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Sample records for al amyloid deposits

  1. Pituicytoma with gelsolin amyloid deposition.

    PubMed

    Ida, Cristiane M; Yan, Xiaoling; Jentoft, Mark E; Kip, N Sertac; Scheithauer, Bernd W; Morris, Jonathan M; Dogan, Ahmet; Parisi, Joseph E; Kovacs, Kalman

    2013-09-01

    Pituicytoma is a rare low-grade (WHO grade I) sellar region glioma. Among sellar tumors, pituitary adenomas, mainly prolactinomas, may show amyloid deposits. Gelsolin is a ubiquitous calcium-dependent protein that regulates actin filament dynamics. Two known gene point mutations result in gelsolin amyloid deposition, a characteristic feature of a rare type of familial amyloid polyneuropathy (FAP), the Finnish-type FAP, or hereditary gelsolin amyloidosis (HGA). HGA is an autosomal-dominant systemic amyloidosis, characterized by slowly progressive neurological deterioration with corneal lattice dystrophy, cranial neuropathy, and cutis laxa. A unique case of pituicytoma with marked gelsolin amyloid deposition in a 67-year-old Chinese woman is described. MRI revealed a 2.6-cm well-circumscribed, uniformly contrast-enhancing solid sellar mass with suprasellar extension. Histologically, the lesion was characterized by solid sheets and fascicles of spindle cells with slightly fibrillary cytoplasm and oval nuclei with pinpoint nucleoli. Surrounding brain parenchyma showed marked reactive piloid gliosis. Remarkably, conspicuous amyloid deposits were identified as pink homogeneous spherules on light microscopy that showed apple-green birefringence on Congo red with polarization. Mass spectrometric-based proteomic analysis identified the amyloid as gelsolin type. Immunohistochemically, diffuse reactivity to S100 protein and TTF1, focal reactivity for GFAP, and no reactivity to EMA, synaptophysin, and chromogranin were observed. HGA-related mutations were not identified in the tumor. No recurrence was noted 14 months after surgery. To the knowledge of the authors, amyloid deposition in pituicytoma or tumor-associated gelsolin amyloidosis has not been previously described. This novel finding expands the spectrum of sellar tumors that may be associated with amyloid deposition. PMID:23817895

  2. Reduced Alzheimer's disease β-amyloid deposition in transgenic mice expressing S-palmitoylation-deficient APH1aL and nicastrin

    PubMed Central

    Meckler, Xavier; Roseman, Jelita; Das, Pritam; Cheng, Haipeng; Pei, Susan; Keat, Marcia; Kassarjian, Breanne; Golde, Todd E.; Parent, Angèle T.; Thinakaran, Gopal

    2010-01-01

    Sequential cleavage of amyloid precursor protein by β- and γ-secretases generates β-amyloid peptides (Aβ), which accumulate in the brains of patients with Alzheimer's disease. We recently identified S-palmitoylation of two γ-secretase subunits, APH1 and nicastrin. S-palmitoylation is an essential post-translational modification for the proper trafficking and function of many neuronal proteins. In cultured cell lines, lack of S-palmitoylation causes instability of nascent APH1 and nicastrin, but does not affect γ-secretase processing of amyloid precursor protein. To determine the importance of γ-secretase S-palmitoylation for Aβ deposition in the brain, we generated transgenic mice co-expressing human wild-type or S-palmitoylation-deficient APH1aL and nicastrin in neurons in the forebrain. We found that lack of S-palmitoylation did not impair the ability of APH1aL and nicastrin to form enzymatically active protein complexes with endogenous presenilin 1 and PEN2, or affect the localization of γ-secretase subunits in dendrites and axons of cortical neurons. When we crossed these mice with 85Dbo transgenic mice, which co-express familial Alzheimer's disease-causing amyloid precursor protein and presenilin 1 variants, we found that co-expression of wild-type or mutant APH1aL and nicastrin led to marked stabilization of transgenic presenilin 1 in the brains of double transgenic mice. Interestingly, we observed a moderate, but significant, reduction in amyloid deposits in the forebrain of mice expressing S-palmitoylation-deficient γ-secretase subunits as compared with mice overexpressing wild-type subunits, as well as a reduction in the levels of insoluble Aβ40-42. These results indicate that γ-secretase S-palmitoylation modulates Aβ deposition in the brain. PMID:21123562

  3. Reduced Alzheimer's disease ß-amyloid deposition in transgenic mice expressing S-palmitoylation-deficient APH1aL and nicastrin.

    PubMed

    Meckler, Xavier; Roseman, Jelita; Das, Pritam; Cheng, Haipeng; Pei, Susan; Keat, Marcia; Kassarjian, Breanne; Golde, Todd E; Parent, Angèle T; Thinakaran, Gopal

    2010-12-01

    Sequential cleavage of amyloid precursor protein by β- and γ-secretases generates β-amyloid peptides (Aβ), which accumulate in the brains of patients with Alzheimer's disease. We recently identified S-palmitoylation of two γ-secretase subunits, APH1 and nicastrin. S-Palmitoylation is an essential posttranslational modification for the proper trafficking and function of many neuronal proteins. In cultured cell lines, lack of S-palmitoylation causes instability of nascent APH1 and nicastrin but does not affect γ-secretase processing of amyloid precursor protein. To determine the importance of γ-secretase S-palmitoylation for Aβ deposition in the brain, we generated transgenic mice coexpressing human wild-type or S-palmitoylation-deficient APH1aL and nicastrin in neurons in the forebrain. We found that lack of S-palmitoylation did not impair the ability of APH1aL and nicastrin to form enzymatically active protein complexes with endogenous presenilin 1 and PEN2 or affect the localization of γ-secretase subunits in dendrites and axons of cortical neurons. When we crossed these mice with 85Dbo transgenic mice, which coexpress familial Alzheimer's disease-causing amyloid precursor protein and presenilin 1 variants, we found that coexpression of wild-type or mutant APH1aL and nicastrin led to marked stabilization of transgenic presenilin 1 in the brains of double-transgenic mice. Interestingly, we observed a moderate, but significant, reduction in amyloid deposits in the forebrain of mice expressing S-palmitoylation-deficient γ-secretase subunits compared with mice overexpressing wild-type subunits, as well as a reduction in the levels of insoluble Aβ(40-42). These results indicate that γ-secretase S-palmitoylation modulates Aβ deposition in the brain. PMID:21123562

  4. Template-directed deposition of amyloid

    NASA Astrophysics Data System (ADS)

    Ha, Chanki

    The formation of amyloid plaques in tissue is a pathological feature of many neurodegenerative diseases. Amyloid deposition, the process of amyloid plaque growth by the association of individual soluble amyloid molecules with a pre-existing amyloid template (i.e. plaque), is known to be critical for amyloid formation in vivo. In order to characterize amyloid deposition, we developed novel, synthetic amyloid templates like amyloid plaques in the human Alzheimer's brain by attaching amyloid seeds covalently onto an N-hydroxysuccinimide-activated surface. Amyloid plaques with a characteristic beta-sheet structure formed through a conformational rearrangement of soluble insulin or Abeta monomers upon interaction with the template. The amyloid deposition rate followed saturation kinetics with respect to insulin concentration in the solution. According to visualization of temporal evolution of Abeta plaque deposition on a template, it was found that mature amyloid plaques serve as a sink of soluble Abeta in a solution as well as a reservoir of small aggregates such as oligomers and protofibrils. Quantitative analysis of seeding efficiencies of three different Abeta species revealed that oligomeric forms of Abeta act more efficiently as seeds than monomers or fibrils do. Furthermore, studies on the interaction between Abeta40 and 42 showed an important role of Abeta42 in amyloid deposition. A slightly acidic condition was found to be unfavorable for amyloid plaque formation. Effects of metal ions on amyloid deposition indicated that Fe3+, but not Cu3 and Zn2+, is important for the deposition of amyloid plaques. The binding of Fe3+ to Abeta42 peptide was confirmed by using SIMS analysis. Zn2+ induced nonfibrillar amorphous aggregates, but the release of Zn2+ from Abeta42 deposits by Fe3+ triggered the formation of amyloid fibers. Effects or metal ion chelators such as ethylenediamine tetraacetic acid, deferoxamine, and clioquinol on amyloid deposition were tested to

  5. [Amyloid deposition in chronic joint disease].

    PubMed

    Saitou, H

    1994-07-01

    As a screening procedure for the detection of amyloidosis secondary to rheumatoid arthritis, abdominal subcutaneous fat tissues were aspirated, and were examined after Congo red staining by polarized microscopy. Positive amyloid deposits were found in 7.1 percent of the rheumatoid patients, and the amyloid in the subcutaneous fat was determined to be AA type by permanganate oxidation. The occurrence of amyloid deposition was significantly correlated with the duration of the articular symptoms, the progression of the class, and also with proteinuria. Additionally the joint capsules, including the synovium and synovial fluid sediment, from patients with rheumatoid arthritis and osteoarthritis were examined for amyloid deposition. Deposits of amyloid in the hip and knee joints were found more frequently in those with rheumatoid arthritis than in those with osteoarthritis. In osteoarthritis, the frequency of amyloid deposition tended to increase with advancing age. However these amyloid deposits in the joint structure were discovered to be resistant to permanganate oxidation. Therefore it was suspected that these amyloid deposits were of a type different from AA amyloid. PMID:8071579

  6. The multiple mechanisms of amyloid deposition

    PubMed Central

    Mena, Maria A; Rodríguez-Navarro, José A

    2009-01-01

    Amyloid deposition is one of the central neuropathological abnormalities in Alzheimer disease (AD) but it also takes places in many neurodegenerative diseases such as prionic disorders, Huntington's disease (HD) and others. Up to very recently amyloid formation was considered a very slow process of deposition of an abnormal protein due to genetic abnormalities or post-translational modification of the deposited protein. Recent data suggest that the process of amyloidogenesis may be much more rapid in many cases and due to multiple mechanisms. We have found a mouse model of progressive neurodegeneration that resemble motor, behavioral and pathological hallmarks of parkinsonism and tauopathies, but surprisingly, also present amyloid deposits in brain and peripheral organs. Here we review some of these recent works which may provide new insight into the process of formation of amyloid and, perhaps, new ideas for its treatment. PMID:19270506

  7. Scintigraphic quantification and serial monitoring of human visceral amyloid deposits provide evidence for turnover and regression.

    PubMed

    Hawkins, P N; Richardson, S; MacSweeney, J E; King, A D; Vigushin, D M; Lavender, J P; Pepys, M B

    1993-06-01

    Radiolabelled serum amyloid P component scintigraphy provides information on the diagnosis and distribution of amyloid which was not previously available. A simple reproducible method for quantifying the uptake of 123I-labelled serum amyloid P component into individual livers, spleens and kidneys was devised and evaluated in 22 patients with different types of systemic amyloidosis. Prospective studies in 10 patients were undertaken in order to monitor aspects of the natural history of visceral amyloid deposits. Although measurements of tracer uptake were not as discriminating for diagnostic purposes as the opinions of two highly experienced visual observers, the availability of objective scintigraphic parameters should facilitate interpretation of serum amyloid P component scans in centres unfamiliar with the technique. The follow-up studies demonstrated several intriguing features of amyloidogenesis. There was very rapid progression of deposits in some individuals with differential rates of accretion in different organs. The single patient with AL amyloidosis treated with cytotoxic drugs showed substantial regression of hepatic amyloid deposits whilst his splenic amyloid increased. His spleen was then removed and further regression of the hepatic amyloid was observed. It is concluded that quantitative serum amyloid P component scintigraphy is a useful method for assessing visceral amyloid and that the deposits not only progress at extremely variable rates, but can evidently also be mobilized. These findings encourage active therapeutic approaches in the management of amyloidosis. PMID:8171184

  8. Are elevated serum amyloid A levels and amyloid-enhancing factor sufficient to induce inflammation-associated amyloid deposition?

    PubMed

    Kisilevsky, R; Tan, R; Subrahmanyan, L; Snow, A

    1984-01-01

    During inflammation-associated amyloidosis two coincident factors, serum amyloid A (SAA) and amyloid-enhancing factor (AEF) are apparently necessary for amyloid A (AA) deposition. It is shown by passive transfer of cytokines, which stimulate SAA production, and AEF that these are not sufficient. A further factor(s) is necessary, which stems from the acute inflammatory response. Potential candidates are serum or tissue glycosaminoglycans. PMID:6400464

  9. Peptide p5 binds both heparinase-sensitive glycosaminoglycans and fibrils in patient-derived AL amyloid extracts

    SciTech Connect

    Martin, Emily B.; Williams, Angela; Heidel, Eric; Macy, Sallie; Kennel, Stephen J.; Wall, Jonathan S.

    2013-06-21

    Highlights: •Polybasic peptide p5 binds human light chain amyloid extracts. •The binding of p5 with amyloid involves both glycosaminoglycans and fibrils. •Heparinase treatment led to a correlation between p5 binding and fibril content. •p5 binding to AL amyloid requires electrostatic interactions. -- Abstract: In previously published work, we have described heparin-binding synthetic peptides that preferentially recognize amyloid deposits in a mouse model of reactive systemic (AA) amyloidosis and can be imaged by using positron and single photon emission tomographic imaging. We wanted to extend these findings to the most common form of visceral amyloidosis, namely light chain (AL); however, there are no robust experimental animal models of AL amyloidosis. To further define the binding of the lead peptide, p5, to AL amyloid, we characterized the reactivity in vitro of p5 with in situ and patient-derived AL amyloid extracts which contain both hypersulfated heparan sulfate proteoglycans as well as amyloid fibrils. Histochemical staining demonstrated that the peptide specifically localized with tissue-associated AL amyloid deposits. Although we anticipated that p5 would undergo electrostatic interactions with the amyloid-associated glycosaminoglycans expressing heparin-like side chains, no significant correlation between peptide binding and glycosaminoglycan content within amyloid extracts was observed. In contrast, following heparinase I treatment, although overall binding was reduced, a positive correlation between peptide binding and amyloid fibril content became evident. This interaction was further confirmed using synthetic light chain fibrils that contain no carbohydrates. These data suggest that p5 can bind to both the sulfated glycosaminoglycans and protein fibril components of AL amyloid. Understanding these complex electrostatic interactions will aid in the optimization of synthetic peptides for use as amyloid imaging agents and potentially as

  10. Prevalence of amyloid deposition in mature healthy chickens in the flock that previously had outbreaks of vaccine-associated amyloidosis

    PubMed Central

    IBI, Kanata; MURAKAMI, Tomoaki; GODA, Wael Mohamed; KOBAYASHI, Naoki; ISHIGURO, Naotaka; YANAI, Tokuma

    2015-01-01

    Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic inflammation, such as that caused by bacterial infection. We previously described vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of amyloid deposition was measured in mature healthy chickens that survived a previous outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the amyloid deposition in mature chickens and compared the prevalence of amyloid deposition with juvenile chickens obtained in our previous study (Murakami et al., 2013). We found that: 1) amyloid deposition in the liver was absent in mature chickens, while juvenile chickens had a rate of 24%; 2) amyloid deposition in the spleen was observed in 36% of juvenile chickens and in 40% of mature chickens; 3) amyloid deposition in the pectoral muscle of mature chickens (43.75%) was approximately half that of juvenile chickens (88%). These results suggest that additional amyloid deposition in chickens previously exposed to AA amyloidosis may not worsen with age. Further, amyloid deposition in chickens may tend to regress when causative factors, such as vaccinations and/or chronic inflammation, are absent. PMID:25985816

  11. Prevalence of amyloid deposition in mature healthy chickens in the flock that previously had outbreaks of vaccine-associated amyloidosis.

    PubMed

    Ibi, Kanata; Murakami, Tomoaki; Goda, Wael Mohamed; Kobayashi, Naoki; Ishiguro, Naotaka; Yanai, Tokuma

    2015-10-01

    Avian amyloid A (AA) amyloidosis is commonly observed in adult birds with chronic inflammation, such as that caused by bacterial infection. We previously described vaccine-associated AA amyloidosis in juvenile chickens. In this study, the prevalence of amyloid deposition was measured in mature healthy chickens that survived a previous outbreak of avian AA amyloidosis while they were juveniles. Herein, we analyzed the amyloid deposition in mature chickens and compared the prevalence of amyloid deposition with juvenile chickens obtained in our previous study (Murakami et al., 2013). We found that: 1) amyloid deposition in the liver was absent in mature chickens, while juvenile chickens had a rate of 24%; 2) amyloid deposition in the spleen was observed in 36% of juvenile chickens and in 40% of mature chickens; 3) amyloid deposition in the pectoral muscle of mature chickens (43.75%) was approximately half that of juvenile chickens (88%). These results suggest that additional amyloid deposition in chickens previously exposed to AA amyloidosis may not worsen with age. Further, amyloid deposition in chickens may tend to regress when causative factors, such as vaccinations and/or chronic inflammation, are absent. PMID:25985816

  12. Pharmacological removal of serum amyloid P component from intracerebral plaques and cerebrovascular Aβ amyloid deposits in vivo

    PubMed Central

    Millar, David J.; Richard-Londt, Angela

    2016-01-01

    Human amyloid deposits always contain the normal plasma protein serum amyloid P component (SAP), owing to its avid but reversible binding to all amyloid fibrils, including the amyloid β (Aβ) fibrils in the cerebral parenchyma plaques and cerebrovascular amyloid deposits of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). SAP promotes amyloid fibril formation in vitro, contributes to persistence of amyloid in vivo and is also itself directly toxic to cerebral neurons. We therefore developed (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC), a drug that removes SAP from the blood, and thereby also from the cerebrospinal fluid (CSF), in patients with AD. Here we report that, after introduction of transgenic human SAP expression in the TASTPM double transgenic mouse model of AD, all the amyloid deposits contained human SAP. Depletion of circulating human SAP by CPHPC administration in these mice removed all detectable human SAP from both the intracerebral and cerebrovascular amyloid. The demonstration that removal of SAP from the blood and CSF also removes it from these amyloid deposits crucially validates the strategy of the forthcoming ‘Depletion of serum amyloid P component in Alzheimer's disease (DESPIAD)’ clinical trial of CPHPC. The results also strongly support clinical testing of CPHPC in patients with CAA. PMID:26842068

  13. Memory decline shows stronger associations with estimated spatial patterns of amyloid deposition progression than total amyloid burden.

    PubMed

    Yotter, Rachel A; Doshi, Jimit; Clark, Vanessa; Sojkova, Jitka; Zhou, Yun; Wong, Dean F; Ferrucci, Luigi; Resnick, Susan M; Davatzikos, Christos

    2013-12-01

    The development of amyloid imaging compounds has allowed in vivo imaging of amyloid deposition. In this study, we examined the spatial patterns of amyloid deposition throughout the brain using Pittsburgh Compound Blue ((11)C-PiB) positron emission tomography data from the Baltimore Longitudinal Study of Aging. We used a new methodology that allowed us to approximate spatial patterns of the temporal progression of amyloid plaque deposition from cross-sectional data. Our results are consistent with patterns of progression known from autopsy studies, with frontal and precuneus regions affected early and occipital and sensorimotor cortices affected later in disease progression--here, disease progression means lower-to-higher total amyloid burden. Furthermore, we divided participants into subgroups based on longitudinal change in memory performance, and demonstrated significantly different spatial patterns of the estimated progression of amyloid deposition between these subgroups. Our results indicate that the spatial pattern of amyloid deposition is related to cognitive performance and may be more informative than a biomarker reflecting total amyloid burden, the use of which is the current practice. This finding has broad implications for our understanding of the relationship between cognitive decline/resilience and amyloid deposition, as well as for the use of amyloid imaging as a biomarker in research and clinical applications. PMID:23859610

  14. [Salmon-pink colored conjunctival tumor with amyloid deposits].

    PubMed

    Müller, P L; Loeffler, K U; Holz, F G; Fischer, H-P; Herwig, M C

    2016-07-01

    An 82-year-old male patient presented with a salmon-pink colored conjunctival tumor of the left eye. A circumscribed, dense and whitish portion was detected by clinical examination. The histophological and immunhistochemical examination of the biopsy tissue revealed a CD20+ marginal zone lymphoma of the conjunctiva with amyloid deposits. Extranodal marginal zone lymphoma at this site is the most common lymphoma of the ocular adnexa and accounts for 5-10% of malignant diseases. An association with amyloid production is very rare and according to the current state of knowledge has no known impact on the outcome. PMID:26362570

  15. Engineering theranostic nanovehicles capable of targeting cerebrovascular amyloid deposits.

    PubMed

    Agyare, Edward K; Jaruszewski, Kristen M; Curran, Geoffry L; Rosenberg, Jens T; Grant, Samuel C; Lowe, Val J; Ramakrishnan, Subramanian; Paravastu, Anant K; Poduslo, Joseph F; Kandimalla, Karunya K

    2014-07-10

    Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid beta (Aβ) proteins within the walls of the cerebral vasculature with subsequent aggressive vascular inflammation leading to recurrent hemorrhagic strokes. The objective of the study was to develop theranostic nanovehicles (TNVs) capable of a) targeting cerebrovascular amyloid; b) providing magnetic resonance imaging (MRI) contrast for the early detection of CAA; and c) treating cerebrovascular inflammation resulting from CAA. The TNVs comprised of a polymeric nanocore made from Magnevist (MRI contrast agent) conjugated chitosan. The nanocore was also loaded with cyclophosphamide (CYC), an immunosuppressant shown to reduce the cerebrovascular inflammation in CAA. Putrescine modified F(ab')2 fragment of anti-amyloid antibody, IgG4.1 (pF(ab')24.1) was conjugated to the surface of the nanocore to target cerebrovascular amyloid. The average size of the control chitosan nanoparticles (conjugated with albumin and are devoid of Magnevist, CYC, and pF(ab')24.1) was 164±1.2 nm and that of the TNVs was 239±4.1 nm. The zeta potential values of the CCNs and TNVs were 21.6±1.7 mV and 11.9±0.5 mV, respectively. The leakage of Magnevist from the TNVs was a modest 0.2% over 4 days, and the CYC release from the TNVs followed Higuchi's model that describes sustained drug release from polymeric matrices. The studies conducted in polarized human microvascular endothelial cell monolayers (hCMEC/D3) in vitro as well as in mice in vivo have demonstrated the ability of TNVs to target cerebrovascular amyloid. In addition, the TNVs provided contrast for imaging cerebrovascular amyloid using MRI and single photon emission computed tomography. Moreover, the TNVs were shown to reduce pro-inflammatory cytokine production by the Aβ challenged blood brain barrier (BBB) endothelium more effectively than the cyclophosphamide alone. PMID:24735640

  16. Non-amyloid and amyloid prion protein deposits in prion-infected mice differ in blockage of interstitial brain fluid

    PubMed Central

    Rangel, Alejandra; Race, Brent; Striebel, James; Chesebro, Bruce

    2012-01-01

    Aims Prion diseases are characterized by brain deposits of misfolded aggregated protease-resistant prion protein (PrP), termed PrPres. In humans and animals, PrPres is found as either disorganized non-amyloid aggregates or organized amyloid fibrils. Both PrPres forms are found in extracellular spaces of the brain. Thus, both might block drainage of brain interstitial fluid (ISF). The present experiments studied whether ISF blockage occurred during amyloid and/or non-amyloid prion diseases. Methods Various-sized fluorescein-labeled ISF tracers were stereotactically inoculated into the striatum of adult mice. At times from 5 min to 77 hours, uninfected and scrapie-infected mice were compared. C57BL/10 mice expressing wild-type anchored PrP, which develop non-amyloid PrPres similar to humans with sporadic CJD, were compared with Tg44+/+ mice expressing anchorless PrP, which develop amyloid PrPres similar to certain human familial prion diseases. Results In C57BL/10 mice, extensive non-amyloid PrPres aggregate deposition was not associated with abnormal clearance kinetics of tracers. In contrast, scrapie-infected Tg44+/+ mice showed blockage of tracer clearance and co-localization of tracer with perivascular PrPres amyloid. Conclusions Since tracer localization and clearance was normal in infected C57BL/10 mice, ISF blockage was not an important pathogenic mechanism in this model. Therefore, ISF blockage is unlikely to be a problem in non-amyloid human prion diseases such as sporadic CJD. In contrast, partial ISF blockage appeared to be a possible pathogenic mechanism in Tg44+/+ mice. Thus this mechanism might also influence human amyloid prion diseases where expression of anchorless or mutated PrP results in perivascular amyloid PrPres deposition and cerebral amyloid angiopathy (CAA). PMID:22998478

  17. Risk Factors for β-Amyloid Deposition in Healthy Aging

    PubMed Central

    Rodrigue, Karen M.; Rieck, Jennifer R.; Kennedy, Kristen M.; Devous, Michael D.; Diaz-Arrastia, Ramon; Park, Denise C.

    2013-01-01

    Importance Identifying risk factors for increased β-amyloid (Aβ) deposition is important for targeting individuals most at risk for developing Alzheimer disease and informing clinical practice concerning prevention and early detection. Objective To investigate risk factors for Aβ deposition in cognitively healthy middle-aged and older adults. Specifically, we hypothesized that individuals with a vascular risk factor such as hypertension, in combination with a genetic risk factor for Alzheimer disease (apolipoprotein E ε4 allele), would show greater amyloid burden than those without such risk. Design Cross-sectional study. Setting General community. Participants One hundred eighteen well-screened and cognitively normal adults, aged 47 to 89 years. Participants were classified in the hypertension group if they reported a medical diagnosis of hypertension or if blood pressure exceeded 140 mm Hg systolic/90 mm Hg diastolic, as measured across 7 occasions at the time of study. Intervention Participants underwent Aβ positron emission tomography imaging with radiotracer fluorine 18–labeled florbetapir. Participants were genotyped for apolipoprotein E and were classified as ε4+ or ε4−. Main Outcome Measure Amyloid burden. Results Participants in the hypertension group with at least 1 ε4 allele showed significantly greater amyloid burden than those with only 1 risk factor or no risk factors. Furthermore, increased pulse pressure was strongly associated with increased mean cortical amyloid level for subjects with at least 1 ε4 allele. Conclusions and Relevance Vascular disease is a prevalent age-related condition that is highly responsive to both behavioral modification and medical treatment. Proper control and prevention of risk factors such as hypertension earlier in the life span may be one potential mechanism to ameliorate or delay neuropathological brain changes with aging. PMID:23553344

  18. Longitudinal cerebral blood flow and amyloid deposition: an emerging pattern?

    PubMed Central

    Sojkova, Jitka; Beason-Held, Lori; Zhou, Yun; An, Yang; Kraut, Michael A; Ye, Weigo; Ferrucci, Luigi; Mathis, Chester A; Klunk, William E; Wong, Dean F; Resnick, Susan M

    2008-01-01

    Although cerebral amyloid deposition may precede cognitive impairment by decades, the relationship between amyloid deposition and longitudinal change in neuronal function has not been studied. The aim of this paper is to determine whether nondemented individuals with high and low amyloid burden show different patterns of longitudinal regional cerebral blood flow (rCBF) changes in the years preceding measurement of amyloid deposition. Methods Twenty-eight nondemented participants (mean (SD) age at [11C] PIB 82.5(4.8) yrs; 6 mildly impaired) from the Baltimore Longitudinal Study of Aging underwent yearly resting-state [15O]H2O PET scans for up to 8 years. [11C]PIB images of amyloid deposition were acquired on average 10.8(0.8) years after the first CBF scan. [11C]PIB distribution volume ratios (DVR) of regions of interest were estimated by fitting a reference tissue model to the measured time activity curves. Based on mean cortical DVR, participants were divided into high and low [11C]PIB retention groups. Differences in longitudinal rCBF changes between high and low [11C]PIB groups were investigated by voxel-based analysis. Results Longitudinal rCBF changes differed significantly between high (n=10) and low (n=18) [11C]PIB groups (p<=0.001). Greater longitudinal decreases in rCBF in the high [11C]PIB group were seen in right anterior/mid cingulate, right supramarginal gyrus, left thalamus and midbrain bilaterally relative to the low group. Greater increases in rCBF over time in the high [11C]PIB group were found in left medial and inferior frontal gyri, right precuneus, left inferior parietal lobule, and the left postcentral gyrus. Conclusion In this group of nondemented older adults, those with high [11C]PIB show greater longitudinal declines in rCBF in certain areas, representing regions with greater decrements in neuronal function. Greater longitudinal increases in rCBF are also observed in those with higher amyloid load and may represent an attempt to preserve

  19. Characterization of AmyloidDeposits in Bovine Brains

    PubMed Central

    Vallino Costassa, Elena; Fiorini, Michele; Zanusso, Gianluigi; Peletto, Simone; Acutis, Pierluigi; Baioni, Elisa; Maurella, Cristiana; Tagliavini, Fabrizio; Catania, Marcella; Gallo, Marina; Faro, Monica Lo; Chieppa, Maria Novella; Meloni, Daniela; D’Angelo, Antonio; Paciello, Orlando; Ghidoni, Roberta; Tonoli, Elisa; Casalone, Cristina; Corona, Cristiano

    2016-01-01

    Amyloid-β (Aβ) deposits are seen in aged individuals of many mammalian species that possess the same aminoacid sequence as humans. This study describes Aβ deposition in 102 clinically characterized cattle brains from animals aged 0 to 20 years. Extracellular and intracellular Aβ deposition was detected with 4G8 antibody in the cortex, hippocampus, and cerebellum. X-34 staining failed to stain Aβ deposits, indicating the non β-pleated nature of these deposits. Western blot analysis and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry revealed in Tris, Triton, and formic acid fractions the presence of different Aβ peptides, characterized mainly by C-terminally truncated forms. Exploration of the genetic variability of APOE, PSEN1, and PSEN2 genes involved in Alzheimer’s disease pathogenesis revealed several previously unreported polymorphisms. This study demonstrates certain similarities between Aβ deposition patterns exhibited in cattle brains and those in the human brain in early stages of aging. Furthermore, the identification of the same Aβ peptides reported in humans, but unable to form aggregates, supports the hypothesis that cattle may be protected against amyloid plaque formation. PMID:26890772

  20. 18F-Florbetapir Binds Specifically to Myocardial Light Chain and Transthyretin Amyloid Deposits: An Autoradiography Study

    PubMed Central

    Park, Mi-Ae; Padera, Robert F.; Belanger, Anthony; Dubey, Shipra; Hwang, David H.; Veeranna, Vikas; Falk, Rodney H.; Di Carli, Marcelo F.; Dorbala, Sharmila

    2015-01-01

    Background 18F-florbetapir is a promising imaging biomarker for light chain (AL) and transthyretin (ATTR) cardiac amyloidosis. Our aim, using human autopsy myocardial specimens, was to test the hypothesis that 18F-florbetapir binds specifically to myocardial AL and ATTR amyloid deposits. Methods and Results We studied myocardial sections from 30 subjects with autopsy documented AL (N = 10), ATTR (N = 10) and non-amyloid controls (N = 10), using 18F-florbetapir and cold florbetapir compound and digital autoradiography. Total and non-specific binding of 18F-florbetapir was determined using the maximum signal intensity values. Specific binding of 18F-florbetapir was calculated by subtracting non-specific from total binding measurements (in decays per minute/mm2, DPM mm2), and was compared to cardiac structure and function on echocardiography and the histological extent of amyloid deposits. Diffuse or focally increased 18F-florbetapir uptake was noted in all AL and ATTR samples and in none of the control samples. Compared to control samples, mean 18F-florbetapir specific uptake was significantly higher in the amyloid samples (0.94 ± 0.43 vs. 2.00 ± 0.58 DPM/mm2, p < 0.001), and in the AL compared to the ATTR samples (2.48 ± 0.40 vs. 1.52 ± 0.22 DPM/mm2, p < 0.001). The samples from subjects with atypical echocardiographic features of amyloidosis showed quantitatively more intense 18F-florbetapir specific uptake compared to control samples (1.50 ± 0.17 vs. 0.94 ± 0.43 DPM/mm2, p = 0.004), despite smaller amyloid extent than in subjects with typical echocardiograms. Conclusions 18F-florbetapir specifically binds to myocardial AL and ATTR deposits in humans and offers the potential to screen for the two most common types of myocardial amyloid. PMID:26259579

  1. Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain.

    PubMed

    Cox, Paul Alan; Davis, David A; Mash, Deborah C; Metcalf, James S; Banack, Sandra Anne

    2016-01-27

    Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer's disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer's, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk. PMID:26791617

  2. Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain

    PubMed Central

    Cox, Paul Alan; Davis, David A.; Mash, Deborah C.; Metcalf, James S.; Banack, Sandra Anne

    2016-01-01

    Neurofibrillary tangles (NFT) and β-amyloid plaques are the neurological hallmarks of both Alzheimer's disease and an unusual paralytic illness suffered by Chamorro villagers on the Pacific island of Guam. Many Chamorros with the disease suffer dementia, and in some villages one-quarter of the adults perished from the disease. Like Alzheimer's, the causal factors of Guamanian amyotrophic lateral sclerosis/parkinsonism dementia complex (ALS/PDC) are poorly understood. In replicated experiments, we found that chronic dietary exposure to a cyanobacterial toxin present in the traditional Chamorro diet, β-N-methylamino-l-alanine (BMAA), triggers the formation of both NFT and β-amyloid deposits similar in structure and density to those found in brain tissues of Chamorros who died with ALS/PDC. Vervets (Chlorocebus sabaeus) fed for 140 days with BMAA-dosed fruit developed NFT and sparse β-amyloid deposits in the brain. Co-administration of the dietary amino acid l-serine with l-BMAA significantly reduced the density of NFT. These findings indicate that while chronic exposure to the environmental toxin BMAA can trigger neurodegeneration in vulnerable individuals, increasing the amount of l-serine in the diet can reduce the risk. PMID:26791617

  3. Imaging of dialysis-related amyloid (AB-amyloid) deposits with sup 131 I-beta 2-microglobulin

    SciTech Connect

    Floege, J.; Burchert, W.; Brandis, A.; Gielow, P.; Nonnast-Daniel, B.; Spindler, E.; Hundeshagen, H.; Shaldon, S.; Koch, K.M. )

    1990-12-01

    The diagnosis of dialysis-related amyloid (AB-amyloid) has been based usually on clinical and radiological criteria. Following the discovery that beta 2-microglobulin was the major protein of this amyloid, we isolated and radiolabelled uremic plasma beta 2-microglobulin. After intravenous injection, gamma-camera images of selected joint areas were obtained from 42 patients who were on regular hemodialysis therapy. Positive scans involving the shoulder, hip, knee and carpal regions were found in 13 of 14 patients treated for more than 10 years and 10 of 16 patients treated for 5 to 10 years. Patients treated for less time had negative scans. Specificity was indicated by negative scans in non-amyloid inflammatory lesions in control hemodialysis patients. Up to 48-fold tracer enrichment was detected in excised AB-amyloid containing tissue as compared to amyloid-free tissue. These findings suggest that circulating radiolabelled beta 2-microglobulin is taken up by the amyloid deposits. This method may non-invasively detect tissue infiltrates of amyloid. It may also permit prospective evaluation of the efficacy of prophylactic dialysis strategies which are designed to prevent or delay the onset of this complication of long-term dialysis.

  4. Marked shrinkage of amyloid lymphadenopathy after an intensive chemotherapy in a patient with IgM-associated AL amyloidosis.

    PubMed

    Tazawa, Ko-Ichi; Katoh, Nagaaki; Shimojima, Yasuhiro; Matsuda, Masayuki; Ikeda, Shu-Ichi

    2009-12-01

    A male patient with primary AL amyloidosis who had been suffering from systemic lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab followed by autologous peripheral blood stem cell transplantation. Four years after complete hematological remission he showed marked reduction in size of the amyloid-laden lymph nodes. Deposits of AL amyloid may regress from the tissue if the chemotherapy succeeds in persistent inhibition of the production of an amyloidogenic immunoglobulin light chain. PMID:19922338

  5. Marked shrinkage of amyloid lymphadenopathy after an intensive chemotherapy in a patient with IgM-associated AL amyloidosis.

