving techniques, which shows a great potential for space-limited high temperature sensing applications.

  14. Microscopic theory of dipole-dipole interaction in ensembles of impurity atoms in a Fabry-Perot cavity

    Science.gov (United States)

    Kuraptsev, A. S.; Sokolov, I. M.

    2016-08-01

    We develop a consistent quantum theory of the collective effects that take place when electromagnetic radiation interacts with a dense ensemble of impurity centers embedded in a transparent dielectric and placed in a Fabry-Perot cavity. We have calculated the spontaneous decay dynamics of an excited impurity atom as a specific example of applying the developed general theory. We analyze the dependence of the decay rate on the density of impurity centers and the sample sizes as well as on the characteristic level shifts of impurity atoms caused by the internal fields of the dielectric. We show that a cavity can affect significantly the pattern of collective processes, in particular, the lifetimes of collective states.

  15. Far-field super-resolution imaging with a planar hyperbolic metamaterial lens beyond the Fabry-Perot resonance condition

    CERN Document Server

    Lv, Cheng; Jiang, Xunya; Cao, Juncheng

    2014-01-01

    We demonstrate achieving the far-field super-resolution imaging can be realized by using a planar hyperbolic metamaterial lens (PHML), beyond the Fabry-Perot resonance condition. Although the thickness of the PHML is much larger than wavelength, the PHML not only can transmit radiative waves and evanescent waves with high transmission, but also can collect all the waves in the image region with the amplitudes of them being the same order of magnitude. We present a design for a PHML to realize the far-field super-resolution imaging, with the distance between the sources and the images 10 times larger than wavelength. We show the superresolution of our PHML is robust against losses, and the PHML can be fabricated by periodic stacking of metal and dielectric layers.

  16. Amplification of the Signal Intensity of Fluorescence-Based Fiber-Optic Biosensors Using a Fabry-Perot Resonator Structure

    Directory of Open Access Journals (Sweden)

    Meng-Chang Hsieh

    2015-02-01

    Full Text Available Fluorescent biosensors have been widely used in biomedical applications. To amplify the intensity of fluorescence signals, this study developed a novel structure for an evanescent wave fiber-optic biosensor by using a Fabry-Perot resonator structure. An excitation light was coupled into the optical fiber through a laser-drilled hole on the proximal end of the resonator. After entering the resonator, the excitation light was reflected back and forth inside the resonator, thereby amplifying the intensity of the light in the fiber. Subsequently, the light was used to excite the fluorescent molecules in the reactive region of the sensor. The experimental results showed that the biosensor signal was amplified eight-fold when the resonator reflector was formed using a 92% reflective coating. Furthermore, in a simulation, the biosensor signal could be amplified 20-fold by using a 99% reflector.

  17. Genetic variation and recombination of RdRp and HSP 70h genes of Citrus tristeza virus isolates from orange trees showing symptoms of citrus sudden death disease

    Directory of Open Access Journals (Sweden)

    Pappas Georgios J

    2008-01-01

    Full Text Available Abstract Background Citrus sudden death (CSD, a disease that rapidly kills orange trees, is an emerging threat to the Brazilian citrus industry. Although the causal agent of CSD has not been definitively determined, based on the disease's distribution and symptomatology it is suspected that the agent may be a new strain of Citrus tristeza virus (CTV. CTV genetic variation was therefore assessed in two Brazilian orange trees displaying CSD symptoms and a third with more conventional CTV symptoms. Results A total of 286 RNA-dependent-RNA polymerase (RdRp and 284 heat shock protein 70 homolog (HSP70h gene fragments were determined for CTV variants infecting the three trees. It was discovered that, despite differences in symptomatology, the trees were all apparently coinfected with similar populations of divergent CTV variants. While mixed CTV infections are common, the genetic distance between the most divergent population members observed (24.1% for RdRp and 11.0% for HSP70h was far greater than that in previously described mixed infections. Recombinants of five distinct RdRp lineages and three distinct HSP70h lineages were easily detectable but respectively accounted for only 5.9 and 11.9% of the RdRp and HSP70h gene fragments analysed and there was no evidence of an association between particular recombinant mosaics and CSD. Also, comparisons of CTV population structures indicated that the two most similar CTV populations were those of one of the trees with CSD and the tree without CSD. Conclusion We suggest that if CTV is the causal agent of CSD, it is most likely a subtle feature of population structures within mixed infections and not merely the presence (or absence of a single CTV variant within these populations that triggers the disease.

  18. 99mTc-bicisate reliably images CBF in chronic brain diseases but fails to show reflow hyperemia in subacute stroke

    DEFF Research Database (Denmark)

    Lassen, N A; Sperling, B

    1994-01-01

    A multicenter study was performed in seven European centers comparing 99mTc-bicisate with 133Xe as a means of evaluating bicisate as a tracer of CBF distribution in humans. The same type of single photon emission computed tomography (SPECT) instrument (Tomomatic) was used in all centers. A total...... a normal or elevated flow (luxury perfusion) as sign of spontaneous thrombolysis with reperfusion; in fact, these seven cases comprised all the reperfusion cases in the series. The results validate bicisate as a tracer of CBF in normal humans and in chronic brain diseases. Only in a subgroup of subacute...

  19. A dual infection/competition assay shows a correlation between ex vivo human immunodeficiency virus type 1 fitness and disease progression.

    Science.gov (United States)

    Quiñones-Mateu, M E; Ball, S C; Marozsan, A J; Torre, V S; Albright, J L; Vanham, G; van Der Groen, G; Colebunders, R L; Arts, E J

    2000-10-01

    This study was designed to examine the impact of human immunodeficiency virus type 1 (HIV-1) fitness on disease progression through the use of a dual competition/heteroduplex tracking assay (HTA). Despite numerous studies on the impact of HIV-1 diversity and HIV-specific immune response on disease progression, we still do not have a firm understanding of the long-term pathogenesis of this virus. Strong and early CD8-positive cytotoxic T-cell and CD4-positive T-helper cell responses directed toward HIV-infected cells appear to curb HIV pathogenesis. However, the rate at which the virus infects the CD4(+) T-cell population and possibly destroys the HIV-specific immune response may also alter the rate of disease progression. For HIV-1 fitness studies, we established conditions for dual HIV-1 infections of peripheral blood mononuclear cells (PBMC) and a sensitive HTA to measure relative virus production. A pairwise comparison was then performed to estimate the relative fitness of various non-syncytium-inducing/CCR5-tropic (NSI/R5) and syncytium-inducing/CXCR4-tropic (SI/X4) HIV-1 isolates. Four HIV-1 strains (two NSI/R5 and two SI/X4) with moderate ex vivo fitness were then selected as controls and competed against primary HIV-1 isolates from an HIV-infected Belgian cohort. HIV-1 isolates from long-term survivors (LTS) were outcompeted by control strains and were significantly less fit than HIV-1 isolates from patients with accelerated progression to AIDS (PRO). In addition, NSI/R5 HIV-1 isolates from PRO overgrew control SI/X4 strains, suggesting that not all SI/X4 HIV-1 isolates replicate more efficiently than all NSI/R5 isolates. Finally, there were strong, independent correlations between viral load and the total relative fitness values of HIV-1 isolates from PRO (r = 0.84, P = 0.033) and LTS (r = 0.86, P = 0.028). Separation of the PRO and LTS plots suggest that HIV-1 fitness together with viral load may be a strong predictor for the rate of disease progression.

  20. Study on Fabry-Perot interference optic fiber temperature sensor%Fabry-Perot干涉式光纤温度传感器的研究

    Institute of Scientific and Technical Information of China (English)

    曹满婷

    2001-01-01

    分析了温度对相位的调制作用以及Fabry-Perot干涉结构检测相位变化的原理,提出了一种具有高灵敏度和高分辨率的相位调制型全光纤结构,并进行了系统的噪声分析

  1. Optic Fiber Fabry-Perot Interferometer Applied to Measuring Temperature and Displacement%测量温度和位移的光纤Fabry-Perot干涉仪

    Institute of Scientific and Technical Information of China (English)

    陈国霖; 戴福隆; 周辛庚

    2002-01-01

    本文描述了两种光纤Fabry-Peort干涉仪的原理、结构和制造方法.采用光频调制方法用以辨别干涉时域条纹的移动方向,实现了对温度和位移的测量.另外还介绍了条纹计数检测的电路原理.

  2. A New Method of processing the Fabry-Perot Interference Fringes%一种新的Fabry-Perot干涉条纹处理方法

    Institute of Scientific and Technical Information of China (English)

    鄂非; 高秋艳; 艾勇

    2009-01-01

    介绍了一种提取Fabry-Perot(法布里-帕罗)干涉条纹圆心点坐标和条纹半径的新方法.首先对干涉图像依次进行二值化处理,对所得到的条纹强度曲线进行均平滤波和自适应滤波,根据条纹灰度值强度余弦函数分布的特点,对条纹灰度值数据进行最小二乘法拟合,获得条纹强度峰值坐标,通过精确的迭代算法,进而获得Fabry-Perot干涉条纹圆心点的坐标;然后再对干涉条纹进行圆周积分,从而可以确定每级Fabry-Perot干涉条纹的半径长度.该方法可提高计算精度,减小计算误差.

  3. Podocitúria na doença de Fabry

    Directory of Open Access Journals (Sweden)

    Ester Miranda Pereira

    2016-03-01

    Full Text Available Resumo Introdução: A doença de Fabry (DF é uma desordem lisossômica ligada ao cromossomo X ocasionada por mutações no gene que codifica a enzima lisossômica α-galactosidase A (α-GAL. A redução ou ausência da atividade dessa enzima leva ao acúmulo progressivo de gb3. A doença renal é uma importante consequência clínica da acumulação de Gb3. Podócito é o tipo celular mais afetado na doença renal, que mostra apenas uma resposta parcial à Terapia de Reposição Enzimática. Além disso, a disfunção podocitária é a principal contribuinte para a perda progressiva da função renal e pode ser encontrada alterada mesmo antes do início da microalbuminúria. Assim, a podocitúria na DF pode ser uma ferramenta importante para prever a doença renal. Objetivo: O objetivo deste estudo foi quantificar a excreção urinária de podócitos em pacientes com DF (V269M, n = 14 e controles saudáveis (n = 40, e relacioná-las com as variáveis sexo, idade, tempo de terapia e a razão albumina: creatinina (AUC. Métodos: Podócitos urinários foram identificados utilizando imunofluorescência para podocalixina e DAPI. O número de células podocalixina positivo foi contado e o número médio foi utilizado (faixa normal 0-0.6 podócitos/mL. Resultados: O número médio de podócitos na urina de pacientes com DF foi significativamente maior do que os controles saudáveis (p < 0.0001. Observou-se uma correlação positiva entre podocitúria e AUC (p = 0.004; r2 = 0.6417. Conclusão: A podocitúria pode ser uma ferramenta adicional para avaliar a progressão da doença renal em pacientes que se espera que tenha um fenótipo mais agressivo.

  4. Effects of disturbance on regeneration of Abies fabri forests at the upper reaches of the Yangtze River

    Institute of Scientific and Technical Information of China (English)

    Gao Jia-rong; Gao Yang

    2007-01-01

    Mudflow is the principal disturbance in Abies fabri forests. In the Gongga Mountain areas of the upper reaches of the Yangtze River, the intensities and periodicity of different scale mudflows vary. Small-scale mudflows are more frequent, occurring every one or two years while large-scale mudflows may occur once in more than one hundred years. Through a field study of A. fabri forests during different stages of growth, we analyzed their structural characteristics and discovered that after different sizes of mudflow, poplar and birch often occupy the dominant canopy at the expense of the slow growing A. fabri, for only a small number of saplings are A. fabri that occurs in the first regeneration stage. However, a large number of seed resources can be found in mature A.fabri forests and as a unique regeneration species, A. fabri will gradually replace all the other species and form a stable community of strong shade-tolerant trees. Because of the intimate relationship between growing conditions and soil and water conservation at the upper reaches of the Yangtze River, we should carry out some artificial measurements to control and promote the slow regeneration process of A. fabri.

  5. Absorption enhancement through Fabry-Pérot resonant modes in a 430 nm thick InGaAs/GaAsP multiple quantum wells solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Behaghel, B. [Laboratory for Photonics and Nanostructures (LPN–CNRS), Marcoussis 91460 (France); Institute of Research and Development on Photovoltaic Energy (IRDEP–CNRS), Chatou 78401 (France); NextPV, RCAST and CNRS, The University of Tokyo, Meguro-ku, Tokyo 153-8904 (Japan); Tamaki, R.; Watanabe, K.; Sodabanlu, H. [Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo 153-8904 (Japan); Vandamme, N.; Dupuis, C.; Bardou, N.; Cattoni, A. [Laboratory for Photonics and Nanostructures (LPN–CNRS), Marcoussis 91460 (France); Okada, Y. [NextPV, RCAST and CNRS, The University of Tokyo, Meguro-ku, Tokyo 153-8904 (Japan); Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Meguro-ku, Tokyo 153-8904 (Japan); Sugiyama, M. [NextPV, RCAST and CNRS, The University of Tokyo, Meguro-ku, Tokyo 153-8904 (Japan); School of Engineering, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656 (Japan); Collin, S. [Laboratory for Photonics and Nanostructures (LPN–CNRS), Marcoussis 91460 (France); NextPV, RCAST and CNRS, The University of Tokyo, Meguro-ku, Tokyo 153-8904 (Japan); Guillemoles, J.-F., E-mail: jf-guillemoles@chimie-paristech.fr [Institute of Research and Development on Photovoltaic Energy (IRDEP–CNRS), Chatou 78401 (France); NextPV, RCAST and CNRS, The University of Tokyo, Meguro-ku, Tokyo 153-8904 (Japan)

    2015-02-23

    We study light management in a 430 nm-thick GaAs p-i-n single junction solar cell with 10 pairs of InGaAs/GaAsP multiple quantum wells (MQWs). The epitaxial layer transfer on a gold mirror improves light absorption and increases the external quantum efficiency below GaAs bandgap by a factor of four through the excitation of Fabry-Perot resonances. We show a good agreement with optical simulation and achieve around 10% conversion efficiency. We demonstrate numerically that this promising result can be further improved by anti-reflection layers. This study paves the way to very thin MQWs solar cells.