    PubMed

    Tazawa, Ko-Ichi; Katoh, Nagaaki; Shimojima, Yasuhiro; Matsuda, Masayuki; Ikeda, Shu-Ichi

    2009-01-01

    A male patient with primary AL amyloidosis who had been suffering from systemic lymphadenopathy with IgMkappa-type M-proteinemia received two courses of VAD and high-dose melphalan with in vivo elimination of CD20(+) cells using rituximab followed by autologous peripheral blood stem cell transplantation. Four years after complete hematological remission he showed marked reduction in size of the amyloid-laden lymph nodes. Deposits of AL amyloid may regress from the tissue if the chemotherapy succeeds in persistent inhibition of the production of amyloidogenic immunoglobulin light chains. PMID:19590992

  6. Cerebral Amyloid Angiopathy and Parenchymal Amyloid Deposition in Transgenic Mice Expressing the Danish Mutant Form of Human BRI2

    PubMed Central

    Vidal, Ruben; Barbeito, Ana G; Miravalle, Leticia; Ghetti, Bernardino

    2009-01-01

    Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease clinically characterized by the presence of cataracts, hearing impairment, cerebellar ataxia and dementia. Neuropathologically, FDD is characterized by the presence of widespread cerebral amyloid angiopathy (CAA), parenchymal amyloid deposition and neurofibrillary tangles. FDD is caused by a 10-nucleotide duplication-insertion in the BRI2 gene that generates a larger-than-normal precursor protein, of which the Danish amyloid subunit (ADan) comprises the last 34 amino acids. Here, we describe a transgenic mouse model for FDD (Tg-FDD) in which the mouse Prnp (prion protein) promoter drives the expression of the Danish mutant form of human BRI2. The main neuropathological findings in Tg-FDD mice are the presence of widespread CAA and parenchymal deposition of ADan. In addition, we observe the presence of amyloid-associated gliosis, an inflammatory response and deposition of oligomeric ADan. As the animals aged, they showed abnormal grooming behavior, an arched back, and walked with a wide-based gait and shorter steps. This mouse model may give insights on the pathogenesis of FDD and will prove useful for the development of therapeutics. Moreover, the study of Tg-FDD mice may offer new insights into the role of amyloid in neurodegeneration in other disorders, including Alzheimer disease. PMID:18410407

  7. Mesenteric amyloid deposition as the initial presentation of multiple myeloma

    PubMed Central

    Asadi, Mehrnaz

    2011-01-01

    Despite many recent progresses in diagnostic modalities, occasionally the initial manifestation of the diseases may be misleading. Therefore, to consider the uncommon presentations of prevalent diseases may be of help. Plasma-cell dyscrasia is one of the most well-known haematological malignancies. Clonal expansion of plasma cells results in diverse clinical findings, such as renal failure, lytic bone lesion, anaemia, hyperviscosity syndrome and so forth. However, this disease entity rarely presents with abdominal mass due to mesenteric amyloid deposition. Here we report a case of a 53-year-old Iranian woman who presented with a 4-month history of abdominal pain and fullness; she was finally found to suffer from small bowel mesenteric amyloidosis in the context of multiple myeloma. PMID:22714598

  8. Distinct binding of amyloid imaging ligands to unique amyloiddeposited in the presubiculum of Alzheimer's disease.

    PubMed

    Ji, Bin; Chen, Chun-Jen; Bando, Kazunori; Ashino, Hiroki; Shiraishi, Hideaki; Sano, Hiroaki; Kasahara, Hiroyuki; Minamizawa, Takao; Yamada, Kazutaka; Ono, Maiko; Zhang, Ming-Rong; Seki, Chie; Farde, Lars; Suhara, Tetsuya; Higuchi, Makoto

    2015-12-01

    Non-invasive determination of amyloid-β peptide (Aβ) deposition with radioligands serves for the early diagnosis and clarification of pathogenetic mechanisms of Alzheimer's disease (AD). The polymorphic binding site on multimeric Aβ for current radioligands, however, is little understood. In this study, we investigated the binding of several radioligands including (11)C-Pittsburgh Compound B ((11)C-PiB), (3)H-AZD2184, and two recently developed compounds, (125)I-DRM106 and (125)I-DRK092, with unique presubicular Aβ deposits lacking interaction with the commonly used amyloid dyes FSB. (11)C-PiB, (3)H-AZD2184, and (125)I-DRK092 showed overt binding to presubicular Aβ deposits, while (125)I-DRM106 barely bound to these aggregates despite its strong binding in the hippocampal CA1 sector. Unlike neuritic plaques in the CA1, Aβ lesions in the presubiculum were not accompanied by inflammatory gliosis enriched with 18-kDa translocator protein (TSPO). Thus, there are at least two different components in Aβ aggregates providing distinct binding sites for the current amyloid radioligands, and one of these binding components is distinctly present in the presubicular Aβ deposits. Amyloid radioligands lacking affinity for this component, such as (125)I-DRM106, may selectively capture Aβ deposits tightly associated with TSPO neuroinflammation and neurodegeneration as exemplified by CA1 neuritic plaques. Hence, comparative autoradiographic assessments of radioligand binding in CA1 and presubiculum could serve for the development of an amyloid PET imaging agent visualizing neurotoxicity-related Aβ pathologies. Non-invasive determination of amyloid-β peptide (Aβ) serves for the early diagnosis and clarification of pathogenetic mechanisms of Alzheimer's disease (AD). We found that there are at least two different amyloid components in hippocampal CA1 and presubiculum providing distinct binding sites for the current amyloid radioligands. Comparative analysis for

  9. Electron tomography reveals the fibril structure and lipid interactions in amyloid deposits.

    PubMed

    Kollmer, Marius; Meinhardt, Katrin; Haupt, Christian; Liberta, Falk; Wulff, Melanie; Linder, Julia; Handl, Lisa; Heinrich, Liesa; Loos, Cornelia; Schmidt, Matthias; Syrovets, Tatiana; Simmet, Thomas; Westermark, Per; Westermark, Gunilla T; Horn, Uwe; Schmidt, Volker; Walther, Paul; Fändrich, Marcus

    2016-05-17

    Electron tomography is an increasingly powerful method to study the detailed architecture of macromolecular complexes or cellular structures. Applied to amyloid deposits formed in a cell culture model of systemic amyloid A amyloidosis, we could determine the structural morphology of the fibrils directly in the deposit. The deposited fibrils are arranged in different networks, and depending on the relative fibril orientation, we can distinguish between fibril meshworks, fibril bundles, and amyloid stars. These networks are frequently infiltrated by vesicular lipid inclusions that may originate from the death of the amyloid-forming cells. Our data support the role of nonfibril components for constructing fibril deposits and provide structural views of different types of lipid-fibril interactions. PMID:27140609

  10. Serum amyloid A1 levels and amyloid deposition following a high-fat diet challenge in transgenic mice overexpressing hepatic serum amyloid A1.

    PubMed

    Jang, Woo Young; Jeong, Jain; Kim, Seonggon; Kang, Min-Cheol; Sung, Yong Hun; Choi, Minjee; Park, Si Jun; Kim, Myoung Ok; Kim, Sung Hyun; Ryoo, Zae Young

    2016-06-01

    Serum amyloid A (SAA) is an acute-phase response protein in the liver, and SAA1 is the major precursor protein involved in amyloid A amyloidosis. This amyloidosis has been reported as a complication in chronic inflammatory conditions such as arthritis, lupus, and Crohn's disease. Obesity is also associated with chronic, low-grade inflammation and sustained, elevated levels of SAA1. However, the contribution of elevated circulating SAA1 to metabolic disturbances and their complications is unclear. Furthermore, in several recent studies of transgenic (TG) mice overexpressing SAA1 that were fed a high-fat diet (HFD) for a relatively short period, no relationship was found between SAA1 up-regulation and metabolic disturbances. Therefore, we generated TG mice overexpressing SAA1 in the liver, challenged these mice with an HFD, and investigated the influence of elevated SAA1 levels. Sustained, elevated levels of SAA1 were correlated with metabolic parameters and local cytokine expression in the liver following 16 weeks on the HFD. Moreover, prolonged consumption (52 weeks) of the HFD was associated with impaired glucose tolerance and elevated SAA1 levels and resulted in systemic SAA1-derived amyloid deposition in the kidney, liver, and spleen of TG mice. Thus, we concluded that elevated SAA1 levels under long-term HFD exposure result in extensive SAA1-derived amyloid deposits, which may contribute to the complications associated with HFD-induced obesity and metabolic disorders. PMID:27218680

  11. Phosphorylation modifies the molecular stability of β-amyloid deposits

    NASA Astrophysics Data System (ADS)

    Rezaei-Ghaleh, Nasrollah; Amininasab, Mehriar; Kumar, Sathish; Walter, Jochen; Zweckstetter, Markus

    2016-04-01

    Protein aggregation plays a crucial role in neurodegenerative diseases. A key feature of protein aggregates is their ubiquitous modification by phosphorylation. Little is known, however, about the molecular consequences of phosphorylation of protein aggregates. Here we show that phosphorylation of β-amyloid at serine 8 increases the stability of its pathogenic aggregates against high-pressure and SDS-induced dissociation. We further demonstrate that phosphorylation results in an elevated number of hydrogen bonds at the N terminus of β-amyloid, the region that is critically regulated by a variety of post-translational modifications. Because of the increased lifetime of phosphorylated β-amyloid aggregates, phosphorylation can promote the spreading of β-amyloid in Alzheimer pathogenesis. Our study suggests that regulation of the molecular stability of protein aggregates by post-translational modifications is a crucial factor for disease progression in the brain.

  12. Phosphorylation modifies the molecular stability of β-amyloid deposits

    PubMed Central

    Rezaei-Ghaleh, Nasrollah; Amininasab, Mehriar; Kumar, Sathish; Walter, Jochen; Zweckstetter, Markus

    2016-01-01

    Protein aggregation plays a crucial role in neurodegenerative diseases. A key feature of protein aggregates is their ubiquitous modification by phosphorylation. Little is known, however, about the molecular consequences of phosphorylation of protein aggregates. Here we show that phosphorylation of β-amyloid at serine 8 increases the stability of its pathogenic aggregates against high-pressure and SDS-induced dissociation. We further demonstrate that phosphorylation results in an elevated number of hydrogen bonds at the N terminus of β-amyloid, the region that is critically regulated by a variety of post-translational modifications. Because of the increased lifetime of phosphorylated β-amyloid aggregates, phosphorylation can promote the spreading of β-amyloid in Alzheimer pathogenesis. Our study suggests that regulation of the molecular stability of protein aggregates by post-translational modifications is a crucial factor for disease progression in the brain. PMID:27072999

  13. Beta-protein deposition: a pathogenetic link between Alzheimer's disease and cerebral amyloid angiopathies.

    PubMed

    Coria, F; Prelli, F; Castaño, E M; Larrondo-Lillo, M; Fernandez-Gonzalez, J; van Duinen, S G; Bots, G T; Luyendijk, W; Shelanski, M L; Frangione, B

    1988-10-25

    Cerebral amyloid angiopathy (CAA) refers to a group of hereditary (hereditary cerebral hemorrhage with amyloidosis, HCHWA and sporadic (SCAA) disorders characterized by amyloid fibril deposition restricted to the leptomeningeal and cortical vasculature leading to recurrent hemorrhagic and/or ischemic accidents. On clinical and biochemical grounds, two forms of HCHWA can be distinguished. The amyloid subunit of the HCHWA of Icelandic origin is related to Cystatin C, while amyloid from patients of Dutch origin (HCHWA-D) is related to the beta-protein (or A4), the main component of vascular and plaque core amyloid in Alzheimer's disease (AD) and Down's syndrome (DS) [corrected]. SCAA is an increasingly recognized cause of stroke in normotensive individual amounting to 5-10% of all cerebrovascular accidents. We now report the isolation and partial amino acid sequence of the amyloid subunit from a case of SCAA and a new case of HCHWA-D. The recognition that a heterogeneous group of diseases are linked by similar pathological and chemical features suggests that diversity of etiological factors may promote a common pathogenetic mechanism leading to amyloid-beta (A beta) deposition, and open new ways of research in AD and CAA as they are related to dementia and stroke. PMID:3058268

  14. Imbalance in Fatty-Acid-Chain Length of Gangliosides Triggers Alzheimer Amyloid Deposition in the Precuneus

    PubMed Central

    Oikawa, Naoto; Matsubara, Teruhiko; Fukuda, Ryoto; Yasumori, Hanaki; Hatsuta, Hiroyuki; Murayama, Shigeo; Sato, Toshinori; Suzuki, Akemi; Yanagisawa, Katsuhiko

    2015-01-01

    Amyloid deposition, a crucial event of Alzheimer’s disease (AD), emerges in distinct brain regions. A key question is what triggers the assembly of the monomeric amyloid ß-protein (Aß) into fibrils in the regions. On the basis of our previous findings that gangliosides facilitate the initiation of Aß assembly at presynaptic neuritic terminals, we investigated how lipids, including gangliosides, cholesterol and sphingomyelin, extracted from synaptic plasma membranes (SPMs) isolated from autopsy brains were involved in the Aß assembly. We focused on two regions of the cerebral cortex; precuneus and calcarine cortex, one of the most vulnerable and one of the most resistant regions to amyloid deposition, respectively. Here, we show that lipids extracted from SPMs isolated from the amyloid-bearing precuneus, but neither the amyloid-free precuneus nor the calcarine cortex, markedly accelerate the Aß assembly in vitro. Through liquid chromatography-mass spectrometry of the lipids, we identified an increase in the ratio of the level of GD1b-ganglioside containing C20:0 fatty acid to that containing C18:0 as a cause of the enhanced Aß assembly in the precuneus. Our results suggest that the local glycolipid environment play a critical role in the initiation of Alzheimer amyloid deposition. PMID:25798597

  15. Inhibition of Insulin-Degrading Enzyme Does Not Increase Islet Amyloid Deposition in Vitro.

    PubMed

    Hogan, Meghan F; Meier, Daniel T; Zraika, Sakeneh; Templin, Andrew T; Mellati, Mahnaz; Hull, Rebecca L; Leissring, Malcolm A; Kahn, Steven E

    2016-09-01

    Islet amyloid deposition in human type 2 diabetes results in β-cell loss. These amyloid deposits contain the unique amyloidogenic peptide human islet amyloid polypeptide (hIAPP), which is also a known substrate of the protease insulin-degrading enzyme (IDE). Whereas IDE inhibition has recently been demonstrated to improve glucose metabolism in mice, inhibiting it has also been shown to increase cell death when synthetic hIAPP is applied exogenously to a β-cell line. Thus, we wanted to determine whether a similar deleterious effect is observed when hIAPP is endogenously produced and secreted from islets. To address this issue, we cultured hIAPP transgenic mouse islets that have the propensity to form amyloid for 48 and 144 hours in 16.7 mM glucose in the presence and absence of the IDE inhibitor 1. At neither time interval did IDE inhibition increase amyloid formation or β-cell loss. Thus, the inhibition of IDE may represent an approach to improve glucose metabolism in human type 2 diabetes, without inducing amyloid deposition and its deleterious effects. PMID:27404391

  16. Late gadolinium enhancement in cardiac amyloidosis: attributable both to interstitial amyloid deposition and subendocardial fibrosis caused by ischemia.

    PubMed

    Hashimura, Hiromi; Ishibashi-Ueda, Hatsue; Yonemoto, Yumiko; Ohta-Ogo, Keiko; Matsuyama, Taka-Aki; Ikeda, Yoshihiko; Morita, Yoshiaki; Yamada, Naoaki; Yasui, Hiroki; Naito, Hiroaki

    2016-06-01

    Gadolinium contrast agents used for late gadolinium enhancement (LGE) distribute in the extracellular space. Global diffuse myocardial LGE pronounced in the subendocardial layers is common in cardiac amyloidosis. However, the pathophysiological basis of these findings has not been sufficiently explained. A 64-year-old man was admitted to our hospital with leg edema and nocturnal dyspnea. Bence Jones protein was positive in the urine, and an endomyocardial and skin biopsy showed light-chain (AL) amyloidosis. He died of ventricular fibrillation 3 months later. 9 days before death, the patient was examined by cardiac magnetic resonance (CMR) imaging on a 3-T system. We acquired LGE data at 2, 5, 10, and 20 min after the injection of gadolinium contrast agents, with a fixed inversion time of 350 ms. Myocardial LGE developed sequentially. The myocardium was diffusely enhanced at 2 min, except for the subendocardium, but LGE had extended to almost the entire left ventricle at 5 min and predominantly localized to the subendocardial region at 10 and 20 min. An autopsy revealed massive and diffused amyloid deposits in perimyocytes throughout the myocardium. Old and recent ischemic findings, such as replacement fibrosis and coagulative myocyte necrosis, were evident in the subendocardium. In the intramural coronary arteries, mild amyloid deposits were present within the subepicardial to the mid layer of the left ventricle, but no stenotic lesions were evident. However, capillaries were obstructed by amyloid deposits in the subendocardium. In conclusion, the late phase of dynamic LGE (at 10 and 20 min) visualized in the subendocardium corresponded to the interstitial amyloid deposition and subendocardial fibrosis caused by ischemia in our patient. PMID:25794983

  17. Cerebral amyloid angiopathy

    MedlinePlus

    Cerebral amyloid angiopathy is a neurological condition in which proteins called amyloid build up on the walls of the arteries ... The cause of cerebral amyloid angiopathy is unknown. Sometimes, it ... Persons with this condition have deposits of amyloid protein ...

  18. CX3CR1 in microglia regulates brain amyloid deposition through selective protofibrillar Aβ phagocytosis

    PubMed Central

    Liu, Zhiqiang; Condello, Carlo; Schain, Aaron; Harb, Roa; Grutzendler, Jaime

    2010-01-01

    In Alzheimer’s disease (AD), amyloid-β (Aβ) deposits are frequently surrounded by activated microglia but the precise role of these cells in disease progression remains unclear. The chemokine receptor CX3CR1 is selectively expressed in microglia and is thought to modulate their activity. To study the specific effects of microglia activation on amyloid pathology in vivo, we crossbred mice lacking CX3CR1 with the Alzheimer’s mouse model CRND8. Surprisingly, we found that CX3CR1 deficient mice had lower brain levels of Aβ40 and Aβ42 and reduced amyloid deposits. Quantification of Aβ within microglia and time-lapse two photon microscopy in live mice revealed that these cells were highly effective at the uptake of protofibrillar amyloid but were incapable of phagocytosis of fibrillar congophilic Aβ. CX3CR1 deletion was associated with increased phagocytic ability which led to greater amyloid content within microglial phagolysosomes. Furthermore, CX3CR1 deficient mice had an increased number of microglia around individual plaques due to higher proliferative rates, which likely contributed to an overall greater phagocytic capacity. CX3CR1 deletion did not affect the degree of neuronal or synaptic damage around plaques despite increased microglia density. Our results demonstrate that microglia can regulate brain Aβ levels and plaque deposition via selective protofibrillar Aβ phagocytosis. Modulation of microglia activity and proliferation by CX3CR1 signaling may represent a therapeutic strategy for AD. PMID:21159979

  19. Visual Hallucinations and Amyloid Deposition in Parkinson's Disease Dementia: A Case Report.

    PubMed

    Um, Yoo Hyun; Kim, Tae-Won; Jeong, Jong-Hyun; Seo, Ho-Jun; Han, Jin-Hee; Hong, Seung-Chul; Jung, Won-Sang; Choi, Woo Hee; Lee, Chang-Uk; Lim, Hyun Kook

    2016-05-01

    Parkinson's disease dementia (PDD) is notorious for its debilitating clinical course and high mortality rates. Consequently, various attempts to investigate predictors of cognitive decline in Parkinson's disease (PD) have been made. Here we report a case of a 75-year-old female patient with PD who visited the clinic with complaints of recurrent visual hallucinations and cognitive decline, whose symptoms were ameliorated by the titration of rivastigmine. Imaging results showed pronounced diffuse cortical amyloid deposition evidenced by 18F-florbetaben amyloid positron emission tomography (PET) imaging. This observation suggests that pronounced amyloid deposition and visual hallucinations in PD patients could be clinically significant predictors of cognitive decline in PD patients. Future research should concentrate on accumulating more evidence for possible predictors of cognitive decline and their association with PD pathology that can enable an early intervention and standardized treatment in PDD patients. PMID:27247605

  20. Visual Hallucinations and Amyloid Deposition in Parkinson's Disease Dementia: A Case Report

    PubMed Central

    Um, Yoo Hyun; Kim, Tae-Won; Jeong, Jong-Hyun; Seo, Ho-Jun; Han, Jin-Hee; Hong, Seung-Chul; Jung, Won-Sang; Choi, Woo Hee; Lee, Chang-Uk

    2016-01-01

    Parkinson's disease dementia (PDD) is notorious for its debilitating clinical course and high mortality rates. Consequently, various attempts to investigate predictors of cognitive decline in Parkinson's disease (PD) have been made. Here we report a case of a 75-year-old female patient with PD who visited the clinic with complaints of recurrent visual hallucinations and cognitive decline, whose symptoms were ameliorated by the titration of rivastigmine. Imaging results showed pronounced diffuse cortical amyloid deposition evidenced by 18F-florbetaben amyloid positron emission tomography (PET) imaging. This observation suggests that pronounced amyloid deposition and visual hallucinations in PD patients could be clinically significant predictors of cognitive decline in PD patients. Future research should concentrate on accumulating more evidence for possible predictors of cognitive decline and their association with PD pathology that can enable an early intervention and standardized treatment in PDD patients. PMID:27247605

  1. AZD2184: a radioligand for sensitive detection of beta-amyloid deposits.

    PubMed

    Johnson, Allan E; Jeppsson, Fredrik; Sandell, Johan; Wensbo, David; Neelissen, Jan A M; Juréus, Anders; Ström, Peter; Norman, Henrietta; Farde, Lars; Svensson, Samuel P S

    2009-03-01

    The presence of beta-amyloid plaques in brain is a hallmark of Alzheimer's disease (AD) and serves as a biomarker for confirmation of diagnosis postmortem. Positron emission tomography (PET) radioligands such as Pittsburgh compound B ([(11)C]-2-(3-fluoro-4-methylamino-phenyl)-benzothiazol-6-ol) (PIB) binds selectively to beta-amyloid and are promising new tools supporting the clinical diagnoses of AD. In addition, such methodology may be useful for evaluation of new drugs aiming at reduction of amyloid plaque load. The objective of this study is to develop a new amyloid selective PET radioligand with higher signal-to-background ratio when compared with existing amyloid PET ligands. The lead compound, AZD2184, (2-[6-(methylamino)pyridin-3-yl]-1,3-benzothiazol-6-ol) was found to have high affinity for amyloid fibrils in vitro (K(d): 8.4 +/- 1.0 nM). Two minutes after i.v. administration in rats, about 1% of the dose was in brain. In vitro autoradiography on cortical brain sections from amyloid-beta precursor protein/presenilin 1 (APP/PS1) mice and AD patients showed that while [(3)H]AZD2184 and [(3)H]PIB are mutually displaceable, [(3)H]AZD2184 displays a higher signal-to-background ratio primarily by virtue of lower background binding levels. The ratio of binding ability in prefrontal cortex (high plaque load) to subcortical white matter (background) was 4.5 for [(3)H]AZD2184 and 0.8 for [(3)H]PIB at 1 nM. In adjacent cortical sections from APP/PS1 mouse as well as from AD cortical tissue, [(3)H]AZD2184 and antibodies to human beta-amyloid labeled identical structures. In vivo administration of [(3)H]AZD2184 to APP/PS1 mice further showed that [(3)H]AZD2184 labels amyloid deposits with low non-specific background binding. Taken together, the pre-clinical profile of AZD2184 in relation to the reference ligand PIB, suggests that (11)C-labeled AZD2184 is a potential radioligand for PET-visualization of beta-amyloid deposits in the living human brain. PMID:19141073

  2. Tissue distribution of amyloid deposits in Abyssinian cats with familial amyloidosis.

    PubMed

    DiBartola, S P; Tarr, M J; Benson, M D

    1986-07-01

    The tissue distribution of amyloid deposits was studied in 15 related Abyssinian cats with familial amyloidosis. There was interstitial medullary amyloidosis in the kidneys of all 15 cats but only 11 had detectable glomerular involvement. The thyroid glands, stomach and colon were affected in all cats examined. Most of the cats also had amyloid deposits in the small intestine, spleen, heart, adrenals, pancreas, liver, lymph nodes and bladder. In 50 per cent or fewer of the cats examined, there was involvement of the parathyroids, lung and gonads. The central nervous system was not involved in any of the 3 cats evaluated. In 8 of the cats, no concurrent inflammatory disease could be detected. The tissue distribution of amyloid deposits resembled that found in other breeds of domestic cats with systemic amyloidosis. Despite the wide tissue distribution of amyloid deposits, clinical signs were related to renal amyloidosis. Familial amyloidosis in the Abyssinian cat may represent a valuable spontaneous animal model for the study of Familial Mediterranean Fever in man and the pathogenesis of reactive amyloidosis in general. PMID:3734172

  3. Amyloid deposition in Parkinson Disease and Cognitive Impairment: A Systematic Review

    PubMed Central

    Petrou, Myria; Dwamena, Ben A.; Foerster, Bradley R.; MacEachern, Mark P.; Bohnen, Nicolaas I.; Muller, Martijn; Albin, Roger L.; Frey, Kirk A.

    2015-01-01

    Background Varying degrees of cortical amyloid deposition are reported in the setting of Parkinsonism with cognitive impairment. We performed a systematic review to estimate the prevalence of Alzheimer disease (AD) range cortical amyloid deposition amongst patients with Parkinson disease with dementia (PDD), Parkinson disease with mild cognitive impairment (PD-MCI) and dementia with Lewy bodies (DLB). We included amyloid PET imaging studies using Pittsburgh Compound B (PiB). Methods We searched the databases Ovid MEDLINE, PubMed, Embase, Scopus, and Web of Science for articles pertaining to amyloid imaging in Parkinsonism and impaired cognition. We identified 11 articles using PiB imaging to quantify cortical amyloid. We used the metan module in Stata, version 11.0, to calculate point prevalence estimates of patients with “PiB-positive” studies, ie patients showing AD range cortical Aβ-amyloid deposition. Heterogeneity was assessed. A scatterplot was used to assess publication bias. Results Overall pooled prevalence of “PiB-positive” studies across all three entities along the spectrum of Parkinson disease and impaired cognition (specifically PDD, PD-MCI and DLB) was 0.41 (95% CI 0.24-0.57). Prevalence of “PiB-positive” studies was 0.68 (95% CI 0.55-0.82) in the DLB group, 0.34 (95% CI 0.13-0.56) in the PDD group and 0.05 (95% CI -0.07-0.17) in the PD-MCI group. Conclusion There is substantial variability in the prevalence of “PiB-positive” studies in subjects with Parkinsonism and cognitive impairment. Higher prevalence of PiB positive studies was encountered among subjects with DLB as opposed to subjects with PDD. PD-MCI subjects showed overall lower prevalence of PiB positive studies than reported findings in non-PD related MCI. PMID:25879534

  4. Early cortical thickness changes predict β-amyloid deposition in a mouse model of Alzheimer's disease.

    PubMed

    Grand'maison, Marilyn; Zehntner, Simone P; Ho, Ming-Kai; Hébert, François; Wood, Andrew; Carbonell, Felix; Zijdenbos, Alex P; Hamel, Edith; Bedell, Barry J

    2013-06-01

    Magnetic resonance imaging (MRI) studies have identified aberrant cortical structure in Alzheimer's disease (AD). The association between MRI-derived cortical morphometry measures and β-amyloid, however, remains poorly understood. In this study, we explored the potential relationship between early alterations in cortical thickness and later stage β-amyloid deposition, using a novel approach, in a transgenic AD mouse model. We acquired longitudinal anatomical MRI scans from mutant amyloid precursor protein (APP) transgenic mice and age-matched wild-type mice at 1 and 3.5months-of-age, and employed fully-automated image processing methods to derive objective, quantitative measures of cortical thickness on a region-of-interest basis. We also generated 3D quantitative immunohistochemistry (qIHC) volumes of deposited β-amyloid burden from 18month-old transgenic mice using an automated, production-level process. These studies revealed thinner cortex in most regions in the 1month-old transgenic mice relative to age-matched wild-types, with the exception of the frontal, perirhinal/entorhinal, posterior cingulate, and retrosplenial cortical regions. Between 1 and 3.5months-of-age, the transgenic mice demonstrated stable or increasing cortical thickness, while the wild-type mice showed cortical thinning. Based on data from co-registered 3D MRI and qIHC volumes, we identified an association between abnormal, early, regional cortical thickness change over 2.5months and later β-amyloid deposition. These observations suggest that the spatio-temporal pattern of early (pre-plaque) alterations in cerebral cortical structure is indicative of regional predisposition to later β-amyloid pathology in a transgenic AD mouse model. PMID:23454197

  5. Beta-Amyloid Deposition and Alzheimer's Type Changes Induced by Borrelia Spirochetes

    SciTech Connect

    Miklossy,J.; Kis, A.; Radenovic, A.; Miller, L.; Forro, L.; Martins, R.; Reiss, K.; Darbinian, N.; Darekar, P.; et al.

    2006-01-01

    The pathological hallmarks of Alzheimer's disease (AD) consist of {beta}-amyloid plaques and neurofibrillary tangles in affected brain areas. The processes, which drive this host reaction are unknown. To determine whether an analogous host reaction to that occurring in AD could be induced by infectious agents, we exposed mammalian glial and neuronal cells in vitro to Borrelia burgdorferi spirochetes and to the inflammatory bacterial lipopolysaccharide (LPS). Morphological changes analogous to the amyloid deposits of AD brain were observed following 2-8 weeks of exposure to the spirochetes. Increased levels of {beta}-amyloid presursor protein (A{beta}PP) and hyperphosphorylated tau were also detected by Western blots of extracts of cultured cells that had been treated with spirochetes or LPS. These observations indicate that, by exposure to bacteria or to their toxic products, host responses similar in nature to those observed in AD may be induced.

  6. Luteinizing hormone, a reproductive regulator that modulates the processing of amyloid-beta precursor protein and amyloid-beta deposition.

    PubMed

    Bowen, Richard L; Verdile, Giuseppe; Liu, Tianbing; Parlow, Albert F; Perry, George; Smith, Mark A; Martins, Ralph N; Atwood, Craig S

    2004-05-01

    Hormonal changes associated with the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis following menopause/andropause have been implicated in the pathogenesis of Alzheimer's disease (AD). Experimental support for this has come from studies demonstrating an increase in amyloid-beta (Abeta) deposition following ovariectomy/castration. Because sex steroids and gonadotropins are both part of the HPG feedback loop, any loss in sex steroids results in a proportionate increase in gonadotropins. To assess whether Abeta generation was due to the loss of serum 17beta-estradiol or to the up-regulation of serum gonadotropins, we treated C57Bl/6J mice with the anti-gonadotropin leuprolide acetate, which suppresses both sex steroids and gonadotropins. Leuprolide acetate treatment resulted in a 3.5-fold (p < 0.0001) and a 1.5-fold (p < 0.024) reduction in total brain Abeta1-42 and Abeta1-40 concentrations, respectively, after 8 weeks of treatment. To further explore the role of gonadotropins in promoting amyloidogenesis, M17 neuroblastoma cells were treated with the gonadotropin luteinizing hormone (LH) at concentrations equivalent to early adulthood (10 mIU/ml) or post-menopause/andropause (30 mIU/ml). LH did not alter amyloid-beta precursor protein (AbetaPP) expression but did alter AbetaPP processing toward the amyloidogenic pathway as evidenced by increased secretion and insolubility of Abeta, decreased alphaAbetaPP secretion, and increased AbetaPP-C99 levels. These results suggest the marked increases in serum LH following menopause/andropause as a physiologically relevant signal that could promote Abeta secretion and deposition in the aging brain. Suppression of the age-related increase in serum gonadotropins using anti-gonadotropin agents may represent a novel therapeutic strategy for AD. PMID:14871891

  7. Distribution of amyloid deposits in the kidneys of a patient with reactive amyloidosis associated with rheumatoid arthritis

    PubMed Central

    2013-01-01

    Background We previously reported that the amount of amyloid A (AA) amyloid deposited in renal biopsy specimens was highly correlated with parameters of renal function. However, the distribution of amyloid deposits throughout the kidneys of these patients, and the degree of renal abnormality, remained unclear. Therefore, we describe the features of reactive amyloidosis associated with rheumatoid arthritis (RA) in an autopsied patient. Case presentation The present report case is a 50-year-old female with RA and reactive amyloidosis. She was diagnosed as RA in 1978. Diagnosis of AA amylodosis was made by renal biopsy in 1991 for the reason of proteinuria. Because of the pancreatitis, she was died in 2006 and autopsy was performed. Renal tissues from autopsy specimens were evaluated for their proportions of amyloid-positive areas. A total of 6 specimens (three tissue blocks from each kidney obtained at autopsy) were evaluated in this study. The size of each block was approximately 20 mm × 20 mm. One section of whole tissue was photographed in each case. The borders of the amyloid-positive areas in each specimen were traced in each photograph, excluding any tissue-free spaces. The total amyloid-positive area was measured, and the percentage area of amyloid per whole-tissue section (percent (%) area of amyloid deposition) was calculated. The distribution of amyloid deposits in the kidneys was examined. The significance of differences in the mean percent (%) area of amyloid deposition between the right and left sides and among three long-axis levels (upper, middle and lower) were analyzed by two-way analysis of variance (ANOVA) at a significance level of p <0.05. Conclusion The area of amyloid deposition in these samples was about 7-11%, and the degree of variability among them seemed to be small. It also shows a comparison of amyloid deposition between the right and left sides and between the long axis samples for quadruplicate determinations; no significant

  8. Exercise engagement as a moderator of APOE effects on amyloid deposition

    PubMed Central

    Head, Denise; Bugg, Julie M.; Goate, Alison M.; Fagan, Anne M.; Mintun, Mark A.; Benzinger, Tammie; Holtzman, David M.; Morris, John C.

    2012-01-01

    Objective APOE ε4 status has been associated with greater cortical amyloid deposition whereas exercise has been associated with less in cognitively normal adults. The primary objective here was to examine whether physical exercise moderates the association between APOE genotype and amyloid deposition in cognitively normal adults. Method APOE genotyping and a questionnaire on physical exercise engagement over the last decade were obtained in conjunction with cerebrospinal fluid (CSF) samples and amyloid imaging with PET-PIB. Participants were classified as either low or high exercisers based on exercise guidelines of the American Heart Association. Subjects 201 cognitively normal adults (135 females) aged 45–88 were recruited from the Knight Alzheimer Disease Research Center at Washington University. CSF samples were collected from 165 participants. Amyloid imaging was performed on 163 participants. Results APOE ε4 carriers evidenced higher PIB binding (p<.001) and lower CSF Aβ42 levels (p<.001) than non-carriers. Our previous findings of higher PIB binding (p=.005) and lower CSF Aβ42 levels (p=.009) in more sedentary individuals were replicated. Most importantly, we observed a novel interaction between APOE status and exercise engagement for PIB binding (p=.008) such that a more sedentary lifestyle was significantly associated with higher PIB binding for ε4 carriers (p=.013) but not for ε4 non-carriers (p=.208). All findings remained significant after controlling for age, gender, education, hypertension, body mass index, diabetes, heart problems, history of depression and interval between assessments. Conclusion Collectively, these results suggest that cognitively normal sedentary APOE ε4+ individuals may be at augmented risk for cerebral amyloid deposition. PMID:22232206

  9. Beta amyloid and hyperphosphorylated tau deposits in the pancreas in type 2 diabetes

    SciTech Connect

    Miklossy, J.; Miller, L.; Qing, H.; Radenovic, A.; Kis, A.; Vileno, B.; Laszlo, F.; Martins, R.N.; Waeber, G.; Mooser, V.; Bosman, F.; Khalili, K.; Darbinian, N.; McGeer, P.L.

    2008-08-25

    Strong epidemiologic evidence suggests an association between Alzheimer disease (AD) and type 2 diabetes. To determine if amyloid beta (A{beta}) and hyperphosphorylated tau occurs in type 2 diabetes, pancreas tissues from 21 autopsy cases (10 type 2 diabetes and 11 controls) were analyzed. APP and tau mRNAs were identified in human pancreas and in cultured insulinoma beta cells (INS-1) by RT-PCR. Prominent APP and tau bands were detected by Western blotting in pancreatic extracts. Aggregated A{beta}, hyperphosphorylated tau, ubiquitin, apolipoprotein E, apolipoprotein(a), IB1/JIP-1 and JNK1 were detected in Langerhans islets in type 2 diabetic patients. A{beta} was co-localized with amylin in islet amyloid deposits. In situ beta sheet formation of islet amyloid deposits was shown by infrared microspectroscopy (SIRMS). LPS increased APP in non-neuronal cells as well. We conclude that A{beta} deposits and hyperphosphorylated tau are also associated with type 2 diabetes, highlighting common pathogenetic features in neurodegenerative disorders, including AD and type 2 diabetes and suggesting that A{beta} deposits and hyperphosphorylated tau may also occur in other organs than the brain.

  10. Delayed Amyloid Plaque Deposition and Behavioral Deficits in Outcrossed AβPP/PS1 Mice

    PubMed Central

    Couch, Brian A.; Kerrisk, Meghan E.; Kaufman, Adam C.; Nygaard, Haakon B.; Strittmatter, Stephen M.; Koleske, Anthony J.

    2012-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4–9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment is delayed considerably in outcrossed AβPP/PS1 mice relative to inbred mice on a C57BL/6 background. While inbred AβPP/PS1 mice develop deficits in radial-arm water maze performance and novel object recognition as early as 8 months, outcrossed AβPP/PS1 mice do not display defects until 18 months. Within the forebrain, we find that inbred AβPP/PS1 mice have significantly higher amyloid plaque burden at 12 months than outcrossed AβPP/PS1 mice of the same age. Surprisingly, inbred AβPP/PS1 mice at 8 months have low plaque burden suggesting that plaque burden alone cannot explain the accompanying behavioral deficits. Analysis of AβPP processing revealed that elevated levels of soluble Aβ correlate with the degree of behavioral impairment in both strains. Taken together, these findings suggest that animal behavior, amyloid plaque deposition, and AβPP processing are sensitive to genetic differences between mouse strains. PMID:23047754

  11. Alzheimer Precursor Protein Interaction with the Nogo-66 Receptor Reduces Amyloid-β Plaque Deposition

    PubMed Central

    Park, James H.; Gimbel, David A.; GrandPre, Tadzia; Lee, Jung-Kil; Kim, Ji-Eun; Li, Weiwei; Lee, Daniel H. S.; Strittmatter, Stephen M.

    2010-01-01

    Pathophysiologic hypotheses for Alzheimer’s disease (AD) are centered on the role of the amyloid plaque Aβpeptide and the mechanism of its derivation from the amyloid precursor protein (APP). As part of the disease process, an aberrant axonal sprouting response is known to occur near Aβ deposits. A Nogo to Nogo-66 receptor (NgR) pathway contributes to determining the ability of adult CNS axons to extend after traumatic injuries. Here, we consider the potential role of NgR mechanisms in AD. Both Nogo and NgR are mislocalized in AD brain samples. APP physically associates with the NgR. Overexpression of NgR decreases Aβ production in neuroblastoma culture, and targeted disruption of NgR expression increases transgenic mouse brain Aβ levels, Aβ plaque deposition, and dystrophic neurites. Infusion of a soluble NgR fragment reduces Aβlevels, amyloid plaque deposits, and dystrophic neurites in a mouse transgenic AD model. Changes in NgR level produce parallel changes in secreted APPαand Aβ, implicating NgR as a blocker of secretase processing of APP. The NgR provides a novel site for modifying the course of AD and highlights the role of axonal dysfunction in the disease. PMID:16452662

  12. Extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum.

    PubMed

    Carneiro, Fabiana Pirani; Sobreira, Maria Nazareth Machado; Maia, Lívia Bravo; Sartorelli, Alesso Cervantes; Franceschi, Luiz Eduardo de Almeida Prado; Brandão, Mauro Brito; Calaça, Bárbara Wosnjuk; Lustosa, Fernando Silva; Lopes, João Vieira

    2009-07-28

    We report a rare case of extramedullary plasmocytoma associated with a massive deposit of amyloid in the duodenum. A 72-year-old Japanese man was admitted to our hospital presenting with a 3-mo history of epigastric pain, vomiting and weight loss. On computed tomography (CT) a wall thickening of the fourth part of the duodenum was observed. Multiple biopsies obtained from the lesion showed infiltration of plasma cells and lymphocytes, but they were not conclusive. The patient underwent resection of the lesion and, on histopathological examination, the lesion consisted of a dense and diffuse infiltrate of plasma cells and a few admixed lymphocytes with reactive follicles extending to the muscular propria. An extensive deposition of amyloid was also observed. Immunohistochemical stains revealed that a few plasmacytoid cells showed lambda light chain staining, though most were kappa light chain positive. These cells also were positive for CD138 and CD56 but negative for CD20 and CD79. The findings were consistent with extramedullary plasmocytoma associated with a massive deposit of amyloid in duodenum. A subsequent workup for multiple myeloma was completely negative. The patient showed no signs of local recurrence or dissemination of the disease after 12 mo follow-up. Because of the association of plasmocytoma and amyloidosis, the patient must be followed up because of the possible systemic involvement of the neoplasm and amyloidosis in future. PMID:19630116

  13. Occurrence of extensive spherical amyloid deposits in a prolactin-secreting pituitary macroadenoma: a radiologic-pathologic correlation.

    PubMed

    Levine, Steven N; Ishaq, Shmaila; Nanda, Anil; Wilson, Jon D; Gonzalez-Toledo, Eduardo

    2013-08-01

    Pituitary adenomas are the most common tumors of the sellar region, but the occurrence of spherical amyloid deposits in a pituitary adenoma is rare. We describe the clinical features, radiologic characteristics, and pathologic findings of 45-year-old man who presented with galactorrhea, hypogonadism, and hyperprolactinemia who had a pituitary adenoma with extensive spherical amyloid deposits. Approximately 30 cases have been reported, almost exclusively in patients with prolactinomas. Treatment with dopaminergic agonists will result in the expected reduction in prolactin levels; however, in most cases, macroadenomas with spherical amyloid deposits fail to decrease in size. The source of the amyloid deposits in prolactinomas is not clearly defined but may be due to abnormal processing of prolactin or its prohormone. These adenomas with spherical amyloid have a characteristic appearance on magnetic resonance imaging with low or heterogeneous intensity on T1 and low intensity on T2-weighted images. Following infusion of gadolinium, there is enhancement of the periphery but not most of the tumor mass. These magnetic resonance imaging characteristics are different than those of typical pituitary adenomas. These differences should alert clinicians to the possibility of extensive spherical amyloid deposits in a prolactin-secreting pituitary adenoma, which may have important clinical implications. In this report, we correlate the radiologic finds with the pathology and compared them with other sellar and parasellar lesions. PMID:23602507

  14. Neural compensation in older people with brain β-amyloid deposition

    PubMed Central

    Elman, Jeremy A.; Oh, Hwamee; Madison, Cindee M.; Baker, Suzanne L.; Vogel, Jacob W.; Marks, Shawn M.; Crowley, Sam; O'Neil, James P.; Jagust, William J.

    2014-01-01

    The recruitment of additional neural resources may allow elderly adults to maintain normal cognition despite β-amyloid (Aβ) plaques. Previous fMRI studies have reported such hyperactivation, but it is currently unclear if these increases represent compensation or aberrant over-excitation. We found that older adults with Aβ deposition had reduced deactivations in task negative regions, but increased activation in task positive regions related to more detailed memory encoding. The association between higher activity levels and more detailed memories suggests that Aβ-related hyperactivation is a compensatory mechanism, potentially reflecting brain plasticity in response to Aβ deposition. PMID:25217827

  15. Dissociation between Brain Amyloid Deposition and Metabolism in Early Mild Cognitive Impairment

    PubMed Central

    Wu, Liyong; Rowley, Jared; Mohades, Sara; Leuzy, Antoine; Dauar, Marina Tedeschi; Shin, Monica; Fonov, Vladimir; Jia, Jianping; Gauthier, Serge; Rosa-Neto, Pedro

    2012-01-01

    Background The hypothetical model of dynamic biomarkers for Alzheimer’s disease (AD) describes high amyloid deposition and hypometabolism at the mild cognitive impairment (MCI) stage. However, it remains unknown whether brain amyloidosis and hypometabolism follow the same trajectories in MCI individuals. We used the concept of early MCI (EMCI) and late MCI (LMCI) as defined by the Alzheimer’s disease Neuroimaging Initiative (ADNI)-Go in order to compare the biomarker profile between EMCI and LMCI. Objectives To examine the global and voxel-based neocortical amyloid burden and metabolism among individuals who are cognitively normal (CN), as well as those with EMCI, LMCI and mild AD. Methods In the present study, 354 participants, including CN (n = 109), EMCI (n = 157), LMCI (n = 39) and AD (n = 49), were enrolled between September 2009 and November 2011 through ADNI-GO and ADNI-2. Brain amyloid load and metabolism were estimated using [18F]AV45 and [18F]fluorodeoxyglucose ([18F]FDG) PET, respectively. Uptake ratio images of [18F]AV45 and [18F]FDG were calculated by dividing the summed PET image by the median counts of the grey matter of the cerebellum and pons, respectively. Group differences of global [18F]AV45 and [18F]FDG were analyzed using ANOVA, while the voxel-based group differences were estimated using statistic parametric mapping (SPM). Results EMCI patients showed higher global [18F]AV45 retention compared to CN and lower uptake compared to LMCI. SPM detected higher [18F]AV45 uptake in EMCI compared to CN in the precuneus, posterior cingulate, medial and dorsal lateral prefrontal cortices, bilaterally. EMCI showed lower [18F]AV45 retention than LMCI in the superior temporal, inferior parietal, as well as dorsal lateral prefrontal cortices, bilaterally. Regarding to the global [18F]FDG, EMCI patients showed no significant difference from CN and a higher uptake ratio compared to LMCI. At the voxel level, EMCI showed higher metabolism in

  16. A nontransgenic mouse model shows inducible amyloid-β (Aβ) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade

    PubMed Central

    Dolev, Iftach; Michaelson, Daniel M.

    2004-01-01

    The amyloid-β (Aβ) peptide, a major pathological hallmark of Alzheimer's disease (AD), undergoes a cascade of interactions resulting in the formation of soluble aggregates and their conversion in the brain to insoluble deposits and mature senile plaques. Furthermore, the apoE4 isoform of apolipoprotein E (apoE), which is the major genetic risk factor of AD, is associated with increased Aβ deposition. It is not known how the different Aβ aggregates in the amyloid cascade are formed, contribute to the pathogenesis of AD, or are affected by apoE4. To investigate the initial aggregation stages underlying the amyloid cascade in vivo and how apoE affects them, we examined the effects of prolonged inhibition and subsequent reactivation of the Aβ-degrading protease neprilysin on deposition, disaggregation, and fibrillization of Aβ in apoE-transgenic and control mice. In control mice, intracerebroventricular infusion of thiorphan, which inhibits neprilysin, induced Aβ42 and Aβ40 deposition and fibrillization. On termination of thiorphan treatment, the number of Aβ deposits decreased, whereas the fibrillar Aβ deposits were unaffected. Similar treatments in apoE-deficient mice and mice transgenic for human apoE4 or apoE3 revealed that apoE4 enhances specifically the nucleation and aggregation of immunopositive Aβ deposits and that reversible disaggregation of these deposits and their irreversible conversion to fibrillar deposits are stimulated similarly by the different apoE isoforms. Deposition of Aβ and its enhancement by apoE4 were accompanied by increased astrogliosis both far from and near the Aβ deposits, suggesting that astrogliosis might be triggered by both insoluble and soluble Aβ aggregates. PMID:15365176

  17. Progranulin Protects against Amyloid β Deposition and Toxicity in Alzheimer’s Disease Mouse Models

    PubMed Central

    Minami, S. Sakura; Min, Sang-Won; Krabbe, Grietje; Wang, Chao; Zhou, Yungui; Asgarov, Rustam; Li, Yaqiao; Martens, Lauren H.; Elia, Lisa P.; Ward, Michael E.; Mucke, Lennart; Farese, Robert V.; Gan, Li

    2014-01-01

    Haploinsufficiency of progranulin (PGRN) gene (GRN) causes familial frontotemporal lobar degeneration (FTLD), and modulates an innate immune response in humans and mouse models. GRN polymorphism may be linked to late-onset Alzheimer’s disease (AD). However, PRGN’s role in AD pathogenesis is unknown. Here, we show PGRN inhibits amyloid β (Aβ) deposition. Selectively reducing microglial PGRN in AD mice impaired phagocytosis and increased plaque load threefold. Lentivirus-mediated PGRN overexpression lowered plaque load in AD mice with aggressive amyloid plaque pathology. Aβ plaque load correlated negatively with levels of hippocampal PGRN, showing PGRN’s dose-dependent inhibitory effects on plaque deposition. PGRN also protected against Aβ toxicity. Reducing microglial PGRN exacerbated cognitive deficits in AD mice. Lentivirus-mediated PGRN overexpression prevented spatial memory deficits and hippocampal neuronal loss in AD mice. PGRN’s protective effects against Aβ deposition and toxicity have important therapeutic implications. We propose enhancing PGRN as a potential treatment for PGRN-deficient FTD and AD. PMID:25261995

  18. Progranulin protects against amyloid β deposition and toxicity in Alzheimer's disease mouse models.

    PubMed

    Minami, S Sakura; Min, Sang-Won; Krabbe, Grietje; Wang, Chao; Zhou, Yungui; Asgarov, Rustam; Li, Yaqiao; Martens, Lauren H; Elia, Lisa P; Ward, Michael E; Mucke, Lennart; Farese, Robert V; Gan, Li

    2014-10-01

    Haploinsufficiency of the progranulin (PGRN) gene (GRN) causes familial frontotemporal lobar degeneration (FTLD) and modulates an innate immune response in humans and in mouse models. GRN polymorphism may be linked to late-onset Alzheimer's disease (AD). However, the role of PGRN in AD pathogenesis is unknown. Here we show that PGRN inhibits amyloid β (Aβ) deposition. Selectively reducing microglial expression of PGRN in AD mouse models impaired phagocytosis, increased plaque load threefold and exacerbated cognitive deficits. Lentivirus-mediated PGRN overexpression lowered plaque load in AD mice with aggressive amyloid plaque pathology. Aβ plaque load correlated negatively with levels of hippocampal PGRN, showing the dose-dependent inhibitory effects of PGRN on plaque deposition. PGRN also protected against Aβ toxicity. Lentivirus-mediated PGRN overexpression prevented spatial memory deficits and hippocampal neuronal loss in AD mice. The protective effects of PGRN against Aβ deposition and toxicity have important therapeutic implications. We propose enhancing PGRN as a potential treatment for PGRN-deficient FTLD and AD. PMID:25261995

  19. Progression of cardiac amyloid deposition in hereditary transthyretin amyloidosis patients after liver transplantation.

    PubMed

    Liepnieks, Juris J; Benson, Merrill D

    2007-12-01

    It has been hypothesized that transthyretin (TTR) amyloidosis may progress after orthotopic liver transplantation (OLT) as a result of continued amyloid fibril synthesis and deposition from normal TTR. To test this hypothesis amyloid fibrils were isolated from cardiac tissues of three patients who died 1(1/2) to 5(1/2) years after OLT: two with Val30Met and one with Thr60Ala TTR. The ratio of variant to normal TTR in each case was determined and compared with the ratio of variant to normal in cardiac tissues from seven patients who died with TTR amyloidosis but who had not had liver transplantation. Tissues from patients with TTR amyloidosis without OLT included three with Val30Met, two with Thr60Ala, one with deltaVal122, and one with Val122Ile. All tissues from patients without OLT had greater amounts of variant TTR than normal TTR except for the Val122Ile in which the ratio was 50:50. The overall median variant to normal ratio was 60:40 with a range of 50-70% variant. In contrast, the mean percentage of variant TTR in the three tissues from patients after OLT was 25% (range 20-35). These data are consistent with the continued deposition of normal TTR in cardiac tissue after liver transplantation. PMID:17968687

  20. Dynamic relationships between age, amyloiddeposition, and glucose metabolism link to the regional vulnerability to Alzheimer's disease.

    PubMed

    Oh, Hwamee; Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

    2016-08-01

    SEE HANSSON AND GOURAS DOI101093/AWW146 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer's disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer's disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloiddeposition, we tested whether and how life-long changes in glucose metabolism relate to amyloiddeposition and Alzheimer's disease-related hypometabolism. Nine healthy young adults (age range: 20-30), 96 cognitively normal older adults (age range: 61-96), and 20 patients with Alzheimer's disease (age range: 50-90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloiddeposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloiddeposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P < 0.001) were maintained both in Pittsburgh compound B-negative cognitively normal older subjects (T = 6.66, P < 0.001) and Pittsburgh compound B-positive cognitively normal older subjects (T

  1. Pathologic deposition of non-amyloid immunoglobulin in the brain leading to mass effect and neurological deficits.

    PubMed

    Hersh, David S; Houbova, Petra; Castellani, Rudolph J; Rodriguez, Fausto J; Mehta, Minesh P; Woodworth, Graeme F

    2016-08-01

    We report a 31-year-old man with multiple large, non-enhancing intracerebral lesions exerting significant mass effect. Following debulking, histopathological analysis revealed abundant amorphous non-amyloid eosinophilic material, while liquid chromatography mass spectrometry revealed κ light chains and immunoglobulin A heavy chains, leading to the diagnosis of multiple intracerebral light-and-heavy chain aggregomas. Localized intracranial deposits of non-amyloid immunoglobulin may rarely mimic space-occupying intracranial neoplasms and should be considered in the differential diagnosis. PMID:26954763

  2. Amyloiddeposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression.

    PubMed

    Huijbers, Willem; Mormino, Elizabeth C; Schultz, Aaron P; Wigman, Sarah; Ward, Andrew M; Larvie, Mykol; Amariglio, Rebecca E; Marshall, Gad A; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A

    2015-04-01

    Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity--consistent with findings in genetic at-risk populations--and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer's disease continuum. Here, we examine the contribution of amyloiddeposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model

  3. Amyloiddeposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression

    PubMed Central

    Mormino, Elizabeth C.; Schultz, Aaron P.; Wigman, Sarah; Ward, Andrew M.; Larvie, Mykol; Amariglio, Rebecca E.; Marshall, Gad A.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.

    2015-01-01

    Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity—consistent with findings in genetic at-risk populations—and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer’s disease continuum. Here, we examine the contribution of amyloiddeposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model

  4. Modeling of age-dependent amyloid accumulation and γ-secretase inhibition of soluble and insoluble Aβ in a transgenic mouse model of amyloid deposition.

    PubMed

    Parkinson, Joanna; Ploeger, Bart; Appelkvist, Paulina; Bogstedt, Anna; Dillner Bergstedt, Karin; Eketjäll, Susanna; Visser, Sandra A G

    2013-12-01

    According to the "amyloid hypothesis," accumulation of amyloid beta (Aβ) peptides in the brain is linked to the development of Alzheimer's disease. The aims of this investigation were to develop a model for the age-dependent amyloid accumulation and to quantify the age- and treatment-duration-dependent efficacy of the γ-secretase inhibitor MRK-560 in the Tg2576 transgenic mouse model of amyloid deposition. Soluble and insoluble Aβ40 and Aβ42 brain concentrations were compiled from multiple naïve, vehicle, and MRK-560-treated animals. The age of Tg2576 mice in the studies ranged between 3.5 and 26 months. Single doses of MRK-560 inhibited soluble Aβ40 levels in animals up to 9 months old. In contrast, MRK-560 did not cause significant acute effects on soluble Aβ40 levels in animals older than 13 months. Absolute levels of Aβ variants increased exponentially over age and reached a plateau at ∼20 months. In the final model, it was assumed that MRK-560 inhibited the Aβ production rate with an Aβ level-dependent IC50.The age-dependent increase in Aβ levels was best described by a logistic model that stimulated the production rate of soluble Aβ. The increase in insoluble Aβ was defined as a function of soluble Aβ by using a scaling factor and a different turnover rate. The turnover half-life for insoluble Aβ was estimated at 30 days, explaining that at least a 4-week treatment in young animals was required to demonstrate a reduction in insoluble Aβ. Taken together, the derived knowledge could be exploited for an improved design of new experiments in Tg2576 mice. PMID:25505567

  5. Rare and unusual clinicopathologic presentation of renal AL amyloidosis

    PubMed Central

    Zuppan, Craig; Pi, Alexander; Zhang, Zhiwei; Jaipaul, Navin

    2016-01-01

    Lesson Rarely, renal light chain (AL) amyloidosis may present without significant proteinuria owing to glomerular sparing and amyloid deposition confined to the vasculature and tubulointerstitium. PMID:27186381

  6. Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects.

    PubMed

    Mormino, E C; Kluth, J T; Madison, C M; Rabinovici, G D; Baker, S L; Miller, B L; Koeppe, R A; Mathis, C A; Weiner, M W; Jagust, W J

    2009-05-01

    Although beta-amyloid (Abeta) plaques are a primary diagnostic criterion for Alzheimer's disease, this pathology is commonly observed in the brains of non-demented older individuals. To explore the importance of this pathology in the absence of dementia, we compared levels of amyloid deposition (via 'Pittsburgh Compound-B' (PIB) positron emission tomography (PET) imaging) to hippocampus volume (HV) and episodic memory (EM) in three groups: (i) normal controls (NC) from the Berkeley Aging Cohort (BAC NC, n = 20); (ii) normal controls (NC) from the Alzheimer's disease neuroimaging initiative (ADNI NC, n = 17); and (iii) PIB+ mild cognitive impairment subjects from the ADNI (ADNI PIB+ MCI, n = 39). Age, gender and education were controlled for in each statistical model, and HV was adjusted for intracranial volume (aHV). In BAC NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.0016) and worse EM (P = 0.0086). Within ADNI NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.047) but not EM (P = 0.60); within ADNI PIB+ MCI, elevated PIB uptake was significantly associated with both smaller aHV (P = 0.00070) and worse EM (P = 0.046). To further understand these relationships, a recursive regression procedure was conducted within all ADNI NC and PIB+ MCI subjects (n = 56) to test the hypothesis that HV mediates the relationship between Abeta and EM. Significant correlations were found between PIB index and EM (P = 0.0044), PIB index and aHV (P < 0.0001), as well as between aHV and EM (P < 0.0001). When both aHV and PIB were included in the same model to predict EM, aHV remained significant (P = 0.0015) whereas PIB index was no longer significantly associated with EM (P = 0.50). These results are consistent with a model in which Abeta deposition, hippocampal atrophy, and EM occur sequentially in elderly subjects, with Abeta deposition as the primary event in this cascade. This pattern suggests that declining EM in older

  7. Amyloid beta immunization worsens iron deposits in the choroid plexus and cerebral microbleeds.

    PubMed

    Joseph-Mathurin, Nelly; Dorieux, Olène; Trouche, Stéphanie G; Boutajangout, Allal; Kraska, Audrey; Fontès, Pascaline; Verdier, Jean-Michel; Sigurdsson, Einar M; Mestre-Francés, Nadine; Dhenain, Marc

    2013-11-01

    Anti-amyloid beta (Aβ) immunotherapy provides potential benefits in Alzheimer's disease patients. Nevertheless, strategies based on Aβ1-42 peptide induced encephalomyelitis and possible microhemorrhages. These outcomes were not expected from studies performed in rodents. It is critical to determine if other animal models better predict side effects of immunotherapies. Mouse lemur primates can develop amyloidosis with aging. Here we used old lemurs to study immunotherapy based on Aβ1-42 or Aβ-derivative (K6Aβ1-30). We followed anti-Aβ40 immunoglobulin G and M responses and Aβ levels in plasma. In vivo magnetic resonance imaging and histology were used to evaluate amyloidosis, neuroinflammation, vasogenic edema, microhemorrhages, and brain iron deposits. The animals responded mainly to the Aβ1-42 immunogen. This treatment induced immune response and increased Aβ levels in plasma and also microhemorrhages and iron deposits in the choroid plexus. A complementary study of untreated lemurs showed iron accumulation in the choroid plexus with normal aging. Worsening of iron accumulation is thus a potential side effect of Aβ-immunization at prodromal stages of Alzheimer's disease, and should be monitored in clinical trials. PMID:23796662

  8. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy☆

    PubMed Central

    Keable, Abby; Fenna, Kate; Yuen, Ho Ming; Johnston, David A.; Smyth, Neil R.; Smith, Colin; Salman, Rustam Al-Shahi; Samarasekera, Neshika; Nicoll, James A.R.; Attems, Johannes; Kalaria, Rajesh N.; Weller, Roy O.; Carare, Roxana O.

    2016-01-01

    Deposition of amyloid β (Aβ) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble Aβ from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as Aβ accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, Aβ and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: Aβ initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by Aβ. The pattern of development of CAA in the human brain suggests expansion of Aβ from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of Aβ in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26327684

  9. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy.

    PubMed

    Keable, Abby; Fenna, Kate; Yuen, Ho Ming; Johnston, David A; Smyth, Neil R; Smith, Colin; Al-Shahi Salman, Rustam; Samarasekera, Neshika; Nicoll, James A R; Attems, Johannes; Kalaria, Rajesh N; Weller, Roy O; Carare, Roxana O

    2016-05-01

    Deposition of amyloid β (Aβ) in the walls of cerebral arteries as cerebral amyloid angiopathy (CAA) suggests an age-related failure of perivascular drainage of soluble Aβ from the brain. As CAA is associated with Alzheimer's disease and with intracerebral haemorrhage, the present study determines the unique sequence of changes that occur as Aβ accumulates in artery walls. Paraffin sections of post-mortem human occipital cortex were immunostained for collagen IV, fibronectin, nidogen 2, Aβ and smooth muscle actin and the immunostaining was analysed using Image J and confocal microscopy. Results showed that nidogen 2 (entactin) increases with age and decreases in CAA. Confocal microscopy revealed stages in the progression of CAA: Aβ initially deposits in basement membranes in the tunica media, replaces first the smooth muscle cells and then the connective tissue elements to leave artery walls completely or focally replaced by Aβ. The pattern of development of CAA in the human brain suggests expansion of Aβ from the basement membranes to progressively replace all tissue elements in the artery wall. Establishing this full picture of the development of CAA is pivotal in understanding the clinical presentation of CAA and for developing therapies to prevent accumulation of Aβ in artery walls. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26327684

  10. Early Postmenopausal Transdermal 17β-Estradiol Therapy and AmyloidDeposition

    PubMed Central

    Kantarci, Kejal; Lowe, Val J.; Lesnick, Timothy G.; Tosakulwong, Nirubol; Bailey, Kent R.; Fields, Julie A.; Shuster, Lynne T.; Zuk, Samantha M.; Senjem, Matthew L.; Mielke, Michelle M.; Gleason, Carey; Jack, Clifford R.; Rocca, Walter A.; Miller, Virginia M.

    2016-01-01

    Background: It remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer’s disease (AD). Objective: To investigate the effects of hormone therapy on amyloiddeposition in recently postmenopausal women. Methods: Participants within 5–36 months past menopause in the Kronos Early Estrogen Prevention Study, a randomized, double blinded placebo-controlled clinical trial, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50μg/day transdermal 17β-estradiol; or 3) placebo pills and patch for four years. Oral progesterone (200 mg/day) was given to active treatment groups for 12 days each month. 11C Pittsburgh compound B (PiB) PET imaging was performed in 68 of the 118 participants at Mayo Clinic approximately seven years post randomization and three years after stopping randomized treatment. PiB Standard unit value ratio (SUVR) was calculated. Results: Women (age = 52–65) randomized to transdermal 17β-estradiol (n = 21) had lower PiB SUVR compared to placebo (n = 30) after adjusting for age [odds ratio (95% CI) = 0.31(0.11–0.83)]. In the APOE ɛ4 carriers, transdermal 17β-estradiol treated women (n = 10) had lower PiB SUVR compared to either placebo (n = 5) [odds ratio (95% CI) = 0.04(0.004–0.44)], or the oral CEE treated group (n = 3) [odds ratio (95% CI) = 0.01(0.0006–0.23)] after adjusting for age. Hormone therapy was not associated with PiB SUVR in the APOE ɛ4 non-carriers. Conclusion: In this pilot study, transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloiddeposition, particularly in APOE ɛ4 carriers. This finding may have important implications for the prevention of AD in postmenopausal women, and needs to be confirmed in a larger sample. PMID:27163830

  11. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech.

    PubMed

    Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R; Strand, Edythe A; Machulda, Mary M; Senjem, Matthew L; Gunter, Jeffrey L; Lowe, Val J; Jack, Clifford R; Josephs, Keith A

    2016-01-01

    Beta-amyloid (Aβ) deposition can be observed in primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified) and PAOS (n = 42) subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+) status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+) status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+) status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified PPA subjects

  12. Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech

    PubMed Central

    Whitwell, Jennifer L.; Weigand, Stephen D.; Duffy, Joseph R.; Strand, Edythe A.; Machulda, Mary M.; Senjem, Matthew L.; Gunter, Jeffrey L.; Lowe, Val J.; Jack, Clifford R.; Josephs, Keith A.

    2016-01-01

    Beta-amyloid (Aβ) deposition can be observed in primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS). While it is typically associated with logopenic PPA, there are exceptions that make predicting Aβ status challenging based on clinical diagnosis alone. We aimed to determine whether MRI regional volumes or clinical data could help predict Aβ deposition. One hundred and thirty-nine PPA (n = 97; 15 agrammatic, 53 logopenic, 13 semantic and 16 unclassified) and PAOS (n = 42) subjects were prospectively recruited into a cross-sectional study and underwent speech/language assessments, 3.0 T MRI and C11-Pittsburgh Compound B PET. The presence of Aβ was determined using a 1.5 SUVR cut-point. Atlas-based parcellation was used to calculate gray matter volumes of 42 regions-of-interest across the brain. Penalized binary logistic regression was utilized to determine what combination of MRI regions, and what combination of speech and language tests, best predicts Aβ (+) status. The optimal MRI model and optimal clinical model both performed comparably in their ability to accurately classify subjects according to Aβ status. MRI accurately classified 81% of subjects using 14 regions. Small left superior temporal and inferior parietal volumes and large left Broca's area volumes were particularly predictive of Aβ (+) status. Clinical scores accurately classified 83% of subjects using 12 tests. Phonological errors and repetition deficits, and absence of agrammatism and motor speech deficits were particularly predictive of Aβ (+) status. In comparison, clinical diagnosis was able to accurately classify 89% of subjects. However, the MRI model performed well in predicting Aβ deposition in unclassified PPA. Clinical diagnosis provides optimum prediction of Aβ status at the group level, although regional MRI measurements and speech and language testing also performed well and could have advantages in predicting Aβ status in unclassified PPA subjects

  13. Viscoelastic response of neural cells governed by the deposition of amyloid-β peptides (Aβ)

    NASA Astrophysics Data System (ADS)

    Gong, Ze; You, Ran; Chang, Raymond Chuen-Chung; Lin, Yuan

    2016-06-01

    Because of its intimate relation with Alzheimer's disease (AD), the question of how amyloid-β peptide (Aβ) deposition alters the membrane and cytoskeltal structure of neural cells and eventually their mechanical response has received great attention. In this study, the viscoelastic properties of primary neurons subjected to various Aβ treatments were systematically characterized using atomic force microrheology. It was found that both the storage ( G ') and loss ( G ″) moduli of neural cells are rate-dependent and grow by orders of magnitude as the driving frequency ω varies from 1 to 100 Hz. However, a much stronger frequency dependence was observed in the loss moduli (with a scaling exponent of ˜0.96) than that in G ' ( ˜ ω 0.2 ). Furthermore, both cell moduli increase gradually within the first 6 h of Aβ treatment before steady-state values are reached, with a higher dosage of Aβ leading to larger changes in cell properties. Interestingly, we showed that the measured neuron response can be well-explained by a power law structural damping model. Findings here establish a quantitative link between Aβ accumulation and the physical characteristics of neural cells and hence could provide new insights into how disorders like AD affect the progression of different neurological processes from a mechanics point of view.

  14. β-Amyloid infusion results in delayed and age-dependent learning deficits without role of inflammation or β-amyloid deposits

    PubMed Central

    Malm, Tarja; Ort, Michael; Tähtivaara, Leena; Jukarainen, Niko; Goldsteins, Gundars; Puoliväli, Jukka; Nurmi, Antti; Pussinen, Raimo; Ahtoniemi, Toni; Miettinen, Taina-Kaisa; Kanninen, Katja; Leskinen, Suvi; Vartiainen, Nina; Yrjänheikki, Juha; Laatikainen, Reino; Harris-White, Marni E.; Koistinaho, Milla; Frautschy, Sally A.; Bures, Jan; Koistinaho, Jari

    2006-01-01

    β-Amyloid (Aβ) polypeptide plays a critical role in the pathogenesis of Alzheimer's disease (AD), which is characterized by progressive decline of cognitive functions, formation of Aβ deposits and neurofibrillary tangles, and loss of neurons. Increased genetic production or direct intracerebral administration of Aβ in animal models results in Aβ deposition, gliosis, and impaired cognitive functions. Whether aging renders the brain prone to Aβ and whether inflammation is required for Aβ-induced learning deficits is unclear. We show that intraventricular infusion of Aβ1–42 results in learning deficits in 9-month-old but not 2.5-month-old mice. Deficits that become detectable 12 weeks after the infusion are associated with a slight reduction in Cu,Zn superoxide dismutase activity but do not correlate with Aβ deposition and are not associated with gliosis. In rats, Aβ infusion induced learning deficits that were detectable 6 months after the infusion. Approximately 20% of the Aβ immunoreactivity in rats was associated with astrocytes. NMR spectrum analysis of the animals cerebrospinal fluid revealed a strong reduction trend in several metabolites in Aβ-infused rats, including lactate and myo-inositol, supporting the idea of dysfunctional astrocytes. Even a subtle increase in brain Aβ1–42 concentration may disrupt normal metabolism of astrocytes, resulting in altered neuronal functions and age-related development of learning deficits independent of Aβ deposition and inflammation. PMID:16723396

  15. Amyloid-Peptide Vaccinations Reduce β-Amyloid Plaques but Exacerbate Vascular Deposition and Inflammation in the Retina of Alzheimer’s Transgenic Mice

    PubMed Central

    Liu, Bingqian; Rasool, Suhail; Yang, Zhikuan; Glabe, Charles G.; Schreiber, Steven S.; Ge, Jian; Tan, Zhiqun

    2009-01-01

    Alzheimer’s disease (AD) is pathologically characterized by accumulation of β-amyloid (Aβ) protein deposits and/or neurofibrillary tangles in association with progressive cognitive deficits. Although numerous studies have demonstrated a relationship between brain pathology and AD progression, the Alzheimer’s pathological hallmarks have not been found in the AD retina. A recent report showed Aβ plaques in the retinas of APPswe/PS1ΔE9 transgenic mice. We now report the detection of Aβ plaques with increased retinal microvascular deposition of Aβ and neuroinflammation in Tg2576 mouse retinas. The majority of Aβ-immunoreactive plaques were detected from the ganglion cell layer to the inner plexiform layer, and some plaques were observed in the outer nuclear layer, photoreceptor outer segment, and optic nerve. Hyperphosphorylated tau was labeled in the corresponding areas of the Aβ plaques in adjacent sections. Although Aβ vaccinations reduced retinal Aβ deposits, there was a marked increase in retinal microvascular Aβ deposition as well as local neuroinflammation manifested by microglial infiltration and astrogliosis linked with disruption of the retinal organization. These results provide evidence to support further investigation of the use of retinal imaging to diagnose AD and to monitor disease activity. PMID:19834067

  16. Amyloid fibrils

    PubMed Central

    Rambaran, Roma N

    2008-01-01

    Amyloid refers to the abnormal fibrous, extracellular, proteinaceous deposits found in organs and tissues. Amyloid is insoluble and is structurally dominated by β-sheet structure. Unlike other fibrous proteins it does not commonly have a structural, supportive or motility role but is associated with the pathology seen in a range of diseases known as the amyloidoses. These diseases include Alzheimer's, the spongiform encephalopathies and type II diabetes, all of which are progressive disorders with associated high morbidity and mortality. Not surprisingly, research into the physicochemical properties of amyloid and its formation is currently intensely pursued. In this chapter we will highlight the key scientific findings and discuss how the stability of amyloid fibrils impacts on bionanotechnology. PMID:19158505

  17. CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta deposit and impaired memory function.

    PubMed

    Hwang, Chul Ju; Park, Mi Hee; Hwang, Jae Yeon; Kim, Ju Hwan; Yun, Na Young; Oh, Sang Yeon; Song, Ju Kyung; Seo, Hyun Ok; Kim, Yun-Bae; Hwang, Dae Yeon; Oh, Ki-Wan; Han, Sang-Bae; Hong, Jin Tae

    2016-03-15

    Chemokine receptors are implicated in inflammation and immune responses. Neuro-inflammation is associated with activation of astrocyte and amyloid-beta (Aβ) generations that lead to pathogenesis of Alzheimer disease (AD). Previous our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in activation of astrocytes and Aβ deposit, and thus memory dysfunction through increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were used as an animal model with memory dysfunction. For the purpose LPS was injected i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS injected CCR5 knockout mice, LPS injection significant increase expression of inflammatory proteins, astrocyte activation, expressions of β-secretase as well as Aβ deposition in the brain of CCR5 knockout mice as compared with that of CCR5 wild type mice. In CCR5 knockout mice, CCR2 expressions were high and co-localized with GFAP which was significantly elevated by LPS. Expression of monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased by LPS injection, and increment of MCP-1 expression is much higher in CCR5 knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS (1 μg/ml) and CCR2 antagonist, decreased the NF-ĸB activation and Aβ level. These findings suggest that the deficiency of CCR5 enhances response of LPS, which accelerates to neuro-inflammation and memory impairment. PMID:26910914

  18. CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta deposit and impaired memory function

    PubMed Central

    Hwang, Jae Yeon; Kim, Ju Hwan; Yun, Na Young; Oh, Sang Yeon; Song, Ju Kyung; Seo, Hyun Ok; Kim, Yun-Bae; Hwang, Dae Yeon; Oh, Ki-Wan; Han, Sang-Bae; Hong, Jin Tae

    2016-01-01

    Chemokine receptors are implicated in inflammation and immune responses. Neuro-inflammation is associated with activation of astrocyte and amyloid-beta (Aβ) generations that lead to pathogenesis of Alzheimer disease (AD). Previous our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in activation of astrocytes and Aβ deposit, and thus memory dysfunction through increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were used as an animal model with memory dysfunction. For the purpose LPS was injected i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS injected CCR5 knockout mice, LPS injection significant increase expression of inflammatory proteins, astrocyte activation, expressions of β-secretase as well as Aβ deposition in the brain of CCR5 knockout mice as compared with that of CCR5 wild type mice. In CCR5 knockout mice, CCR2 expressions were high and co-localized with GFAP which was significantly elevated by LPS. Expression of monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased by LPS injection, and increment of MCP-1 expression is much higher in CCR5 knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS (1 μg/ml) and CCR2 antagonist, decreased the NF-ĸB activation and Aβ level. These findings suggest that the deficiency of CCR5 enhances response of LPS, which accelerates to neuro-inflammation and memory impairment. PMID:26910914

  19. Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment.