  6. Frequency locking to a high-finesse Fabry-Perot cavity of a Frequency doubled Nd YAG laser used as the optical phase modulator

    CERN Document Server

    Bregant, M; Valle, F D; Ruoso, G; Zavattini, G

    2002-01-01

    We report on the frequency locking of a frequency doubled Nd:YAG laser to a 45 000 finesse, 87-cm-long, Fabry-Perot cavity using a modified form of the Pound-Drever-Hall technique. Necessary signals, such as light phase modulation and frequency correction feedback, are fed direcly to the infrared pump laser. This is sufficient to achieve a stable locking of the 532 nm visible beam to the cavity, also showing that the doubling process does not degrade laser performances.

  7. Cancellation of Fabry-Perot interference effects in terahertz time-domain spectroscopy of optically thin samples

    Science.gov (United States)

    Fastampa, Renato; Pilozzi, Laura; Missori, Mauro

    2017-06-01

    Terahertz time-domain spectroscopy is increasingly used in many fields of research. For strongly absorbing materials with refraction index close to 1, optical parameters at terahertz frequencies are most conveniently quantified using transmission measurements through thin samples. Unfortunately, extracting optical parameters from raw data implies the use and/or development of complicated numerical data processing procedures. In this work we present an efficient computational procedure for extracting the optical parameters in very thin samples (≲100 μ m) from transmission terahertz time-domain spectroscopy. In our procedure, we are able to successfully remove from raw data the Fabry-Perot interference effects, which are commonly recognized to be the leading cause of inaccuracy in the extracted parameters, introducing fictitious oscillations in their frequency dependence. The procedure is based on the Davidenko method to identify the roots of complex functions used to numerically solve the implicit equation obtained by equating the experimental and theoretical transfer functions. The advantage of the method is the possibility of obtaining the roots using the numerical solution of a system of real differential equations using standard mathematical packages. In addition, we show that complete removal of the Fabry-Perot oscillations is achieved by including in the computational procedure, besides the sample thickness, the instrumental error on the starting instant of the terahertz signal sampling. This error could be common to many terahertz time-domain systems, especially those using optical fibers. This correction is necessary in general to preserve the terahertz spectroscopic features in the extracted optical parameters for strongly absorbing materials with refraction index close to 1, such as water, biological matter, and several organic materials.

  8. Simultaneous wavelength and orbital angular momentum demultiplexing using tunable MEMS-based Fabry-Perot filter

    DEFF Research Database (Denmark)

    Lyubopytov, Vladimir; Porfirev, Alexey P.; Gurbatov, Stanislav O.

    2017-01-01

    In this paper, we experimentally demonstrate simultaneous wavelength and orbital angular momentum (OAM) multiplexing/demultiplexing of 10 Gbit/s data streams using a new on-chip micro-component-tunable MEMS-based Fabry-Perot filter integrated with a spiral phase plate. In the experiment, two...

  9. Broadband Measurement of Coating Thermal Noise in Rigid Fabry-Perot Cavities

    CERN Document Server

    Chalermsongsak, Tara; Hall, Evan D; Arai, Koji; Gustafson, Eric K; Adhikari, Rana X

    2014-01-01

    We report on the relative length fluctuation of two fixed-spacer Fabry-Perot cavities with mirrors fabricated from silica/tantala dielectric coatings on fused silica substrates. By locking a laser to each cavity and reading out the beat note $\\hat{\

  10. A Lossy Fabry-perot Based Optical Filter for Natural Gas Analysis

    NARCIS (Netherlands)

    Ayerden, N.P.; Ghaderi, M.; De Graaf, G.; Wolffenbuttel, R.F.

    2014-01-01

    A set-up for optical gas composition measurement based on absorption spectroscopy is composed of a white light source, a gas cell and a spectrometer. The Fabry-Perot optical filter is suitable for miniaturization of this system, as it is composed of only two reflectors with a transparent layer in-be

  11. High precision planar waveguide propagation loss measurement technique using a Fabry-Perot cavity

    DEFF Research Database (Denmark)

    Feuchter, Thomas; Thirstrup, Carsten

    1994-01-01

    A high precision measurement technique for characterizing the propagation loss in silica low-loss optical waveguides, based on measuring the contrast of a Fabry-Perot cavity, is demonstrated. The cavity consists of the waveguide coupled to two polarization-maintaining fibers, each end facet coated...

  12. All-Optical Switching Using Fabry-Perot Laser Diodes(Invited paper)

    Institute of Scientific and Technical Information of China (English)

    P. K. A. Wai; L. Y. Chan; H. Y. Tam

    2003-01-01

    In this paper, we investigate all-optical packet switching using a multi-wavelength mutual injection-locked Fabry-Perot laser diode. We observe error-free packet-switching of a 10 Gb/s signal with an extinction ratio of 16.9.

  13. A Novel Extrinsic Fiber-Optic Fabry-Perot Strain Sensor System Based on Optical Amplification

    Institute of Scientific and Technical Information of China (English)

    Yun-Jiang Rao; Jian Jiang; Zheng-Lin Ran

    2003-01-01

    A novel extrinsic fiber-optic Fabry-Perot interferometric strain sensor system is demonstrated based on the simultaneous use of the amplified spontaneous emission and optical amplification. The improvement of 3~4 orders of magnitude in signal level can be achieved.

  14. Influence of laser frequency noise on scanning Fabry-Perot interferometer based laser Doppler velocimetry

    DEFF Research Database (Denmark)

    Rodrigo, Peter John; Pedersen, Christian

    2014-01-01

    n this work, we study the performance of a scanning Fabry-Perot interferometer based laser Doppler velocimeter (sFPILDV) and compare two candidate 1.5 um single-frequency laser sources for the system – a fiber laser (FL) and a semiconductor laser (SL). We describe a straightforward calibration pr...

  15. Single resonance monolithic Fabry-Perot filters formed by volume Bragg gratings and multilayer dielectric mirrors.

    Science.gov (United States)

    Lumeau, Julien; Koc, Cihan; Mokhun, Oleksiy; Smirnov, Vadim; Lequime, Michel; Glebov, Leonid B

    2011-05-15

    A new class of Fabry-Perot filters produced by a multilayer dielectric mirror deposited on top of a reflecting volume Bragg grating is described. The first fabricated prototype for the 852 nm region demonstrates a 30 pm bandwidth, 90+% transmission at resonance, and a good agreement with theoretical simulation. © 2011 Optical Society of America

  16. Enhanced Transmission in Rolled-up Hyperlenses utilizing Fabry-Pe\\'rot Resonances

    CERN Document Server

    Kerbst, Jochen; Rottler, Andreas; Koitmäe, Aune; Bröll, Markus; Stemmann, Andrea; Heyn, Christian; Heitmann, Detlef; Mendach, Stefan

    2011-01-01

    We experimentally demonstrate that the transmission though rolled-up metal/semiconductor hyperlenses can be enhanced at desired frequencies utilizing Fabry-P\\'erot resonances. By means of finite difference time domain simulations we prove that hyperlensing occurs at frequencies of high transmission.

  17. A Ray-tracing Method to Analyzing Modulated Planar Fabry-Perot Antennas

    DEFF Research Database (Denmark)

    Hougs, Mikkel Dahl; Kim, Oleksiy S.; Breinbjerg, Olav

    2015-01-01

    A new approach for fast modelling of Fabry-Perot antennas with modulated partially reflective surfaces (PRS) using ray-tracing is proposed. For validation of the method, a configuration is introduced which consists of a cavity with a modulated PRS, fed internally by a magnetic dipole. The PRS con...

  18. A Novel Extrinsic Fiber-Optic Fabry-Perot Strain Sensor System Based on Optical Amplification

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A novel extrinsic fiber-optic Fabry-Perot interferometric strain sensor system is demonstrated based on the simultaneous use of the amplified spontaneous emission and optical amplification. The improvement of 3~4 orders of magnitude in signal level can be achieved.

  19. A Ray-tracing Method to Analyzing Modulated Planar Fabry-Perot Antennas

    DEFF Research Database (Denmark)

    Hougs, Mikkel Dahl; Kim, Oleksiy S.; Breinbjerg, Olav

    2015-01-01

    A new approach for fast modelling of Fabry-Perot antennas with modulated partially reflective surfaces (PRS) using ray-tracing is proposed. For validation of the method, a configuration is introduced which consists of a cavity with a modulated PRS, fed internally by a magnetic dipole. The PRS...

  20. Development of tunable Fabry-Perot spectral camera and light source for medical applications

    Science.gov (United States)

    Kaarre, M.; Kivi, S.; Panouillot, P. E.; Saari, H.; Mäkynen, J.; Sorri, I.; Juuti, M.

    2013-05-01

    VTT has developed a fast, tunable Fabry-Perot (FP) filter component and applied it in making small, lightweight spectral cameras and light sources. One application field where this novel technology is now tested is medical field. A demonstrator has been made to test the applicability of FP based spectral filtering in the imaging of retina in visible light wavelength area.

  1. Folded Fabry-Perot quasi-optical ring resonator diplexer Theory and experiment

    Science.gov (United States)

    Pickett, H. M.; Chiou, A. E. T.

    1983-01-01

    Performance of folded Fabry-Perot quasi-optical ring resonator diplexers with different geometries of reflecting surfaces is investigated both theoretically and experimentally. Design of optimum surface geometry for minimum diffraction, together with the figure of merit indicating improvement in performance, are given.

  2. All-Optical Switching Using Fabry-Perot Laser Diodes (Invited paper)

    Institute of Scientific and Technical Information of China (English)

    P.; K.; A.; Wai; L.; Y.; Chan; H.; Y.; Tam

    2003-01-01

    In this paper, we investigate all-optical packet switching using a multi-wavelength mutual injection-locked Fabry-Perot laser diode. We observe error-free packet-switching of a 10 Gb/s signal with an extinction ratio of 16.9.

  3. Large-area Fabry-Perot modulator based on electro-optic polymers

    DEFF Research Database (Denmark)

    Benter, Nils; Bertram, Ralph Peter; Soergel, Elisabeth

    2006-01-01

    We present a large-area electro-optic Fabry-Perot modulator utilizing a photoaddressable bis-azo polymer placed between two dielectric mirrors with an open aperture of 2 cm. A modulation efficientcy of 1% at an effective modulation voltage of 20 V for a wavelength of 1.55 mymeter is demonstrated...

  4. A cross-sectional study showing differences in the clinical diagnosis of pelvic inflammatory disease according to the experience of clinicians: implications for training and audit.

    Science.gov (United States)

    Morris, Georgina C; Stewart, Catherine M W; Schoeman, Sarah A; Wilson, Janet D

    2014-09-01

    Pelvic inflammatory disease (PID) generates diagnostic difficulty even for experienced doctors. Junior doctors and nurses also assess women with symptoms suggestive of PID. We aimed to determine if and how PID diagnoses vary between clinicians with different experience levels. Cross-sectional study conducted in U.K. sexual health clinic, nested within a Chlamydia trachomatis (CT), and Neisseria gonorrhoea diagnostic test accuracy study. Proportions and characteristics of women diagnosed clinically with PID by clinicians with varying experience were compared. Outcomes included demographics, presenting symptoms and signs and CT, and CT and/or gonococcal (GC) (CT/GC) positivity. In 3804 women assessed by 36 clinicians, rates of PID, CT and GC were 4.4%, 10.5%, and 2.5%, with no differences between experienced and inexperienced clinicians (p=0.84, p=0.13 and p=0.07, respectively). 63.7% of PID diagnosed by experienced clinicians met Centers for Disease Control and Prevention (CDC) key clinical criteria versus 41.2% by inexperienced; experienced versus inexperienced OR 2.51; 95% CI 1.16 to 5.40). Proportions of CT (CT/GC)-positive PID increased with experience (5.9% (11.8%) to 31.9% (34.1%)); experienced versus inexperienced (OR 3.90; 95% CI 1.12 to 13.5). Percentages of women with CT (CT/GC) who were diagnosed with PID also rose with experience (2.2% (3.9%) to 14.2% (13.7%)), but CT prevalence in PID cases diagnosed by inexperienced clinicians (8.8%) was no greater than in all women they assessed (9.0%), suggesting poorer discriminative skills. Clinical diagnostic acumen for PID improves with experience. Inexperienced clinicians should focus on the presence of lower abdominal pain with pelvic tenderness and consider additional supportive symptoms, to improve specificity of their diagnoses. ISRCTN 42867448. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. Plasma renin-angiotensin system-regulating aminopeptidase activities are modified in early stage Alzheimer's disease and show gender differences but are not related to apolipoprotein E genotype.