    PubMed

    Chung, Jun Ku; Plitman, Eric; Nakajima, Shinichiro; Chakravarty, M Mallar; Caravaggio, Fernando; Gerretsen, Philip; Iwata, Yusuke; Graff-Guerrero, Ariel

    2016-05-01

    Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer's disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe(18)F-florbetapir (AV-45).(18)F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia. PMID:26400248

  20. Conducting nanowires built by controlled self-assembly of amyloid fibers and selective metal deposition

    PubMed Central

    Scheibel, Thomas; Parthasarathy, Raghuveer; Sawicki, George; Lin, Xiao-Min; Jaeger, Heinrich; Lindquist, Susan L.

    2003-01-01

    Recent research in the field of nanometer-scale electronics has focused on the operating principles of small-scale devices and schemes to realize useful circuits. In contrast to established “top-down” fabrication techniques, molecular self-assembly is emerging as a “bottom-up” approach for fabricating nanostructured materials. Biological macromolecules, especially proteins, provide many valuable properties, but poor physical stability and poor electrical characteristics have prevented their direct use in electrical circuits. Here we describe the use of self-assembling amyloid protein fibers to construct nanowire elements. Self-assembly of a prion determinant from Saccharomyces cerevisiae, the N-terminal and middle region (NM) of Sup35p, produced 10-nm-wide protein fibers that were stable under a wide variety of harsh physical conditions. Their lengths could be roughly controlled by assembly conditions in the range of 60 nm to several hundred micrometers. A genetically modified NM variant that presents reactive, surface-accessible cysteine residues was used to covalently link NM fibers to colloidal gold particles. These fibers were placed across gold electrodes, and additional metal was deposited by highly specific chemical enhancement of the colloidal gold by reductive deposition of metallic silver and gold from salts. The resulting silver and gold wires were ≈100 nm wide. These biotemplated metal wires demonstrated the conductive properties of a solid metal wire, such as low resistance and ohmic behavior. With such materials it should be possible to harness the extraordinary diversity and specificity of protein functions to nanoscale electrical circuitry. PMID:12672964

  1. Loss of Metal Ions, Disulfide Reduction and Mutations Related to Familial ALS Promote Formation of Amyloid-Like Aggregates from Superoxide Dismutase

    PubMed Central

    Oztug Durer, Zeynep A.; Cohlberg, Jeffrey A.; Dinh, Phong; Padua, Shelby; Ehrenclou, Krista; Downes, Sean; Tan, James K.; Nakano, Yoko; Bowman, Christopher J.; Hoskins, Jessica L.; Kwon, Chuhee; Mason, Andrew Z.; Rodriguez, Jorge A.; Doucette, Peter A.; Shaw, Bryan F.; Valentine, Joan Selverstone

    2009-01-01

    Mutations in the gene encoding Cu-Zn superoxide dismutase (SOD1) are one of the causes of familial amyotrophic lateral sclerosis (FALS). Fibrillar inclusions containing SOD1 and SOD1 inclusions that bind the amyloid-specific dye thioflavin S have been found in neurons of transgenic mice expressing mutant SOD1. Therefore, the formation of amyloid fibrils from human SOD1 was investigated. When agitated at acidic pH in the presence of low concentrations of guanidine or acetonitrile, metalated SOD1 formed fibrillar material which bound both thioflavin T and Congo red and had circular dichroism and infrared spectra characteristic of amyloid. While metalated SOD1 did not form amyloid-like aggregates at neutral pH, either removing metals from SOD1 with its intramolecular disulfide bond intact or reducing the intramolecular disulfide bond of metalated SOD1 was sufficient to promote formation of these aggregates. SOD1 formed amyloid-like aggregates both with and without intermolecular disulfide bonds, depending on the incubation conditions, and a mutant SOD1 lacking free sulfhydryl groups (AS-SOD1) formed amyloid-like aggregates at neutral pH under reducing conditions. ALS mutations enhanced the ability of disulfide-reduced SOD1 to form amyloid-like aggregates, and apo-AS-SOD1 formed amyloid-like aggregates at pH 7 only when an ALS mutation was also present. These results indicate that some mutations related to ALS promote formation of amyloid-like aggregates by facilitating the loss of metals and/or by making the intramolecular disulfide bond more susceptible to reduction, thus allowing the conversion of SOD1 to a form that aggregates to form resembling amyloid. Furthermore, the occurrence of amyloid-like aggregates per se does not depend on forming intermolecular disulfide bonds, and multiple forms of such aggregates can be produced from SOD1. PMID:19325915

  2. Cerebrolysin reduces amyloiddeposits, apoptosis and autophagy in the thalamus and improves functional recovery after cortical infarction.

    PubMed

    Xing, Shihui; Zhang, Jian; Dang, Chao; Liu, Gang; Zhang, Yusheng; Li, Jingjing; Fan, Yuhua; Pei, Zhong; Zeng, Jinsheng

    2014-02-15

    Focal cerebral infarction causes amyloid-β (Aβ) deposits and secondary thalamic neuronal degeneration. The present study aimed to determine the protective effects of Cerebrolysin on Aβ deposits and secondary neuronal damage in thalamus after cerebral infarction. At 24h after distal middle cerebral artery occlusion (MCAO), Cerebrolysin (5 ml/kg) or saline as control was once daily administered for consecutive 13 days by intraperitoneal injection. Sensory function and secondary thalamic damage were assessed with adhesive-removal test, Nissl staining and immunofluorescence at 14 days after MCAO. Aβ deposits, activity of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), apoptosis and autophagy were determined by TUNEL staining, immunofluorescence and immunoblot. The results showed that Cerebrolysin significantly improved sensory deficit compared to controls (p<0.05). Aβ deposits and BACE1 were obviously reduced by Cerebrolysin, which was accompanied by decreases in neuronal loss and astroglial activation compared to controls (all p < 0.05). Coincidently, Cerebrolysin markedly inhibited cleaved caspase-3, conversion of LC3-II, downregulation of Bcl-2 and upregulation of Bax in the ipsilateral thalamus compared to controls (all p<0.05). These findings suggest that Cerebrolysin reduces Aβ deposits, apoptosis and autophagy in the ipsilateral thalamus, which may be associated with amelioration of secondary thalamic damage and functional recovery after cerebral infarction. PMID:24315581

  3. Arresting Amyloid with Coulomb’s Law: Acetylation of ALS-Linked SOD1 by Aspirin Impedes Aggregation

    PubMed Central

    Abdolvahabi, Alireza; Shi, Yunhua; Rhodes, Nicholas R.; Cook, Nathan P.; Martí, Angel A.; Shaw, Bryan F.

    2015-01-01

    Although the magnitude of a protein’s net charge (Z) can control its rate of self-assembly into amyloid, and its interactions with cellular membranes, the net charge of a protein is not viewed as a druggable parameter. This article demonstrates that aspirin (the quintessential acylating pharmacon) can inhibit the amyloidogenesis of superoxide dismutase (SOD1) by increasing the intrinsic net negative charge of the polypeptide, i.e., by acetylation (neutralization) of multiple lysines. The protective effects of acetylation were diminished (but not abolished) in 100 mM NaCl and were statistically significant: a total of 432 thioflavin-T amyloid assays were performed for all studied proteins. The acetylation of as few as three lysines by aspirin in A4V apo-SOD1—a variant that causes familial amyotrophic lateral sclerosis (ALS)—delayed amyloid nucleation by 38% and slowed amyloid propagation by twofold. Lysines in wild-type- and ALS-variant apo-SOD1 could also be peracetylated with aspirin after fibrillization, resulting in supercharged fibrils, with increases in formal net charge of ∼2 million units. Peracetylated SOD1 amyloid defibrillized at temperatures below unacetylated fibrils, and below the melting temperature of native Cu2,Zn2-SOD1 (e.g., fibril Tm = 84.49°C for acetylated D90A apo-SOD1 fibrils). Targeting the net charge of native or misfolded proteins with small molecules—analogous to how an enzyme’s Km or Vmax are medicinally targeted—holds promise as a strategy in the design of therapies for diseases linked to protein self-assembly. PMID:25762331

  4. Bioenergetic Mechanisms in Astrocytes May Contribute to Amyloid Plaque Deposition and Toxicity*

    PubMed Central

    Fu, Wen; Shi, Diya; Westaway, David; Jhamandas, Jack H.

    2015-01-01

    Alzheimer disease (AD) is characterized neuropathologically by synaptic disruption, neuronal loss, and deposition of amyloid β (Aβ) protein in brain structures that are critical for memory and cognition. There is increasing appreciation, however, that astrocytes, which are the major non-neuronal glial cells, may play an important role in AD pathogenesis. Unlike neurons, astrocytes are resistant to Aβ cytotoxicity, which may, in part, be related to their greater reliance on glycolytic metabolism. Here we show that, in cultures of human fetal astrocytes, pharmacological inhibition or molecular down-regulation of a main enzymatic regulator of glycolysis, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB3), results in increased accumulation of Aβ within and around astrocytes and greater vulnerability of these cells to Aβ toxicity. We further investigated age-dependent changes in PFKFB3 and astrocytes in AD transgenic mice (TgCRND8) that overexpress human Aβ. Using a combination of Western blotting and immunohistochemistry, we identified an increase in glial fibrillary acidic protein expression in astrocytes that paralleled the escalation of the Aβ plaque burden in TgCRND8 mice in an age-dependent manner. Furthermore, PFKFB3 expression also demonstrated an increase in these mice, although at a later age (9 months) than GFAP and Aβ. Immunohistochemical staining showed significant reactive astrogliosis surrounding Aβ plaques with increased PFKFB3 activity in 12-month-old TgCRND8 mice, an age when AD pathology and behavioral deficits are fully manifested. These studies shed light on the unique bioenergetic mechanisms within astrocytes that may contribute to the development of AD pathology. PMID:25814669

  5. Proliferation in the Alzheimer Hippocampus Is due to Microglia, Not Astroglia, and Occurs at Sites of Amyloid Deposition

    PubMed Central

    Marlatt, Michael W.; Bauer, Jan; Aronica, Eleonora; van Haastert, Elise S.; Hoozemans, Jeroen J. M.; Joels, Marian; Lucassen, Paul J.

    2014-01-01

    Microglia and astrocytes contribute to Alzheimer's disease (AD) etiology and may mediate early neuroinflammatory responses. Despite their possible role in disease progression and despite the fact that they can respond to amyloid deposition in model systems, little is known about whether astro- or microglia can undergo proliferation in AD and whether this is related to the clinical symptoms or to local neuropathological changes. Previously, proliferation was found to be increased in glia-rich regions of the presenile hippocampus. Since their phenotype was unknown, we here used two novel triple-immunohistochemical protocols to study proliferation in astro- or microglia in relation to amyloid pathology. We selected different age-matched cohorts to study whether proliferative changes relate to clinical severity or to neuropathological changes. Proliferating cells were found across the hippocampus but never in mature neurons or astrocytes. Almost all proliferating cells were colabeled with Iba1+, indicating that particularly microglia contribute to proliferation in AD. Proliferating Iba1+ cells was specifically seen within the borders of amyloid plaques, indicative of an active involvement in, or response to, plaque accumulation. Thus, consistent with animal studies, proliferation in the AD hippocampus is due to microglia, occurs in close proximity of plaque pathology, and may contribute to the neuroinflammation common in AD. PMID:25215243

  6. [The concurrence of light-chain deposition disease, AL-amyloidosis, and cast nephropathy in a patient with multiple myeloma].

    PubMed

    Rekhtina, I G; Zakharova, E V; Stoliarevich, E S; Sinitsina, M N; Denisova, E N

    2015-01-01

    Despite of the fact that their clinical manifestations are similar, AL-amyloidosis (AL-A) and light chain deposition disease (LCDD) are individual nosological entities in view of considerable differences in their pathogenesis and pathomorphology. The paper describes a rare case of the concurrence of LCDD and AL-A in a patient with multiple myeloma. Clinically, there was dialysis-dependent renal failure, flail leg syndrome, myocardiopathy, and rhabdomyolysis. At the disease onset, his nephrobiopsy specimen could diagnose LCDD and myeloma or cast nephropathy. The disease was characterized by an aggressive course. Despite the administration of innovative agents, the patient had a short-term remission and died from disease progression. Autopsy additionally revealed amyloid deposition in the heart and kidney. The development of AL-A in the presence of prior LCDD may reflect the progression of the tumor and the appearance of an additional subclone of plasma cells that produce amyloidogenic light chains. The uncommonness of this case is that renal amyloid was found in the tubular casts and absent in the glomeruli, which may be considered as a special form--tubular AL-amyloidosis. PMID:26281203

  7. Correlation of amyloid PET ligand florbetapir F 18 (18F-AV-45) binding with β-amyloid aggregation and neuritic plaque deposition in postmortem brain tissue

    PubMed Central

    Choi, Seok Rye; Schneider, Julie A.; Bennett, David A.; Beach, Thomas G.; Bedell, Barry J.; Zehntner, Simone P.; Krautkramer, Michael; Kung, Hank F.; Skovronsky, Daniel M.; Hefti, Franz; Clark, Christopher M.

    2011-01-01

    Background Florbetapir F 18 (18F-AV-45) is a positron emission tomography (PET) imaging ligand for the detection of amyloid aggregation associated with Alzheimer’s disease. Earlier data showed that florbetapir F 18 binds with high affinity to β-amyloid plaques in human brain homogenates (Kd = 3.7 nM) and has favorable imaging pharmacokinetic properties, including rapid brain penetration and washout. The present study used human autopsy brain tissue to evaluate the correlation between in vitro florbetapir F 18 binding and β-amyloid density measured by established neuropathological methods. Methods The localization and density of florbetapir F 18 binding in frozen and formalin-fixed paraffin-embedded sections of postmortem brain tissue from 40 subjects with a varying degree of neurodegenerative pathology was assessed by standard florbetapir F 18 autoradiography and correlated with the localization and density of β-amyloid identified by silver staining, thioflavin S staining, and immunohistochemistry. Results There were strong quantitative correlations between florbetapir F 18 tissue binding and both β-amyloid plaques identified by light microscopy (sliver staining and thioflavin S fluorescence) and by immunohistochemical measurements of β-amyloid using three antibodies recognizing different epitopes of the β-amyloid peptide (Aβ). Florbetapir F 18 did not bind to neurofibrillary tangles. Conclusion Florbetapir F 18 selectively binds β-amyloid in human brain tissue. The binding intensity was quantitatively correlated with the density of β-amyloid plaques identified by standard neuropathological techniques and correlated with the density of Aβ measured by immunohistochemistry. Since β-amyloid plaques are a defining neuropathological feature for Alzheimer’s disease, these results support the use of florbetapir F 18 as an amyloid PET ligand to identify the presence of AD pathology in patients with signs and symptoms of progressive late-life cognitive

  8. Effects of brain amyloid deposition and reduced glucose metabolism on the default mode of brain function in normal aging.

    PubMed

    Kikuchi, Mitsuru; Hirosawa, Tetsu; Yokokura, Masamichi; Yagi, Shunsuke; Mori, Norio; Yoshikawa, Etsuji; Yoshihara, Yujiro; Sugihara, Genichi; Takebayashi, Kiyokazu; Iwata, Yasuhide; Suzuki, Katsuaki; Nakamura, Kazuhiko; Ueki, Takatoshi; Minabe, Yoshio; Ouchi, Yasuomi

    2011-08-01

    Brain β-amyloid (Aβ) deposition during normal aging is highlighted as an initial pathogenetic event in the development of Alzheimer's disease. Many recent brain imaging studies have focused on areas deactivated during cognitive tasks [the default mode network (DMN), i.e., medial frontal gyrus/anterior cingulate cortex and precuneus/posterior cingulate cortex], where the strength of functional coordination was more or less affected by cerebral Aβ deposits. In the present positron emission tomography study, to investigate whether regional glucose metabolic alterations and Aβ deposits seen in nondemented elderly human subjects (n = 22) are of pathophysiological importance in changes of brain hemodynamic coordination in DMN during normal aging, we measured cerebral glucose metabolism with [(18)F]FDG, Aβ deposits with [(11)C]PIB, and regional cerebral blood flow during control and working memory tasks by H(2)(15)O on the same day. Data were analyzed using both region of interest and statistical parametric mapping. Our results indicated that the amount of Aβ deposits was negatively correlated with hemodynamic similarity between medial frontal and medial posterior regions, and the lower similarity was associated with poorer working memory performance. In contrast, brain glucose metabolism was not related to this medial hemodynamic similarity. These findings suggest that traceable Aβ deposition, but not glucose hypometabolism, in the brain plays an important role in occurrence of neuronal discoordination in DMN along with poor working memory in healthy elderly people. PMID:21813680

  9. Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease.

    PubMed

    Beauquis, Juan; Vinuesa, Angeles; Pomilio, Carlos; Pavía, Patricio; Galván, Verónica; Saravia, Flavia

    2014-03-01

    In the context of Alzheimer's disease (AD), hippocampal alterations have been well described in advanced stages of the pathology, when amyloid deposition, inflammation and glial activation occur, but less attention has been directed to studying early brain and behavioral changes. Using an animal model of AD, the transgenic PDAPP-J20 mouse at 5 months of age, when no amyloid plaques are present and low cerebral levels of amyloid peptides are detectable, we found structural, morphological, and cellular alterations in the hippocampus. Young transgenic mice showed a reduced hippocampal volume with less number of pyramidal and granular neurons, which additionally exhibited cell atrophy. The neurogenic capability in this zone, measured as DCX+ cells, was strongly diminished and associated to alterations in cell maturity. A decrease in presynaptic synaptophysin optical density was detected in mossy fibers reaching CA3 subfield but not in Golgi stained- CA1 dendritic spine density. Employing confocal microscopy and accurate stereological tools we also found a reduction in the number of GFAP+ cells, along with decreased astrocyte complexity, suggesting a potential detriment of neural support. According with untimely neuroglial alterations, young PDAPP mice failed in the novel location recognition test, that depends on hippocampal function. Moreover, multivariate statistical analysis of the behavioral outcome in the open-field test evidenced an elevated anxiety score in Tg mice compared with age-matched control mice. In line with this, the transgenic group showed a higher number of c-Fos+ nuclei in central and basolateral amygdala, a result that supports the early involvement of the emotionality factor in AD pathology. Applying an integrative approach, this work focuses on early structural, morphological and functional changes and provides new and compelling evidence of behavioral alterations that precede manifest AD. PMID:24132937

  10. Contemporary treatment of amyloid heart disease.

    PubMed

    Palecek, Tomas; Fikrle, Michal; Nemecek, Eduard; Bauerova, Lenka; Kuchynka, Petr; Louch, William E; Spicka, Ivan; Rysava, Romana

    2015-01-01

    The amyloidoses represent a group of diseases characterized by extracellular deposition of abnormal protein, amyloid, which is formed by insoluble extracellular fibrils in β-pleated sheets. Although cardiac involvement may occur in all types of amyloidoses, clinically relevant amyloid cardiomyopathy is a typical feature of AL amyloidosis and transthyretin-related amyloidoses. Congestive heart failure represents the commonest manifestation of amyloid heart disease. Noninvasive imaging techniques, especially echocardiography and cardiac magnetic resonance, play a major role in the diagnosis of amyloid cardiomyopathy; however, histological confirmation and exact typing of amyloid deposits is necessary whether in extracardiac location or directly in the myocardium. Early diagnosis of amyloid heart disease is of utmost importance as the presence and especially the severity of cardiac involvement generally drives the prognosis of affected subjects and plays a major role in determining the intensity of specific treatment, namely in AL amyloidosis. The management of patients with amyloid heart disease is complex. Loop diuretics together with aldosterone antagonists represent the basis for influencing signs of congestion. In AL amyloidosis, high-dose chemotherapy followed by autologous stem cell transplantation is generally considered to be a front-line treatment option, if the disease is diagnosed at its early stage. The combination of mephalan with dexamethasone has been the standard therapy for severely affected individuals; however, the combinations with several novel agents including immunomodulatory drugs and bortezomibe have been tested in clinical trials with promising results. New therapeutic substances with the potential to slow or even stop the progression of transthyretin-related amyloidosis are also extensively studied. PMID:25483951

  11. Environmental impact of multi-wall carbon nanotubes in a novel model of exposure: systemic distribution, macrophage accumulation, and amyloid deposition

    PubMed Central

    Albini, Adriana; Pagani, Arianna; Pulze, Laura; Bruno, Antonino; Principi, Elisa; Congiu, Terenzio; Gini, Elisabetta; Grimaldi, Annalisa; Bassani, Barbara; De Flora, Silvio; de Eguileor, Magda; Noonan, Douglas M

    2015-01-01

    Carbon nanotubes (CNTs) have been extensively investigated and employed for industrial use because of their peculiar physical properties, which make them ideal for many industrial applications. However, rapid growth of CNT employment raises concerns about the potential risks and toxicities for public health, environment, and workers associated with the manufacture and use of these new materials. Here we investigate the main routes of entry following environmental exposure to multi-wall CNTs (MWCNTs; currently the most widely used in industry). We developed a novel murine model that could represent a surrogate of a workplace exposure to MWCNTs. We traced the localization of MWCNTs and their possible role in inducing an innate immune response, inflammation, macrophage recruitment, and inflammatory conditions. Following environmental exposure of CD1 mice, we observed that MWCNTs rapidly enter and disseminate in the organism, initially accumulating in lungs and brain and later reaching the liver and kidney via the bloodstream. Since recent experimental studies show that CNTs are associated with the aggregation process of proteins associated with neurodegenerative diseases, we investigated whether MWCNTs are able to induce amyloid fibril production and accumulation. Amyloid deposits in spatial association with macrophages and MWCNT aggregates were found in the brain, liver, lungs, and kidneys of exposed animals. Our data suggest that accumulation of MWCNTs in different organs is associated with inflammation and amyloid accumulation. In the brain, where we observed rapid accumulation and amyloid fibril deposition, exposure to MWCNTs might enhance progression of neurodegenerative and other amyloid-related diseases. Our data highlight the conclusion that, in a novel rodent model of exposure, MWCNTs may induce macrophage recruitment, activation, and amyloid deposition, causing potential damage to several organs. PMID:26457053

  12. Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice

    PubMed Central

    Stöhr, Jan; Condello, Carlo; Watts, Joel C.; Bloch, Lillian; Oehler, Abby; Nick, Mimi; DeArmond, Stephen J.; Giles, Kurt; DeGrado, William F.; Prusiner, Stanley B.

    2014-01-01

    An increasing number of studies continue to show that the amyloid β (Aβ) peptide adopts an alternative conformation and acquires transmissibility; hence, it becomes a prion. Here, we report on the attributes of two strains of Aβ prions formed from synthetic Aβ peptides composed of either 40 or 42 residues. Modifying the conditions for Aβ polymerization increased both the protease resistance and prion infectivity compared with an earlier study. Approximately 150 d after intracerebral inoculation, both synthetic Aβ40 and Aβ42 prions produced a sustained rise in the bioluminescence imaging signal in the brains of bigenic Tg(APP23:Gfap-luc) mice, indicative of astrocytic gliosis. Pathological investigations showed that synthetic Aβ40 prions produced amyloid plaques containing both Aβ40 and Aβ42 in the brains of inoculated bigenic mice, whereas synthetic Aβ42 prions stimulated the formation of smaller, more numerous plaques composed predominantly of Aβ42. Synthetic Aβ40 preparations consisted of long straight fibrils; in contrast, the Aβ42 fibrils were much shorter. Addition of 3.47 mM (0.1%) SDS to the polymerization reaction produced Aβ42 fibrils that were indistinguishable from Aβ40 fibrils produced in the absence or presence of SDS. Moreover, the Aβ amyloid plaques in the brains of bigenic mice inoculated with Aβ42 prions prepared in the presence of SDS were similar to those found in mice that received Aβ40 prions. From these results, we conclude that the composition of Aβ plaques depends on the conformation of the inoculated Aβ polymers, and thus, these inocula represent distinct synthetic Aβ prion strains. PMID:24982137

  13. Amyloid in biopsies of the gastrointestinal tract-a retrospective observational study on 542 patients.

    PubMed

    Freudenthaler, Sophie; Hegenbart, Ute; Schönland, Stefan; Behrens, Hans-Michael; Krüger, Sandra; Röcken, Christoph

    2016-05-01

    In this retrospective observational study, we investigated the histopathological and demographic characteristics of amyloid in gastrointestinal biopsies. From the Amyloid Registry Kiel, we retrieved all cases with amyloid in biopsies of the stomach, duodenum, small intestine, large intestine, and rectum submitted for tertiary referral between January 2003 and April 2013. Amyloid was identified by Congo red staining in combination with polarization microscopy and classified by immunohistochemistry. The TTR-genotype was assessed in 56 patients. Amyloid type was correlated with demographic patient characteristics. Six hundred sixty-three biopsies from 542 patients were retrieved. Amyloid was found in each biopsy as vascular and/or interstitial amyloid deposits. Biopsies were obtained from the colon [254 biopsies (38.3 %)], stomach, [153 (23.1 %)], rectum [112 (16.9 %)], duodenum [105 (15.8 %)], and jejunum/ileum [39 (5.9 %)]. ALλ amyloid was found in 286 (52.8 %), ATTR in 88 (16.2 %), ALκ in 74 (13.7 %), AA in 58 (10.7 %), and ApoAI amyloid in 4 (0.7 %) patients. The remaining 21 cases were ALys amyloid in 4 (0.7 %), AL n.o.s. in 14 (2.6 %), and mixed type amyloidosis in 3 (0.6 %). The amyloid of 11 (2.0 %) cases remained unclassified. The median age of the patients was 68 years. Men [332 (61.7 %)] were significantly more prevalent than women [206 (38.3 %); p < 0.001]. TTR mutations were found in 24 % of the patients with ATTR amyloidosis. The median age, the histoanatomical distribution (proximal to distal; mucosal to submucosal), and the deposition pattern (vascular/interstitial) varied between different amyloid types. Amyloid in gastrointestinal biopsies mainly affects male elderly patients and shows amyloid-type-specific demographic patient characteristics. PMID:26915034

  14. AlN thin films prepared by DC arc deposition

    NASA Astrophysics Data System (ADS)

    Liang, Hai-feng; Yan, Yi-xin; Miao, Shu-fan

    2006-02-01

    Many researchers are interested in AlN films because of their novel thermal, chemical, mechanical, acoustic, and optical properties. Many methodsincluding such as DC/RF sputtering, chemical vapor deposition (CVD), laser chemical vapor deposition(LCVD), molecular beam epitaxy (MBE), thermal vapor deposition, can be used to prepare AlN films. In this paper, a new method, DC arc deposition, is used to deposite AlN films. It is an anti-reflective, protective film on optical elements. FTIR are used to determine the ALN structure and measure the transmittance spectrum. Ellipsometry is used to determine the films' refractive index, extinction index and thickness. The films' anti-wear properties are tested by pin-on-disc way and the anti-corrosion(anti-acid, anti-alkali, anti-salt) properties are also tested. The results show that the films is AlN films by the 670cm -1 typical peak, the films' extinction index is near to zero in the range of visible and infrared waveband, the films' refractive index is varied from 1.7 to 2.1 at range of visible and infrared waveband. The films have better anti-wear, anti-acid and anti-alkali properties, but their anti-salt properties are not good.

  15. Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI

    NASA Astrophysics Data System (ADS)

    Akamatsu, G.; Ikari, Y.; Ohnishi, A.; Nishida, H.; Aita, K.; Sasaki, M.; Yamamoto, Y.; Sasaki, M.; Senda, M.

    2016-08-01

    Amyloid PET is useful for early and/or differential diagnosis of Alzheimer’s disease (AD). Quantification of amyloid deposition using PET has been employed to improve diagnosis and to monitor AD therapy, particularly in research. Although MRI is often used for segmentation of gray matter and for spatial normalization into standard Montreal Neurological Institute (MNI) space where region-of-interest (ROI) template is defined, 3D MRI is not always available in clinical practice. The purpose of this study was to examine the feasibility of PET-only amyloid quantification with an adaptive template and a pre-defined standard ROI template that has been empirically generated from typical cases. A total of 68 subjects who underwent brain 11C-PiB PET were examined. The 11C-PiB images were non-linearly spatially normalized to the standard MNI T1 atlas using the same transformation parameters of MRI-based normalization. The automatic-anatomical-labeling-ROI (AAL-ROI) template was applied to the PET images. All voxel values were normalized by the mean value of cerebellar cortex to generate the SUVR-scaled images. Eleven typical positive images and eight typical negative images were normalized and averaged, respectively, and were used as the positive and negative template. Positive and negative masks which consist of voxels with SUVR  ⩾1.7 were extracted from both templates. Empirical PiB-prone ROI (EPP-ROI) was generated by subtracting the negative mask from the positive mask. The 11C-PiB image of each subject was non-rigidly normalized to the positive and negative template, respectively, and the one with higher cross-correlation was adopted. The EPP-ROI was then inversely transformed to individual PET images. We evaluated differences of SUVR between standard MRI-based method and PET-only method. We additionally evaluated whether the PET-only method would correctly categorize 11C-PiB scans as positive or negative. Significant correlation was observed between the SUVRs

  16. Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI.

    PubMed

    Akamatsu, G; Ikari, Y; Ohnishi, A; Nishida, H; Aita, K; Sasaki, M; Yamamoto, Y; Sasaki, M; Senda, M

    2016-08-01

    Amyloid PET is useful for early and/or differential diagnosis of Alzheimer's disease (AD). Quantification of amyloid deposition using PET has been employed to improve diagnosis and to monitor AD therapy, particularly in research. Although MRI is often used for segmentation of gray matter and for spatial normalization into standard Montreal Neurological Institute (MNI) space where region-of-interest (ROI) template is defined, 3D MRI is not always available in clinical practice. The purpose of this study was to examine the feasibility of PET-only amyloid quantification with an adaptive template and a pre-defined standard ROI template that has been empirically generated from typical cases. A total of 68 subjects who underwent brain (11)C-PiB PET were examined. The (11)C-PiB images were non-linearly spatially normalized to the standard MNI T1 atlas using the same transformation parameters of MRI-based normalization. The automatic-anatomical-labeling-ROI (AAL-ROI) template was applied to the PET images. All voxel values were normalized by the mean value of cerebellar cortex to generate the SUVR-scaled images. Eleven typical positive images and eight typical negative images were normalized and averaged, respectively, and were used as the positive and negative template. Positive and negative masks which consist of voxels with SUVR  ⩾1.7 were extracted from both templates. Empirical PiB-prone ROI (EPP-ROI) was generated by subtracting the negative mask from the positive mask. The (11)C-PiB image of each subject was non-rigidly normalized to the positive and negative template, respectively, and the one with higher cross-correlation was adopted. The EPP-ROI was then inversely transformed to individual PET images. We evaluated differences of SUVR between standard MRI-based method and PET-only method. We additionally evaluated whether the PET-only method would correctly categorize (11)C-PiB scans as positive or negative. Significant correlation was observed between the

  17. Modulation of γ-secretase by EVP-0015962 reduces amyloid deposition and behavioral deficits in Tg2576 mice

    PubMed Central

    2012-01-01

    Background A hallmark of Alzheimer’s disease is the presence of senile plaques in human brain primarily containing the amyloid peptides Aβ42 and Aβ40. Many drug discovery efforts have focused on decreasing the production of Aβ42 through γ-secretase inhibition. However, identification of γ-secretase inhibitors has also uncovered mechanism-based side effects. One approach to circumvent these side effects has been modulation of γ-secretase to shift Aβ production to favor shorter, less amyloidogenic peptides than Aβ42, without affecting the overall cleavage efficiency of the enzyme. This approach, frequently called γ-secretase modulation, appears more promising and has lead to the development of new therapeutic candidates for disease modification in Alzheimer’s disease. Results Here we describe EVP-0015962, a novel small molecule γ-secretase modulator. EVP-0015962 decreased Aβ42 in H4 cells (IC50 = 67 nM) and increased the shorter Aβ38 by 1.7 fold at the IC50 for lowering of Aβ42. AβTotal, as well as other carboxyl-terminal fragments of amyloid precursor protein, were not changed. EVP-0015962 did not cause the accumulation of other γ-secretase substrates, such as the Notch and ephrin A4 receptors, whereas a γ-secretase inhibitor reduced processing of both. A single oral dose of EVP-0015962 (30 mg/kg) decreased Aβ42 and did not alter AβTotal peptide levels in a dose-dependent manner in Tg2576 mouse brain at an age when overt Aβ deposition was not present. In Tg2576 mice, chronic treatment with EVP-0015962 (20 or 60 mg/kg/day in a food formulation) reduced Aβ aggregates, amyloid plaques, inflammatory markers, and cognitive deficits. Conclusions EVP-0015962 is orally bioavailable, detected in brain, and a potent, selective γ-secretase modulator in vitro and in vivo. Chronic treatment with EVP-0015962 was well tolerated in mice and lowered the production of Aβ42, attenuated memory deficits, and reduced Aβ plaque formation and inflammation in Tg

  18. Valproic acid alleviates memory deficits and attenuates amyloiddeposition in transgenic mouse model of Alzheimer's disease.

    PubMed

    Xuan, Ai-Guo; Pan, Xue-Bing; Wei, Peng; Ji, Wei-Dong; Zhang, Wen-Juan; Liu, Ji-Hong; Hong, Le-Peng; Chen, Wen-Liang; Long, Da-Hong

    2015-02-01

    In the brains of patients with Alzheimer's disease (AD) and transgenic AD mouse models, astrocytes and microglia activated by amyloid-β (Aβ) contribute to the inflammatory process that develops around injury in the brain. Valproic acid (VPA) has been shown to have anti-inflammatory function. The present study intended to explore the therapeutic effect of VPA on the neuropathology and memory deficits in APPswe/PS1ΔE9 (APP/PS1) transgenic mice. Here, we report that VPA-treated APP/PS1 mice markedly improved memory deficits and decreased Aβ deposition compared with the vehicle-treated APP/PS1 mice. Moreover, the extensive astrogliosis and microgliosis as well as the increased expression in interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the hippocampus and cortex of APP/PS1 transgenic mice were significantly reduced following administration of VPA, which attenuated neuronal degeneration. Concomitantly, VPA alleviated the levels of p65 NF-κB phosphorylation and enhanced the levels of acetyl-H3, Bcl-2, and phospho-glycogen synthase kinase (GSK)-3β that occurred in the hippocampus of APP/PS1 transgenic mice. These results demonstrate that VPA could significantly ameliorate spatial memory impairment and Aβ deposition at least in part via the inhibition of inflammation, suggesting that administration of VPA could provide a therapeutic approach for AD. PMID:24854198

  19. Discovery of a novel fluorescent probe for the sensitive detection of β-amyloid deposits.

    PubMed

    Ren, Wenming; Xu, Mingming; Liang, Steven H; Xiang, Huaijiang; Tang, Li; Zhang, Minkui; Ding, Dejun; Li, Xin; Zhang, Haiyan; Hu, Youhong

    2016-01-15

    Here we reported the development of the first photoinduced electron transfer (PeT) probe (1) to directly locate β-amyloid aggregates (Aβ plaques) in the brain without the need of post-washing procedures. The probe showed a high affinity for Aβ aggregates with a Kd value of 3.5nM. It is weakly emissive by itself with its fluorescence quenched by electron transfer from PeT donor to the excited fluorophore. But selective binding to Aβ plaques would attenuate the PeT process and restore the fluorescence, therefore facilitating the tracking of Aβ plaques. The probe is advantageous in that its fluorescence is environment-less-sensitive and no washing procedure is required to provide high contrast fluorescent signal when applied to stain brain tissues. As a proof of concept, its application has been exemplified by staining Aβ plaques in slices of brain tissue from double transgenic (APP/PS1) mice of Alzheimer's disease. PMID:26313423

  20. Detection of Alzheimer’s disease amyloid-beta plaque deposition by deep brain impedance profiling

    NASA Astrophysics Data System (ADS)

    Béduer, Amélie; Joris, Pierre; Mosser, Sébastien; Fraering, Patrick C.; Renaud, Philippe

    2015-04-01

    Objective. Alzheimer disease (AD) is the most common form of neurodegenerative disease in elderly people. Toxic brain amyloid-beta (Aß) aggregates and ensuing cell death are believed to play a central role in the pathogenesis of the disease. In this study, we investigated if we could monitor the presence of these aggregates by performing in situ electrical impedance spectroscopy measurements in AD model mice brains. Approach. In this study, electrical impedance spectroscopy measurements were performed post-mortem in APPPS1 transgenic mice brains. This transgenic model is commonly used to study amyloidogenesis, a pathological hallmark of AD. We used flexible probes with embedded micrometric electrodes array to demonstrate the feasibility of detecting senile plaques composed of Aß peptides by localized impedance measurements. Main results. We particularly focused on deep brain structures, such as the hippocampus. Ex vivo experiments using brains from young and old APPPS1 mice lead us to show that impedance measurements clearly correlate with the percentage of Aβ plaque load in the brain tissues. We could monitor the effects of aging in the AD APPPS1 mice model. Significance. We demonstrated that a localized electrical impedance measurement constitutes a valuable technique to monitor the presence of Aβ-plaques, which is complementary with existing imaging techniques. This method does not require prior Aβ staining, precluding the risk of variations in tissue uptake of dyes or tracers, and consequently ensuring reproducible data collection.