    Science.gov (United States)

    Puertas, María Del Carmen; Martínez-Martos, José Manuel; Cobo, Manuela; Lorite, Pedro; Sandalio, Rosa María; Palomeque, Teresa; Torres, María Isabel; Carrera-González, María Pilar; Mayas, María Dolores; Ramírez-Expósito, María Jesús

    2013-06-01

    Alterations in blood pressure and components of the renin-angiotensin system (RAS) contribute to the development and progression of Alzheimer's disease (AD), resulting in changes that can lead or contribute to cognitive decline. Aspartyl aminopeptidase (ASAP), aminopeptidase A (APA), aminopeptidase N (APN) and aminopeptidase B (APB) catabolise circulating angiotensins, whereas insulin-regulated aminopeptidase (IRAP) has been described as the AT4 receptor. We have found in AD patients a significant decrease of APA activity in men but not in women, and of APN, APB and IRAP in both genders, when compared with control subjects. No changes were found in ASAP activity. Also, APN, APB and IRAP but not APA correlated with the Mini-Mental test, but no relationship with APOE genotype was found. We conclude that several components of the RAS are modified in AD patients, with gender differences. Furthermore, ROC analysis indicates that APN, APB and IRAP activities could be useful non-invasive biomarkers of AD from the earliest stages.

  6. Huntington disease iPSCs show early molecular changes in intracellular signaling, the expression of oxidative stress proteins and the p53 pathway.

    Science.gov (United States)

    Szlachcic, Wojciech J; Switonski, Pawel M; Krzyzosiak, Wlodzimierz J; Figlerowicz, Marek; Figiel, Maciej

    2015-09-01

    Huntington disease (HD) is a brain disorder characterized by the late onset of motor and cognitive symptoms, even though the neurons in the brain begin to suffer dysfunction and degeneration long before symptoms appear. There is currently no cure. Several molecular and developmental effects of HD have been identified using neural stem cells (NSCs) and differentiated cells, such as neurons and astrocytes. Still, little is known regarding the molecular pathogenesis of HD in pluripotent cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Therefore, we examined putative signaling pathways and processes involved in HD pathogenesis in pluripotent cells. We tested naïve mouse HD YAC128 iPSCs and two types of human HD iPSC that were generated from HD and juvenile-HD patients. Surprisingly, we found that a number of changes affecting cellular processes in HD were also present in undifferentiated pluripotent HD iPSCs, including the dysregulation of the MAPK and Wnt signaling pathways and the dysregulation of the expression of genes related to oxidative stress, such as Sod1. Interestingly, a common protein interactor of the huntingtin protein and the proteins in the above pathways is p53, and the expression of p53 was dysregulated in HD YAC128 iPSCs and human HD iPSCs. In summary, our findings demonstrate that multiple molecular pathways that are characteristically dysregulated in HD are already altered in undifferentiated pluripotent cells and that the pathogenesis of HD might begin during the early stages of life.

  7. Enhanced chiral response from the Fabry-Perot cavity coupled meta-surfaces

    Science.gov (United States)

    Yang, Ze-Jian; Hu, De-Jiao; Gao, Fu-Hua; Hou, Yi-Dong

    2016-08-01

    The circular dichroism (CD) signal of a two-dimensional (2D) chiral meta-surface is usually weak, where the difference between the transmitted (or reflected) right and left circular polarization is barely small. We present a general method to enhance the reflective CD spectrum, by adding a layer of reflective film behind the meta-surface. The light passes through the chiral meta-surface and propagates towards the reflector, where it is reflected back and further interacts with the chiral meta-surface. The light is reflected back and forth between these two layers, forming a Fabry-Perot type resonance, which interacts with the localized surface plasmonic resonance (LSPR) mode and greatly enhances the CD signal of the light wave leaving the meta-surface. We numerically calculate the CD enhancing effect of an L-shaped chiral meta-surface on a gold film in the visible range. Compared with the single layer meta-surface, the L-shaped chiral meta-surface has a CD maximum that is dramatically increased to 1. The analysis of reflection efficiency reveals that our design can be used to realize a reflective circular polarizer. Corresponding mode analysis shows that the huge CD originates from the hybrid mode comprised of FP mode and LSPR. Our results provide a general approach to enhancing the CD signal of a chiral meta-surface and can be used in areas like biosensing, circular polarizer, integrated photonics, etc. Project supported by the National Natural Science Foundation of China (Grant No. 61377054).

  8. Evaluation of thermal expansion coefficient of Fabry-Perot cavity using an optical frequency comb

    Science.gov (United States)

    Oulehla, Jindřich; Šmíd, Radek; Buchta, Zdeněk; Čížek, Martin; Mikel, Břetislav; Jedlička, Petr; Lazar, Josef; Číp, Ondřej

    2011-05-01

    In construction of highly mechanically stable measuring devices like AFM microscopes or nano-comparators the use of low expansion materials is very necessary. We can find Zerodur ceramics or ULE glasses used as a frame or basement of these devices. The expansion coefficient of such low-expansion materials is lower than 0.01 x 10-6 m•K-1. For example in case of a frame or basement 20 cm long it leads to a dilatation approximately 4 nm per 1 K. For calculation of the total uncertainty of the mentioned measuring devices the knowledge of the thermal expansion coefficient of the frame or basement is necessary. In this work we present a method, where small distance changes are transformed into rf-frequency signal. The frequency of this signal is detected by a counter which measures the value of the frequency with respect to an ultra-stable time-base. This method uses a Fabry-Perot cavity as a distance measuring tool. The spacer of the optical resonator is made from the investigated low-expansion material. It is placed into a vacuum chamber where the inside temperature is controlled. A selected mode of the femtosecond frequency of the femtosecond comb which represent the distance changes of the optical resonator. The frequency is measured by the rf-counter which is synchronized by a time-base signal from an atomic clock. The first results show the resolution of the method in the 0.1 nm order. Therefore the method has a potential in characterisation of materials in the nanoworld.

  9. Influence of the Fineness of Optical Fiber Fabry-Perot Resonant Cavity on the Phase Sensitivity%光纤Fabry-Perot谐振腔的精细度对相位灵敏度的影响

    Institute of Scientific and Technical Information of China (English)

    康崇; 王政平; 黄宗军; 吴强; 韩占国

    2005-01-01

    分析了光纤Fabry-Perot谐振腔的工作原理及其工作点的选择问题,推导了谐振腔的光学相位灵敏度与精细度的关系,给出了理论公式及曲线,并与光纤Math-Zehnder干涉进行了对比,指出了在相位灵敏度上两者的巨大差距,证明了光纤Fabry-Perot干涉的独特优点.介绍了光纤Fabry-Perot干涉的实验系统,提出了检测及计算Fabry-Perot谐振腔有效精细度的方法,实验结果与理论仿真基本吻合.

  10. Infants with complex congenital heart diseases show poor short-term memory in the mobile paradigm at 3 months of age.

    Science.gov (United States)

    Chen, Chao-Ying; Harrison, Tondi; Heathcock, Jill

    2015-08-01

    The purpose of this study was to examine learning, short-term memory and general development including cognitive, motor, and language domains in infants with Complex Congenital Heart Defects (CCDH). Ten infants with CCHD (4 males, 6 females) and 14 infants with typical development (TD) were examined at 3 months of age. The mobile paradigm, where an infant's leg is tethered to an overhead mobile, was used to evaluate learning and short-term memory. The Bayley Scales of Infant Development 3rd edition (Bayley-III) was used to evaluate general development in cognitive, motor, and language domains. Infants with CCHD and infants with TD both showed learning with significant increase in kicking rate (pshort-term memory (p=0.017) in the mobile paradigm. There were no differences on cognitive, motor, and language development between infants with CCHD and infants with TD on the Bayley-III. Early assessment is necessary to guide targeted treatment in infants with CCHD. One-time assessment may fail to detect potential cognitive impairments during early infancy in infants with CCHD. Supportive intervention programs for infants with CCHD that focuses on enhancing short-term memory are recommended. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. 基于Fabry-Perot干涉测量技术的大坝安全监测系统探究%Research on Monitoring System for Dam Safety Based on Fabry-Perot Interferometry Technology

    Institute of Scientific and Technical Information of China (English)

    周柏兵; 朱劭宇; 谢福临; 王振平

    2006-01-01

    Fabry-Perot干涉测量技术的原理及基于该技术的光纤传感系统作了介绍,分析了Fabry-Perot干涉测量技术原理并推导了有关计算公式,展望此类技术在大坝安全监测中的应用.

  12. Measurements of the phase shift on reflection for low-order infrared Fabry-Perot interferometer dielectric stack mirrors.

    Science.gov (United States)

    Mielke, S L; Ryan, R E; Hilgeman, T; Lesyna, L; Madonna, R G; Van Nostrand, W C

    1997-11-01

    A simple technique based on a Fizeau interferometer to measure the absolute phase shift on reflection for a Fabry-Perot interferometer dielectric stack mirror is described. Excellent agreement between the measured and predicted phase shift on reflection was found. Also described are the salient features of low-order Fabry-Perot interferometers and the demonstration of a near ideal low-order (1-10) Fabry-Perot interferometer through minimizing the phase dispersion on reflection of the dielectric stack. This near ideal performance of a low-order Fabry-Perot interferometer should enable several applications such as compact spectral imagers for solid and gas detection. The large free spectral range of such systems combined with an active control system will also allow simple interactive tuning of wavelength agile laser sources such as CO(2) lasers, external cavity diode lasers, and optical parametric oscillators.

  13. Simultaneous measurement of pressure and temperature by employing Fabry-Perot interferometer based on pendant polymer droplet.

    Science.gov (United States)

    Sun, Bing; Wang, Yiping; Qu, Junle; Liao, Changrui; Yin, Guolu; He, Jun; Zhou, Jiangtao; Tang, Jian; Liu, Shen; Li, Zhengyong; Liu, Yingjie

    2015-02-01

    We investigated a novel and ultracompact polymer-capped Fabry-Perot interferometer, which is based on a polymer capped on the endface of a single mode fiber (SMF). The proposed Fabry-Perot interferometer has advantages of easy fabrication, low cost, and high sensitivity. The variation of the Fabry-Perot cavity length can be easily controlled by using the motors of a normal arc fusion splicer. Moreover, the enhanced mechanical strength of the Fabry-Perot interferometer makes it suitable for high sensitivity pressure and temperature sensing in harsh environments. The proposed interferometer exhibits a wavelength shift of the interference fringes that corresponds to a temperature sensitivity of 249 pm/°C and a pressure sensitivity of 1130 pm/MPa, respectively, around the wavelength of 1560 nm.

  14. Recent Progress in Multiparameter Measurement Based on Extrinsic Fiber-Optic Fabry-Perot Interferometers and Fiber Gratings

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    This paper presents a review of recent progress in simultaneous measurement of multiparameters including strain, temperature, vibration, transverse load, based on the combinations of extrinsic fiber-optic Fabry-Perot interferometers and fiber gratings.

  15. Determination of Absolute Plate Spacing for the Fabry-Perot Subassembly of the Thermosphere Imager for Global Observations Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Task 1: rad test AD7746 component for failure dosage for use in GEO Task 2: Algorithm for determining absolute plate spacing of the TIGO Fabry-Perot plates,...

  16. Coherent electron transparent tunneling through a single barrier within a Fabry-Perot cavity

    Science.gov (United States)

    Stolle, Jason; Baum, Chaz; Amann, Ryan; Haman, Ryan; Call, Tanner; Li, Wei

    2016-07-01

    Electromagnetic wave and quantum DeBroglie wave have many parallels between each other. We investigate the quantum mechanical counterpart of electromagnetic resonant tunneling through a non-absorbing metal layer. It is confirmed that an electron also has transparent transmission through a single barrier within a Fabry-Perot like cavity. This tunneling structure is actually a distortion of the Fabry-Perot echelon. We find that for a specific resonant electron energy, the cavity length is related to the electron's DeBroglie wavelength; and the single barrier can be located at a series positions with an interval equal to a half of the DeBroglie wavelength, not just at the center of the cavity. This tunneling phenomenon will have novel applications in quantum devices such as the resonant tunneling diode and scanning tunneling microscope. The results of this paper should also have impact on related electromagnetic research and application.

  17. Resolution limits of extrinsic Fabry-Perot interferometric displacement sensors utilizing wavelength scanning interrogation.

    Science.gov (United States)

    Ushakov, Nikolai; Liokumovich, Leonid

    2014-08-10

    The factors limiting the resolution of displacement sensors based on the extrinsic Fabry-Perot interferometer were studied. An analytical model giving the dependency of extrinsic Fabry-Perot interferometric (EFPI) resolution on the parameters of an optical setup and a sensor interrogator was developed. The proposed model enables one to either estimate the limit of possible resolution achievable with a given setup, or derive the requirements for optical elements and/or a sensor interrogator necessary for attaining the desired sensor resolution. An experiment supporting the analytical derivations was performed, demonstrating a large dynamic measurement range (with cavity length from tens of microns to 5 mm), a high baseline resolution (from 14 pm), and good agreement with the model.

  18. Analyzing the temperature sensitivity of Fabry-Perot sensor using multilayer graphene diaphragm.

    Science.gov (United States)

    Li, Cheng; Liu, Qianwen; Peng, Xiaobin; Fan, Shangchun

    2015-10-19

    A miniature Fabry-Perot interferometric sensor with an ultra-high temperature sensitivity was constructed by using an approximate 8-layer graphene diaphragm. The extremely thin diaphragm was transferred onto the endface of a ferrule with an inner diameter of 125 μm, and van der Waals interactions between the graphene diaphragm and its substrate created a low finesse Fabry-Perot interferometer with a cavity length of 42.86 μm. Temperature testing demonstrated a temperature-induced cavity length change of 352 nm/°C with a good linearity in the range of 20-60 °C. The result conformed well to the proposed analytical models relating to thermal expansion of trapped gas, thermal-optical property of graphene diaphragm and deflection behavior of bulged graphene blister. However, the ultra-thin diaphragm exhibited a small deflection deformation characteristic due to the applied higher loads.

  19. 两种提取Fabry-Perot干涉条纹圆心的新方法

    Institute of Scientific and Technical Information of China (English)

    陈龙; 黎玉雯; 朱昭华

    2014-01-01

    本文介绍两种提取Fabry-Perot干涉条纹圆心点坐标的新方法。首先对干涉图像依次进行二值化处理,对所得到的条纹强度曲线进行均平滤波和自适应滤波,根据条纹灰度值强度余弦函数分布的特点,对条纹灰度值数据进行最小二乘法拟合,获得条纹强度峰值坐标,然后通过本文介绍的算法,进而获得Fabry-Perot干涉条纹圆心点的坐标。

  20. Manipulating the optical bistability at terahertz frequency in the Fabry-Perot cavity with graphene.

    Science.gov (United States)

    Jiang, Leyong; Guo, Jun; Wu, Leiming; Dai, Xiaoyu; Xiang, Yuanjiang

    2015-11-30

    We investigate theoretically the optical bistability from a Fabry-Perot cavity with graphene in the terahertz (THz) frequency. It is demonstrated that the optical bistablility in this cavity can be realized due to the electric field enhancement and the giant third-order nonlinear conductivity of graphene. The optical bistable behavior is strongly dependent on the transmission amplitude of the mirror and the position of the graphene in the cavity. It is especially important that the hysterical behaviors of the transmitted light rely on the optical conductivity of graphene, making the Fabry-Perot cavity to be a good candidate for dynamic tunable optical bistable device in the THz frequencies, owing to the possibility of high tunability of graphene conductivity by means of external electrostatic or magnetostatic field.

  1. On-Chip High-Finesse Fabry-Perot Microcavities for Optical Sensing and Quantum Information

    Directory of Open Access Journals (Sweden)

    Mohammad H. Bitarafan

    2017-07-01

    Full Text Available For applications in sensing and cavity-based quantum computing and metrology, open-access Fabry-Perot cavities—with an air or vacuum gap between a pair of high reflectance mirrors—offer important advantages compared to other types of microcavities. For example, they are inherently tunable using MEMS-based actuation strategies, and they enable atomic emitters or target analytes to be located at high field regions of the optical mode. Integration of curved-mirror Fabry-Perot cavities on chips containing electronic, optoelectronic, and optomechanical elements is a topic of emerging importance. Micro-fabrication techniques can be used to create mirrors with small radius-of-curvature, which is a prerequisite for cavities to support stable, small-volume modes. We review recent progress towards chip-based implementation of such cavities, and highlight their potential to address applications in sensing and cavity quantum electrodynamics.

  2. All-reflective Michelson, Sagnac, and Fabry-Perot interferometers based on grating beam splitters.

    Science.gov (United States)

    Sun, K X; Byer, R L

    1998-04-15

    All-reflective Michelson, Sagnac, and Fabry-Perot interferometers based on grating beam splitters are experimentally demonstrated at a wavelength of 1064 nm. A 1200-groove/mm grating diffracting 0 and -1 orders with an efficiency of 48.2% for each order was used as a near-50/50 beam splitter. The all-reflective Sagnac and Michelson interferometers were formed by reintroducing both of the diffracted beams back to the grating. The Fabry-Perot interferometer was formed in a Littrow configuration by using a 1700-groove/mm grating with a blazing efficiency of 91% as a cavity coupler. These interferometers encompass all the fundamental configurations of all-reflective laser interferometric gravitational-wave detectors, promising improved wave-front quality by avoiding volume thermal effects in transmissive optics under high-power laser illumination.

  3. Optical Analog-to-digital Conversion Scheme Based on Tunable Fabry-Perot Resonator

    Institute of Scientific and Technical Information of China (English)

    LI Zheng

    2007-01-01

    Proposed is an interference type of optical analog-to-digital conversion(ADC). The refractive index of Fabry-Perot cavity changes with different voltages. The Fabry-Perot resonator converts electronic intensity into light wavelength through selecting lights of different wavelengthes. The parameters of the scheme are acquired with the transmission matrix of optical element and the time of steady-state light field. The maximum sampling speedes of 4-bit, 6-bit, 7-bit, 8-bit and 9-bit(ADC) are 1.695×1010 count/s, 4.33×109 count/s, 2.38×109 count/s, 1.24×109 count/s and 5.9×108 count/s, respectively.

  4. Chronology of Fabry-Perot Interferometer Fiber-Optic Sensors and Their Applications: A Review

    Directory of Open Access Journals (Sweden)

    Md. Rajibul Islam

    2014-04-01

    Full Text Available Optical fibers have been involved in the area of sensing applications for more than four decades. Moreover, interferometric optical fiber sensors have attracted broad interest for their prospective applications in sensing temperature, refractive index, strain measurement, pressure, acoustic wave, vibration, magnetic field, and voltage. During this time, numerous types of interferometers have been developed such as Fabry-Perot, Michelson, Mach-Zehnder, Sagnac Fiber, and Common-path interferometers. Fabry-Perot interferometer (FPI fiber-optic sensors have been extensively investigated for their exceedingly effective, simple fabrication as well as low cost aspects. In this study, a wide variety of FPI sensors are reviewed in terms of fabrication methods, principle of operation and their sensing applications. The chronology of the development of FPI sensors and their implementation in various applications are discussed.

  5. A hybrid Fabry-Perot/Michelson interferometer sensor using a dual asymmetric core microstructured fiber

    Science.gov (United States)

    Frazão, O.; Silva, S. F.; Viegas, J.; Baptista, J. M.; Santos, J. L.; Roy, P.

    2010-02-01

    A hybrid Fabry-Perot/Michelson interferometer sensor using a dual asymmetric core microstructured fiber is demonstrated. The hybrid interferometer presents three waves. Two parallel Fabry-Perot cavities with low finesse are formed between the splice region and the end of a dual-core microstructured fiber. A Michelson configuration is obtained by the two small cores of the microstructured fiber. The spectral response of the hybrid interferometer presents two pattern fringes with different frequencies due to the respective optical path interferometers. The hybrid interferometer was characterized in strain and temperature presenting different sensitivity coefficients for each topology. Due to these characteristics, this novel sensing head is able to measure strain and temperature, simultaneously.

  6. Temperature-independent refractometer based on fiber-optic Fabry-Perot interferometer

    Science.gov (United States)

    Li, Jiacheng; Qiao, Xueguang; Wang, Ruohui; Rong, Qiangzhou; Bao, Weijia; Shao, Zhihua; Yang, Tingting

    2016-04-01

    A miniature fiber-optic refractometer based on Fabry-Perot interferometer (FPI) has been proposed and experimentally demonstrated. The sensing head consists of a short section of photonics crystal fiber (PCF) spliced to a single mode fiber (SMF), in which the end-face of the PCF is etched to remove holey structure with hydrofluoric (HF) acid. A Fabry-Perot interference spectrum is achieved based on the reflections from the fusion splicing interface and the end-face of the core of PCF. The interference fringe is sensitive to the external refractive index (RI) with an intensity-referenced sensitivity of 358.27 dB/RIU ranging from 1.33 to 1.38. The sensor has also been implemented for the concentration measurement of λ-phage DNA solution. In addition, the dip intensity is insensitive to the ambient temperature variation, making it a good candidate for temperature-independent bio-sensing area.

  7. Active vibration suppression in a suspended Fabry-Pérot cavity.

    Science.gov (United States)

    Canuto, Enrico

    2006-07-01

    This paper is concerned with active vibration suppression in a suspended Fabry-Pérot cavity, employed as the sensor in an innovative thrust-stand, called Nanobalance. The Nanobalance aims to exploit the sensitivity of in-vacuum Fabry-Pérot interferometers to sub-nanometric displacements in order to measure thrust (active and the passive) suspended to an athermic spacer. The thruster under test is mounted on the active pendulum and an equal dummy thruster is mounted on the passive one for balancing. The objective of the paper is to suppress the beat motion centered on the mean pendulum natural frequency (10-14 Hz depending on the thruster under test) without affecting the measurement bandwidth (2 Hz) where thrust has to be measured. Beat motion arises because of small pendulum imbalances excited by ground noise. Relevant digital control strategies and experimental results will be presented and discussed.

  8. Understanding the concept of resolving power in the Fabry-Perot interferometer using a digital simulation

    Energy Technology Data Exchange (ETDEWEB)

    Juvells, I [Departament de Fisica Aplicada i Optica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona (Spain); Carnicer, A [Departament de Fisica Aplicada i Optica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona (Spain); Ferre-Borrull, J [Departament d' Enginyeria Electronica, Universitat Rovira i Virgili, Electrica i Automatica. Av. Paisos Catalans 26, Campus Sescelades 43007 Tarragona (Spain); MartIn-Badosa, E [Departament de Fisica Aplicada i Optica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona (Spain); Montes-Usategui, M [Departament de Fisica Aplicada i Optica, Universitat de Barcelona, Diagonal 647, 08028 Barcelona (Spain)

    2006-09-01

    The resolution concept in connection with the Fabry-Perot interferometer is difficult to understand for undergraduate students enrolled in physical optics courses. The resolution criterion proposed in textbooks for distinguishing equal intensity maxima and the deduction of the resolving power equation is formal and non-intuitive. In this paper, we study the practical meaning of the resolution criterion and resolution power using a computer simulation of a Fabry-Perot interferometer. The light source in the program has two monochromatic components, the wavelength difference being tunable by the user. The student can also adjust other physical parameters so as to obtain different simulation results. By analysing the images and graphics of the simulation, the resolving power concept becomes intuitive and understandable.

  9. The low coherence Fabry-Pérot interferometer with diamond and ZnO layers

    Science.gov (United States)

    Majchrowicz, D.; Den, W.; Hirsch, M.

    2016-09-01

    The authors present a fiber-optic Fabry-Pérot interferometer built with the application of diamond and zinc oxide (ZnO) thin layers. Thin ZnO films were deposited on the tip of a standard telecommunication single-mode optical fiber (SMF- 28) while the diamond layer was grown on the plate of silicon substrate. Investigated ZnO layers were fabricated by atomic layer deposition (ALD) and the diamond films were deposited using Microwave Plasma Enhanced Chemical Vapor Deposition (μPE CVD) system. Different thickness of layers was examined. The measurements were performed for the fiber-optic Fabry-Pérot interferometer working in the reflective mode. Spectra were registered for various thicknesses of ZnO layer and various length of the air cavity. As a light source, two superluminescent diodes (SLD) with central wavelength of 1300 nm and 1550 nm were used in measurement set-up.

  10. A VO-compatible Information System for 3D Fabry-Perot Data

    Science.gov (United States)

    Surace, C.; Jegouzot, I.; Granet, Y.; Amram, P.; Balkowski, C.; Carignan, C.; Epinat, B.; Fenouilet, T.; Marcelin, M.

    2009-09-01

    In the astronomical world, Fabry-Perot (FP) data are very specific. Using a scanning Fabry-Perot, extended line emitting targets can be observed with a large field of view, within a short spectral range (from 5 to 100 Å) and with high resolutions (from 1,000 to 20,000). Observation data cubes allow us to derive and to focus mostly on emission line flux maps, velocity maps and velocity dispersion maps. Specific tools are needed to process and analyze FP data and make results available to the community. We present a VO-compliant Information System (http://fabryperot.oamp.fr/) platform dedicated to the 3D FP data. A multi-criteria interface based on SItools 4.0 is available and Cone Search, SIAP, (SIAP2) and Characterization are being implemented. A discussion of ``Added value Tools'' to be implemented has begun. These might include projection of galaxies at high redshift, Tully Fisher diagrams, etc.