  1. Beta amyloid deposition and neurofibrillary tangles spontaneously occur in the brains of captive cheetahs (Acinonyx jubatus).

    PubMed

    Serizawa, S; Chambers, J K; Une, Y

    2012-03-01

    Alzheimer disease is a dementing disorder characterized pathologically by Aβ deposition, neurofibrillary tangles, and neuronal loss. Although aged animals of many species spontaneously develop Aβ deposits, only 2 species (chimpanzee and wolverine) have been reported to develop Aβ deposits and neurofibrillary tangles in the same individual. Here, the authors demonstrate the spontaneous occurrence of Aβ deposits and neurofibrillary tangles in captive cheetahs (Acinonyx jubatus). Among 22 cheetahs examined in this study, Aβ deposits were observed in 13. Immunostaining (AT8) revealed abnormal intracellular tau immunoreactivity in 10 of the cheetahs with Aβ deposits, and they were mainly distributed in the parahippocampal cortex and CA1 in a fashion similar to that in human patients with Alzheimer disease. Ultrastructurally, bundles of straight filaments filled the neuronal somata and axons, consistent with tangles. Interestingly, 2 of the cheetahs with the most severe abnormal tau immunoreactivity showed clinical cognitive dysfunction. The authors conclude that cheetahs spontaneously develop age-related neurodegenerative disease with pathologic changes similar to Alzheimer disease. PMID:21712514

  2. Cerebral amyloid angiopathy

    MedlinePlus

    ... Fenichel GM, Jankovic J, Mazziotta JC, eds. Bradley's Neurology in Clinical Practice . 6th ed. Philadelphia, PA: Elsevier ... al. Course of cerebral amyloid angiopathy-related inflammation. Neurology. 2007;68:1411-1416. PMID: 17452586 www.ncbi. ...

  3. Al/Al-N/AlN compositional gradient film synthesized by ion-beam assisted deposition method

    SciTech Connect

    Amamoto, Yoshiki; Uchiyama, Shingo; Watanabe, Yoshihisa; Nakamura, Yoshikazu

    1997-12-01

    Al/Al-N-AlN compositional gradient thin film was deposited on a Si(100) substrate at room temperature by ion-beam assisted deposition method, with a diminishing ion beam current from 1.4 to 0 mA at increments of 0.3 mA in order to gradually decrease the nitrogen to aluminum ratio at the substrate. The gradual Al and AlN variation in composition was shown by the change of the Al/N atomic ratio analyzed by the energy dispersive X-ray spectroscopy (EDX) and the X-ray photoelectron spectroscopy (XPS) in the cross section of the film. The formation of crystalline Al metal and AlN ceramic layer on the Si substrate was revealed by X-ray diffraction (XRD). The cross sectional image taken by high resolution transmission electron microscope (HRTEM) showed a nano-sized crystalline Al-N ceramic material and the flat interface between the Si substrate and the AlN film.

  4. Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes

    SciTech Connect

    McWilliams-Koeppen, Helen P.; Foster, James S.; Hackenbrack, Nicole; Ramirez-Alvarado, Marina; Donohoe, Dallas; Williams, Angela; Macy, Sallie; Wooliver, Craig; Wortham, Dale; Morrell-Falvey, Jennifer; Foster, Carmen M.; Kennel, Stephen J.; Wall, Jonathan S.

    2015-09-22

    Light chain (AL) amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(P)H-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. Ultimately, these data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils.

  5. Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes

    DOE PAGESBeta

    McWilliams-Koeppen, Helen P.; Foster, James S.; Hackenbrack, Nicole; Ramirez-Alvarado, Marina; Donohoe, Dallas; Williams, Angela; Macy, Sallie; Wooliver, Craig; Wortham, Dale; Morrell-Falvey, Jennifer; et al

    2015-09-22

    Light chain (AL) amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(P)H-dependent oxidoreductase, without causing significant cell death. The presencemore » of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. Ultimately, these data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils.« less

  6. Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes

    PubMed Central

    McWilliams-Koeppen, Helen P.; Foster, James S.; Hackenbrack, Nicole; Ramirez-Alvarado, Marina; Donohoe, Dallas; Williams, Angela; Macy, Sallie; Wooliver, Craig; Wortham, Dale; Morrell-Falvey, Jennifer; Foster, Carmen M.; Kennel, Stephen J.; Wall, Jonathan S.

    2015-01-01

    Light chain (AL) amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(P)H-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. These data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils. PMID:26393799

  7. APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study

    PubMed Central

    Ramanan, Vijay K.; Risacher, Shannon L.; Nho, Kwangsik; Kim, Sungeun; Swaminathan, Shanker; Shen, Li; Foroud, Tatiana M.; Hakonarson, Hakon; Huentelman, Matthew J.; Aisen, Paul S.; Petersen, Ronald C.; Green, Robert C.; Jack, Clifford R.; Koeppe, Robert A.; Jagust, William J.; Weiner, Michael W.; Saykin, Andrew J.

    2013-01-01

    Deposition of amyloid-β (Aβ) in the cerebral cortex is thought to be a pivotal event in Alzheimer’s disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an early noninvasive phenotype but small samples have prohibited genome-wide association studies (GWAS) of cortical Aβ load until now. We employed florbetapir (18F) positron emission tomography (PET) imaging to assess brain Aβ levels in vivo for 555 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). More than six million common genetic variants were tested for association to quantitative global cortical Aβ load controlling for age, gender, and diagnosis. Independent genome-wide significant associations were identified on chromosome 19 within APOE (rs429358, p = 5.5 × 10−14) and on chromosome 3 upstream of BCHE (rs509208, p = 2.7 × 10−8) in a region previously associated with serum butyrylcholinesterase activity. Together, these loci explained 15% of the variance in cortical Aβ levels in this sample (APOE 10.7%, BCHE 4.3%). Suggestive associations were identified within ITGA6, near EFNA5, EDIL3, ITGA1, PIK3R1, NFIB, and ARID1B, and between NUAK1 and C12orf75. These results confirm the association of APOE with Aβ deposition and represent the largest known effect of BCHE on an AD-related phenotype. Butyrylcholinesterase has been found in senile plaques and this new association of genetic variation at the BCHE locus with Aβ burden in humans may have implications for potential disease-modifying effects of butyrylcholinesterase-modulating agents in the AD spectrum. PMID:23419831

  8. WC-Co/Al Multilayer Coatings by Warm Spray Deposition

    NASA Astrophysics Data System (ADS)

    Watanabe, Makoto; Komatsu, Masayuki; Kuroda, Seiji

    2012-06-01

    WC-Co/aluminum multilayer coatings have been developed by using warm spray deposition to improve fracture toughness and damage tolerance of conventional WC-Co coatings and to investigate the effects of ductile layer addition on their fracture properties. Prior to depositing the multilayer coatings, the mechanical properties of three metal coatings of aluminum, copper, and titanium, which were deposited by warm spraying, were evaluated. The aluminum coating showed excellent ductility among them and was selected for use as ductile layers for the multilayer coatings. The fracture behavior of WC-Co/Al coatings was examined by the four-point bending test. The multilayer coatings did not break in a brittle manner after reaching maximum load, but exhibited a plateau as a result of the ductility of the aluminum layers. The fracture behavior was compared with the finite element analysis results, and they showed good agreement in a general trend. It has been concluded that ductile metal reinforcements, by advanced thermal spray techniques such as warm spray deposition, are very effective to enhance the toughness and damage tolerance of sprayed cermet coatings.

  9. Functional Changes in the Language Network in Response to Increased Amyloid β Deposition in Cognitively Intact Older Adults.

    PubMed

    Adamczuk, Katarzyna; De Weer, An-Sofie; Nelissen, Natalie; Dupont, Patrick; Sunaert, Stefan; Bettens, Karolien; Sleegers, Kristel; Van Broeckhoven, Christine; Van Laere, Koen; Vandenberghe, Rik

    2016-01-01

    Word finding symptoms are frequent early in the course of Alzheimer's disease and relate principally to functional changes in left posterior temporal cortex. In cognitively intact older adults, we examined whether amyloid load affects the network for language and associative-semantic processing. Fifty-six community-recruited subjects (52-74 years), stratified for apolipoprotein E and brain-derived neurotrophic factor genotype, received a neurolinguistic assessment, (18)F-flutemetamol positron emission tomography, and a functional MRI of the associative-semantic system. The primary measure of amyloid load was the cerebral-to-cerebellar gray matter standardized uptake value ratio in a composite cortical volume of interest (SUVR(comp)). The primary outcome analysis consisted of a whole-brain voxelwise linear regression between SUVR(comp) and fMRI response during associative-semantic versus visuoperceptual processing. Higher activity in one region, the posterior left middle temporal gyrus, correlated positively with increased amyloid load. The correlation remained significant when only the word conditions were contrasted but not for pictures. According to a stepwise linear regression analysis, offline naming reaction times correlated positively with SUVR(comp). A binary classification into amyloid-positive and amyloid-negative cases confirmed our findings. The left posterior temporal activity increase may reflect higher demands for semantic control in the presence of a higher amyloid burden. PMID:25452579

  10. Amyloid deposits in bioprosthetic cardiac valves after long-term implantation in man. A new localization of amyloidosis.

    PubMed Central

    Goffin, Y. A.; Gruys, E.; Sorenson, G. D.; Wellens, F.

    1984-01-01

    Congo red staining with microscopic examination under polarized light was performed in 30 porcine bioprosthetic cardiac valves and one autologous fascia lata valve explanted from 31 patients in order to detect the presence of amyloid. Microdeposits of amyloid were present in the sewing ring of the fascia lata valve and in 10 porcine bioprostheses, and this finding was confirmed by transmission electron microscopy in 3 porcine bioprostheses. All amyloid-laden porcine valves had been implanted for at least 33 months before removal, and all except two showed dysfunction and/or severe degeneration of cuspal tissue. Statistical analyses failed to establish any correlation between the presence of amyloid and patient-related factors. In a majority of porcine bioprostheses amyloid was permanganate-sensitive and tryptophan-positive. The pathogenesis of this new form of heart valve amyloidosis might consist in penetration of human macrophages in deteriorated bioprosthetic cusps and their interaction with blood-borne amyloid precursors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:6421168

  11. Distinguishable effects of presenilin-1 and APP717 mutations on amyloid plaque deposition.

    PubMed

    Ishii, K; Lippa, C; Tomiyama, T; Miyatake, F; Ozawa, K; Tamaoka, A; Hasegawa, T; Fraser, P E; Shoji, S; Nee, L E; Pollen, D A; St George-Hyslop, P H; Ii, K; Ohtake, T; Kalaria, R N; Rossor, M N; Lantos, P L; Cairns, N J; Farrer, L A; Mori, H

    2001-01-01

    Both APP and PS-1 are causal genes for early-onset familial Alzheimer's disease (AD) and their mutation effects on cerebral Abeta deposition in the senile plaques were examined in human brains of 29 familial AD (23 PS-1, 6 APP) cases and 14 sporadic AD cases in terms of Abeta40 and Abeta42. Abeta isoform data were evaluated using repeated measures analysis of variance which adjusted for within-subject measurement variation and confounding effects of individual APP and PS-1 mutations, age at onset, duration of illness and APOE genotype. We observed that mutations in both APP and PS-1 were associated with a significant increase of Abeta42 in plaques as been documented previously. In comparison to sporadic AD cases, both APP717 and PS-1 mutation cases had an increased density (measured as the number of plaques/mm(2)) and area (%) of Abeta42 plaques. However, we found an unexpected differential effect of PS-1 but not APP717 mutation cases. At least some of PS-1 but not APP717 mutation cases had the significant increase of density and area of Abeta40-plaques as compared to sporadic AD independently of APOE genotype. Our results suggest that PS-1 mutations affect cerebral accumulation of Abeta burden in a different fashion from APP717 mutations in their familial AD brains. PMID:11378241

  12. Electromagnetic Treatment to Old Alzheimer's Mice Reverses β-Amyloid Deposition, Modifies Cerebral Blood Flow, and Provides Selected Cognitive Benefit

    PubMed Central

    Arendash, Gary W.; Mori, Takashi; Dorsey, Maggie; Gonzalez, Rich; Tajiri, Naoki; Borlongan, Cesar

    2012-01-01

    Few studies have investigated physiologic and cognitive effects of “long-term" electromagnetic field (EMF) exposure in humans or animals. Our recent studies have provided initial insight into the long-term impact of adulthood EMF exposure (GSM, pulsed/modulated, 918 MHz, 0.25–1.05 W/kg) by showing 6+ months of daily EMF treatment protects against or reverses cognitive impairment in Alzheimer's transgenic (Tg) mice, while even having cognitive benefit to normal mice. Mechanistically, EMF-induced cognitive benefits involve suppression of brain β-amyloid (Aβ) aggregation/deposition in Tg mice and brain mitochondrial enhancement in both Tg and normal mice. The present study extends this work by showing that daily EMF treatment given to very old (21–27 month) Tg mice over a 2-month period reverses their very advanced brain Aβ aggregation/deposition. These very old Tg mice and their normal littermates together showed an increase in general memory function in the Y-maze task, although not in more complex tasks. Measurement of both body and brain temperature at intervals during the 2-month EMF treatment, as well as in a separate group of Tg mice during a 12-day treatment period, revealed no appreciable increases in brain temperature (and no/slight increases in body temperature) during EMF “ON" periods. Thus, the neuropathologic/cognitive benefits of EMF treatment occur without brain hyperthermia. Finally, regional cerebral blood flow in cerebral cortex was determined to be reduced in both Tg and normal mice after 2 months of EMF treatment, most probably through cerebrovascular constriction induced by freed/disaggregated Aβ (Tg mice) and slight body hyperthermia during “ON" periods. These results demonstrate that long-term EMF treatment can provide general cognitive benefit to very old Alzheimer's Tg mice and normal mice, as well as reversal of advanced Aβ neuropathology in Tg mice without brain heating. Results further underscore the potential for EMF

  13. Replacement of brain-resident myeloid cells does not alter cerebral amyloiddeposition in mouse models of Alzheimer's disease.

    PubMed

    Varvel, Nicholas H; Grathwohl, Stefan A; Degenhardt, Karoline; Resch, Claudia; Bosch, Andrea; Jucker, Mathias; Neher, Jonas J

    2015-10-19

    Immune cells of myeloid lineage are encountered in the Alzheimer's disease (AD) brain, where they cluster around amyloid-β plaques. However, assigning functional roles to myeloid cell subtypes has been problematic, and the potential for peripheral myeloid cells to alleviate AD pathology remains unclear. Therefore, we asked whether replacement of brain-resident myeloid cells with peripheral monocytes alters amyloid deposition in two mouse models of cerebral β-amyloidosis (APP23 and APPPS1). Interestingly, early after repopulation, infiltrating monocytes neither clustered around plaques nor showed Trem2 expression. However, with increasing time in the brain, infiltrating monocytes became plaque associated and also Trem2 positive. Strikingly, however, monocyte repopulation for up to 6 mo did not modify amyloid load in either model, independent of the stage of pathology at the time of repopulation. Our results argue against a long-term role of peripheral monocytes that is sufficiently distinct from microglial function to modify cerebral β-amyloidosis. Therefore, myeloid replacement by itself is not likely to be effective as a therapeutic approach for AD. PMID:26458770

  14. Wharton's Jelly-derived mesenchymal stem cells alleviate memory deficits and reduce amyloiddeposition in an APP/PS1 transgenic mouse model.

    PubMed

    Xie, Zhao-Hong; Liu, Zhen; Zhang, Xiao-Ran; Yang, Hui; Wei, Li-Fei; Wang, Yun; Xu, Shun-Liang; Sun, Lin; Lai, Chao; Bi, Jian-Zhong; Wang, Xiao-Yun

    2016-02-01

    Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles, and neuronal loss. Cumulative evidence supports that neuroinflammation is an important factor for the pathogenesis of AD and contributes to amyloid beta (Aβ) generation. However, there has been no effective treatment for AD. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have a potential therapeutic effect in the treatment for neurological diseases. In the present study, we evaluated the therapeutic effect of WJ-MSC transplantation on the neuropathology and memory deficits in amyloid precursor protein (APP) and presenilin-1 (PS1) double-transgenic mice and discussed the mechanism. WJ-MSCs were intravenously transplanted into the APP/PS1 mice. Four weeks after treatment, WJ-MSCs significantly improved the spatial learning and alleviated the memory decline in the APP/PS1 mice. Aβ deposition and soluble Aβ levels were significantly reduced after WJ-MSC treatment. Furthermore, WJ-MSCs significantly increased the expression of the anti-inflammatory cytokine, IL-10. Meanwhile, pro-inflammatory microglial activation and the expressions of pro-inflammatory cytokines, IL-1β and TNFα, were significantly down-regulated by WJ-MSC treatment. Thus, our findings suggest that WJ-MSCs might produce beneficial effects on the prevention and treatment for AD through modulation of neuroinflammation. PMID:26188488

  15. Antimicrobial Properties of Amyloid Peptides

    PubMed Central

    Kagan, Bruce L.; Jang, Hyunbum; Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh; Nussinov, Ruth

    2011-01-01

    More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-β structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape β-strand-turn-β-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids are not only toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function. PMID:22081976

  16. Early vitamin E supplementation in young but not aged mice reduces Abeta levels and amyloid deposition in a transgenic model of Alzheimer's disease.

    PubMed

    Sung, Syuan; Yao, Yuemang; Uryu, Kunihiro; Yang, Hengxuan; Lee, Virginia M-Y; Trojanowski, John Q; Praticò, Domenico

    2004-02-01

    Increased brain oxidative stress is a key feature of Alzheimer's disease (AD) and manifests predominantly as lipid peroxidation. However, clinical evidence that antioxidants can affect the clinical course of the disease is limited. In the present study, we investigated the effect of the antioxidant Vitamin E on the AD-like phenotype when given to a transgenic mouse model (Tg2576) of the disease before or after the amyloid plaques are deposited. One group of Tg2576 received Vitamin E starting at 5 months of age until they were 13 months old, the second group started at 14 months of age until they were 20 months old. Brain levels of 8,12-iso-iPF2alpha-VI, a specific marker of lipid peroxidation, were significantly reduced in both groups of mice receiving Vitamin E compared with placebo. Tg2576 administered with Vitamin E at a younger age showed a significant reduction in Abeta levels and amyloid deposition. By contrast, mice receiving the diet supplemented with Vitamin E at a later age did not show any significant difference in either marker when compared with placebo. These results support the hypothesis that oxidative stress is an important early event in AD pathogenesis, and antioxidant therapy may be beneficial only if given at this stage of the disease process. PMID:14656990

  17. In vivo detection of amyloiddeposits using heavy chain antibody fragments in a transgenic mouse model for Alzheimer's disease.

    PubMed

    Nabuurs, Rob J A; Rutgers, Kim S; Welling, Mick M; Metaxas, Athanasios; de Backer, Maaike E; Rotman, Maarten; Bacskai, Brian J; van Buchem, Mark A; van der Maarel, Silvère M; van der Weerd, Louise

    2012-01-01

    This study investigated the in vivo properties of two heavy chain antibody fragments (V(H)H), ni3A and pa2H, to differentially detect vascular or parenchymal amyloiddeposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled V(H)H in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for Aβ was examined in more detail with fluorescently labeled V(H)H by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All V(H)H showed rapid renal clearance (10-20 min). Twenty-four hours post-injection (99m)Tc-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for (99m)Tc-ni3A or DTPA((111)In)-pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for Aβ was confirmed for both fluorescently labeled V(H)H, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both V(H)H showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular Aβ. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that V(H)H detect Aβ deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different Aβ deposits. PMID:22675537

  18. In Vivo Detection of AmyloidDeposits Using Heavy Chain Antibody Fragments in a Transgenic Mouse Model for Alzheimer's Disease

    PubMed Central

    Welling, Mick M.; Metaxas, Athanasios; de Backer, Maaike E.; Rotman, Maarten; Bacskai, Brian J.; van Buchem, Mark A.; van der Maarel, Silvère M.; van der Weerd, Louise

    2012-01-01

    This study investigated the in vivo properties of two heavy chain antibody fragments (VHH), ni3A and pa2H, to differentially detect vascular or parenchymal amyloiddeposits characteristic for Alzheimer's disease and cerebral amyloid angiopathy. Blood clearance and biodistribution including brain uptake were assessed by bolus injection of radiolabeled VHH in APP/PS1 mice or wildtype littermates. In addition, in vivo specificity for Aβ was examined in more detail with fluorescently labeled VHH by circumventing the blood-brain barrier via direct application or intracarotid co-injection with mannitol. All VHH showed rapid renal clearance (10–20 min). Twenty-four hours post-injection 99mTc-pa2H resulted in a small yet significant higher cerebral uptake in the APP/PS1 animals. No difference in brain uptake were observed for 99mTc-ni3A or DTPA(111In)-pa2H, which lacked additional peptide tags to investigate further clinical applicability. In vivo specificity for Aβ was confirmed for both fluorescently labeled VHH, where pa2H remained readily detectable for 24 hours or more after injection. Furthermore, both VHH showed affinity for parenchymal and vascular deposits, this in contrast to human tissue, where ni3A specifically targeted only vascular Aβ. Despite a brain uptake that is as yet too low for in vivo imaging, this study provides evidence that VHH detect Aβ deposits in vivo, with high selectivity and favorable in vivo characteristics, making them promising tools for further development as diagnostic agents for the distinctive detection of different Aβ deposits. PMID:22675537

  19. Fabrication and kinetics study of nano-Al/NiO thermite film by electrophoretic deposition.

    PubMed

    Zhang, Daixiong; Li, Xueming

    2015-05-21

    Nano-Al/NiO thermites were successfully prepared as film by electrophoretic deposition (EPD). For the key issue of this EPD, a mixture solvent of ethanol-acetylacetone (1:1 in volume) containing 0.00025 M nitric acid was proved to be a suitable dispersion system for EPD. The kinetics of electrophoretic deposition for both nano-Al and nano-NiO were investigated; the linear relation between deposition weight and deposition time in short time and parabolic relation in prolonged time were observed in both EPDs. The critical transition time between linear deposition kinetics and parabolic deposition kinetics for nano-Al and nano-NiO were 20 and 10 min, respectively. The theoretical calculation of the kinetics of electrophoretic deposition revealed that the equivalence ratio of nano-Al/NiO thermites film would be affected by the behavior of electrophoretic deposition for nano-Al and nano-NiO. The equivalence ratio remained steady when the linear deposition kinetics dominated for both nano-Al and nano-NiO. The equivalence ratio would change with deposition time when deposition kinetics for nano-NiO changed into parabolic kinetics dominated after 10 min. Therefore, the rule was suggested to be suitable for other EPD of bicomposites. We also studied thermodynamic properties of electrophoretic nano-Al/NiO thermites film as well as combustion performance. PMID:25950271

  20. Thermodynamic and fibril formation studies of full length immunoglobulin light chain AL-09 and its germline protein using scan rate dependent thermal unfolding.

    PubMed

    Blancas-Mejía, Luis M; Horn, Timothy J; Marin-Argany, Marta; Auton, Matthew; Tischer, Alexander; Ramirez-Alvarado, Marina

    2015-12-01

    Light chain (AL) amyloidosis is a fatal disease where monoclonal immunoglobulin light chains deposit as insoluble amyloid fibrils. For many years it has been considered that AL amyloid deposits are formed primarily by the variable domain, while its constant domain has been considered not to be amyloidogenic. However recent studies identify full length (FL) light chains as part of the amyloid deposits. In this report, we compare the stabilities and amyloidogenic properties of two light chains, an amyloid-associated protein AL-09 FL, and its germline protein κ I O18/O8 FL (IGKV 1-33). We demonstrate that the thermal unfolding for both proteins is irreversible and scan rate dependent, with similar stability parameters compared to their VL counterparts. In addition, the constant domain seems to modulate their amyloidogenic properties and affect the morphology of the amyloid fibrils. These results allow us to understand the role of the kappa constant domain in AL amyloidosis. PMID:26263488

  1. Apatite deposition and collagen coating effects in Ti-Al-V and Ti-Al-Nb alloys

    NASA Astrophysics Data System (ADS)

    Choi, Y.; Hong, S. I.

    2014-12-01

    The biomimetic deposition rate of apatite for Ti-6Al-4V was found to be greater than that for Ti-6Al-7Nb in regular 1 × Modified SBF. The coating of collagen was found to enhance the biomimetic deposition of apatite on Ti-6Al-4V and Ti-6Al-7Nb. The nucleation and growth of the apatite deposition layer was faster on collagen coated Ti alloys. An interesting observation is that the granular structure became less clear and the nodular boundary became obscure in apatite deposited on the collagen-coated Ti alloys. The ill-defined granular structure may be associated with the presence of more amorphous calcium phosphate. The morphology of apatite nodules was found to be modified by collagen coating and collagen addition.

  2. Reduction of low-density lipoprotein receptor-related protein (LRP1) in hippocampal neurons does not proportionately reduce, or otherwise alter, amyloid deposition in APPswe/PS1dE9 transgenic mice

    PubMed Central

    2012-01-01

    Introduction The low-density lipoprotein receptor-related protein (LRP1) and its family members have been implicated in the pathogenesis of Alzheimer's disease. Multiple susceptibility factors converge to metabolic pathways that involve LRP1, including modulation of the processing of amyloid precursor protein (APP) and the clearance of Aβ peptide. Methods We used the Cre-lox system to lower LRP1 levels in hippocampal neurons of mice that develop Alzheimer-type amyloid by crosses between mice that express Cre recombinase under the transcriptional control of the GFAP promoter, mice that harbor loxp sites in the LRP1 gene, and the APPswe/PS1dE9 transgenic model. We compared amyloid plaque numbers in APPswe/PS1dE9 mice lacking LRP1 expression in hippocampus (n = 13) to mice with normal levels of LRP1 (n = 12). Student t-test was used to test whether there were significant differences in plaque numbers and amyloid levels between the groups. A regression model was used to fit two regression lines for these groups, and to compare the rates of Aβ accumulation. Results Immunohistochemical analyses demonstrated efficient elimination of LRP1 expression in the CA fields and dentate gyrus of the hippocampus. Within hippocampus, we observed no effect on the severity of amyloid deposition, the rate of Aβ40/42 accumulation, or the architecture of amyloid plaques when LRP1 levels were reduced. Conclusions Expression of LRP1 by neurons in proximity to senile amyloid plaques does not appear to play a major role in modulating the formation of these proximal deposits or in the appearance of the associated neuritic pathology. PMID:22537779

  3. Selenomethionine reduces the deposition of beta-amyloid plaques by modulating β-secretase and enhancing selenoenzymatic activity in a mouse model of Alzheimer's disease.

    PubMed

    Zhang, Zhong-Hao; Chen, Chen; Wu, Qiu-Yan; Zheng, Rui; Liu, Qiong; Ni, Jia-Zuan; Hoffmann, Peter R; Song, Guo-Li

    2016-08-01

    Alzheimer's disease (AD) is characterized by the production of large amounts of beta-amyloid (Aβ) and the accumulation of extracellular senile plaques, which have been considered to be potential targets in the treatment of AD. Selenium (Se) is a nutritionally essential trace element with known antioxidant potential and Se status has been shown to decrease with age and has a close relationship with cognitive competence in AD. Selenomethionine (Se-Met), a major reserve form of Se in organisms, has been shown in our previous study to ameliorate the decline in cognitive function, increase oxidation resistance, and reduce tau hyperphosphorylation in a triple transgenic mouse model of AD. However, it has not been reported whether Se-Met has any effects on Aβ pathology in AD mice. To study the effect of Se-Met on Aβ pathology and the function of selenoproteins/selenoenzymes in 3× Tg-AD mice, 3× Tg-AD mice at 8 months of age were treated with Se-Met for 3 months. Se-Met led to significantly reduced production and deposition of Aβ, down-regulation of β-secretase levels and enhanced activity of selenoenzymes as well as increased levels of Se in the hippocampus and cortex. Se-Met reduces amyloidogenic processing of amyloid precursor protein while modulating β-secretase and selenoenzymatic activity in AD mice. These results indicate that Se-Met might exert its therapeutic effect through multiple pathways in AD. PMID:27465436

  4. Changes in the distribution of anionic sites in brain micro-blood vessels with and without amyloid deposits in scrapie-infected mice.

    PubMed

    Vorbrodt, A W; Dobrogowska, D H; Lossinsky, A S; Wisniewski, H M

    1990-01-01

    Cationic colloidal gold (CCG) and scrapie-infected mouse brain samples embedded in Lowicryl K4M were used for ultrastructural localization of negatively charged microdomains (anionic sites) in the cerebral microvasculature. The distribution of anionic sites on both fronts (luminal and abluminal) of endothelial cells and in the basement membrane (BM) in the majority of micro-blood vessels (MBVs) located outside the plaque area and in the remaining cerebral cortex was similar to that which has been previously observed in non-infected animals. Some MBVs (especially capillaries), however, located inside the plaque areas and surrounded directly by amyloid fibers contained attenuated endothelium, the luminal surface of which showed a segmental lack or diminution of anionic sites. In these vessels the BM was frequently infiltrated and replaced by the amyloid fibers. In some vessels located mainly in the areas of the neuropil vacuolization deposits of homogenous material causing the thickening of the BM were noted. These changes were accompanied by irregular labeling of the BM with gold particles. At the sites of bifurcation of some MBVs, predominantly in the area of the venular estuary at the mouth of capillary (at capillary-venular connections), a discontinuity in the distribution of anionic sites was noted. The observed disturbances in the distribution of anionic sites can be associated with a previously noted increased permeability of some MBVs in the brains of scrapie-infected mice. PMID:2339589

  5. Transmissible amyloid.

    PubMed

    Tjernberg, L O; Rising, A; Johansson, J; Jaudzems, K; Westermark, P

    2016-08-01

    There are around 30 human diseases associated with protein misfolding and amyloid formation, each one caused by a certain protein or peptide. Many of these diseases are lethal and together they pose an enormous burden to society. The prion protein has attracted particular interest as being shown to be the pathogenic agent in transmissible diseases such as kuru, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Whether similar transmission could occur also in other amyloidoses such as Alzheimer's disease, Parkinson's disease and serum amyloid A amyloidosis is a matter of intense research and debate. Furthermore, it has been suggested that novel biomaterials such as artificial spider silk are potentially amyloidogenic. Here, we provide a brief introduction to amyloid, prions and other proteins involved in amyloid disease and review recent evidence for their potential transmission. We discuss the similarities and differences between amyloid and silk, as well as the potential hazards associated with protein-based biomaterials. PMID:27002185

  6. Genesis and evolution of the Baid al Jimalah tungsten deposit, Kingdom of Saudi Arabia

    USGS Publications Warehouse

    Kamilli, Robert J.

    1986-01-01

    Baid al Jimalah is similar in character and origin to other tungsten-tin greisen deposits in the world, especially the Hemerdon deposit in Devon, England. It is also analogous to Climax-type molybdenum deposits, which contain virtually identical mineral assemblages, but with the relative intensities of the molybdenum and tungsten mineralization reversed.

  7. Vacuum ultraviolet photochemical selective area atomic layer deposition of Al2O3 dielectrics

    NASA Astrophysics Data System (ADS)

    Chalker, P. R.; Marshall, P. A.; Dawson, K.; Brunell, I. F.; Sutcliffe, C. J.; Potter, R. J.

    2015-01-01

    We report the photochemical atomic layer deposition of Al2O3 thin films and the use of this process to achieve area-selective film deposition. A shuttered vacuum ultraviolet (VUV) light source is used to excite molecular oxygen and trimethyl aluminum to deposit films at 60°C. In-situ QCM and post-deposition ellipsometric measurements both show that the deposition rate is saturative as a function of irradiation time. Selective area deposition was achieved by projecting the VUV light through a metalized magnesium fluoride photolithographic mask and the selectivity of deposition on the illuminated and masked regions of the substrate is a logarithmic function of the UV exposure time. The Al2O3 films exhibit dielectric constants of 8 - 10 at 1 MHz after forming gas annealing, similar to films deposited by conventional thermal ALD.

  8. Atomic layer controlled deposition of Al 2O 3 films using binary reaction sequence chemistry

    NASA Astrophysics Data System (ADS)

    Ott, A. W.; McCarley, K. C.; Klaus, J. W.; Way, J. D.; George, S. M.

    1996-11-01

    Al 2O 3 films with precise thicknesses and high conformality were deposited using sequential surface chemical reactions. To achieve this controlled deposition, a binary reaction for Al 2O 3 chemical vapor deposition (2Al(CH 3) 3 + 3H 2O → Al 2O 3 + 6CH 4) was separated into two half-reactions: (A) AlOH ∗ + Al(CH 3) 3 → AlOAl(CH 3) 2∗ + CH 4, (B) AlCH 3∗ + H 2O → AlOH ∗ + CH 4, where the asterisks designate the surface species. Trimethylaluminum (Al(CH 3) 3) (TMA) and H 2O reactants were employed alternately in an ABAB … binary reaction sequence to deposit Al 2O 3 films on single-crystal Si(100) and porous alumina membranes with pore diameters of ˜ 220 Å. Ellipsometric measurements obtained a growth rate of 1.1 Å/AB cycle on the Si(100) substrate at the optimal reaction conditions. The Al 2O 3 films had an index of refraction of n = 1.65 that is consistent with a film density of ϱ = 3.50 g/cm 3. Atomic force microscope images revealed that the Al 2O 3 films were exceptionally flat with a surface roughness of only ±3 Å ( rms) after the deposition of ˜ 270 Å using 250 AB reaction cycles. Al 2O 3 films were also deposited inside the pores of Anodisc alumina membranes. Gas flux measurements for H 2 and N 2 were consistent with a progressive pore reduction versus number of AB reaction cycles. Porosimetry measurements also showed that the original pore diameter of ˜ 220 Å was reduced to ˜ 130 Å after 120 AB reaction cycles.

  9. Establishing the fluorescent amyloid ligand h-FTAA for studying human tissues with systemic and localized amyloid.

    PubMed

    Sjölander, Daniel; Röcken, Christoph; Westermark, Per; Westermark, Gunilla T; Nilsson, K Peter R; Hammarström, Per

    2016-06-01

    Rapid and accurate detection of amyloid deposits in routine surgical pathology settings are of great importance. The use of fluorescence microscopy in combination with appropriate amyloid specific dyes is very promising in this regard. Here we report that a luminescent conjugated oligothiophene, h-FTAA, rapidly and with high sensitivity and selectivity detects amyloid deposits in verified clinical samples from systemic amyloidosis patients with AA, AL and ATTR types; as well as in tissues laden with localized amyloidosis of AANF, AIAPP and ASem1 type. The probe h-FTAA emitted yellow red fluorescence on binding to amyloid deposits, whereas no apparent staining was observed in surrounding tissue. The only functional structure stained with h-FTAA showing the amyloidotypic fluorescence spectrum was Paneth cell granules in intestine. Screening of 114 amyloid containing tissues derived from 107 verified (Congo red birefringence and/or immunohistochemistry) amyloidosis patients revealed complete correlation between h-FTAA and Congo red fluorescence (107/107, 100% sensitivity). The majority of Congo red negative control cases (27 of 32, 85% specificity) were negative with h-FTAA. Small Congo red negative aggregates in kidney, liver, pancreas and duodenum were found by h-FTAA fluorescence in five control patients aged 72-83 years suffering from diverse diseases. The clinical significance of these false-positive lesions is currently not known. Because h-FTAA fluorescence is one magnitude brighter than Congo red and as the staining is performed four magnitudes lower than the concentration of dye, we believe that these inclusions are beyond detection by Congo red. We conclude that h-FTAA is a fluorescent hypersensitive, rapid and powerful tool for identifying amyloid deposits in tissue sections. Use of h-FTAA can be exploited as a rapid complementary technique for accurate detection of amyloid in routine surgical pathology settings. Our results also implicate the potential of

  10. In situ atomic layer deposition half cycle study of Al2O3 growth on AlGaN

    NASA Astrophysics Data System (ADS)

    Brennan, Barry; Qin, Xiaoye; Dong, Hong; Kim, Jiyoung; Wallace, Robert M.

    2012-11-01

    The atomic layer deposition (ALD) of Al2O3 on the native oxide and hydrofluoric acid treated Al0.25Ga0.75 N surface was studied using in situ X-ray photoelectron spectroscopy (XPS), after each individual "half cycle" of the ALD process. Initially, Al2O3, Ga2O3, and N-O states were detected on both surfaces at differing concentrations. During the course of the deposition process, the N-O bonds are seen to decrease to within XPS detection limits, as well as a small decrease in the Ga2O3 concentration. The Al2O3 growth rate initially is seen to be very low, indication of low reactivity between the trimethyl-aluminum molecule and the AlGaN surface.

  11. Prophylactic liraglutide treatment prevents amyloid plaque deposition, chronic inflammation and memory impairment in APP/PS1 mice.

    PubMed

    McClean, Paula L; Jalewa, Jaishree; Hölscher, Christian

    2015-10-15

    Type 2 diabetes is a risk factor for Alzheimer's disease (AD). Previously, we have shown that the diabetes drug liraglutide is protective in middle aged and in old APP/PS1 mice. Here, we show that liraglutide has prophylactic properties. When injecting liraglutide once-daily ip. in two months old mice for 8 months, the main hallmarks of AD were much reduced. Memory formation in object recognition and Morris water maze were normalised and synapse loss and the loss of synaptic plasticity was prevented. In addition, amyloid plaque load, including dense core congophilic plaques, was much reduced. Chronic inflammation (activated microglia) was also reduced in the cortex, and neurogenesis was enhanced in the dentate gyrus. The results demonstrate that liraglutide may protect from progressive neurodegeneration that develops in AD. The drug is currently in clinical trials in patients with AD. PMID:26205827

  12. Pan-PPAR modulation effectively protects APP/PS1 mice from amyloid deposition and cognitive deficits.

    PubMed

    Kummer, Markus P; Schwarzenberger, Rafael; Sayah-Jeanne, Sakina; Dubernet, Mathieu; Walczak, Robert; Hum, Dean W; Schwartz, Stephanie; Axt, Daisy; Heneka, Michael T

    2015-04-01

    Alzheimer's disease (AD) is a neurodegenerative condition that leads to neuronal death and memory dysfunction. In the past, specific peroxisome proliferator-activated receptor (PPAR)γ-agonists, such as pioglitazone, have been tested with limited success to improve AD pathology. Here, we investigated the therapeutic efficacy of GFT1803, a novel potent PPAR agonist that activates all the three PPAR isoforms (α/δ/γ) in the APP/PS1 mouse model in comparison to the selective PPARγ-agonist pioglitazone. Both compounds showed similar brain/plasma partitioning ratios, although whole body and brain exposure to GFT1803 was significantly lower as compared to pioglitazone, at doses used in this study. Oral treatment of APP/PS1 mice with GFT1803 decreased microglial activation, amyloid β (Aβ) plaque area, Aβ levels in sodium dodecyl sulfate- and formic acid-soluble fractions in a concentration-dependent manner. With a single exception of Aβ38 and Aβ40 levels, measured by ELISA, these effects were not observed in mice treated with pioglitazone. Both ligands decreased glial fibrillary acidic protein (GFAP) expression to similar extent and did not affect ApoE expression. Finally, GFT1803 increased insulin-degrading enzyme expression. Analysis of spatial memory formation in the Morris water maze demonstrated that both compounds were able to partially revert the phenotype of APP/PS1 mice in comparison to wild-type mice with GFT1803 being most effective. As compared to pioglitazone, GFT1803 (pan-PPAR agonist) produced both quantitatively superior and qualitatively different therapeutic effects with respect to amyloid plaque burden, insoluble Aβ content, and neuroinflammation at significantly lower whole body and brain exposure rates. PMID:24838579

  13. Reactive sputter-deposition of AlN films by dense plasma focus

    SciTech Connect

    Sadiq, Mehboob; Ahmad, S.; Shafiq, M.; Zakaullah, M.; Ahmad, R.; Waheed, A.

    2006-11-15

    A low energy (1.45 kJ) dense plasma focus device is used to deposit thin films of aluminum nitride (AlN) at room temperature on silicon substrates. For deposition of films, a conventional hollow copper anode is replaced with a solid aluminum anode and nitrogen is used as fill gas. The films are deposited using a multiple number of focus shots by placing the substrate in front of the anode. The deposited films are characterized using x-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy, and a microhardness test. The XRD analysis of the films shows that the deposited films show strong c-axis alignment. The Raman spectra of the films indicate that the deposited films are under compressive stress and crystalline quality decreases with increasing number of focus shots. The microhardness results point toward the uniform deposition of hard AlN layers on silicon substrates.

  14. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice.

    PubMed

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Jennifer Michelle; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-04-15

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer's disease and normal aging is understudied. In the present study, we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer's disease by crossing APP/PSEN1(+) bigenic mice with SVCT2(+/-) heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2(+/-) mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2(+/-) and APP/PSEN1(+) mice and the combination genotype SVCT2(+/-)APP/PSEN1(+) were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2(+/-)) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2(+/-) mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2(+/-)APP/PSEN1(+) mice compared to APP/PSEN1(+) mice with normal brain vitamin C. These data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways. PMID:25642732

  15. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally-aging mice

    PubMed Central

    Dixit, Shilpy; Bernardo, Alexandra; Walker, Michelle Jennifer; Kennard, John Andrew; Kim, Grace Youngeun; Kessler, Eric Sean; Harrison, Fiona Edith

    2015-01-01

    Subclinical vitamin C deficiency is widespread in many populations, but its role in both Alzheimer’s disease and normal aging is understudied. In the present study we decreased brain vitamin C in the APPSWE/PSEN1deltaE9 mouse model of Alzheimer’s disease, by crossing APP/PSEN1+ bigenic mice with SVCT2+/− heterozygous knockout mice, which have lower numbers of the sodium-dependent vitamin C transporter required for neuronal vitamin C transport. SVCT2+/− mice performed less well on the rotarod task at both 5 and 12 months of age compared to littermates. SVCT2+/− and APP/PSEN1+, mice, and the combination genotype SVCT2+/−APP/PSEN1+, were also impaired on multiple tests of cognitive ability (olfactory memory task, Y-maze alternation, conditioned fear, Morris water maze). In younger mice, both low vitamin C (SVCT2+/−) and APP/PSEN1 mutations increased brain cortex oxidative stress (malondialdehyde, protein carbonyls, F2-isoprostanes) and decreased total glutathione compared to wild-type controls. SVCT2+/− mice also had increased amounts of both soluble and insoluble Aβ1-42 and a higher Aβ1-42/1-40 ratio. By 14 months of age, oxidative stress levels were similar among groups, but there were more amyloid-β plaque deposits in both hippocampus and cortex of SVCT2+/−APP/PSEN1+ mice compared to APP/PSEN1+ mice with normal brain vitamin C. The data suggest that even moderate intracellular vitamin C deficiency plays an important role in accelerating amyloid pathogenesis, particularly during early stages of disease development, and that these effects are likely modulated by oxidative stress pathways. PMID:25642732

  16. The Human Disease-Associated Aβ Amyloid Core Sequence Forms Functional Amyloids in a Fungal Adhesin

    PubMed Central

    Rameau, Rachele D.; Jackson, Desmond N.; Beaussart, Audrey; Dufrêne, Yves F.

    2016-01-01

    ABSTRACT There is increasing evidence that many amyloids in living cells have physiological functions. On the surfaces of fungal cells, amyloid core sequences in adhesins can aggregate into 100- to 1,000-nm-wide patches to form high-avidity adhesion nanodomains on the cell surface. The nanodomains form through interactions that have amyloid-like properties: binding of amyloid dyes, perturbation by antiamyloid agents, and interaction with homologous sequences. To test whether these functional interactions are mediated by typical amyloid interactions, we substituted an amyloid core sequence, LVFFA, from human Aβ protein for the native sequence IVIVA in the 1,419-residue Candida albicans adhesin Als5p. The chimeric protein formed cell surface nanodomains and mediated cellular aggregation. The native sequence and chimeric adhesins responded similarly to the amyloid dye thioflavin T and to amyloid perturbants. However, unlike the native protein, the nanodomains formed by the chimeric protein were not force activated and formed less-robust aggregates under flow. These results showed the similarity of amyloid interactions in the amyloid core sequences of native Als5p and Aβ, but they also highlighted emergent properties of the native sequence. Also, a peptide composed of the Aβ amyloid sequence flanked by amino acids from the adhesin formed two-dimensional sheets with sizes similar to the cell surface patches of the adhesins. These results inform an initial model for the structure of fungal cell surface amyloid nanodomains. PMID:26758179

  17. Mechanical and physicochemical properties of AlN thin films obtained by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Cibert, C.; Tétard, F.; Djemia, P.; Champeaux, C.; Catherinot, A.; Tétard, D.

    2004-10-01

    AlN thin films have been deposited on Si(100) substrates by a pulsed laser deposition method. The deposition parameters (pressure, temperature, purity of target) play an important role in the mechanical and physicochemical properties. The films have been characterized using X-ray diffraction, atomic force microscopy, Brillouin light scattering, Fourier transform infrared spectroscopy and wettability testing. With a high purity target of AlN and a temperature deposition of 750 ∘C, the measured Rayleigh wave velocity is close to the one previously determined for AlN films grown at high temperature by metal-organic chemical vapour deposition. Growth of nanocrystalline AlN at low temperature and of AlN film with good crystallinity for samples deposited at higher temperature is confirmed by infrared spectroscopy, as it was by atomic force microscopy, in agreement with X-ray diffraction results. A high hydrophobicity has been measured with zero polar contribution for the surface energy. These results confirm that films made by pulsed laser deposition of pure AlN at relatively low temperature have good prospects for microelectromechanical systems applications.

  18. Amyloid beta deposition and phosphorylated tau accumulation are key features in aged choroidal vessels in the complement factor H knock out model of retinal degeneration.

    PubMed

    Aboelnour, Asmaa; Kam, Jaimie Hoh; Elnasharty, M A; Sayed-Ahmed, Ahmed; Jeffery, Glen

    2016-06-01

    Extra-cellular deposition including amyloid beta (Aβ) is a feature of retinal ageing. It has been documented for Bruch's membrane (BM) where Aβ is elevated in complement factor H knockout mice (Cfh(-/-)) proposed as a model for age related macular degeneration. However, arterial deposition in choroidal vessels prior to perfusion across BM has not been examined. Aβ is associated with tau phosphorylation and these are linked in blood vessels in Alzheimers Disease where they can drive perivascular pathology. Here we ask if Aβ, tau and phosphorylated tau are features of ageing in choroidal vessels in 12 month C57 BL/6 and Cfh(-/-) mice, using immune staining and Western blot analysis. Greater levels of Aβ and phosphorylated tau are found in choroidal vessels in Cfh(-/-) mice. Western blot revealed a 40% increase in Aβ in Cfh(-/-) over C57 BL/6 mice. Aβ deposits coat around 55% of the luminal wall in Cfh(-/-) compared to only about 40% in C57 BL/6. Total tau was similar in both groups, but phosphorylated tau increased by >100% in Cfh(-/-) compared to C57 BL/6 and covered >75% of the luminal wall compared to 50% in C57 BL/6. Hence, phosphorylated tau is a marked choroidal feature in this mouse model. Aβ deposition was clumped in Cfh(-/-) mice and likely to influence blood flow dynamics. Disturbed flow is associated with atherogenesis and may be related to the accumulation of membrane attack complex recently identified between choroidal vessels in those at high risk of macular degeneration due to complement factor H polymorphisms. PMID:27181225

  19. Design, synthesis, and testing of difluoroboron derivatized curcumins as near infrared probes for in vivo detection of amyloiddeposits

    PubMed Central

    Ran, Chongzhao; Xu, Xiaoyin; Raymond, Scott B.; Ferrara, Brian J.; Neal, Krista; Bacskai, Brian J.; Medarova, Zdravka; Moore, Anna

    2009-01-01

    Amyloid-β (Aβ) deposits have been identified as key players in the progression of Alzheimer’s disease (AD). Recent evidence indicates that the deposits probably precede and induce the neuronal atrophy. Therefore, methods that enable monitoring the pathology before clinical symptoms are observed would be beneficial for the early AD detection. Here, we report the design, synthesis, and testing of a curcumin derivatized near infrared (NIR) probe CRANAD-2. Upon interacting with Aβ aggregates, CRANAD-2 undergoes a range of changes, which include a 70-fold fluorescence intensity increase, a 90 nm blue-shift (from 805 nm to 715 nm), and a large increase in quantum yield. Moreover, this probe also shows a high affinity for Aβ aggregates (Kd = 38.0 nM), a reasonable Log P value (Log P = 3), considerable stability in serum and a weak interaction with albumin. After intravenous injection of this probe, 19-month old Tg2576 mice exhibited significantly higher relative signal than that of the control mice over the same period of time. In summary, CRANAD-2 meets all the requirements for a NIR contrast agent for the detection of Aβ plaques both in vitro and in vivo. Our data point towards the feasibility of monitoring the progress of the disease by NIR imaging with CRANAD-2. In addition, we believe that our probe could be potentially used as a tool for drug screening. PMID:19807070

  20. Cerebral Amyloid Angiopathy: Emerging Concepts

    PubMed Central

    2015-01-01

    Cerebral amyloid angiopathy (CAA) involves cerebrovascular amyloid deposition and is classified into several types according to the amyloid protein involved. Of these, sporadic amyloid β-protein (Aβ)-type CAA is most commonly found in older individuals and in patients with Alzheimer's disease (AD). Cerebrovascular Aβ deposits accompany functional and pathological changes in cerebral blood vessels (CAA-associated vasculopathies). CAA-associated vasculopathies lead to development of hemorrhagic lesions [lobar intracerebral macrohemorrhage, cortical microhemorrhage, and cortical superficial siderosis (cSS)/focal convexity subarachnoid hemorrhage (SAH)], ischemic lesions (cortical infarction and ischemic changes of the white matter), and encephalopathies that include subacute leukoencephalopathy caused by CAA-associated inflammation/angiitis. Thus, CAA is related to dementia, stroke, and encephalopathies. Recent advances in diagnostic procedures, particularly neuroimaging, have enabled us to establish a clinical diagnosis of CAA without brain biopsies. Sensitive magnetic resonance imaging (MRI) methods, such as gradient-echo T2* imaging and susceptibility-weighted imaging, are useful for detecting cortical microhemorrhages and cSS. Amyloid imaging with amyloid-binding positron emission tomography (PET) ligands, such as Pittsburgh Compound B, can detect CAA, although they cannot discriminate vascular from parenchymal amyloid deposits. In addition, cerebrospinal fluid markers may be useful, including levels of Aβ40 for CAA and anti-Aβ antibody for CAA-related inflammation. Moreover, cSS is closely associated with transient focal neurological episodes (TFNE). CAA-related inflammation/angiitis shares pathophysiology with amyloid-related imaging abnormalities (ARIA) induced by Aβ immunotherapies in AD patients. This article reviews CAA and CAA-related disorders with respect to their epidemiology, pathology, pathophysiology, clinical features, biomarkers, diagnosis

  1. The amyloid in familial amyloid cardiomyopathy of Danish origin is related to pre-albumin.

    PubMed Central

    Husby, G; Ranløv, P J; Sletten, K; Marhaug, G

    1985-01-01

    Amyloid obtained from the myocardium of a patient (Han) with familial amyloid cardiomyopathy of Danish origin was studied. Gel filtration and electrophoresis of purified and denatured amyloid fibrils Han revealed various fractions ranging in mol. wt from 40,000 to 8,000 daltons. Amyloid Han and fractions reacted with an antiserum against amyloid Han showing a reaction of identity with each other; partial identity between Han and human pre-albumin was observed, while no reaction was seen with AA or AL proteins. Cardiac tissue sections from Han showed reactivity with antisera to amyloid Han, pre-albumin and protein AP, but not with anti-AA or anti-AL in indirect immunofluorescence. Amino acid composition and sequence studies of a protein fraction of amyloid Han with mol. wt 15,000 daltons confirmed the structural relationship with pre-albumin. Images Fig. 2 Fig. 3 PMID:3924450

  2. The amyloid in familial amyloid cardiomyopathy of Danish origin is related to pre-albumin.

    PubMed

    Husby, G; Ranløv, P J; Sletten, K; Marhaug, G

    1985-04-01

    Amyloid obtained from the myocardium of a patient (Han) with familial amyloid cardiomyopathy of Danish origin was studied. Gel filtration and electrophoresis of purified and denatured amyloid fibrils Han revealed various fractions ranging in mol. wt from 40,000 to 8,000 daltons. Amyloid Han and fractions reacted with an antiserum against amyloid Han showing a reaction of identity with each other; partial identity between Han and human pre-albumin was observed, while no reaction was seen with AA or AL proteins. Cardiac tissue sections from Han showed reactivity with antisera to amyloid Han, pre-albumin and protein AP, but not with anti-AA or anti-AL in indirect immunofluorescence. Amino acid composition and sequence studies of a protein fraction of amyloid Han with mol. wt 15,000 daltons confirmed the structural relationship with pre-albumin. PMID:3924450

  3. Matrix Metalloproteinase-9 Reduces Islet Amyloid Formation by Degrading Islet Amyloid Polypeptide*

    PubMed Central

    Aston-Mourney, Kathryn; Zraika, Sakeneh; Udayasankar, Jayalakshmi; Subramanian, Shoba L.; Green, Pattie S.; Kahn, Steven E.; Hull, Rebecca L.

    2013-01-01

    Deposition of islet amyloid polypeptide (IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to β-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces β-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, Aβ, the constituent of amyloid deposits in Alzheimer disease. We therefore investigated whether MMP-2 and MMP-9 play a role in reducing islet amyloid deposition. MMP-2 and MMP-9 mRNA were present in mouse islets but only MMP-9 activity was detectable. In an islet culture model where human IAPP (hIAPP) transgenic mouse islets develop amyloid but nontransgenic islets do not, a broad spectrum MMP inhibitor (GM6001) and an MMP-2/9 inhibitor increased amyloid formation and the resultant β-cell apoptosis. In contrast, a specific MMP-2 inhibitor had no effect on either amyloid deposition or β-cell apoptosis. Mass spectrometry demonstrated that MMP-9 degraded amyloidogenic hIAPP but not nonamyloidogenic mouse IAPP. Thus, MMP-9 constitutes an endogenous islet protease that limits islet amyloid deposition and its toxic effects via degradation of hIAPP. Because islet MMP-9 mRNA levels are decreased in type 2 diabetic subjects, islet MMP-9 activity may also be decreased in human type 2 diabetes, thereby contributing to increased islet amyloid deposition and β-cell loss. Approaches to increase islet MMP-9 activity could reduce or prevent amyloid deposition and its toxic effects in type 2 diabetes. PMID:23229548

  4. Unzipping a Functional Microbial Amyloid

    PubMed Central

    Alsteens, David; Ramsook, Caleen B.; Lipke, Peter N.; Dufrêne, Yves F.

    2012-01-01

    Bacterial and fungal species produce some of the best-characterized functional amyloids, i.e. extracellular fibres that play key roles in mediating adhesion and biofilm formation. Yet, the molecular details underlying their mechanical strength remain poorly understood. Here, we use single-molecule atomic force microscopy to measure the mechanical properties of amyloids formed by Als cell adhesion proteins from the pathogen Candida albicans. We show that stretching Als proteins through their amyloid sequence yields characteristic force signatures corresponding to the mechanical unzipping of β-sheet interactions formed between surfacearrayed Als proteins. The unzipping probability increases with contact time, reflecting the time necessary for optimal inter β-strand associations. These results demonstrate that amyloid interactions provide cohesive strength to a major adhesion protein from a microbial pathogen, thereby strengthening cell adhesion. We suggest that such functional amyloids may represent a generic mechanism for providing mechanical strength to cell adhesion proteins. In nanotechnology, these single-molecule manipulation experiments provide new opportunities to understand the molecular mechanisms driving the cohesion of functional amyloid-based nanostructures. PMID:22924880

  5. Characteristics of nanocomposite ZrO2/Al2O3 films deposited by plasma-enhanced atomic layer deposition.

    PubMed

    Yun, Sun Jin; Lim, Jung Wook; Kim, Hyun-Tak

    2007-11-01

    Nanocomposite ZrO2/Al2O3 (ZAO) films were deposited on Si by plasma-enhanced atomic layer deposition and the film characteristics including interfacial oxide formation, dielectric constant (k), and electrical breakdown strength were investigated without post-annealing process. In both the mixed and nano-laminated ZAO films, the thickness of the interfacial oxide layer (T(IL)) was considerably reduced compared to ZrO2 and Al2O3 films. The T(IL) was 0.8 nm in nano-composite films prepared at a mixing ratio (ZrO2:Al2O3) of 1:1. The breakdown strength and the leakage current level were greatly improved by adding Al2O3 as little as 7.9% compared to that of ZrO2 and were enhanced more with increasing content of Al2O3. The k of ZrO2 and mixed ZAO (Al2O3 7.9%) films were 20.0 and 16.5, respectively. These results indicate that the addition of Al2O3 to ZrO2 greatly improves the electrical properties with less cost of k compared to the addition of SiO2. PMID:18047146

  6. Preparation and characterization of thin films of MgO, Al2O3 and MgAl2O4 by atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Huang, Ron; Kitai, Adrian H.

    1993-02-01

    MgO, Al2O3 and MgAl2O4 thin films were deposited on silicon substrates at various temperatures by the atomic layer deposition (ALD) method using bis(cyclopentadienyl)magnesium, triethylaluminum, and H2O and were characterized systematically. High-quality polycrystalline MgO films were deposited for a substrate temperature above 500°C, and amorphous thin films were deposited around 400°C. The deposited Al2O3 and MgAl2O4 thin films were characterized as amorphous in structure. Applicability of ALD to complex oxides is discussed.

  7. Passive immunotherapy targeting amyloid-β reduces cerebral amyloid angiopathy and improves vascular reactivity.

    PubMed

    Bales, Kelly R; O'Neill, Sharon M; Pozdnyakov, Nikolay; Pan, Feng; Caouette, David; Pi, YeQing; Wood, Kathleen M; Volfson, Dmitri; Cirrito, John R; Han, Byung-Hee; Johnson, Andrew W; Zipfel, Gregory J; Samad, Tarek A

    2016-02-01

    Prominent cerebral amyloid angiopathy is often observed in the brains of elderly individuals and is almost universally found in patients with Alzheimer's disease. Cerebral amyloid angiopathy is characterized by accumulation of the shorter amyloid-β isoform(s) (predominantly amyloid-β40) in the walls of leptomeningeal and cortical arterioles and is likely a contributory factor to vascular dysfunction leading to stroke and dementia in the elderly. We used transgenic mice with prominent cerebral amyloid angiopathy to investigate the ability of ponezumab, an anti-amyloid-β40 selective antibody, to attenuate amyloid-β accrual in cerebral vessels and to acutely restore vascular reactivity. Chronic administration of ponezumab to transgenic mice led to a significant reduction in amyloid and amyloid-β accumulation both in leptomeningeal and brain vessels when measured by intravital multiphoton imaging and immunohistochemistry. By enriching for cerebral vascular elements, we also measured a significant reduction in the levels of soluble amyloid-β biochemically. We hypothesized that the reduction in vascular amyloid-β40 after ponezumab administration may reflect the ability of ponezumab to mobilize an interstitial fluid pool of amyloid-β40 in brain. Acutely, ponezumab triggered a significant and transient increase in interstitial fluid amyloid-β40 levels in old plaque-bearing transgenic mice but not in young animals. We also measured a beneficial effect on vascular reactivity following acute administration of ponezumab, even in vessels where there was a severe cerebral amyloid angiopathy burden. Taken together, the beneficial effects ponezumab administration has on reducing the rate of cerebral amyloid angiopathy deposition and restoring cerebral vascular health favours a mechanism that involves rapid removal and/or neutralization of amyloid-β species that may otherwise be detrimental to normal vessel function. PMID:26493635

  8. Effect of process conditions on the microstructural formation of dc reactively sputter deposited AlN

    SciTech Connect

    Ekpe, Samuel D.; Jimenez, Francisco J.; Dew, Steven K.

    2010-09-15

    Thin film aluminum nitride (AlN), because of its attractive properties, is a material with many applications. Its microstructure and hence properties are greatly influenced by the deposition process conditions. In this work, AlN was reactively deposited in a dc magnetron sputtering system at different proportions of nitrogen in the process gas mixture and at different process conditions. The microstructure and composition of the films were analyzed using x-ray diffraction data, energy dispersive spectroscopy, and scanning electron microscopy. Results show that for a process gas pressure of 0.67 Pa, a magnetron power of 100 W, and a substrate-target distance of 10 cm, a near stoichiometeric AlN can be prepared at nitrogen proportions as low as 20%. At these process conditions, (002) was the preferred crystal orientation. Dense fibrous structures were obtained, especially at low deposition rates with high proportions of nitrogen. Increase in magnetron power and decrease in distance result in a more porous structure. High kinetic energies (average) of the sputtered Al particles and high deposition rates tend to favor AlN(101) formation, while low kinetic energies of the Al particles and low deposition rates generally favor more of the AlN(100) formation.

  9. Bipolar resistive switching properties of AlN films deposited by plasma-enhanced atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Zhang, Jian; Zhang, Qilong; Yang, Hui; Wu, Huayu; Zhou, Juehui; Hu, Liang

    2014-10-01

    AlN thin films deposited by plasma-enhanced atomic layer deposition (PEALD) have been used to investigate the resistive switching (RS) behavior. The bipolar RS properties were observed in the Cu/PEALD-AlN/Pt devices, which are induced upon the formation/disruption of Cu conducting filaments, as confirmed by the temperature dependent resistances relationships at different resistance states. The resistance ratio of the high and low resistance states (HRS/LRS) is 102-105. The dominant conduction mechanisms at HRS and LRS are trap-controlled space charge limited current and Ohmic behavior, respectively. This study demonstrated that the PEALD-AlN films have a great potential for the applications in high-density resistance random access memory.

  10. Low-energy deposition of high-strength Al(0) alloys from an ECR plasma

    SciTech Connect

    Barbour, J.C.; Follstaedt, D.M.; Knapp, J.A.; Myers, S.M.; Marshall, D.A.; Lad, R.J.

    1995-12-31

    Low-energy deposition of Al(O) alloys from an electron cyclotron resonance (ECR) plasma offers a scaleable method for the synthesis of thick, high-strength Al layers. This work compares alloy layers formed by an ECR-0{sub 2} plasma in conjunction with Al evaporation to 0-implanted Al (ion energies 25-200 keV); and it examines the effects of volume fraction of A1{sub 2}0{sub 3} phase and deposition temperature on the yield stress of the material. TEM showed the Al(O) alloys contain a dense dispersion of small {gamma}-Al{sub 2}0{sub 3} precipitates ({approximately}l nm) in a fine-grain (10-100 nm) fcc Al matrix when deposited at a temperature of {approximately}100C, similar to the microstructure for gigapascal-strength 0-implanted Al. Nanoindentation gave hardnesses for ECR films from 1.1 to 3.2 GPa, and finite-element modeling gave yield stresses up to 1.3 {plus_minus} 0.2 GPa with an elastic modulus of 66 GPa {plus_minus} 6 GPa (similar to pure bulk Al). The yield stress of a polycrystalline pure Al layer was only 0.19 {plus_minus} 0.02 GPa, which was increased to 0.87 {plus_minus} 0.15 GPa by implantation with 5 at. % 0.

  11. A study of niobia deposition on α-Al 2O 3(0001) and oxidized Al

    NASA Astrophysics Data System (ADS)

    Roberts, S.; Gorte, R. J.

    1992-02-01

    The deposition of niobia on oxidized Al films and on an α-Al 2O 3(0001) crystal was examined using Auger electron spectroscopy and high-resolution TEM. Vapor deposition of niobia resulted in amorphous, two-dimensional films which were stable upon heating up to at least 900 K in vacuum. The presence of niobia had no measurable effect on the acidity of the samples. Temperature-programmed desorption of 2-propanol and isopropylamine occurred from sharp desorption features at 185 and 140 K, respectively on all surfaces examined, indicating that no acid were present on any of the samples. An alternate approach to deposition of niobia using Nb(C 2H 5O) 5 resulted in significant carbon contamination. The implications of these results to the formation of model, supported-oxide catalysts is discussed.

  12. Deposition of an energetic Al cluster on Si(111) substrate: a molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Li, He; Zongning, Xia; Hao, Zhang; Jiayou, Feng; Yunwen, Lu

    1998-11-01

    A molecular dynamics simulation on the deposition of an energetic Al cluster on Si(111) substrate was studied. We employed the Stillinger-Weber three-body potential to simulate the Si substrate and the Born-Mayer-Higgins potential to compute the interactions between cluster and substrate. For one impacting Al cluster, the migration distance of the cluster atoms and the deposition morphology were investigated under different substrate temperatures, impacting cluster energies and cluster sizes. It can be found that diffusion distance increases with the increasing substrate temperature, cluster energy and cluster size; moreover the deposition morphologies also change under similar conditions.

  13. Atomic layer deposition of Al-doped ZnO thin films

    SciTech Connect

    Tynell, Tommi; Yamauchi, Hisao; Karppinen, Maarit; Okazaki, Ryuji; Terasaki, Ichiro

    2013-01-15

    Atomic layer deposition has been used to fabricate thin films of aluminum-doped ZnO by depositing interspersed layers of ZnO and Al{sub 2}O{sub 3} on borosilicate glass substrates. The growth characteristics of the films have been investigated through x-ray diffraction, x-ray reflection, and x-ray fluorescence measurements, and the efficacy of the Al doping has been evaluated through optical reflectivity and Seebeck coefficient measurements. The Al doping is found to affect the carrier density of ZnO up to a nominal Al dopant content of 5 at. %. At nominal Al doping levels of 10 at. % and higher, the structure of the films is found to be strongly affected by the Al{sub 2}O{sub 3} phase and no further carrier doping of ZnO is observed.

  14. Preparation of γ-Al2O3 films by laser chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Gao, Ming; Ito, Akihiko; Goto, Takashi

    2015-06-01

    γ- and α-Al2O3 films were prepared by chemical vapor deposition using CO2, Nd:YAG, and InGaAs lasers to investigate the effects of varying the laser wavelength and deposition conditions on the phase composition and microstructure. The CO2 laser was found to mostly produce α-Al2O3 films, whereas the Nd:YAG and InGaAs lasers produced γ-Al2O3 films when used at a high total pressure. γ-Al2O3 films had a cauliflower-like structure, while the α-Al2O3 films had a dense and columnar structure. Of the three lasers, it was the Nd:YAG laser that interacted most with intermediate gas species. This promoted γ-Al2O3 nucleation in the gas phase at high total pressure, which explains the cauliflower-like structure of nanoparticles observed.

  15. Cholesterol enhances amyloid {beta} deposition in mouse retina by modulating the activities of A{beta}-regulating enzymes in retinal pigment epithelial cells

    SciTech Connect

    Wang, Jiying; Ohno-Matsui, Kyoko; Morita, Ikuo

    2012-08-10

    Highlights: Black-Right-Pointing-Pointer Cholesterol-treated RPE produces more A{beta} than non-treated RPE. Black-Right-Pointing-Pointer Neprilysin expression and activity decreased in cholesterol-treated RPE. Black-Right-Pointing-Pointer {alpha}-Secretase expression and activity decreased in cholesterol-treated RPE. Black-Right-Pointing-Pointer Cholesterol-enriched diet induced subRPE deposits in aged mice. Black-Right-Pointing-Pointer A{beta} were present in cholesterol-enriched-diet-induced subRPE deposits in aged mice. -- Abstract: Subretinally-deposited amyloid {beta} (A{beta}) is a main contributor of developing age-related macular degeneration (AMD). However, the mechanism causing A{beta} deposition in AMD eyes is unknown. Hypercholesterolemia is a significant risk for developing AMD. Thus, we investigated the effects of cholesterol on A{beta} production in retinal pigment epithelial (RPE) cells in vitro and in the mouse retina in vivo. RPE cells isolated from senescent (12-month-old) C57BL/6 mice were treated with 10 {mu}g/ml cholesterol for 48 h. A{beta} amounts in culture supernatants were measured by ELISA. Activity and expression of enzymes and proteins that regulate A{beta} production were examined by activity assay and real time PCR. The retina of mice fed cholesterol-enriched diet was examined by transmission electron microscopy. Cholesterol significantly increased A{beta} production in cultured RPE cells. Activities of A{beta} degradation enzyme; neprilysin (NEP) and anti-amyloidogenic secretase; {alpha}-secretase were significantly decreased in cell lysates of cholesterol-treated RPE cells compared to non-treated cells, but there was no change in the activities of {beta}- or {gamma}-secretase. mRNA levels of NEP and {alpha}-secretase (ADAM10 and ADAM17) were significantly lower in cholesterol-treated RPE cells than non-treated cells. Senescent (12-month-old) mice fed cholesterol-enriched chow developed subRPE deposits containing A{beta}, whereas

  16. Sporadic Cerebral Amyloid Angiopathy: Pathophysiology, Neuroimaging Features, and Clinical Implications.

    PubMed

    Boulouis, Gregoire; Charidimou, Andreas; Greenberg, Steven M

    2016-06-01

    Sporadic cerebral amyloid angiopathy is a small vessel disorder defined pathologically by progressive amyloid deposition in the walls of cortical and leptomeningeal vessels resulting from disruption of a complex balance between production, circulation, and clearance of amyloid-β peptide (Aβ) in the brain. Cerebral amyloid angiopathy is a major cause of lobar symptomatic intracerebral hemorrhage, transient focal neurologic episodes, and a key contributor to vascular cognitive impairment. The mechanisms and consequences of amyloiddeposition at the pathological level and its neuroimaging manifestations, clinical consequences, and implications for patient care are addressed in this review. PMID:27214698

  17. Insight into Amyloid Structure Using Chemical Probes

    PubMed Central

    Reinke, Ashley A.; Gestwicki, Jason E.

    2011-01-01

    Alzheimer’s disease (AD) is a common neurodegenerative disorder characterized by the deposition of amyloids in the brain. One prominent form of amyloid is composed of repeating units of the amyloid-β (Aβ) peptide. Over the past decade, it has become clear that these Aβ amyloids are not homogeneous; rather, they are composed of a series of structures varying in their overall size and shape and the number of Aβ peptides they contain. Recent theories suggest that these different amyloid conformations may play distinct roles in disease, although their relative contributions are still being discovered. Here, we review how chemical probes, such as congo red, thioflavin T and their derivatives, have been powerful tools for better understanding amyloid structure and function. Moreover, we discuss how design and deployment of conformationally selective probes might be used to test emerging models of AD. PMID:21457473

  18. Amyloid Goiter Secondary to Ulcerative Colitis

    PubMed Central

    Aydin, Bunyamin; Koca, Tugba; Yildiz, Ihsan; Gerek Celikden, Sevda; Ciris, Metin

    2016-01-01

    Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn's disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis. PMID:27051538

  19. Amyloid Goiter Secondary to Ulcerative Colitis.

    PubMed

    Aydin, Bunyamin; Koca, Yavuz Savas; Koca, Tugba; Yildiz, Ihsan; Gerek Celikden, Sevda; Ciris, Metin

    2016-01-01

    Diffuse amyloid goiter (AG) is an entity characterized by the deposition of amyloid in the thyroid gland. AG may be associated with either primary or secondary amyloidosis. Secondary amyloidosis is rarely caused by inflammatory bowel diseases. Secondary amyloidosis is relatively more common in the patients with Crohn's disease, whereas it is highly rare in patients with ulcerative colitis. Diffuse amyloid goiter caused by ulcerative colitis is also a rare condition. In the presence of amyloid in the thyroid gland, medullary thyroid cancer should be kept in mind in the differential diagnosis. Imaging techniques and biochemical tests are not very helpful in the diagnosis of secondary amyloid goiter and the definitive diagnosis is established based on the histopathologic analysis and histochemical staining techniques. In this report, we present a 35-year-old male patient with diffuse amyloid goiter caused by secondary amyloidosis associated with ulcerative colitis. PMID:27051538

  20. Sulforaphane ameliorates neurobehavioral deficits and protects the brain from amyloid β deposits and peroxidation in mice with Alzheimer-like lesions.

    PubMed

    Zhang, Rui; Miao, Qian-Wei; Zhu, Chun-Xiao; Zhao, Yue; Liu, Li; Yang, Jun; An, Li

    2015-03-01

    Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly individuals and its effective therapies are still unavailable. This study was designed to investigate the neuroprotection of sulforaphane (SFN) in AD-lesion mice induced by combined administration of d-galactose and aluminium. Results showed that SFN ameliorated spatial cognitive impairment and locomotor activity decrease in Morris water maze and open field test, respectively. And attenuated numbers of amyloid β (Aβ) plaques in both hippocampus and cerebral cortex of AD-lesion mice were detected by immunohistochemistry. According to spectrophotometry and quantitative reverse-transcriptase polymerase chain reaction results, a significant increase in carbonyl group level and obvious decreases in both activity and messenger RNA expression of glutathione peroxidase were found in brain of AD-lesion mice compared with control, but not in SFN-treated AD-lesion mice. In conclusion, SFN ameliorates neurobehavioral deficits and protects the brain from Aβ deposits and peroxidation in mice with Alzheimer-like lesions, suggesting SFN is likely a potential phytochemical to be used in AD therapeutics. PMID:25024455

  1. Transthyretin stabilization by iododiflunisal promotes amyloid-β peptide clearance, decreases its deposition, and ameliorates cognitive deficits in an Alzheimer's disease mouse model.