  11. Diaphragm based long cavity Fabry-Perot fiber acoustic sensor using phase generated carrier

    Science.gov (United States)

    Liu, Bin; Lin, Jie; Liu, Huan; Ma, Yuan; Yan, Lei; Jin, Peng

    2017-01-01

    A diaphragm based long cavity Fabry-Perot interferometric fiber acoustic sensor is proposed. The Fabry-Perot cavity is formed by a flat fiber facet and an ultra-thin silver diaphragm with a 6-meter long fiber inserted in the cavity. A narrow-linewidth ring-cavity erbium-doped fiber laser is applied to demodulate the sensing signal in the phase generated carrier algorithm. Experimental results have demonstrated that the phase sensitivity is about -140 dB re 1 rad/μPa at 2 kHz. The noise equivalent acoustic signal level is 60.6 μPa/Hz1/2 and the dynamic range is 65.1 dB-SPL at 2 kHz. The sensor is suitable for sensing of weak acoustic signals.

  12. Chronology of Fabry-Perot interferometer fiber-optic sensors and their applications: a review.

    Science.gov (United States)

    Islam, Md Rajibul; Ali, Muhammad Mahmood; Lai, Man-Hong; Lim, Kok-Sing; Ahmad, Harith

    2014-04-24

    Optical fibers have been involved in the area of sensing applications for more than four decades. Moreover, interferometric optical fiber sensors have attracted broad interest for their prospective applications in sensing temperature, refractive index, strain measurement, pressure, acoustic wave, vibration, magnetic field, and voltage. During this time, numerous types of interferometers have been developed such as Fabry-Perot, Michelson, Mach-Zehnder, Sagnac Fiber, and Common-path interferometers. Fabry-Perot interferometer (FPI) fiber-optic sensors have been extensively investigated for their exceedingly effective, simple fabrication as well as low cost aspects. In this study, a wide variety of FPI sensors are reviewed in terms of fabrication methods, principle of operation and their sensing applications. The chronology of the development of FPI sensors and their implementation in various applications are discussed.

  13. Fabry-Perot Study in the Orion Nebula (M 42: Protoplanetary Disks

    Directory of Open Access Journals (Sweden)

    Eduardo de la Fuente

    2003-01-01

    Full Text Available Se presenta un resumen de los resultados cinemáticas obtenidos del estudio Fabry-Perot en Hα de algunos proplyds en la nebulosa de Orión. Estos resultados se presentan en detalle en de la Fuente et al. (2003 a,b. Se obtienen velocidades sistémicas, tasas de perdida de masa, edad de los discos y perfiles de velocidad radial. Encontramos que la interferometria Fabry-Perot constituye una técnica efectiva para la detección de proplyds. Se discuten algunos aspectos astrobiológicos de estos resultados que ilustramos usando los proplyds 168-326, 167-317, 163-317, 158-323, 158-327 y 161-314.

  14. An analytical study on bistability of Fabry-Perot semiconductor optical amplifiers

    Science.gov (United States)

    Wang, Gang; Chen, Shuqiang; Yang, Huajun

    2016-09-01

    Optical bistabilities have been considered to be useful for sensor applications. As a typical nonlinear device, Fabry-Perot semiconductor optical amplifiers (FPSOAs) exhibit bistability under certain conditions. In this paper, the bistable characteristics in FPSOAs are investigated theoretically. Based on Adams's relationship between the incident optical intensity I in and the z-independent average intracavity intensity I av, an analytical expression of the bistable loop width in SOAs is derived. Numerical simulations confirm the accuracy of the analytical result.

  15. A SENSITIVE AND STABLE CONFOCAL FABRY-PEROT INTERFEROMETER FOR SURFACE ULTRASONIC VIBRATION DETECTION

    Institute of Scientific and Technical Information of China (English)

    DING HONG-SHENG; TONG LI-GE; CHEN GENG-HUA

    2001-01-01

    A new confocal Fabry-Pérot interferometer (CFPI) has been constructed. By using both of the conjugate rays,the sensitivity of the system was doubled. Moreover, the negative feedback control loop of a single-chip microcomputer (MCS-51) was applied to stabilize the working point at an optimum position. The system has been used in detecting the piezoelectric ultrasonic vibration on the surface of an aluminium sample.

  16. Analysis of a Piezo Electric Driver Circuit for Use in a Fabry-Perot Interferometer

    Directory of Open Access Journals (Sweden)

    Maithya J. Mutuku

    2013-09-01

    Full Text Available The design and fabrication of piezo electric driver circuit is presented and analysed. The output voltage which is a triangular wave voltage and frequency of the driver circuit were measured and set at 80 V peak to peak and an output frequency of 1 KHz. A photo detector circuit which receives the output beam from the confocal Fabry- perot interferometer (CFPI through the photodiode is as well presented

  17. Reduction of CCD observations made with a scanning Fabry--Perot interferometer. III. Wavelength scale refinement

    CERN Document Server

    Moiseev, A V

    2015-01-01

    We describe the recent modifications to the data reduction technique for observations acquired with the scanning Fabry-Perot interferometer (FPI) mounted on the 6-m telescope of the Special Astrophysical Observatory that allow the wavelength scale to be correctly computed in the case of large mutual offsets of studied objects in interferograms. Also the parameters of the scanning FPIs used in the SCORPIO-2 multimode focal reducer are considered.

  18. Fabry-Perot micro-structured polymer optical fibre sensors for opto-acoustic endoscopy

    DEFF Research Database (Denmark)

    Broadway, Christian; Gallego, Daniel; Woyessa, Getinet;

    2015-01-01

    Opto-Acoustic Endoscopy (OAE) requires sensors with a high sensitivity and small physical dimensions in order to facilitate integration into an endoscope of less than 1mm in diameter. We present fibre Bragg grating (FBG) and Fabry- Perot intrinsic fibre sensors for ultrasound detection. We presen...... and a simplification of the detection regime for an optimal interferometric OAE configuration. © (2015) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only....

  19. Quantum transport in bilayer graphene. Fabry-Perot interferences and proximity-induced superconductivity

    Energy Technology Data Exchange (ETDEWEB)

    Du, Renjun

    2015-10-30

    Bilayer graphene (BLG) p-n junctions made of hBN-BLG-hBN (hexagonal boron nitride) heterostructures enable ballistic transport over long distances. We investigate Fabry-Perot interferences, and detect that the bilayer-like anti-Klein tunneling transits into single-layer-like Klein tunneling when tuning the Fermi level towards the band edges. Furthermore, the proximity-induced superconductivity has been studied in these devices with Al leads.

  20. Topological Boundary States in 1D: An Effective Fabry-Perot Model

    CERN Document Server

    Levy, Eli

    2016-01-01

    We present a general and useful method to predict the existence, frequency, and spatial properties of gap states in photonic (and other) structures with a gapped spectrum. This method is established using the scattering approach. It offers a viewpoint based on a geometrical Fabry-Perot model. We demonstrate the capabilities of this model by predicting the behaviour of topological edge states in quasi-periodic structures. A proposition to use this model in Casimir physics is presented.

  1. Fabry-Perot-based Fourier-transform hyperspectral imaging allows multi-labeled fluorescence analysis.

    Science.gov (United States)

    Pisani, Marco; Zucco, Massimo

    2014-05-10

    We demonstrate the ability of our hyperspectral imaging device, based on a scanning Fabry-Perot interferometer, to obtain a single hyper-image of a sample marked with different fluorescent molecules, and to unambiguously discriminate them by observing their spectral fingerprints. An experiment carried out with cyanines, fluorescein, and quantum dots emitting in the yellow-orange region, demonstrates the feasibility of multi-labeled fluorescence microscopy without the use of multiple filter sets or dispersive means.

  2. Fiber-Tip Fabry-Perot Interferometric Sensor based on a Thin Silver Film

    Science.gov (United States)

    2012-11-01

    interferometer (FPI), named after French physicists Charles Fabry and Alfred Perot, is typically formed by two reflecting surfaces or mirrors. It has been...utilized for sensing applications for a long time 13,14 . The interference is caused by waves successively reflected between the two parallel...Film Assume the film act as a free vibrating circular plate clamped rigidly at the edge. Its lowest resonant frequency f0 is expressed as follows

  3. Polar cap mesosphere wind observations: comparisons of simultaneous measurements with a Fabry-Perot interferometer and a field-widened Michelson interferometer.

    Science.gov (United States)

    Fisher, G M; Killeen, T L; Wu, Q; Reeves, J M; Hays, P B; Gault, W A; Brown, S; Shepherd, G G

    2000-08-20

    Polar cap mesospheric winds observed with a Fabry-Perot interferometer with a circle-to-line interferometer optical (FPI/CLIO) system have been compared with measurements from a field-widened Michelson interferometer optimized for E-region winds (ERWIN). Both instruments observed the Meinel OH emission emanating from the mesopause region (approximately 86 km) at Resolute Bay, Canada (74.9 degrees N, 94.9 degrees W). This is the first time, to our knowledge, that winds measured simultaneously from a ground-based Fabry-Perot interferometer and a ground-based Michelson interferometer have been compared at the same location. The FPI/CLIO and ERWIN instruments both have a capability for high temporal resolution (less than 10 min for a full scan in the four cardinal directions and the zenith). Statistical comparisons of hourly mean winds for both instruments by scatterplots show excellent agreement, indicating that the two optical techniques provide equivalent observations of mesopause winds. Small deviations in the measured wind can be ascribed to the different zenith angles used by the two instruments. The combined measurements illustrate the dominance of the 12-h wave in the mesopause winds at Resolute Bay, with additional evidence for strong gravity wave activity with much shorter periods (tens of minutes). Future operations of the two instruments will focus on observation of complementary emissions, providing a unique passive optical capability for the determination of neutral winds in the geomagnetic polar cap at various altitudes near the mesopause.

  4. ZnO coated Fabry-Perot interferometric optical fiber for detection of gasoline blend vapors: Refractive index and fringe visibility manipulation studies

    Science.gov (United States)

    Pawar, Dnyandeo; Kitture, Rohini; Kale, S. N.

    2017-03-01

    ZnO nanoparticles-coated Fabry-Perot interferometer based optical fiber sensor is demonstrated to detect different gasoline blend concentrations in ethanol. Different gasoline blends (with ethanol varying from 0% (E0) to 100% (E100)) have been subjected to the sensor to observe the change in refractive index of the material that leads to the wavelength shift and fringe visibility change of the interference spectrum. The sensor shows the remarkable response with different gasoline blend mixtures within the time span of 0-60 s in terms of wavelength and Intensity (power) shift. The maximum wavelength shift of 12.1 nm is observed for E0 mixture and least of 3 nm for E100 in 60 s, respectively. A fast response time and recovery time of 5 s and 9 s, respectively, are obtained for E0 mixture. The results are related to the formation of interference pattern due the ZnO-mediated-Fabry-Perot cavity, changes in refractive index with the change in external gaseous environment, changes in fringe visibility of the spectrum and the interaction of oxygen vacancies on ZnO surface with the gasoline moieties. The rates of sensing and recovery times are related to the Reid vapor pressures of ethanol and gasoline. Hence a dual scale of sensing, both in terms of wavelength shift (refractive index) and intensity shift (fringe visibility) has been proposed for gasoline blend sensing.

  5. HST Imagery and CFHT Fabry-Perot 2-D Spectroscopy in Halpha of the Ejected Nebula M1-67 Turbulent Status

    CERN Document Server

    Grosdidier, Y; Blais-Ouellette, S; Joncas, G; Acker, A; Grosdidier, Yves; Moffat, Anthony F.J.; Joncas, Gilles; Acker, Agnès

    2001-01-01

    With HST-WFPC2 we have obtained a deep, H-alpha image of the WR nebula M1-67. With the interferometer of the Universite Laval (Quebec, Canada), we have obtained complementary Fabry-Perot H-alpha data using CFHT MOS/SIS. On the deep H-alpha image we have performed continuous wavelet transforms to isolate stochastic structures of different characteristic size and look for scaling laws. Small-scale wavelet coefficients show that the density field of M1-67 is remarkably structured in chaotically oriented filaments. We draw attention to a short, marginally inertial range at the smallest scales (6.7-15.0 X 10^{-3} pc), which can be attributed to turbulence in M1-67, and a strong scale break at larger scales. Using our Fabry-Perot interferograms, we also present an investigation of the statistical properties of fluctuating gas motions using structure functions traced by H-alpha emission-line centroid velocities. We find that there is a clear correlation at scales 0.02-0.22 pc between the mean quadratic differences o...

  6. Statistical analysis of thermospheric gravity waves from Fabry-Perot Interferometer measurements of atomic oxygen

    Directory of Open Access Journals (Sweden)

    E. A. K. Ford

    2008-02-01

    Full Text Available Data from the Fabry-Perot Interferometers at KEOPS (Sweden, Sodankylä (Finland, and Svalbard (Norway, have been analysed for gravity wave activity on all the clear nights from 2000 to 2006. A total of 249 nights were available from KEOPS, 133 from Sodankylä and 185 from the Svalbard FPI. A Lomb-Scargle analysis was performed on each of these nights to identify the periods of any wave activity during the night. Comparisons between many nights of data allow the general characteristics of the waves that are present in the high latitude upper thermosphere to be determined. Comparisons were made between the different parameters: the atomic oxygen intensities, the thermospheric winds and temperatures, and for each parameter the distribution of frequencies of the waves was determined. No dependence on the number of waves on geomagnetic activity levels, or position in the solar cycle, was found. All the FPIs have had different detectors at various times, producing different time resolutions of the data, so comparisons between the different years, and between data from different sites, showed how the time resolution determines which waves are observed. In addition to the cutoff due to the Nyquist frequency, poor resolution observations significantly reduce the number of short-period waves (<1 h period that may be detected with confidence. The length of the dataset, which is usually determined by the length of the night, was the main factor influencing the number of long period waves (>5 h detected. Comparisons between the number of gravity waves detected at KEOPS and Sodankylä over all the seasons showed a similar proportion of waves to the number of nights used for both sites, as expected since the two sites are at similar latitudes and therefore locations with respect to the auroral oval, confirming this as a likely source region. Svalbard showed fewer waves with short periods than KEOPS data for a season when both had the same time resolution data

  7. A case report of locally advanced triple negative breast cancer showing pathological complete response to weekly paclitaxel with bevacizumab treatment following disease progression during anthracycline-based neoadjuvant chemotherapy.

    Science.gov (United States)

    Shigematsu, Hideo; Ozaki, Shinji; Yasui, Daisuke; Hirata, Taizo

    2017-09-01

    Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced triple negative breast cancer, however, approximately 5% of cases show disease progression during NAC. Although downstaging is essential to create an opportunity for curative surgery and to improve the local control outcome in such a case, no additional line of chemotherapy has been established. A 60-year-old woman was referred to our hospital for an axillary mass presenting three weeks ago and was diagnosed as having right locally advanced (T2N2M0, stage IIIA) triple negative breast cancer. After two courses of epirubicine and cyclophosphamide as NAC, disease progression was recognized and curative resection was considered impossible due to enlarged axillary lymph nodes showing invasion to surrounding tissue. As second-line chemotherapy, weekly paclitaxel with bevacizumab treatment was initiated and significant shrinkage was immediately obtained. A clinically complete response was diagnosed after four courses of weekly paclitaxel with bevacizumab and she underwent a right breast mastectomy with axillary lymph node dissection without major complications. Histopathological examination of surgical specimens showed no residual invasive or noninvasive disease and she was diagnosed as having a pathological complete response. Although the addition of bevacizumab to standard adjuvant chemotherapy is not recommended in unselected triple negative breast cancer, the potent effect on tumor shrinkage should be considered in the treatment of locally advanced triple negative breast cancer showing disease progression during standard NAC. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Polymer waveguide Fabry-Perot resonator for high-frequency ultrasound detection.

    Science.gov (United States)

    Tadayon, Mohammad Amin; Baylor, Martha-Elizabeth; Ashkenazi, Shai

    2014-12-01

    Piezoelectric technology is the backbone of most medical ultrasound imaging arrays; however, signal transduction efficiency severely deteriorates in scaling the technology to element size smaller than 0.1 mm, often required for high-frequency operation (>20 MHz). Optical sensing and generation of ultrasound has been proposed and studied as an alternative technology for implementing sub-millimeter size arrays with element size down to 10 μm. The application of thin polymer film Fabry-Perot resonators has been demonstrated for high-frequency ultrasound detection; however, their sensitivity is limited by light diffraction loss. Here, we introduce a new method to increase the sensitivity of an optical ultrasound receiver by utilizing a waveguide between the mirrors of the Fabry-Perot resonator. This approach eliminates diffraction loss from the cavity, and therefore the finesse is only limited by mirror loss and absorption. By applying this method, we have achieved noise equivalent pressure of 178 Pa over a bandwidth of 30 MHz or 0.03 Pa/Hz1/2, which is about 20-fold better than a similar device without a waveguide. The finesse of the tested Fabry-Perot resonator was around 200. This result is 5 times higher than the finesse measured in the same device outside the waveguide region.

  9. FABSOAR--A Fabry-Perot Spectrometer for Oxygen A-band Research Final Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Watchorn, Steven

    2010-09-10

    Because this was a Phase I project, it did not add extensively to the body of A-band knowledge. There was no basic research performed on that subject. The principal addition was that a mechanical and optical design for a triple-etalon Fabry-Perot interferometer (FABSOAR) capable of A-band sensing was sketched out and shown to be within readily feasible instrument fabrication parameters. The parameters for the proposed triple-etalon Fabry-Perot were shown to be very similar to existing Fabry-Perots built by Scientific Solutions. The mechanical design for the FABSOAR instrument incorporated the design of previous Scientific Solutions imagers, condensing the three three-inch-diameter etalons into a single, sturdy tube. The design allowed for the inclusion of a commercial off-the-shelf (COTS) filter wheel and a thermocooled CCD detector from Andor. The tube has supports to mount to a horizontal or vertical opticaltable surface, and was to be coupled to a Scientific Solutions pointing head at the Millstone Hill Observatory in Massachusetts for Phase II calibration and testing.

  10. Differential Radiometers Using Fabry-Perot Interferometric Technique for Remote Sensing of Greenhouse Gases

    Science.gov (United States)

    Georgieva, Elena M.; Heaps,William S.; Wilson, Emily L.

    2007-01-01

    A new type of remote sensing radiometer based upon the Fabry-Perot interferometric technique has been developed at NASA's Goddard Space Flight Center and tested from both ground and aircraft platform. The sensor uses direct or reflected sunlight and has channels for measuring column concentration of carbon dioxide at 1570 nm, oxygen lines sensitive to pressure and temperature at 762 and 768 nm, and water vapor (940 nm). A solid Fabry-Perot etalon is used as a tunable narrow bandpass filter to restrict the measurement to the gas of interest's absorption bands. By adjusting the temperature of the etalon, which changes the index of refraction of its material, the transmission fringes can be brought into nearly exact correspondence with absorption lines of the particular species. With this alignment between absorption lines and fringes, changes in the amount of a species in the atmosphere strongly affect the amount of light transmitted by the etalon and can be related to gas concentration. The technique is applicable to different chemical species. We have performed simulations and instrument design studies for CH4, "Cot isotope, and CO detection. Index Terms- Absorbing media, Atmospheric measurements, Fabry-Perot interferometers, Optical interferometry, Remote sensing.

  11. Indium phosphide all air-gap Fabry-Pérot filters for near-infrared spectroscopic applications

    Science.gov (United States)

    Ullah, A.; Butt, M. A.; Fomchenkov, S. A.; Khonina, S. N.

    2016-08-01

    Food quality can be characterized by noninvasive techniques such as spectroscopy in the Near Infrared wavelength range. For example, 930 -1450 nm wavelength range can be used to detect diseases and differentiate between meat samples. Miniaturization of such NIR spectrometers is useful for quick and mobile characterization of food samples. Spectrometers can be miniaturized, without compromising the spectral resolution, using Fabry-Pérot (FP) filters consisting of two highly reflecting mirrors with a central cavity in between. The most commonly used mirrors in the design of FP filters are Distributed Bragg Reflections (DBRs) consisting of alternating high and low refractive index material pairs, due to their high reflectivity compared to metal mirrors. However, DBRs have high reflectivity for a selected range of wavelengths known as the stopband of the DBR. This range is usually much smaller than the sensitivity range of the spectrometer detector. Therefore, a bandpass filter is usually required to restrict wavelengths outside the stopband of the FP DBRs. Such bandpass filters are difficult to design and implement. Alternatively, high index contrast materials must be can be used to broaden the stopband width of the FP DBRs. In this work, Indium phosphide all air-gap filters are proposed in conjunction with InGaAs based detectors. The designed filter has a wide stopband covering the entire InGaAs detector sensitivity range. The filter can be tuned in the 950-1450 nm with single mode operation. The designed filter can hence be used for noninvasive meat quality control.

  12. A tunable electrochromic fabry-perot filter for adaptive optics applications.

    Energy Technology Data Exchange (ETDEWEB)

    Blaich, Jonathan David; Kammler, Daniel R.; Ambrosini, Andrea; Sweatt, William C.; Verley, Jason C.; Heller, Edwin J.; Yelton, William Graham

    2006-10-01

    The potential for electrochromic (EC) materials to be incorporated into a Fabry-Perot (FP) filter to allow modest amounts of tuning was evaluated by both experimental methods and modeling. A combination of chemical vapor deposition (CVD), physical vapor deposition (PVD), and electrochemical methods was used to produce an ECFP film stack consisting of an EC WO{sub 3}/Ta{sub 2}O{sub 5}/NiO{sub x}H{sub y} film stack (with indium-tin-oxide electrodes) sandwiched between two Si{sub 3}N{sub 4}/SiO{sub 2} dielectric reflector stacks. A process to produce a NiO{sub x}H{sub y} charge storage layer that freed the EC stack from dependence on atmospheric humidity and allowed construction of this complex EC-FP stack was developed. The refractive index (n) and extinction coefficient (k) for each layer in the EC-FP film stack was measured between 300 and 1700 nm. A prototype EC-FP filter was produced that had a transmission at 500 nm of 36%, and a FWHM of 10 nm. A general modeling approach that takes into account the desired pass band location, pass band width, required transmission and EC optical constants in order to estimate the maximum tuning from an EC-FP filter was developed. Modeling shows that minor thickness changes in the prototype stack developed in this project should yield a filter with a transmission at 600 nm of 33% and a FWHM of 9.6 nm, which could be tuned to 598 nm with a FWHM of 12.1 nm and a transmission of 16%. Additional modeling shows that if the EC WO{sub 3} absorption centers were optimized, then a shift from 600 nm to 598 nm could be made with a FWHM of 11.3 nm and a transmission of 20%. If (at 600 nm) the FWHM is decreased to 1 nm and transmission maintained at a reasonable level (e.g. 30%), only fractions of a nm of tuning would be possible with the film stack considered in this study. These tradeoffs may improve at other wavelengths or with EC materials different than those considered here. Finally, based on our limited investigation and material set

  13. Dispersive infrared spectroscopy measurements of atmospheric CO₂ using a Fabry-Pérot interferometer sensor.

    Science.gov (United States)

    Chan, K L; Ning, Z; Westerdahl, D; Wong, K C; Sun, Y W; Hartl, A; Wenig, M O

    2014-02-15

    In this paper, we present the first dispersive infrared spectroscopic (DIRS) measurement of atmospheric carbon dioxide (CO2) using a new scanning Fabry-Pérot interferometer (FPI) sensor. The sensor measures the optical spectra in the mid infrared (3,900 nm to 5,220 nm) wavelength range with full width half maximum (FWHM) spectral resolution of 78.8 nm at the CO2 absorption band (~4,280 nm) and sampling resolution of 20 nm. The CO2 concentration is determined from the measured optical absorption spectra by fitting it to the CO2 reference spectrum. Interference from other major absorbers in the same wavelength range, e.g., carbon monoxide (CO) and water vapor (H2O), was taken out by including their reference spectra in the fit as well. The detailed descriptions of the instrumental setup, the retrieval procedure, a modeling study for error analysis as well as laboratory validation using standard gas concentrations are presented. An iterative algorithm to account for the non-linear response of the fit function to the absorption cross sections due to the broad instrument function was developed and tested. A modeling study of the retrieval algorithm showed that errors due to instrument noise can be considerably reduced by using the dispersive spectral information in the retrieval. The mean measurement error of the prototype DIRS CO2 measurement for 1 minute averaged data is about ±2.5 ppmv, and down to ± 0.8ppmv for 10 minute averaged data. A field test of atmospheric CO2 measurements were carried out in an urban site in Hong Kong for a month and compared to a commercial non-dispersive infrared (NDIR) CO2 analyzer. 10 minute averaged data shows good agreement between the DIRS and NDIR measurements with Pearson correlation coefficient (R) of 0.99. This new method offers an alternative approach of atmospheric CO2 measurement featuring high accuracy, correction of non-linear absorption and interference of water vapor.

  14. All-fiber upconversion high spectral resolution wind lidar using a Fabry-Perot interferometer

    Science.gov (United States)

    Shangguan, Mingjia; Xia, Haiyun; Wang, Chong; Qiu, Jiawei; Shentu, Guoliang; Zhang, Qiang; Dou, Xiankang; Pan, Jian-wei

    2016-08-01

    An all-fiber, micro-pulse and eye-safe high spectral resolution wind lidar (HSRWL) at 1550nm is proposed and demonstrated by using a pair of upconversion single-photon detectors and a fiber Fabry-Perot scanning interferometer (FFP-SI). In order to improve the optical detection efficiency, both the transmission spectrum and the reflection spectrum of the FFP-SI are used for spectral analyses of the aerosol backscatter and the reference laser pulse. The reference signal is tapped from the outgoing laser and served as a zero velocity indicator. The Doppler shift is retrieved from a frequency response function Q, which is defined as the ratio of difference of the transmitted signal and the reflected signal to their sum. Taking advantages of high signal-to-noise ratio of the detectors and high spectral resolution of the FFP-SI, the Q spectra of the aerosol backscatter are reconstructed along the line-of-sight (LOS) of the telescope. By applying a least squares fit procedure to the measured Q spectra, the center frequencies and the bandwidths are obtained simultaneously. And then the Doppler shifts are determined relative to the center frequency of the reference signal. To eliminate the influence of temperature fluctuations on the FFP-SI, the FFP-SI is cased in a chamber with temperature stability of 0.001 during the measurement. Continuous LOS wind observations are carried out on two days at Hefei (31.843 N, 117.265 E), China. In the meantime, LOS wind measurements from the HSRWL show good agreement with the results from an ultrasonic wind sensor (Vaisala windcap WMT52). Due to the computational expensive of the convolution operation of the Q function, an empirical method is adopted to evaluate the quality of the measurements. The standard deviation of the wind speed is 0.76 m/s at the 1.8 km. The standard deviation of the retrieved bandwidth variation is 2.07 MHz at the 1.8 km.