    PubMed

    Ribeiro, Carlos A; Oliveira, Sandra Marisa; Guido, Luis F; Magalhães, Ana; Valencia, Gregorio; Arsequell, Gemma; Saraiva, Maria João; Cardoso, Isabel

    2014-01-01

    Alzheimer's disease (AD) is the most common form of dementia and now represents 50-70% of total dementia cases. Over the last two decades, transthyretin (TTR) has been associated with AD and, very recently, a novel concept of TTR stability has been established in vitro as a key factor in TTR/amyloid-β (Aβ) interaction. Small compounds, TTR stabilizers (usually non-steroid anti-inflammatory drugs), bind to the thyroxine (T4) central binding channel, increasing TTR tetrameric stability and TTR/Aβ interaction. In this work, we evaluated in vivo the effects of one of the TTR stabilizers identified as improving TTR/Aβ interaction, iododiflunisal (IDIF), in Aβ deposition and other AD features, using AβPPswe/PS1A246E transgenic mice, either carrying two or just one copy of the TTR gene (AD/TTR+/+ or AD/TTR+/-, respectively), available and characterized in our laboratory. The results showed that IDIF administered orally bound TTR in plasma and stabilized the protein, as assessed by T4 displacement assays, and was able to enter the brain as revealed by mass spectrometry analysis of cerebrospinal fluid. TTR levels, both in plasma and cerebrospinal fluid, were not altered. In AD/TTR+/- mice, IDIF administration resulted not only in decreased brain Aβ levels and deposition but also in improved cognitive function associated with the AD-like neuropathology in this mouse model, although no improvements were detectable in the AD/TTR+/+ animals. Further, in AD/TTR+/- mice, Aβ levels were reduced in plasma suggesting TTR promoted Aβ clearance from the brain and from the periphery. Taken together, these results strengthen the importance of TTR stability in the design of therapeutic drugs, highlighting the capacity of IDIF to be used in AD treatment to prevent and to slow the progression of the disease. PMID:24169237

  2. Traumatic brain injury accelerates amyloiddeposition and impairs spatial learning in the triple-transgenic mouse model of Alzheimer's disease.

    PubMed

    Shishido, Hajime; Kishimoto, Yasushi; Kawai, Nobuyuki; Toyota, Yasunori; Ueno, Masaki; Kubota, Takashi; Kirino, Yutaka; Tamiya, Takashi

    2016-08-26

    Several pathological and epidemiological studies have demonstrated a possible relationship between traumatic brain injury (TBI) and Alzheimer's disease (AD). However, the exact contribution of TBI to AD onset and progression is unclear. Hence, we examined AD-related histopathological changes and cognitive impairment after TBI in triple transgenic (3×Tg)-AD model mice. Five- to seven-month-old 3×Tg-AD model mice were subjected to either TBI by the weight-drop method or a sham treatment. In the 3×Tg-AD mice subjected to TBI, the spatial learning was not significantly different 7 days after TBI compared to that of the sham-treated 3×Tg-AD mice. However, 28 days after TBI, the 3×Tg-AD mice exhibited significantly lower spatial learning than the sham-treated 3×Tg-AD mice. Correspondingly, while a few amyloid-β (Aβ) plaques were observed in both sham-treated and TBI-treated 3×Tg-AD mouse hippocampus 7 days after TBI, the Aβ deposition was significantly greater in 3×Tg-AD mice 28 days after TBI. Thus, we demonstrated that TBI induced a significant increase in hippocampal Aβ deposition 28 days after TBI compared to that of the control animals, which was associated with worse spatial learning ability in 3×Tg-AD mice. The present study suggests that TBI could be a risk factor for accelerated AD progression, particularly when genetic and hereditary predispositions are involved. PMID:27373531

  3. Comparing α7 nicotinic acetylcholine receptor binding, amyloiddeposition, and mitochondria complex-I function in living brain: A PET study in aged monkeys.

    PubMed

    Nishiyama, Shingo; Ohba, Hiroyuki; Kanazawa, Masakatsu; Kakiuchi, Takeharu; Tsukada, Hideo

    2015-10-01

    This study was aimed to assess the correlations among α7 nicotinic acetylcholine receptor (α7-nAChR) binding, amyloid-β (Aβ) deposition, and mitochondrial complex I (MC-I) activity in the brain of aged monkeys (Macaca mulatta). Positron emission tomography (PET) measurements with [(11) C](R)-MeQAA, [(11) C]PIB, and [(18) F]BCPP-EF were conducted in monkeys in a conscious condition. [(11) C](R)-MeQAA binding was analyzed by a simplified reference tissue model to calculate nondisplaceable binding potential (BPND), [(11) C]PIB uptake was calculated by standard uptake value ratio (SUVR), and [(18) F]BCPP-EF binding was determined by Logan graphical analysis to calculate total distribution volume (VT) with arterial blood sampling. Higher brain uptake was determined in the thalamus, hippocampus, striatum, and cortical regions for [(11) C](R)-MeQAA, while being lower in the cerebellum. Significant age-related reduction of [(11) C](R)-MeQAA binding to α7-nAChR was determined only in the occipital cortex. The plot of Vt of [(18) F]BCPP-EF against BPND of [(11) C](R)-MeQAA indicated a significant negative correlation in the hippocampus and cortical regions in aged animals. Plotting of SUVR of [(11) C]PIB against BPND of [(11) C](R)-MeQAA showed a positive correlation. The in vivo binding of [(11) C](R)-MeQAA could reflect the upregulation of α7-nAChR induced by neurodegenerative damage determined by Aβ deposition as well as impaired MC-I activity in living brain. PMID:26234533

  4. In Vivo Imaging of Amyloid Deposition in Alzheimer’s Disease using the Novel Radioligand [18F]AV-45 (Florbetapir F 18)

    PubMed Central

    Wong, Dean F.; Rosenberg, Paul B.; Zhou, Yun; Kumar, Anil; Raymont, Vanessa; Ravert, Hayden T.; Dannals, Robert F.; Nandi, Ayon; Brašić, James R.; Ye, Weiguo; Hilton, John; Lyketsos, Constantine; Kung, Hank F.; Joshi, Abhinay D.; Skovronsky, Daniel M.; Pontecorvo, Michael J.

    2011-01-01

    Introduction An [18F] labeled PET amyloid (Aβ) imaging agent could facilitate clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer’s disease (AD) pathology. Here we present the results of the first clinical trial with [18F]AV-45 (Florbetapir F 18). Methods An open-label, multicenter, brain imaging, metabolism and safety study of [18F]AV-45 was performed on 16 patients with Alzheimer’s disease (AD: MMSE 19.3 +/− 3.1; Age 75.8 +/− 9.2) and 16 cognitively healthy controls (HC: MMSE 29.8 +/− 0.45; Age 72.5 +/− 11.6 ). Dynamic PET imaging was performed over a period of approximately 90 minutes following 10 mCi injection of the tracer. Standard uptake values (SUV) and cortical to cerebellum SUV ratios (SUVR) were calculated. A simplified reference tissue method was used to generate distribution volume ratio (DVR) parametric maps in a subset of subjects Results Valid PET imaging data were available for 11 AD and 15 HC subjects [18F]AV-45 accumulated in cortical regions expected to be high in amyloid deposition (e.g., precuneus, frontal and temporal cortex) of AD patients; minimal accumulation of tracer was seen in cortical regions of HC subjects. The cortical to cerebellar SUVR values in AD patients showed continual substantial increases through 30 minutes post-administration, reaching a plateau within 50 minutes. The 10 minute period from 50–60 minutes post administration was taken as a representative sample for further analysis. The cortical average SUVR for this period was 1.67 +/− 0.175 for patients with AD vs. 1.25 +/− 0.177 for HC subjects. Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR (r= 0.58–0.88, p<0.005) and were significantly greater for AD patients than for HC subjects in cortical regions, but not in subcortical white matter or cerebellar regions. There were no clinically significant changes in vital signs, ECG or laboratory values. Conclusions

  5. Preparation of the c-axis oriented AlN film by laser chemical vapor deposition using a newly proposed Al(acac)3 precursor

    NASA Astrophysics Data System (ADS)

    You, Yu; Ito, Akihiko; Tu, Rong; Goto, Takashi

    2013-02-01

    Highly oriented AlN film was prepared on a c-plane sapphire substrate by laser chemical vapor deposition using a newly proposed aluminum acetylacetonate precursor and ammonia gas as source reactants. The c-axis oriented AlN films were obtained on the c-plane sapphire substrate at deposition temperatures from 900 to 1230 K. AlN film prepared at 1047 K showed an epitaxial relation as (//( [//[. The full width at half maximum (FWHM) of the X-ray rocking curve for AlN (0002) plane increased with increasing deposition temperature. The c-axis lattice parameter decreased with increasing deposition temperature.

  6. Evaluation of ARCAM Deposited Ti-6Al-4V

    NASA Technical Reports Server (NTRS)

    Slattery, Kevin; Slaughter, Blake; Speorl, Emily; Good, James; Gilley, Scott; McLemore, Carole

    2008-01-01

    A wide range of Metal Additive Manufacturing (MAM) technologies are becoming available. One of the challenges in using new technologies for aerospace systems is demonstrating that the process and system has the ability to manufacture components that meet the high quality requirements on a statistically significant basis. The widest-used system for small to medium sized components is the ARCAM system manufactured in Gothenburg, Sweden. This system features a 4kW electron-beam gun, and has a chamber volume of 250mm long x 250mm wide x 250mm to 400mm tall. This paper will describe the basis for the quality and consistency requirements, the experimental and evaluation procedures used for the evaluation, and an analysis of the results for Ti-6Al-4V.

  7. Florbetapir PET analysis of amyloiddeposition in the presenilin 1 E280A autosomal dominant Alzheimer’s disease kindred: a cross-sectional study

    PubMed Central

    Fleisher, Adam S; Chen, Kewei; Quiroz, Yakeel T; Jakimovich, Laura J; Gomez, Madelyn Gutierrez; Langois, Carolyn M; Langbaum, Jessica B S; Ayutyanont, Napatkamon; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Mo, Hua; Lopez, Liliana; Moreno, Sonia; Acosta-Baena, Natalia; Giraldo, Margarita; Garcia, Gloria; Reiman, Rebecca A; Huentelman, Matthew J; Kosik, Kenneth S; Tariot, Pierre N; Lopera, Francisco; Reiman, Eric M

    2012-01-01

    Summary Background Fibrillar amyloid-β (Aβ) is thought to begin accumulating in the brain many years before the onset of clinical impairment in patients with Alzheimer’s disease. By assessing the accumulation of Aβ in people at risk of genetic forms of Alzheimer’s disease, we can identify how early preclinical changes start in individuals certain to develop dementia later in life. We sought to characterise the age-related accumulation of Aβ deposition in presenilin 1 (PSEN1) E280A mutation carriers across the spectrum of preclinical disease. Methods Between Aug 1 and Dec 6, 2011, members of the familial Alzheimer’s disease Colombian kindred aged 18–60 years were recruited from the Alzheimer’s Prevention Initiative’s registry at the University of Antioquia, Medellín, Colombia. Cross-sectional assessment using florbetapir PET was done in symptomatic mutation carriers with mild cognitive impairment or mild dementia, asymptomatic carriers, and asymptomatic non-carriers. These assessments were done at the Banner Alzheimer’s Institute in Phoenix, AZ, USA. A cortical grey matter mask consisting of six predefined regions. was used to measure mean cortical florbetapir PET binding. Cortical-to-pontine standard-uptake value ratios were used to characterise the cross-sectional accumulation of fibrillar Aβ deposition in carriers and non-carriers with regression analysis and to estimate the trajectories of fibrillar Aβ deposition. Findings We enrolled a cohort of 11 symptomatic individuals, 19 presymptomatic mutation carriers, and 20 asymptomatic non-carriers, ranging in age from 20 to 56 years. There was greater florbetapir binding in asymptomatic PSEN1 E280A mutation carriers than in age matched non-carriers. Fibrillar Aβ began to accumulate in PSEN 1E280A mutation carriers at a mean age of 28·2 years (95% CI 27·3–33·4), about 16 years and 21 years before the predicted median ages at mild cognitive impairment and dementia onset, respectively. 18F

  8. Method of making AlInSb by metal-organic chemical vapor deposition

    DOEpatents

    Biefeld, Robert M.; Allerman, Andrew A.; Baucom, Kevin C.

    2000-01-01

    A method for producing aluminum-indium-antimony materials by metal-organic chemical vapor deposition (MOCVD). This invention provides a method of producing Al.sub.X In.sub.1-x Sb crystalline materials by MOCVD wherein an Al source material, an In source material and an Sb source material are supplied as a gas to a heated substrate in a chamber, said Al source material, In source material, and Sb source material decomposing at least partially below 525.degree. C. to produce Al.sub.x In.sub.1-x Sb crystalline materials wherein x is greater than 0.002 and less than one.

  9. Atomic Layer Deposition of Al2O3 on WSe2 Functionalized by Titanyl Phthalocyanine.

    PubMed

    Park, Jun Hong; Fathipour, Sara; Kwak, Iljo; Sardashti, Kasra; Ahles, Christopher F; Wolf, Steven F; Edmonds, Mary; Vishwanath, Suresh; Xing, Huili Grace; Fullerton-Shirey, Susan K; Seabaugh, Alan; Kummel, Andrew C

    2016-07-26

    To deposit an ultrathin dielectric onto WSe2, monolayer titanyl phthalocyanine (TiOPc) is deposited by molecular beam epitaxy as a seed layer for atomic layer deposition (ALD) of Al2O3 on WSe2. TiOPc molecules are arranged in a flat monolayer with 4-fold symmetry as measured by scanning tunneling microscopy. ALD pulses of trimethyl aluminum and H2O nucleate on the TiOPc, resulting in a uniform deposition of Al2O3, as confirmed by atomic force microscopy and cross-sectional transmission electron microscopy. The field-effect transistors (FETs) formed using this process have a leakage current of 0.046 pA/μm(2) at 1 V gate bias with 3.0 nm equivalent oxide thickness, which is a lower leakage current than prior reports. The n-branch of the FET yielded a subthreshold swing of 80 mV/decade. PMID:27305595

  10. Current transport mechanisms in plasma-enhanced atomic layer deposited AlN thin films

    SciTech Connect

    Altuntas, Halit E-mail: biyikli@unam.bilkent.edu.tr; Ozgit-Akgun, Cagla; Donmez, Inci; Biyikli, Necmi E-mail: biyikli@unam.bilkent.edu.tr

    2015-04-21

    Here, we report on the current transport mechanisms in AlN thin films deposited at a low temperature (i.e., 200 °C) on p-type Si substrates by plasma-enhanced atomic layer deposition. Structural characterization of the deposited AlN was carried out using grazing-incidence X-ray diffraction, revealing polycrystalline films with a wurtzite (hexagonal) structure. Al/AlN/ p-Si metal-insulator-semiconductor (MIS) capacitor structures were fabricated and investigated under negative bias by performing current-voltage measurements. As a function of the applied electric field, different types of current transport mechanisms were observed; i.e., ohmic conduction (15.2–21.5 MV/m), Schottky emission (23.6–39.5 MV/m), Frenkel-Poole emission (63.8–211.8 MV/m), trap-assisted tunneling (226–280 MV/m), and Fowler-Nordheim tunneling (290–447 MV/m). Electrical properties of the insulating AlN layer and the fabricated Al/AlN/p-Si MIS capacitor structure such as dielectric constant, flat-band voltage, effective charge density, and threshold voltage were also determined from the capacitance-voltage measurements.

  11. MCNPX benchmark of out-of-beam energy deposition in LiAl

    SciTech Connect

    Corzine, K.; Ferguson, P.; Morgan, G.; Quintana, D.; Waters, L.; Cooper, R.; Liljestrand, R.; Whiteson, A.

    2000-07-01

    The MCNPX code is currently being used to calculate energy deposition in the accelerator production of tritium (APT) target/blanket system components. To ensure that these components are properly designed, the code must be validated. An energy deposition experiment was designed to aid in the code validation using thermocouple sensors in-beam and thermistor-type sensors in decoupler- and blanketlike regions. This paper focuses on the out-of-beam thermistor sensors constructed of LiAl.

  12. Electron transport in Al-doped ZnO nanolayers obtained by atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Blagoev, B. S.; Dimitrov, D. Z.; Mehandzhiev, V. B.; Kovacheva, D.; Terziyska, P.; Pavlic, J.; Lovchinov, K.; Mateev, E.; Leclercq, J.; Sveshtarov, P.

    2016-03-01

    Al-doped ZnO thin films with different Al content were prepared by atomic layer deposition (ALD). To carry out thermal ALD, diethyl zinc (DEZ) and tri-methyl aluminium (TMA) were used as Zn and Al precursors, respectively, and water vapor as oxidant. Various numbers n of DEZ and m TMA cycles was used to obtain different [ZnO] n [Al2O3] m films, where n = 100 – 95, m = 1 – 5. The X-ray diffraction analysis showed a predominantly (100) oriented polycrystalline phase for the ZnO:Al films with a low Al content (m = 1 – 3) and an amorphous structure for pure Al2O3. In ZnO:Al with a higher Al content (m = 4 – 6) the (100) reflection disappeared and the (002) peak increased. The resistivity of the films decreased with the increase in the Al content, reaching a minimum of 3.3×10-3 Ω cm at about 1.1 % Al2O3 for the [ZnO]99[Al2O3]2 sample; for higher dopant concentrations, the resistivity increased because of the increased crystal inhomogeneity due to axis reorientation.

  13. Enhanced Barrier Performance of Engineered Paper by Atomic Layer Deposited Al2O3 Thin Films.

    PubMed

    Mirvakili, Mehr Negar; Van Bui, Hao; van Ommen, J Ruud; Hatzikiriakos, Savvas G; Englezos, Peter

    2016-06-01

    Surface modification of cellulosic paper is demonstrated by employing plasma assisted atomic layer deposition. Al2O3 thin films are deposited on paper substrates, prepared with different fiber sizes, to improve their barrier properties. Thus, a hydrophobic paper is created with low gas permeability by combining the control of fiber size (and structure) with atomic layer deposition of Al2O3 films. Papers are prepared using Kraft softwood pulp and thermomechanical pulp. The cellulosic wood fibers are refined to obtain fibers with smaller length and diameter. Films of Al2O3, 10, 25, and 45 nm in thickness, are deposited on the paper surface. The work demonstrates that coating of papers prepared with long fibers efficiently reduces wettability with slight enhancement in gas permeability, whereas on shorter fibers, it results in significantly lower gas permeability. Wettability studies on Al2O3 deposited paper substrates have shown water wicking and absorption over time only in papers prepared with highly refined fibers. It is also shown that there is a certain fiber size at which the gas permeability assumes its minimum value, and further decrease in fiber size will reverse the effect on gas permeability. PMID:27165172

  14. Rapid Generation of Amyloid from Native Proteins In vitro

    PubMed Central

    Dorta-Estremera, Stephanie M; Li, Jingjing; Cao, Wei

    2013-01-01

    Proteins carry out crucial tasks in organisms by exerting functions elicited from their specific three dimensional folds. Although the native structures of polypeptides fulfill many purposes, it is now recognized that most proteins can adopt an alternative assembly of beta-sheet rich amyloid. Insoluble amyloid fibrils are initially associated with multiple human ailments, but they are increasingly shown as functional players participating in various important cellular processes. In addition, amyloid deposited in patient tissues contains nonproteinaceous components, such as nucleic acids and glycosaminoglycans (GAGs). These cofactors can facilitate the formation of amyloid, resulting in the generation of different types of insoluble precipitates. By taking advantage of our understanding how proteins misfold via an intermediate stage of soluble amyloid precursor, we have devised a method to convert native proteins to amyloid fibrils in vitro. This approach allows one to prepare amyloid in large quantities, examine the properties of amyloid generated from specific proteins, and evaluate the structural changes accompanying the conversion. PMID:24335677

  15. Cubic AlN thin film formation on quartz substrate by pulse laser deposition

    NASA Astrophysics Data System (ADS)

    Biju, Zheng; Wen, Hu

    2016-06-01

    Cubic AlN thin films were obtained on quartz substrate by pulse laser deposition in a nitrogen reactive atmosphere. A Nd-YAG laser with a wavelength of 1064 nm was used as the laser source. In order to study the influence of the process parameters on the deposited AlN film, the experiments were performed at various technique parameters of laser energy density from 70 to 260 J/cm2, substrate temperature from room temperature to 800 °C and nitrogen pressure from 0.1 to 50 Pa. X-ray diffraction, scanning electron microscopy and X-ray photoelectron spectroscopy were applied to characterize the structure and surface morphology of the deposited AlN films. It was found that the structure of AlN films deposited in a vacuum is rocksalt under the condition of substrate temperature 600-800 °C, nitrogen pressure 10-0.1 Pa and a moderate laser energy density (190 J/cm2). The high quality AlN film exhibited good optical property. Project supported by the Yunnan Provincial Natural of Science Foundation of China (No. KKSY201251089).

  16. Interfacial development of electrophoretically deposited graphene oxide films on Al alloys

    DOE PAGESBeta

    Jin, Sumin; Dickerson, James H.; Pham, Viet Hung; Brochu, Mathieu

    2015-07-28

    Adhesion between film and substrate is critical for electronic device and coating applications. Interfacial development between electrophoretically deposited graphene oxide films on Al 1100 and Al 5052 alloys were investigated using FT-IR and XPS depth profiling techniques. Obtained results suggest metal ion permeation from the substrates into deposited graphene oxide films. The interface between the films and the substrates were primarily composed of Al-O-C bonds from oxygenated defects on graphene oxide plane rather than expected Al-C formation. Films heat treated at 150 °C had change in microstructure and peak shifts in XPS spectra suggesting change in chemical structure of bondsmore » between the films and the substrates.« less

  17. Interfacial development of electrophoretically deposited graphene oxide films on Al alloys

    SciTech Connect

    Jin, Sumin; Dickerson, James H.; Pham, Viet Hung; Brochu, Mathieu

    2015-07-28

    Adhesion between film and substrate is critical for electronic device and coating applications. Interfacial development between electrophoretically deposited graphene oxide films on Al 1100 and Al 5052 alloys were investigated using FT-IR and XPS depth profiling techniques. Obtained results suggest metal ion permeation from the substrates into deposited graphene oxide films. The interface between the films and the substrates were primarily composed of Al-O-C bonds from oxygenated defects on graphene oxide plane rather than expected Al-C formation. Films heat treated at 150 °C had change in microstructure and peak shifts in XPS spectra suggesting change in chemical structure of bonds between the films and the substrates.

  18. [The disease of beta 2-amyloid deposition in the differential diagnosis of juxta-articular subchondral geode lesions].

    PubMed

    Marri, C; Romagnoli, C; Solano, G; Caldeo, A; Emiliani, G

    1993-01-01

    Beta-2 amyloidosis deposition is a new type of amyloidosis recently observed in long-term hemodialysis patients. One of the major osteoarticular complications of this disease is the appearance of subchondral bone cysts. In this paper the radiologic features of such radiolucencies are described and the criteria are outlined of the differential diagnosis from the geodes found in other arthropathies or para-physiologic conditions. The importance of the status of the joint space is stressed: on the basis of its patterns, arthropathies may be grouped as follows: inhomogeneous space narrowing in degenerative arthritis; homogeneous space narrowing in inflammatory arthritis; normal or nearly normal joint space if there is no/not-prevalent involvement of articular cartilage. PMID:8480044

  19. Geology and genesis of the Baid al Jimalah tungsten deposit, Kingdom of Saudi Arabia

    USGS Publications Warehouse

    Kamilli, R.J.; Cole, J.C.; Elliott, J.E.; Criss, R.E.

    1993-01-01

    The Baid ad Jimalah tungsten deposit in Saudi Arabia consists predominantly of swarms of steeply dipping, subparallel, tungsten-bearing quartz veins and of less abundant, smaller stockwork veins. It is spatially, temporally, and genetically associated with a 569 Ma, highly differentiated, porphyritic, two-feldspar granite that intrudes Late Proterozoic immature sandstones. Baid al Jimalah is similar in character and origin to Phanerozoic tungsten-tin greisen deposits throughout the world, especially the Hemerdon deposit in Devon, England. It is also analogous to Climax-type molybdenum deposits, which contain virtually identical mineral assemblages, but with the relative proportions of molybdenum and tungsten mineralization reversed, primarily owing to differences in oxygen fugacity. This similarity in mineralization styles and fluid histories indicates that metallogenic processes in granite-related deposits in the late Precambrian were similar to those seen in the Phanerozoic. -from Authors

  20. Structural properties of Al-rich AlInN grown on c-plane GaN substrate by metal-organic chemical vapor deposition

    PubMed Central

    2014-01-01

    The attractive prospect for AlInN/GaN-based devices for high electron mobility transistors with advanced structure relies on high-quality AlInN epilayer. In this work, we demonstrate the growth of high-quality Al-rich AlInN films deposited on c-plane GaN substrate by metal-organic chemical vapor deposition. X-ray diffraction, scanning electron microscopy, and scanning transmission electron microscopy show that the films lattice-matched with GaN can have a very smooth surface with good crystallinity and uniform distribution of Al and In in AlInN. PMID:25489282

  1. Homoepitaxial AlN thin films deposited on m-plane ( 1 1 ¯ 00) AlN substrates by metalorganic chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Bryan, Isaac; Bryan, Zachary; Bobea, Milena; Hussey, Lindsay; Kirste, Ronny; Collazo, Ramón; Sitar, Zlatko

    2014-10-01

    AlN homoepitaxial films were grown by metalorganic chemical vapor deposition on chemo-mechanically polished ( 1 1 ¯ 00)-oriented single crystalline AlN substrates. The dependence of the surface morphology, structural quality, and unintentional impurity concentrations on the growth temperature was studied in order to determine the most appropriate growth conditions for high quality ( 1 1 ¯ 00) AlN epitaxial layers. Optically smooth surfaces (RMS roughness of 0.4 nm) and high crystalline quality, as demonstrated by the presence of FWHM values for ( 10 1 ¯ 0) rocking curves along [ 0001] of less than 25 arc.sec, were achieved for films grown above 1350 °C. Furthermore, sharp and intense near band edge luminescence was observed in these high quality films. A reduction in unintentional oxygen impurity levels was seen with an increase in growth temperature. These high crystalline quality films are suitable for device applications and hold great potential for providing an ideal platform for deep UV emitters with high Al content AlGaN without polarization related effects.

  2. AL Amyloidosis

    PubMed Central

    2012-01-01

    Definition of the disease AL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils. Epidemiology AL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50. Clinical description The clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis. Diagnostic methods The diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and/or immunofluorescence. Due to the

  3. Magnetic Fluids Have Ability to Decrease Amyloid Aggregation Associated with Amyloid-Related Diseases

    NASA Astrophysics Data System (ADS)

    Antosova, Andrea; Koneracka, Martina; Siposova, Katarina; Zavisova, Vlasta; Daxnerova, Zuzana; Vavra, Ivo; Fabian, Martin; Kopcansky, Peter; Gazova, Zuzana

    2010-12-01

    At least twenty human proteins can fold abnormally to form pathological deposits that are associated with several amyloid-related diseases. We have investigated the effect of four magnetic fluids (MFs)—electrostatically stabilized Fe3O4 magnetic nanoparticles (MF1) and sterically stabilized Fe3O4 magnetic nanoparticles by sodium oleate (MF2, MF3 and MF4) with adsorbed BSA (MF2) or dextran (MF4)—on amyloid aggregation of two proteins, human insulin and chicken egg lysozyme. The morphology, particle size and size distribution of the prepared magnetic fluids were characterized. We have found that MFs are able to decrease amyloid aggregation of both studied proteins and the extent of depolymerization depended on the MF properties. The most effective reduction was observed for MF4 as 90% decrease of amyloids was detected for insulin and lysozyme amyloid aggregates. Our findings indicate that MFs have potential to be used for treatment of amyloid diseases.

  4. The investigation of Ni-Al and Co-Al based layered double hydroxides and their derived mixed oxides thin films deposited by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Birjega, R.; Matei, A.; Filipescu, M.; Stokker-Cheregi, F.; Luculescu, C.; Colceag, D.; Zavoianu, R.; Pavel, O. D.; Dinescu, M.

    2013-08-01

    Layered Double Hydroxides (LDHs) are host-guest materials consisting of positively charged metal/hydroxides sheets with intercalated anions and water molecules. LDHs can be described by the generic formula [[ṡmHO and their structure is formed by layers containing divalent cations (M2+: Mg, Zn, Ni, Co,…) and trivalent cations (M3+: Al, Ga, Cr,…) with an octahedral coordination. LDH films with well-oriented structure and controlled thickness are needed for numerous applications like sensors, protective coatings, catalysts, components for optoelectronics etc. In this work, we report on the deposition of Ni-Al and Co-Al based LDHs and their derived mixed oxides by pulsed laser deposition as a new approach to fabricate oriented LDHs or highly dispersed metallic mixed oxides. The influence of the laser characteristics, such as wavelength and fluence, on the films properties was studied. The films investigation techniques were X-Ray Diffraction, Atomic Force Microscopy, Scanning Electron Microscopy combined with energy dispersive X-ray analysis, and Secondary Ions Mass Spectrometry.

  5. Seeded strain-like transmission of β-amyloid morphotypes in APP transgenic mice

    PubMed Central

    Heilbronner, Götz; Eisele, Yvonne S; Langer, Franziska; Kaeser, Stephan A; Novotny, Renata; Nagarathinam, Amudha; Åslund, Andreas; Hammarström, Per; Nilsson, K Peter R; Jucker, Mathias

    2013-01-01

    The polymorphic β-amyloid lesions present in individuals with Alzheimer's disease are collectively known as cerebral β-amyloidosis. Amyloid precursor protein (APP) transgenic mouse models similarly develop β-amyloid depositions that differ in morphology, binding of amyloid conformation-sensitive dyes, and Aβ40/Aβ42 peptide ratio. To determine the nature of such β-amyloid morphotypes, β-amyloid-containing brain extracts from either aged APP23 brains or aged APPPS1 brains were intracerebrally injected into the hippocampus of young APP23 or APPPS1 transgenic mice. APPPS1 brain extract injected into young APP23 mice induced β-amyloid deposition with the morphological, conformational, and Aβ40/Aβ42 ratio characteristics of β-amyloid deposits in aged APPPS1 mice, whereas APP23 brain extract injected into young APP23 mice induced β-amyloid deposits with the characteristics of β-amyloid deposits in aged APP23 mice. Injecting the two extracts into the APPPS1 host revealed a similar difference between the induced β-amyloid deposits, although less prominent, and the induced deposits were similar to the β-amyloid deposits found in aged APPPS1 hosts. These results indicate that the molecular composition and conformation of aggregated Aβ in APP transgenic mice can be maintained by seeded conversion. PMID:23999102

  6. The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease.

    PubMed

    Collins, Jessica M; King, Anna E; Woodhouse, Adele; Kirkcaldie, Matthew T K; Vickers, James C

    2015-05-01

    Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24h PI or 7d PI. There was a significant (p<0.001) increase in cross-sectional cortical area occupied by Iba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p>0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p<0.01), but not after 7d PI (p>0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that

  7. Kinetic Spraying Deposition of Reactive-Enhanced Al-Ni Composite for Shaped Charge Liner Applications

    NASA Astrophysics Data System (ADS)

    Byun, Gyeongjun; Kim, Jaeick; Lee, Changhee; Kim, See Jo; Lee, Seong

    2016-02-01

    Liners used in shaped charges (SC) must possess good penetration ability and explosive power. Producing the reactive layer (i.e., the Al-Ni composite) on a well-penetrating liner (i.e., Cu) via spray coating is a novel method; the exothermic reaction of this reactive layer can be enhanced by controlling the structure of the feedstock material. However, preceding studies have been unable to completely succeed in achieving this goal. There is still an opportunity to improve the performance of reactive layers in SC liner applications. In order to address this problem, a reactive Al-Ni composite powder was produced via arrested reactive milling (ARM) and deposited by a kinetic spray process. Afterward, the deposition state and self-propagating high-temperature synthesis (SHS) reaction behavior of the ARMed Al-Ni deposit were investigated. The deposition state was degraded by the ARM process due to the remaining solid lubricant and the strain-hardening effect, but the practically estimated bond strength was not poor (~40 MPa). No SHS reactions were induced by the ARM and kinetic spray process, which resulted in the quantitative maximization of the exothermic reaction. It is noteworthy that the initiation temperature of the SHS reaction was highly advanced (~300 °C) relative to preceding studies (~500 °C); this change is due to the additional mechanical activation initiated by the kinetic spray deposition.

  8. Functionalizing Aluminum Oxide by Ag Dendrite Deposition at the Anode during Simultaneous Electrochemical Oxidation of Al.

    PubMed

    Rafailović, Lidija D; Gammer, Christoph; Rentenberger, Christian; Trišović, Tomislav; Kleber, Christoph; Karnthaler, Hans Peter

    2015-11-01

    A novel synthesis strategy is presented for depositing metallic Ag at the anode during simultaneous electrochemical oxidation of Al. This unexpected result is achieved based on galvanic coupling. Metallic dendritic nanostructures well-anchored in a high surface area supporting matrix are envisioned to open up a new avenue of applications. PMID:26398487

  9. Growth evolution of AlN films on silicon (111) substrates by pulsed laser deposition

    SciTech Connect

    Wang, Haiyan; Wang, Wenliang; Yang, Weijia; Zhou, Shizhong; Lin, Zhiting; Li, Guoqiang

    2015-05-14

    AlN films with various thicknesses have been grown on Si(111) substrates by pulsed laser deposition (PLD). The surface morphology and structural property of the as-grown AlN films have been investigated carefully to comprehensively explore the epitaxial behavior. The ∼2 nm-thick AlN film initially grown on Si substrate exhibits an atomically flat surface with a root-mean-square surface roughness of 0.23 nm. As the thickness increases, AlN grains gradually grow larger, causing a relatively rough surface. The surface morphology of ∼120 nm-thick AlN film indicates that AlN islands coalesce together and eventually form AlN layers. The decreasing growth rate from 240 to 180 nm/h is a direct evidence that the growth mode of AlN films grown on Si substrates by PLD changes from the islands growth to the layer growth. The evolution of AlN films throughout the growth is studied deeply, and its corresponding growth mechanism is hence proposed. These results are instructional for the growth of high-quality nitride films on Si substrates by PLD, and of great interest for the fabrication of AlN-based devices.

  10. Graphene-assisted growth of high-quality AlN by metalorganic chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Zeng, Qing; Chen, Zhaolong; Zhao, Yun; Wei, Tongbo; Chen, Xiang; Zhang, Yun; Yuan, Guodong; Li, Jinmin

    2016-08-01

    High-quality AlN films were directly grown on graphene/sapphire substrates by metalorganic chemical vapor deposition (MOCVD). The graphene layers were directly grown on sapphire by atmospheric-pressure chemical vapor deposition (APCVD), a low-cost catalyst-free method. We analyzed the influence of the graphene layer on the nucleation of AlN at the initial stage of growth and found that sparse AlN grains on graphene grew and formed a continuous film via lateral coalescence. Graphene-assisted AlN films are smooth and continuous, and the full width at half maximum (FWHM) values for (0002) and (10\\bar{1}2) reflections are 360 and 622.2 arcsec, which are lower than that of the film directly grown on sapphire. The high-resolution TEM images near the AlN/sapphire interface for graphene-assisted AlN films clearly show the presence of graphene, which kept its original morphology after the 1200 °C growth of AlN.

  11. Properties of TiAlN coating deposited by MPIIID on TiN substrates

    NASA Astrophysics Data System (ADS)

    El-Hossary, F. M.; Abd El-Rahman, A. M.; Raaif, M.; Ghareeb, D. A.

    2016-03-01

    Metal plasma immersion ion implantation and deposition (MPIIID) is employed to produce TiAlN hard coatings on Ti substrate. To improve the load-bearing capacity of Ti substrate, nitrogen PIII is used to prepare a bearing TiN layer on Ti-base substrate. The MPIIID process is performed using Ti50:Al50 target for different nitrogen/argon gas fractions. The effect of N2/Ar gas ratio on the microstructure, mechanical and tribological properties of TiAlN coatings has been studied. The plastic microhardness of TiAlN increases with increasing the nitrogen gas fraction to reach a maximum value of 30 GPa at 100 % N2. The plasticity index and the resistance to plastic deformation increase with increasing the nitrogen gas fraction. The wear volume loss of TiAlN coating deposited on TiN substrate decreases by a factor of 103 in comparison with pure Ti. Moreover, the friction coefficient decreases from nearly 0.8 for Ti to 0.25 for TiAlN coatings. The enhanced mechanical and tribological properties of the coating are correlated with the formation of TiAlN hard phase. This phase has random-oriented microstructure, finer grain size, high oxidation resistance and residual internal stress. Moreover, the TiN interface acts as a barrier for the motion of dislocations.