  15. Design and experimental research of a high-precision wavelength controller for tunable fiber Fabry-Perot filters

    Science.gov (United States)

    Qi, Hai-bing; Wei, Shu-hua; Wei, Chen

    2013-03-01

    A high-precision wavelength controller is presented in this paper. It is necessary to find out the difference between the central wavelength of a tunable fiber Fabry-Perot (FFP) filter and that of the input laser, while the wavelength controller operates at the states of wavelength-scanning and wavelength-locking modes. Firstly, a dynamic simulation model of tunable FFP filter is established, and the dynamic characteristic of tunable FFP filter modulated by an alternating current (AC) signal is simulated. Then the measuring time at wavelength-scanning mode compared with the theory time is discussed, and this time difference shows the difference between the central wavelength of a tunable FFP filter and that of the input laser. At last, the effects on wavelength-locking precision of time delays, including the time delay of opened-loop circuit, the time constant of the closed-loop circuit and the intrinsic hysteresis of piezoelectric (PZT) element, are analyzed. A wavelength controller of tunable FFP filter is designed and prepared. The experimental results at wavelength-locking mode show that a high locking precision is obtained.

  16. Theoretical analysis of transmission characteristics for all fiber, multi-cavity Fabry-Perot filters based on fiber Bragg gratings

    Institute of Scientific and Technical Information of China (English)

    XU OU; LU ShaoHua; DONG XiaoWei; LI Bin; NING TiGang; JIAN ShuiSheng

    2008-01-01

    The characteristics of transmission spectra for the all fiber, multi-cavity FabryPerot (FP) configuration based on fiber Bragg gratings (FBG) are theoretically analyzed and modeled. The general transmission matrix function for the structure with any number of cavities is derived, and explicit expression of the power trans-mission coefficient for symmetrical two-cavity FP is presented. The general condi-tions for flat-top single resonant peak at the central wavelength in FBG stop band are derived and verified in the numerical simulation section. The transmission peaks of single-cavity and two-cavity FP structures are compared and discussed, and results show that compared to the single-cavity FP, flatness of the top and steepness at the edge of transmission peak can be improved by introducing one more cavity. The resonant transmission peak properties of two-cavity structure are investigated in detail for various values of cavity length and FBGs with different reflection characteristics, and the design guidelines for transmission-type filters are presented. The results show that the steepness of peak slope can be improved by increase of FBG reflectivities, and these kinds of filters can be used as nar-row-band single-channel selectors and multi-channel wavelength de-multiplexing by properly choosing the length of cavities and reflectivities of FBGs.

  17. DISEASES

    DEFF Research Database (Denmark)

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi;

    2015-01-01

    Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...

  18. A Variant Form of the Human Deleted in Malignant Brain Tumor 1 (DMBT1) Gene Shows Increased Expression in Inflammatory Bowel Diseases and Interacts with Dimeric Trefoil Factor 3 (TFF3)

    DEFF Research Database (Denmark)

    Madsen, Jens; Sorensen, Grith Lykke; Nielsen, Ole Stig;

    2013-01-01

    The protein deleted in malignant brain tumors (DMBT1) and the trefoil factor (TFF) proteins have all been proposed to have roles in epithelial cell growth and cell differentiation and shown to be up regulated in inflammatory bowel diseases. A panel of monoclonal antibodies was raised against human......-1 showed no reaction. Hyb213-6 showed strong cytoplasmic staining in epithelial cells of both the small and large intestine whereas no staining was seen with Hyb213-1. The number of DMBT1(gp340) positive epithelial cells, stained with Hyb213-6, was significantly up regulated in inflammatory colon tissue...

  19. A fiber-optic water flow sensor based on laser-heated silicon Fabry-Pérot cavity

    Science.gov (United States)

    Liu, Guigen; Sheng, Qiwen; Resende Lisboa Piassetta, Geraldo; Hou, Weilin; Han, Ming

    2016-05-01

    A hot-wire fiber-optic water flow sensor based on laser-heated silicon Fabry-Pérot interferometer (FPI) has been proposed and demonstrated in this paper. The operation of the sensor is based on the convective heat loss to water from a heated silicon FPI attached to the cleaved enface of a piece of single-mode fiber. The flow-induced change in the temperature is demodulated by the spectral shifts of the reflection fringes. An analytical model based on the FPI theory and heat transfer analysis has been developed for performance analysis. Numerical simulations based on finite element analysis have been conducted. The analytical and numerical results agree with each other in predicting the behavior of the sensor. Experiments have also been carried to demonstrate the sensing principle and verify the theoretical analysis. Investigations suggest that the sensitivity at low flow rates are much larger than that at high flow rates and the sensitivity can be easily improved by increasing the heating laser power. Experimental results show that an average sensitivity of 52.4 nm/(m/s) for the flow speed range of 1.5 mm/s to 12 mm/s was obtained with a heating power of ~12 mW, suggesting a resolution of ~1 μm/s assuming a wavelength resolution of 0.05 pm.

  20. Strong fiber Bragg grating based asymmetric Fabry-Perot sensor system with multiple reflections for high sensitivity enhancement

    Science.gov (United States)

    Wang, Wei; Hu, Zhengliang; Ma, Mingxiang; Lin, Huizu; Hu, Yongming

    2014-03-01

    A fiber Bragg grating based (FBG-based) Fabry-Perot (FP) sensor system utilizing multiple reflections between two strong FBGs with different reflectiveties to enhance the sensitivity is proposed. The different interference signals are obtained by using different multiple-path-matched Michelson interferometers (MIs). The system is lighted by the ultra-narrow line width erbium-doped fiber ring laser and the signal is demodulated by phase-generated carrier (PGC) scheme. The method to choose the optimal parameters of the FBG-based asymmetric FP sensor and the different matching MIs is analyzed. The experimental results show that each matching MI can steadily enhance the sensitivity of the demodulated signal in the bandwidth of 80-8000 Hz. The sensitivity of the system can be enhanced about 19.1 dB when the light reflects nine times between the two FBGs. Further more, this system can be used to extend the dynamic range and the effective working bandwidth and so on.

  1. A power and wavelength detuning-dependent hysteresis loop in a single mode Fabry-Pérot laser diode

    Institute of Scientific and Technical Information of China (English)

    Wu Jian-Wei; Bikash Nakarmi

    2013-01-01

    In this paper,we observe experimentally the optical bistability induced by the side-mode injection power and wavelength detuning in a single mode Fabry-Pérot laser diode (SMFP-LD).Results show that the bistability characteristics of the dominant and injected modes are strongly dependent on the injected input optical power and wavelength detuning in an SMFP-LD.We observe three types of hysteresis loops:counterclockwise,clockwise,and butterfly hysteresis with various loop widths.In the case of a bistability loop caused by injection power,the transition from counterclockwise to clockwise in the hysteresis direction with the wavelength detuning from 0.028 nm to 0.112 nm is observed in a way of butterfly hysteresis for the dominant mode by increasing the wavelength detuning.The width of hysteresis loop,induced by wavelength detuning is also changed while the injection power is enhanced from-7 dBm to-5 dBm.

  2. Bragg grating-based Fabry-Perot interferometer fabricated in a polymer fiber for sensing with improved resolution

    Science.gov (United States)

    Statkiewicz-Barabach, G.; Mergo, P.; Urbanczyk, W.

    2017-01-01

    We demonstrate for the first time a Bragg grating-based Fabry-Perot interferometer (FPI) fabricated in the polymer fiber with a core made of PMMA/PS copolymer and pure PMMA cladding. The FPI was formed by two gratings with the same Bragg wavelength, λ B = 1312 nm, separated by a small gap. The FP cavity was created directly during the grating inscription process by placing a narrow blocking aperture, in the center of the UV beam. Good long-term stability was achieved by fabricating the gratings of type II with long irradiation time (8 min). By choosing an appropriate width of the blocking aperture, we could control the number and the width of interference fringes visible in the grating’s reflection spectrum. Sharp fringes were obtained, of 3 dB width within the range of 50-100 pm, allowing for a significant increase in measurement resolution compared to direct interrogation of a single grating. The proposed interferometer was tested in measurements of strain and temperature in the range of 0-20 mstrain and 20 °C-70 °C, showing the sensitivity of 1.074 nm mstrain-1 and -25.1 pm °C-1, respectively.

  3. Miniature fiber-optic force sensor for vitreoretinal microsurgery based on low-coherence Fabry-Pérot interferometry

    Science.gov (United States)

    Liu, Xuan; Iordachita, Iulian I.; He, Xingchi; Taylor, Russell H.; Kang, Jin U.

    2012-01-01

    Vitreoretinal surgery requires delicate manipulation of retinal tissue. However, tool-to-tissue interaction forces in the order of sub-millinewton are usually below the human sensory threshold. A surgical force sensor (FS) compatible with conventional surgical tools may significantly improve the surgery outcome by preventing tissue damage. We have designed and built a miniature FS for vitreoretinal surgery using a fiber-optic common-path phase-sensitive optical coherence tomography (OCT) system where the distal end of the fiber probe forms a low-finesse Fabry-Pérot (FP) cavity between the cleaved tip of the lead-in single mode fiber and the polished back surface of a stainless steel surgical tool tip. To accurately measure the change of the FP cavity length, the cavity is interrogated by the fiber-optic common-path phase-sensitive OCT. The FP cavity was illuminated with a broadband light source, and the interferometric signal was detected using a broadband spectrometer. The phase of the interferometric signal, which is proportional to the cavity length change as well as the exerted force, was extracted. We have conducted calibration experiments to characterize our one dimensional FS. Our result shows that the FS responses linearly to force in axial direction with force sensitivity better than 0.25 millinewton.

  4. 光纤Fabry-Perot干涉仪在传感应用中的数学模型%MATHEMATICAL MODELS FOR FIBER-OPTICAL FABRY-PEROT INTERFEROMETRIC CAVITY

    Institute of Scientific and Technical Information of China (English)

    毕卫红

    1999-01-01

    本文应用光学和数学理论导出光纤Fabry-Perot干涉仪在两反射面反射率不同时的反射光与透射光的数学模型、低反射率Fabry-Perot干涉腔长度的变化与干涉光光强的数学模型及传感中的应用;为这种光纤干涉仪的准确使用提供基础.

  5. 用LED作光源的Fabry-Perot光纤甲烷气体传感器的研究%Study on Fabry-Perot CH4 Optical Fiber Sensor with LED

    Institute of Scientific and Technical Information of China (English)

    王玉田; 郭增军; 王莉田

    2002-01-01

    利用Fabry-Perot腔的选频特性,考虑与光纤的低损耗窗口相一致和价格等因素,采用价廉的1.3 μm波段的LED作为光源,实现了PZT对Fabry-Perot腔的正弦调制.对甲烷气体浓度进行谐波检测,检测灵敏度可达10×10-6,大大提高了灵敏度和稳定性.

  6. Gain-guided index-antiguided fiber with a Fabry-Perot layer for large mode area laser amplifiers.

    Science.gov (United States)

    Lai, Chih-Hsien; Chen, Hsuan-Yu; Du, Cheng-Han; Chiou, Yih-Peng

    2015-02-23

    We propose a modified gain-guided index-antiguided (GGIAG) fiber structure for large mode area laser amplifiers, in which a thin dielectric layer is placed between the low-index core and the high-index cladding. The introduced dielectric layer functions as a Fabry-Perot etalon. By letting the resonant wavelength of the Fabry-Perot layer coincide with the signal wavelength, the signal is gain-guided in the fiber core. Moreover, the pump is confined in the low-index core owing to the antiresonant reflection originated from the Fabry-Perot layer. Numerical results indicate that the leakage loss of the pump can be minified over two orders of magnitude in the proposed structure, and thus the end-pumping efficiency could be enhanced significantly.

  7. Double Michelson/Fabry-Perot interferometer for laser- and displacement-noise-free gravitational-wave detection

    CERN Document Server

    Tarabrin, Sergey P

    2009-01-01

    In this paper we demonstrate that a double Michelson interferometer with Fabry-Perot cavities in its arms is able to perform laser- and displacement-noise-free gravitational-wave (GW) detection if certain model assumptions are met. Assuming the input mirrors of a single Michelson/Fabry-Perot interferometer can be rigidly attached to beamsplitter on a central platform one can manipulate with interferometer's response signals in a way to cancel laser noise and displacement noise of all test masses except the cental platform. A pair of symmetrically positioned Michelson/Fabry-Perot interferometers with common central platform can be made insusceptible to the later then, thus allowing complete laser- and displacement-noise-free interferometry (DFI). It is demonstrated that the DFI response to GWs of the proposed interferometer is proportional to $f^2_{\\textrm{gw}}/\\gamma$, where $\\gamma$ is the cavity half-bandwidth, that is the strongest DFI response allowed by general relativity.

  8. Fabry-perot modes enhanced pump-probe coupling in gold micro-disk patterned ruby thin film

    Science.gov (United States)

    Kumari, Satchi; Khare, Alika; Gupta, Reema; Tomar, Monika; Gupta, Vinay

    2017-10-01

    Enhanced pump-probe coupling has been experimentally observed in epitaxial Ruby thin film patterned with equidistant gold micro-disks (∼100 μm), as compared to pure Ruby film. This has been attributed to Fabry-Perot and surface plasmon modes in Ruby/gold film. In case of S polarized pump and probe beam, Fabry-Perot modes leads to a two-wave mixing gain of ∼1.35. Moreover gain was ∼1.62 in P-polarization case, it has been attributed to coupling of Fabry-Perot and surface plasmon modes. Enhanced coupling for P-polarization can lead to improved nonlinear response in the thin film geometry. It can find applications in thin film based compact photonic devices.

  9. Guía para el diagnóstico, seguimiento y tratamiento de la enfermedad de Fabry

    Directory of Open Access Journals (Sweden)

    Pablo Neumann

    2013-10-01

    Full Text Available La enfermedad de Fabry es un trastorno de almacenamiento lisosomal hereditario ligado al cromosoma X, ocasionado por el déficit de la enzima alfa galactosidasa A. El conocimiento sobre esta patología, y en particular su manejo médico, ha progresado notablemente en la última década, incluyendo el desarrollo de su tratamiento específico. La presente guía fue desarrollada por profesionales médicos de diversas especialidades involucrados en la atención de pacientes con enfermedad de Fabry. La discusión y análisis de las evidencias científicas disponibles, sumado a la experiencia de cada uno de los participantes, ha permitido desarrollar los conceptos vertidos en esta guía con el objetivo de brindar una herramienta útil para todos los profesionales que asisten a pacientes con enfermedad de Fabry.

  10. Determination of refractive index dispersion using fiber-optic low-coherence Fabry-Perot interferometer: implementation and validation

    Science.gov (United States)

    Karpienko, Katarzyna; Wróbel, Maciej S.; Jędrzejewska-Szczerska, Małgorzata

    2014-07-01

    We present the implementation and validation of low-coherence Fabry-Perot interferometer for refractive index dispersion measurements of liquids. A measurement system has been created with the use of four superluminescent diodes with different optical parameters, a fiber-optic coupler and an optical spectrum analyzer. The Fabry-Perot interferometer cavity has been formed by the fiber-optic end and mirror surfaces mounted on a micromechanical stage. The positive result of the validation procedure has been determined through statistical analysis. All obtained results were 99.999% statistically significant and were characterized by a strong positive correlation (r>0.98). The accuracy of the measured result of implemented low-coherence Fabry-Perot interferometer sensor is from 83% to 94%, which proves that the sensor can be used in the measurement of refractive index dispersion of liquids.

  11. Superluminescent diode versus Fabry-Perot laser diode seeding in pulsed MOPA fiber laser systems for SBS suppression

    Science.gov (United States)

    Melo, M.; Sousa, J. M.; Salcedo, J. R.

    2015-03-01

    We demonstrate the use of a pulsed superluminescent diode (SLD) through direct current injection modulation as seeding source in a master oscillator power amplifier (MOPA) configuration when compared to a Fabry-Perot (FP) laser diode in the same system. The performance limitations imposed by the use of the Fabry-Perot lasers, caused by the backward high peak power pulses triggered due to stimulated Brillouin scattering (SBS) are not observed in the case of the SLD. Compared to conventional Fabry-Perot laser diodes, the SLD provides a smooth and broad output spectrum which is independent of the input pulse parameters. Moreover, the spectrum can be sliced and tailored to the application. Thus, free SBS operation is shown when using the SLD seeder in the same system, allowing for a significant increase on the extractable power and energy.

  12. The Health Show

    OpenAIRE

    Swann, David

    2011-01-01

    Dr David Swann interviewed on The Health Show, Series 1, Episode 5, 2011 for BBC World about the award-winning 21st Century Nursing Bag. BBC World News reaches 241million people every week, available in 296 million homes, 1.8 million hotel rooms and has the highest average viewership on a weekday of any international news channel. The Health Show is a new 26-part series for BBC World News covering the most important news stories from around the world.

  13. A variant form of the human deleted in malignant brain tumor 1 (DMBT1 gene shows increased expression in inflammatory bowel diseases and interacts with dimeric trefoil factor 3 (TFF3.

    Directory of Open Access Journals (Sweden)

    Jens Madsen

    Full Text Available The protein deleted in malignant brain tumors (DMBT1 and the trefoil factor (TFF proteins have all been proposed to have roles in epithelial cell growth and cell differentiation and shown to be up regulated in inflammatory bowel diseases. A panel of monoclonal antibodies was raised against human DMBT1(gp340. Analysis of lung washings and colon tissue extracts by Western blotting in the unreduced state, two antibodies (Hyb213-1 and Hyb213-6 reacted with a double band of 290 kDa in lung lavage. Hyb213-6, in addition, reacted against a double band of 270 kDa in colon extract while Hyb213-1 showed no reaction. Hyb213-6 showed strong cytoplasmic staining in epithelial cells of both the small and large intestine whereas no staining was seen with Hyb213-1. The number of DMBT1(gp340 positive epithelial cells, stained with Hyb213-6, was significantly up regulated in inflammatory colon tissue sections from patients with ulcerative colitis (p<0.0001 and Crohn's disease (p = 0.006 compared to normal colon tissue. Immunohistochemical analysis of trefoil factor TFF1, 2 and 3 showed that TFF1 and 3 localized to goblet cells in both normal colon tissue and in tissue from patients with ulcerative colitis or Crohn's disease. No staining for TFF2 was seen in goblet cells in normal colon tissue whereas the majority of tissue sections in ulcerative colitis and Crohn's disease showed sparse and scattered TFF2 positive goblet cells. DMBT1 and TFF proteins did therefore not co-localize in the same cells but localized in adjacent cells in the colon. The interaction between DMBT1(gp340 and trefoil TFFs proteins was investigated using an ELISA assay. DMBT1(gp340 bound to solid-phase bound recombinant dimeric TFF3 in a calcium dependent manner (p<0.0001 but did not bind to recombinant forms of monomeric TFF3, TFF2 or glycosylated TFF2. This implies a role for DMBT1 and TFF3 together in inflammatory bowel disease.

  14. Correlations between Endomyocardial Biopsies and Cardiac Manifestations in Taiwanese Patients with the Chinese Hotspot IVS4+919G>A Mutation: Data from the Fabry Outcome Survey

    Directory of Open Access Journals (Sweden)

    Ting-Rong Hsu

    2017-01-01

    Full Text Available We retrospectively evaluated correlations between cardiac manifestations and globotriaosylceramide (Gb3 accumulation in cardiomyocytes from Taiwanese patients with Fabry disease and the IVS4+919G>A (IVS4 mutation who underwent endomyocardial biopsy (Shire; Fabry Outcome Survey data; extracted January 2015. Of 24 males and six females (median age [Q1; Q3] at biopsy 60.4 [57.4; 64.1] and 61.3 [60.4; 65.1] years, respectively, 13 males (54.2% and five females (83.3% received agalsidase alfa enzyme replacement therapy (ERT before biopsy. Median left ventricular mass indexed to height (LVMI within ±6 months of biopsy was 65.3 (52.7; 93.1 in males and 53.2 (42.0; 55.0 g/m2.7 in females. A moderate, positive, statistically significant correlation was found between the percentage area Gb3 accumulation in cardiomyocytes and LVMI (Spearman’s ρ, 0.45; p = 0.014; a smaller, positive, non-statistically significant correlation was observed between cardiomyocyte diameter and LVMI (Spearman’s ρ 0.16, p = 0.394. Moderate, statistically significant, negative correlations were found between Gb3 accumulation and ERT duration (Spearman’s ρ, −0.49, p = 0.007 and between cardiomyocyte size and ERT duration (Spearman’s ρ, −0.37, p = 0.048. Longer ERT duration was associated with smaller amounts of Gb3 accumulation and smaller cardiomyocyte size. Further follow-up is recommended to confirm these trends in a larger sample size.

  15. Fabry-Perot CCD annular-summing spectroscopy: study and implementation for aeronomy applications.

    Science.gov (United States)

    Coakley, M M; Roesler, F L; Reynolds, R J; Nossal, S

    1996-11-20

    The technique of Fabry-Perot CCD annular-summing spectroscopy, with particular emphasis on applications in aeronomy, is discussed. Parameter choices for optimizing performance by the use of a standard format CCD array are detailed. Spectral calibration methods, techniques for determining the ring pattern center, and effects imposed by limited radial resolution caused by superpixel size, variable by on-chip binning, are demonstrated. The technique is carefully evaluated experimentally relative to the conventional scanning Fabry-Perot that uses a photomultiplier detector. We evaluate three extreme examples typical of aeronomical spectroscopy using calculated signal-to-noise ratios. Predicted sensitivity gains of 10-30 are typical. Of the cases considered, the largest savings in integration time are estimated for the day sky thermospheric O(1)D case, in which the bright sky background dominates the CCD read noise. For profile measurements of faint night sky emission lines, such as exospheric hydrogen Balmer-α, long integration times are required to achieve useful signal-to-noise ratios. In such cases, CCD read noise is largely overcome. Predictions of a factor of 10-15 savings in integration time for night sky Balmer-α observations are supported by field tests. Bright, isolated night sky lines such as thermospheric O(1)D require shorter integration times, and more modest gains dependent on signal level are predicted. For such cases it appears from estimate results that the Fabry-Perot CCD annular-summing technique with a conventional rectangular format may be outperformed by a factor of 2-5 by special CCD formats or by unusual optical coupling configurations that reduce the importance of read noise, based on the ideal transmission for any additional optics used in these configurations.

  16. Miniaturized Fiber-Optic Fabry-Perot Interferometer for Highly Sensitive Refractive Index Measurement

    Institute of Scientific and Technical Information of China (English)

    Ming Deng; Tao Zhu; Yun-Jiang Rao; Hong Li

    2008-01-01

    This paper presents a novel miniaturized fiber-optic Fabry-Peort interferometer (FPI) for highly sensitive refractive index measurement. This device was tested for the refractive indices of various liquids including acetone and ethanol at room temperature. The sensitivity for measurement of refractive index change of ethanol is 1138 nm/RIU at the wavelength of 1550 nm. In addition, the sensor fabrication is simple including only cleaving, splicing, and etching. The signal is stable with high visibility. Therefore, it provides a valuable tool in biological and chemical applications.

  17. The GREGOR Fabry Perot Interferometer (GFPI), Technical Innovations and Results achieved in 2013

    CERN Document Server

    Puschmann, Klaus Gerhard

    2016-01-01

    This paper shall provide a summary of not yet published technical innovations to the GREGOR Fabry-Perot Interferometer (GFPI) at the 1.5m GREGOR Solar Telescope (Europe's largest solar telescope) that I implemented in 2013 as the Instrument Scientist of the GFPI. It also represents an overview of important and not yet published observational results that I achieved with the GFPI in 2013. The results and achievements can be considered a milestone in the further development, scientific verification and final acceptance of this instrument. The instrument is now in operation and employed by the international scientific community.

  18. Emulation of Fabry-Perot and Bragg resonators with temporal optical solitons

    CERN Document Server

    Voytova, Tanya; Yulin, Alexey; Driben, Rodislav

    2016-01-01

    The scattering of weak dispersive waves (DW) on several equally spaced temporal solitons is studied. It is shown by systematic numerical simulations that the reflection of the DWs from the soliton trains strongly depends on the distance between the solitons. The dependence of the reflection and transmission coefficients on the inter-soliton distance and the frequency of the incident waves is studied in detail, revealing fascinating quasi-periodic behavior. The analogy between the observed nonlinear phenomena in temporal domain and usual Fabry-Perot and Bragg resonators is discussed.

  19. In-fiber Fabry-Perot interferometer for strain and magnetic field sensing.

    Science.gov (United States)

    Costa, Greice K B; Gouvêa, Paula M P; Soares, Larissa M B; Pereira, João M B; Favero, Fernando; Braga, Arthur M B; Palffy-Muhoray, Peter; Bruno, Antonio C; Carvalho, Isabel C S

    2016-06-27

    In this paper we discuss the results obtained with an in-fiber Fabry-Perot interferometer (FPI) used in strain and magnetic field (or force) sensing. The intrinsic FPI was constructed by splicing a small section of a capillary optical fiber between two pieces of standard telecommunication fiber. The sensor was built by attaching the FPI to a magnetostrictive alloy in one configuration and also by attaching the FPI to a small magnet in another. Our sensors were found to be over 4 times more sensitive to magnetic fields and around 10 times less sensitive to temperature when compared to sensors constructed with Fiber Bragg Grating (FBG).

  20. An All Fiber Intrinsic Fabry-Perot Interferometer Based on an Air-Microcavity

    Directory of Open Access Journals (Sweden)

    Ruth I. Mata-Chávez

    2013-05-01

    Full Text Available In this work an Intrinsic Fabry-Perot Interferometer (IFPI based on an air-microcavity is presented. Here the air microcavity, with silica walls, is formed at a segment of a hollow core photonic crystal fiber (HCPCF, which is fusion spliced with a single mode fiber (SMF. Moreover, the spectral response of the IFPI is experimentally characterized and some results are provided. Finally, the viability to use the IFPI to implement a simple, compact size, and low cost refractive index sensor is briefly analyzed.