  12. Growth and electrical properties of AlOx grown by mist chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Kawaharamura, Toshiyuki; Uchida, Takayuki; Sanada, Masaru; Furuta, Mamoru

    2013-03-01

    Aluminum oxide (AlOx) thin films were grown using aluminum acetylacetonate (Al(acac)3) as a source solute by mist chemical vapor deposition (mist CVD). The AlOx thin films grown at temperatures above 400°C exhibited a breakdown field (EBD) over 6 MV/cm and a dielectric constant (κ) over 6. It is suggested that residual OH bonding in the AlOx thin films grown at temperatures below 375°C caused degradation of the breakdown field (EBD). With FC type mist CVD, the reaction proceeded efficiently (Ea = 22-24 kJ/mol) because the solvent, especially H2O, worked as a stronger oxygen source. The AlOx film could be grown at 450°C with a high deposition rate (23 nm/min) and smooth surface (RMS = 1.5 nm). Moreover, the AlOx thin films grown by mist CVD had excellent practicality as insulators because the gate leakage current (IG) of the oxide thin film transistor (TFT) with an IGZO/AlOx stack was suppressed below 1 pA at a gate voltage (VG) of 20 V.

  13. IBA analysis and corrosion resistance of TiAlPtN/TiAlN/TiAl multilayer films deposited over a CoCrMo using magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Canto, C. E.; Andrade, E.; de Lucio, O.; Cruz, J.; Solís, C.; Rocha, M. F.; Alemón, B.; Flores, M.; Huegel, J. C.

    2016-03-01

    The corrosion resistance and the elemental profile of multilayer coatings of TiAlPtN/TiAlN/TiAl synthesized by Physical Vapor Deposition (PVD) reactive magnetron sputtering over a CoCrMo alloy substrate in 10 periods of 30 min each were analyzed and compared to those of the substrate alone and to that of a TiAlPtN single layer coating of the same thickness. The objective of the present work was to create multilayers with different amounts of Pt to enhance the corrosion resistance of a biomedical alloy of CoCrMo. Corrosion tests were performed using Simulated Body Fluid (SBF) using potentiodynamic polarization tests at typical body temperature. The elemental composition and thickness of the coatings were evaluated with the combination of two ion beam analysis (IBA) techniques: a Rutherford Backscattering Spectroscopy (RBS) with alpha beam and a Nuclear Reaction Analysis with a deuteron beam.

  14. Grain growth in thin Al films during deposition from partially ionized vapor

    NASA Astrophysics Data System (ADS)

    Gusev, I. V.; Mokhniuk, A. A.

    2016-07-01

    Grain growth in thin Al films during deposition from partially ionized vapor flux with simultaneous self-ion bombardment was studied in this work. The films were deposited at constant ion energy of 940 eV and total specific power of 0.4 W/cm2 while the deposition time t of 6 s to 246 s and the resulting substrate temperature (Ts/Tm of 0.35-0.96) were varied. Thin continuous Al films exhibited normal grain growth through the entire experimental range of deposition time without limitation of grain growth by the film thickness effect. Three kinetic stages of the grain growth were observed within 100 s of deposition time: the first one exhibits very slow grain growth, accelerated grain growth occurs in the second stage and then it rapidly changes to a retardation and stagnation mode in the third stage. Large average grain sizes Dg up to 11.3 μm at film thickness of 1.4 μm and integral grain growth rates up to 0.16 μm/s were observed in this study. The experimental results were evaluated against various mechanisms of inhibition of grain growth. An estimate of the effective activation energy of the grain growth yields a value of 0.27 eV which is lower than that of the bulk Al and much higher than the activation energy of surface self-diffusion on (1 1 1)Al monocrystal. The power law Dg = (k t)0.5 gives good match with experimental results in the initial deposition phase preceding the grain growth retardation, while another model that is based on the grain size dependent pinning force adequately explains the entire grain size dependence on time. It is deemed both ion enhanced film/surface interaction and impurities on one side and thermal grooves on another side contribute to the rapid retardation of the grain grooves commencing the second growth stage.

  15. Investigation on low thermal emittance of Al films deposited by magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Ning, Yuping; Wang, Wenwen; Sun, Ying; Wu, Yongxin; Liu, Yingfang; Man, Hongliang; Wang, Cong; Zhang, Yong; Zhao, Shuxi; Tomasella, Eric; Bousquet, Angélique

    2016-03-01

    A series of Al films with different thicknesses were deposited on polished stainless steel by direct current (DC) magnetron sputtering as a metal IR-reflector layer in solar selective absorbing coating (SSAC). The effects of the film thickness and the temperature on the thermal emittance of the Al films are studied. An optimal thickness 78 nm of the Al film for the lowest total thermal emittance is obtained. The thermal emittance of the optimal Al film keeps close to 0.02 from 25 °C to 400 °C, which are low enough to satisfy the optical requirements in SSAC. The optical constants of the Al film are deduced by fitting the reflectance and transmission spectra using SCOUT software.

  16. Microstructure and mechanical behavior of spray-deposited high-Li Al-Li alloys

    SciTech Connect

    Del Castillo, L.; Wu, Y.; Hu, H.M.; Lavernia, E.J.

    1999-05-01

    High-Li alloys, with the composition Al-3.8Li-XCu-1.0Mg-0.4Ge-0.2Zr, were synthesized using a spray deposition technique (wt. pct, X = 0 {approximately} 1.5). The microstructure of the spray-deposited Al-Li alloys consisted of equiaxed grains with an average grain size in the range from 20 to 50 {micro}m. The grain-boundary phases were fine and discrete. The spray-deposited and thermomechanically processed materials were isothermally heat treated at 150 C and 170 C to investigate the age-hardening kinetics. It was noted that the spray-deposited Al-3.8Li-XCu-1.0Mg-0.4Ge-0.2Zr alloys exhibited relatively sluggish aging behavior. The peak-aged condition was achieved at 170 C in the range from 20 to 90 hours. It was noted that Cu increases the hardness of alloys during aging. Moreover, the influence of Cu on age-hardening kinetics is marginal. The mechanical properties of the spray-deposited and extruded Al-Li alloys were studied in the underaged, peak-aged, and overaged conditions. For example, the peak-aged yield strength, tensile strength, and ductility of Al-3.8Li-1.0Cu-1.0Mg-0.4Ge-0.2Zr are 455 MPa, 601 MPa, and 3.1 pct, respectively. Moreover, an increase in the Cu content of the alloy led to improvements in strength, with only slight changes in ductility, for Cu contents up to 1.0 wt pct. Beyond this range, an increase in Cu content led to decreases in both strength and ductility.

  17. Proteomic Screening for Amyloid Proteins

    PubMed Central

    Nizhnikov, Anton A.; Alexandrov, Alexander I.; Ryzhova, Tatyana A.; Mitkevich, Olga V.; Dergalev, Alexander A.; Ter-Avanesyan, Michael D.; Galkin, Alexey P.

    2014-01-01

    Despite extensive study, progress in elucidation of biological functions of amyloids and their role in pathology is largely restrained due to the lack of universal and reliable biochemical methods for their discovery. All biochemical methods developed so far allowed only identification of glutamine/asparagine-rich amyloid-forming proteins or proteins comprising amyloids that form large deposits. In this article we present a proteomic approach which may enable identification of a broad range of amyloid-forming proteins independently of specific features of their sequences or levels of expression. This approach is based on the isolation of protein fractions enriched with amyloid aggregates via sedimentation by ultracentrifugation in the presence of strong ionic detergents, such as sarkosyl or SDS. Sedimented proteins are then separated either by 2D difference gel electrophoresis or by SDS-PAGE, if they are insoluble in the buffer used for 2D difference gel electrophoresis, after which they are identified by mass-spectrometry. We validated this approach by detection of known yeast prions and mammalian proteins with established capacity for amyloid formation and also revealed yeast proteins forming detergent-insoluble aggregates in the presence of human huntingtin with expanded polyglutamine domain. Notably, with one exception, all these proteins contained glutamine/asparagine-rich stretches suggesting that their aggregates arose due to polymerization cross-seeding by human huntingtin. Importantly, though the approach was developed in a yeast model, it can easily be applied to any organism thus representing an efficient and universal tool for screening for amyloid proteins. PMID:25549323

  18. Antireflection coatings for deep ultraviolet optics deposited by magnetron sputtering from Al targets.

    PubMed

    Liao, Bo-Huei; Lee, Cheng-Chung

    2011-04-11

    We introduce an innovative technique for the deposition of fluorine doped oxide (F:Al(2)O(3)) films by DC pulse magnetron sputtering from aluminum targets at room temperature. There was almost no change in transmittance even after the film was exposed to air for two weeks. Its refractive index was around 1.69 and the extinction coefficient was smaller than 1.9 × 10(-4) at 193 nm. An AlF(3)/F:Al(2)O(3) antireflection coating was deposited on both sides of a quartz substrate. A high transmittance of 99.32% was attained at the 193 nm wavelength. The cross-sectional morphology showed that the surface of the multilayer films was smooth and there were no columnar or porous structures. PMID:21503058

  19. Electrowetting properties of atomic layer deposited Al2O3 decorated silicon nanowires

    NASA Astrophysics Data System (ADS)

    Rajkumar, K.; Rajavel, K.; Cameron, D. C.; Mangalaraj, D.; Rajendrakumar, R. T.

    2015-06-01

    This paper reports the electrowetting properties of liquid droplet on superhydrophobic silicon nanowires with Atomic layer deposited (ALD) Al2O3 as dielectric layer. Silicon wafer were etched by metal assisted wet chemical etching with silver as catalyst. ALD Al2O3 films of 10nm thickness were conformally deposited over silicon nanowires. Al2O3 dielectric film coated silicon nanowires was chemically modified with Trichloro (1H, 1H, 2H, 2H-perfluorooctyl) silane to make it superhydrophobic(SHP). The contact angle was measured and all the samples exhibited superhydrophobic nature with maximum contact angles of 163° and a minimum contact angle hysteresis of 6°. Electrowetting induced a maximum reversible decrease of the contact angle of 20°at 150V in air.

  20. Industrial Application of Thin Films (TiAl)N Deposited on Thermo-Wells

    SciTech Connect

    Velez, G.; Jaramillo, S.; Arango, Y. C.; Devia, D.; Quintero, J.; Devia, A.

    2006-12-04

    The thermo-well is formed by two layers, one layer is a ceramic and the other layer is anviloy (comprised tungsten). They are used to coat the thermocouple in the control temperature system during the Aluminum-Silicon alloy melting process. After two weeks of continuous work at 750 deg. C of temperature (the alloy temperature), a high wear in this material is observed, affecting the ceramic. (TiAl)N thin films are deposited directly on the anviloy substrates by the PAPVD (Plasma Assisted Physics Vapor Deposition) in arc pulsed technique, using a TiAl target in a mono-vaporizer system, composed by a reactor and a power controlled system. Two opposite electrodes are placed into the reactor and discharge is produced by a controlled power system. The XRD (X-ray diffraction) patterns show the presence of the (TiAl)N thin film peaks. The morphological characteristics are studied by the scanning probe microscopy (SPM)

  1. Thermal stability of atomic layer deposition Al2O3 film on HgCdTe

    NASA Astrophysics Data System (ADS)

    Zhang, P.; Sun, C. H.; Zhang, Y.; Chen, X.; He, K.; Chen, Y. Y.; Ye, Z. H.

    2015-06-01

    Thermal stability of Atomic Layer Deposition Al2O3 film on HgCdTe was investigated by Al2O3 film post-deposition annealing treatment and Metal-Insulator-Semiconductor device low-temperature baking treatment. The effectiveness of Al2O3 film was evaluated by measuring the minority carrier lifetime and capacitance versus voltage characteristics. After annealing treatment, the minority carrier lifetime of the HgCdTe sample presented a slight decrease. Furthermore, the fixed charge density and the slow charge density decreased significantly in the annealed MIS device. After baking treatment, the fixed charge density and the slow charge density of the unannealed and annealed MIS devices decreased and increased, respectively.

  2. Beyond Amyloid: Getting Real about Non-Amyloid Targets in Alzheimer’s Disease

    PubMed Central

    Herrup, Karl; Carrillo, Maria; Schenk, Dale; Cacace, Angela; DeSanti, Susan; Fremeau, Robert; Bhat, Ratan; Glicksman, Marcie; May, Patrick; Swerdlow, Russell; van Eldik, Linda; Bain, Lisa J.; Budd, Samantha

    2014-01-01

    For decades, researchers have focused primarily on a pathway initiated by beta-amyloid (Aβ) aggregation, amyloid deposition, and accumulation in the brain as the key mechanism underlying the disease and the most important treatment target. However, evidence increasingly suggests that amyloid is deposited early in the course of disease, even prior to the onset of clinical symptoms; thus, targeting amyloid in mild-to-moderate patients, as past failed clinical trials have done, may be insufficient to halt further disease progression. Scientists are investigating other molecular and cellular pathways and processes that contribute to AD pathogenesis. Thus, the Alzheimer’s Association’s Research Roundtable convened a meeting in April 2012 to move beyond amyloid and explore AD as a complex multi-factorial disease, with the goal of using a more inclusive perspective to identify novel treatment strategies. PMID:23809366

  3. Deposition of highly textured AlN thin films by reactive high power impulse magnetron sputtering

    SciTech Connect

    Moreira, Milena A.; Törndahl, Tobias; Katardjiev, Ilia; Kubart, Tomas

    2015-03-15

    Aluminum nitride thin films were deposited by reactive high power impulse magnetron sputtering (HiPIMS) and pulsed direct-current on Si (100) and textured Mo substrates, where the same deposition conditions were used for both techniques. The films were characterized by x-ray diffraction and atomic force microscopy. The results show a pronounced improvement in the AlN crystalline texture for all films deposited by HiPIMS on Si. Already at room temperature, the HiPIMS films exhibited a strong preferred (002) orientation and at 400 °C, no contributions from other orientations were detected. Despite the low film thickness of only 200 nm, an ω-scan full width at half maximum value of 5.1° was achieved on Si. The results are attributed to the high ionization of sputtered material achieved in HiPIMS. On textured Mo, there was no significant difference between the deposition techniques.

  4. Pulsed laser deposition of AlMgB14 thin films

    SciTech Connect

    Britson, Jason Curtis

    2008-11-18

    Hard, wear-resistant coatings of thin film borides based on AlMgB14 have the potential to be applied industrially to improve the tool life of cutting tools and pump vanes and may account for several million dollars in savings as a result of reduced wear on these parts. Past work with this material has shown that it can have a hardness of up to 45GPa and be fabricated into thin films with a similar hardness using pulsed laser deposition. These films have already been shown to be promising for industrial applications. Cutting tools coated with AlMgB14 used to mill titanium alloys have been shown to substantially reduce the wear on the cutting tool and extend its cutting life. However, little research into the thin film fabrication process using pulsed laser deposition to make AlMgB14 has been conducted. In this work, research was conducted into methods to optimize the deposition parameters for the AlMgB14 films. Processing methods to eliminate large particles on the surface of the AlMgB14 films, produce films that were at least 1m thick, reduce the surface roughness of the films, and improve the adhesion of the thin films were investigated. Use of a femtosecond laser source rather than a nanosecond laser source was found to be effective in eliminating large particles considered detrimental to wear reduction properties from the films. Films produced with the femtosecond laser were also found to be deposited at a rate 100 times faster than those produced with the nanosecond laser. However, films produced with the femtosecond laser developed a relatively high RMS surface roughness around 55nm. Attempts to decrease the surface roughness were largely unsuccessful. Neither increasing the surface temperature of the substrate during deposition nor using a double pulse to ablate the material was found to be extremely successful to reduce the surface roughness. Finally, the adhesion of the thin films to M2 tool steel

  5. Crystalline gamma-Al2O3 physical vapour deposition-coating for steel thixoforging tools.

    PubMed

    Bobzin, K; Hirt, G; Bagcivan, N; Khizhnyakova, L; Ewering, M

    2011-10-01

    The process of thixoforming, which has been part of many researches during the last decades, combines the advantages of forging and casting for the shaping of metallic components. But due to the high temperatures of semi-solid steel alloys high demands on the tools are requested. To resists the thermal and mechanical loads (wear, friction, thermal and thermomechanical fatigue) protecting thin films are necessary. In this regard crystalline gamma-Al2O3 deposited via Physical Vapour Deposition (PVD) is a promising candidate: It exhibits high thermal stability, high oxidation resistance and high hot hardness. In the present work the application of a (Ti, Al)N/gamma-Al2O3 coating deposited by means of Magnetron Sputter Ion Plating in an industrial coating unit is presented. The coating was analysed by means of Rockwell test, nanoindentation, and Scanning Electron Microscopy (SEM). The coated tool was tested in thixoforging experiments with steel grade X210CrW12 (AlSI D6). The surface of the coated dies was examined with Scanning Electron Microscope (SEM) after 22, 42, 90 and 170 forging cycles. PMID:22400259

  6. Recognition memory and β-amyloid plaques in adult Tg2576 mice are not modified after oral exposure to aluminum.

    PubMed

    Ribes, Diana; Torrente, Margarita; Vicens, Paloma; Colomina, Maria Teresa; Gómez, Mercedes; Domingo, José L

    2012-01-01

    The role of aluminum (Al) in Alzheimer disease is highly controversial. However, this element has been detected in neuritic plaques and neurofibrillary tangles in patients with Alzheimer disease. Its presence in neuritic plaques in hippocampus is especially relevant, as this is an area closely related to spatial learning and memory. In this study, the diet of wild-type and Tg2576 mice (animals overexpressing the human amyloid precursor protein) was supplemented with Al lactate (1 mg/g). General neurotoxic Al effects were evaluated using a functional observational battery and a novel object recognition task. Four experimental groups were used: Control-wild, Al-wild, Control-Tg, and Al-Tg mice. The results show a decreased home-cage activity and an increase in piloerection in all Al-exposed animals, and an increased sensorimotor reactivity in Tg2576 mice given Al. Neither Al treatment nor genotype had any noticeable effect on corticosterone levels and Al concentrations in frontal cortex and cerebellum of the mice. Recognition memory was impaired in Tg2576 mice, whereas β-amyloid plaque depositions were observed in all these animals. However, Al did not alter the recognition memory and β-amyloid plaque loads of Tg2576 mice. PMID:21642811

  7. Metal-AlN cermet solar selective coatings deposited by direct current magnetron sputtering technology

    NASA Astrophysics Data System (ADS)

    Zhang, Qi-Chu

    1998-02-01

    A series of metal-aluminium nitride (M-AlN) cermet materials for solar selective coatings was deposited by a novel direct current (d.c.) magnetron sputtering technology. Aluminium nitride was used as the ceramic component in the cermets, and stainless steel (SS), nickel-based alloy 0022-3727/31/4/003/img1 (NiCr), molybdenum-based alloy 0022-3727/31/4/003/img2 (TZM) and tungsten were used as the metallic components. The aluminium nitride ceramic and metallic components of the cermets were deposited by simultaneously running both an aluminium target and another metallic target in a gas mixture of argon and nitrogen. The ceramic component was deposited by d.c. reactive sputtering and the metallic component by d.c. non-reactive sputtering. The total sputtering gas pressure was 0.8-1.0 Pa and the partial pressure of reactive nitrogen gas was set at 0.020-0.025 Pa which is sufficiently high to ensure that a nearly pure AlN ceramic sublayer was deposited by d.c. reactive sputtering. Because of the excellent nitriding resistance of stainless steel and the other alloys and metal, a nearly pure metallic sublayer was deposited by d.c. sputtering at this low nitrogen partial pressure. A multilayered system, consisting of alternating metallic and AlN ceramic sublayers, was deposited by substrate rotation. This multisublayer system can be considered as a macrohomogeneous cermet layer with metal volume fraction determined by controlling the thicknesses of metallic and ceramic sublayers. Following this procedure, M-AlN cermet solar selective coatings with a double cermet layer structure were deposited. The films of these selective surfaces have the following structure: a low metal volume fraction cermet layer is placed on a high metal volume fraction cermet layer which in turn is placed on an aluminium metal infrared reflection layer. The top surface layer consists of an aluminium nitride antireflection layer. A solar absorptance of 0.92-0.96 and a normal emittance of 0.03-0.05 at

  8. Influence of argon plasma on the deposition of Al2O3 film onto the PET surfaces by atomic layer deposition

    PubMed Central

    2013-01-01

    In this paper, polyethyleneterephthalate (PET) films with and without plasma pretreatment were modified by atomic layer deposition (ALD) and plasma-assisted atomic layer deposition (PA-ALD). It demonstrates that the Al2O3 films are successfully deposited onto the surface of PET films. The cracks formed on the deposited Al2O3 films in the ALD, plasma pretreated ALD, and PA-ALD were attributed to the energetic ion bombardment in plasmas. The surface wettability in terms of water contact angle shows that the deposited Al2O3 layer can enhance the wetting property of modified PET surface. Further characterizations of the Al2O3 films suggest that the elevated density of hydroxyl -OH group improve the initial growth of ALD deposition. Chemical composition of the Al2O3-coated PET film was characterized by X-ray photoelectron spectroscopy, which shows that the content of C 1s reduces with the growing of O 1s in the Al2O3-coated PET films, and the introduction of plasma in the ALD process helps the normal growth of Al2O3 on PET in PA-ALD. PMID:23413804

  9. On the feasibility of silicene encapsulation by AlN deposited using an atomic layer deposition process

    SciTech Connect

    Van Bui, H. E-mail: M.P.deJong@utwente.nl; Wiggers, F. B.; Kovalgin, A. Y.; Jong, M. P. de E-mail: M.P.deJong@utwente.nl; Friedlein, R.; Yamada-Takamura, Y.

    2015-02-14

    Since epitaxial silicene is not chemically inert under ambient conditions, its application in devices and the ex-situ characterization outside of ultrahigh vacuum environments require the use of an insulating capping layer. Here, we report on a study of the feasibility of encapsulating epitaxial silicene on ZrB{sub 2}(0001) thin films grown on Si(111) substrates by aluminum nitride (AlN) deposited using trimethylaluminum (TMA) and ammonia (NH{sub 3}) precursors. By in-situ high-resolution core-level photoelectron spectroscopy, the chemical modifications of the surface due to subsequent exposure to TMA and NH{sub 3} molecules, at temperatures of 300 °C and 400 °C, respectively, have been investigated. While an AlN-related layer can indeed be grown, silicene reacts strongly with both precursor molecules resulting in the formation of Si–C and Si–N bonds such that the use of these precursors does not allow for the protective AlN encapsulation that leaves the electronic properties of silicene intact.

  10. On the feasibility of silicene encapsulation by AlN deposited using an atomic layer deposition process

    NASA Astrophysics Data System (ADS)

    Van Bui, H.; Wiggers, F. B.; Friedlein, R.; Yamada-Takamura, Y.; Kovalgin, A. Y.; de Jong, M. P.

    2015-02-01

    Since epitaxial silicene is not chemically inert under ambient conditions, its application in devices and the ex-situ characterization outside of ultrahigh vacuum environments require the use of an insulating capping layer. Here, we report on a study of the feasibility of encapsulating epitaxial silicene on ZrB2(0001) thin films grown on Si(111) substrates by aluminum nitride (AlN) deposited using trimethylaluminum (TMA) and ammonia (NH3) precursors. By in-situ high-resolution core-level photoelectron spectroscopy, the chemical modifications of the surface due to subsequent exposure to TMA and NH3 molecules, at temperatures of 300 °C and 400 °C, respectively, have been investigated. While an AlN-related layer can indeed be grown, silicene reacts strongly with both precursor molecules resulting in the formation of Si-C and Si-N bonds such that the use of these precursors does not allow for the protective AlN encapsulation that leaves the electronic properties of silicene intact.

  11. [Glomerulopathies with organized monoclonal immunoglobulin deposits].

    PubMed

    Touchard, Guy; Bridoux, Frank; Goujon, Jean-Michel

    2016-02-01

    The spectrum of glomerular disorders with organized immunoglobulin (Ig) deposits is heterogeneous. It encompasses 2 mains categories: glomerulopathies with fibrillary deposits are mostly represented by immunoglobulinic amyloidosis (most commonly AL amyloidosis, characterized by monoclonal light chain deposits often of the lambda isotype), and pseudo-amyloid fibrillary glomerulonephritis in which deposits predominantly contain polyclonal IgG4. Glomerulopathies with microtubular deposits include cryoglobulinemic glomerulonephritis (type I and type II, with or without detectable serum cryoglobulin) and glomerulonephritis with organized microtubular monoclonal Ig deposits (GOMMID) also referred to as immunotactoid glomerulopathy. Pathological diagnosis requires meticulous studies by light microscopy (with systematic Congo red staining), immunofluorescence with specific conjugates, and electron microscopy. Ultrastructural studies are required to differentiate amyloid fibrils (8 to 10 nm in external diameter), pseudo-amyloid fibrils (15-20 nm) and microtubules (10 to 50 nm in external diameter, with a central hollow core). Glomerular deposits in type I cryoglobulinemic glomerulonephritis are arranged into parallel straight microtubules similar to those observed in GOMMID, but with different topography that allows distinction between the two entities. Glomerular substructures composed of circulating Igs should be distinguished from collagen fibrils that are commonly observed in glomerular disorders with or without deposition of monoclonal or polyclonal Igs. PMID:26810049

  12. Al Kushaymiyah as a target for a Colorado-type molybdenite deposit

    USGS Publications Warehouse

    Theobald, P.K.

    1971-01-01

    The granitic complex in the vicinity of Al Kushaymiyah was singled out by Whitlow (19,69, 1969a, 1971), as one of the most promising areas for exploration in the Southern Wajd quadrangle (Jackson and others, 1962). He noted in particular the intensity of shattering and silicification of these potassium-rich granites, and the presence of unusual concentrations of tungsten , molybdenum, and tin in samples from the area. In the light of shield-wide compilations, this area again stands out as the principal geochemical anomaly for the three metals. The similarity of these unusual geologic and geochemical features to those of Colorado-type molybdenite deposits is striking and suggests that the Al Kushaymiyah provides a favorableenvironment to explore for a stockwork molybdenum deposit.

  13. Vacuum ultraviolet photochemical selective area atomic layer deposition of Al{sub 2}O{sub 3} dielectrics

    SciTech Connect

    Chalker, P. R. Marshall, P. A.; Dawson, K.; Brunell, I. F.; Sutcliffe, C. J.; Potter, R. J.

    2015-01-15

    We report the photochemical atomic layer deposition of Al{sub 2}O{sub 3} thin films and the use of this process to achieve area-selective film deposition. A shuttered vacuum ultraviolet (VUV) light source is used to excite molecular oxygen and trimethyl aluminum to deposit films at 60°C. In-situ QCM and post-deposition ellipsometric measurements both show that the deposition rate is saturative as a function of irradiation time. Selective area deposition was achieved by projecting the VUV light through a metalized magnesium fluoride photolithographic mask and the selectivity of deposition on the illuminated and masked regions of the substrate is a logarithmic function of the UV exposure time. The Al{sub 2}O{sub 3} films exhibit dielectric constants of 8 – 10 at 1 MHz after forming gas annealing, similar to films deposited by conventional thermal ALD.

  14. RF reactive sputter deposition and characterization of transparent CuAlO2 thin films

    NASA Astrophysics Data System (ADS)

    Lu, Y. M.; He, Y. B.; Yang, B.; Polity, A.; Volbers, N.; Neumann, C.; Hasselkamp, D.; Meyer, B. K.

    2006-09-01

    CuAlO2 thin films have been prepared on quartz glass and sapphire substrates by radio-frequency (RF) reactive sputtering using a CuAlO2 ceramic target. The deposition process was optimized by varying the sputter parameters, such as the substrate temperature and the oxygen flow. In addition a post-growth annealing has been carried out. X-ray diffraction (XRD) revealed that the as-sputtered films are amorphous, and crystallize in the delafossite-type CuAlO2 or in a phase mixture of CuAlO2 and CuAl2O4 after annealing in air at 1100°C. The surface morphology of the films was characterized by scanning electron microscopy (SEM). The as-grown films are nearly stoichiometric in terms of Cu to Al ratio and have good depth homogeneity as examined by Rutherford backscattering spectroscopy (RBS) and secondary ion mass spectroscopy (SIMS), respectively. The optical bandgap of the films was estimated by wavelength-dependent transmission measurements at room temperature, which revealed a direct bandgap of 3.38 and 3.80 eV for the as-sputtered and post-growth annealed CuAlO2 films, respectively.

  15. Electrical characterization of Si doped AlN films synthesized by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Simeonov, Simeon; Bakalova, Silvia; Szekeres, Anna; Minkov, Ivaylo; Socol, Gabriel; Ristoscu, Carmen; Mihailescu, Ion

    2015-04-01

    The electrical properties of thin AlN films doped with Si (AlN:Si) have been investigated. The films were synthesized on Si substrates at 800 °C by pulsed laser deposition in low-pressure nitrogen ambient. The AlN:Si films exhibit non-ohmic I-V characteristics and the current through these films is controlled by space charge limited current. The C-V dependence of metal-insulator-silicon (MIS) structures with AlN:Si films exhibits an excess capacitance around zero bias voltage. This excess capacitance indicates the presence of deep acceptor levels situated at the boundaries of adjacent grains in the AlN:Si films. The Si donor density in the AlN:Si films, estimated from the 1 MHz C-V characteristics, is of the order of 1018 cm-3. The impedance measurements of these AlN:Si structures at different test voltage frequencies reveal that the charge transport mechanism is dominated by either thermally-activated hopping or electron tunneling from occupied to nearest unoccupied deep levels.

  16. Influence of initial growth stages on AlN epilayers grown by metal organic chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Balaji, M.; Ramesh, R.; Arivazhagan, P.; Jayasakthi, M.; Loganathan, R.; Prabakaran, K.; Suresh, S.; Lourdudoss, S.; Baskar, K.

    2015-03-01

    AlN layers of thickness of about 2 μm have been grown with AlN nucleation layers (NLs) on (001) sapphire substrates using metal organic chemical vapor deposition. Increasing the AlN-NL deposition temperature from 850 to 1250 °C has been found to have significant effect on the surface morphology and the structural quality of the AlN layers. The surface morphology of the AlN-NLs and the AlN layers has been assessed using atomic force microscopy (AFM). The AFM images of the AlN-NLs reveal the coalescence pattern of NLs. AFM images of the AlN layers and the in-situ reflectance measurement disclose the surface morphology and the growth pattern of the AlN layers, respectively. Smooth surface with macro-steps and terrace features has been achieved for the AlN layer grown on the NL deposited at 950 °C. The structural quality of AlN layers has been studied by high resolution X-ray diffraction and Raman spectroscopy. The screw dislocation density from (002) reflection and the average edge dislocation density from (102), (302) and (100) reflections of the AlN layer on NL deposited at 950 °C are estimated to be 9×107 cm-2 and 4.4×109 cm-2, respectively. Lateral correlation length (L) is calculated from the (114) reciprocal space mapping of the AlN layers and correlated with the edge dislocation density of the AlN layers. Raman E2 (high) phonon mode indicates compressive strain in the AlN layers grown on the NLs deposited at various temperatures. From this work, it has been inferred that the uniform coalescence of the nucleation islands and the complete coverage of AlN-NL determine the surface morphology and the structural quality of the subsequently grown AlN layers.

  17. Additive manufactured Ti6Al4V scaffolds with the RF- magnetron sputter deposited hydroxyapatite coating

    NASA Astrophysics Data System (ADS)

    Chudinova, E.; Surmeneva, M.; Koptioug, A.; Scoglund, P.; Surmenev, R.

    2016-01-01

    Present paper reports on the results of surface modification of the additively manufactured porous Ti6Al4V scaffolds. Radio frequency (RF) magnetron sputtering was used to modify the surface of the alloy via deposition of the biocompatible hydroxyapatite (HA) coating. The surface morphology, chemical and phase composition of the HA-coated alloy were studied. It was revealed that RF magnetron sputtering allows preparing a homogeneous HA coating onto the entire surface of scaffolds.

  18. Synchrotron-based Infrared and X-ray Imaging Shows Focalized Accumulation of Cu and Zn Co-localized With Beta-amyloid Deposits in Alzheimer's Disease

    SciTech Connect

    Miller,L.; Wang, Q.; Telivala, T.; Smith, R.; Lanzirotti, A.; Miklossy, J.

    2006-01-01

    Alzheimer's disease (AD) is characterized by the misfolding and plaque-like accumulation of a naturally occurring peptide in the brain called amyloid beta (Abeta). Recently, this process has been associated with the binding of metal ions such as iron (Fe), copper (Cu), and zinc (Zn). It is thought that metal dyshomeostasis is involved in protein misfolding and may lead to oxidative stress and neuronal damage. However, the exact role of the misfolded proteins and metal ions in the degenerative process of AD is not yet clear. In this study, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to image the in situ secondary structure of the amyloid plaques in brain tissue of AD patients. These results were spatially correlated with metal ion accumulation in the same tissue sample using synchrotron X-ray fluorescence (SXRF) microprobe. For both techniques, a spatial resolution of 5-10 microm was achieved. FTIRM results showed that the amyloid plaques have elevated beta-sheet content, as demonstrated by a strong amide I absorbance at 1625cm(-1). Using SXRF microprobe, we find that AD tissue also contains 'hot spots' of accumulated metal ions, specifically Cu and Zn, with a strong spatial correlation between these two ions. The 'hot spots' of accumulated Zn and Cu were co-localized with beta-amyloid plaques. Thus for the first time, a strong spatial correlation has been observed between elevated beta-sheet content in Abeta plaques and accumulated Cu and Zn ions, emphasizing an association of metal ions with amyloid formation in AD.

  19. Amyloid persistence in decellularized liver: biochemical and histopathological characterization

    PubMed Central

    Mazza, Giuseppe; Simons, J. Paul; Al-Shawi, Raya; Ellmerich, Stephan; Urbani, Luca; Giorgetti, Sofia; Taylor, Graham W.; Gilbertson, Janet A.; Hall, Andrew R.; Al-Akkad, Walid; Dhar, Dipok; Hawkins, Philip N.; De Coppi, Paolo; Pinzani, Massimo; Bellotti, Vittorio; Mangione, P. Patrizia

    2016-01-01

    Abstract Systemic amyloidoses are a group of debilitating and often fatal diseases in which fibrillar protein aggregates are deposited in the extracellular spaces of a range of tissues. The molecular basis of amyloid formation and tissue localization is still unclear. Although it is likely that the extracellular matrix (ECM) plays an important role in amyloid deposition, this interaction is largely unexplored, mostly because current analytical approaches may alter the delicate and complicated three-dimensional architecture of both ECM and amyloid. We describe here a decellularization procedure for the amyloidotic mouse liver which allows high-resolution visualization of the interactions between amyloid and the constitutive fibers of the extracellular matrix. The primary structure of the fibrillar proteins remains intact and the amyloid fibrils retain their amyloid enhancing factor activity. PMID:26646718

  20. Amyloid persistence in decellularized liver: biochemical and histopathological characterization.

    PubMed

    Mazza, Giuseppe; Simons, J Paul; Al-Shawi, Raya; Ellmerich, Stephan; Urbani, Luca; Giorgetti, Sofia; Taylor, Graham W; Gilbertson, Janet A; Hall, Andrew R; Al-Akkad, Walid; Dhar, Dipok; Hawkins, Philip N; De Coppi, Paolo; Pinzani, Massimo; Bellotti, Vittorio; Mangione, P Patrizia

    2016-01-01

    Systemic amyloidoses are a group of debilitating and often fatal diseases in which fibrillar protein aggregates are deposited in the extracellular spaces of a range of tissues. The molecular basis of amyloid formation and tissue localization is still unclear. Although it is likely that the extracellular matrix (ECM) plays an important role in amyloid deposition, this interaction is largely unexplored, mostly because current analytical approaches may alter the delicate and complicated three-dimensional architecture of both ECM and amyloid. We describe here a decellularization procedure for the amyloidotic mouse liver which allows high-resolution visualization of the interactions between amyloid and the constitutive fibers of the extracellular matrix. The primary structure of the fibrillar proteins remains intact and the amyloid fibrils retain their amyloid enhancing factor activity. PMID:26646718

  1. Fabrication of AlN/BN bishell hollow nanofibers by electrospinning and atomic layer deposition

    SciTech Connect

    Haider, Ali; Kayaci, Fatma; Uyar, Tamer; Biyikli, Necmi; Ozgit-Akgun, Cagla; Okyay, Ali Kemal

    2014-09-01

    Aluminum nitride (AlN)/boron nitride (BN) bishell hollow nanofibers (HNFs) have been fabricated by successive atomic layer deposition (ALD) of AlN and sequential chemical vapor deposition (CVD) of BN on electrospun polymeric nanofibrous template. A four-step fabrication process was utilized: (i) fabrication of polymeric (nylon 6,6) nanofibers via electrospinning, (ii) hollow cathode plasma-assisted ALD of AlN at 100 °C onto electrospun polymeric nanofibers, (iii) calcination at 500 °C for 2 h in order to remove the polymeric template, and (iv) sequential CVD growth of BN at 450 °C. AlN/BN HNFs have been characterized for their chemical composition, surface morphology, crystal structure, and internal nanostructure using X-ray photoelectron spectroscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy, and selected area electron diffraction. Measurements confirmed the presence of crystalline hexagonal BN and AlN within the three dimensional (3D) network of bishell HNFs with relatively low impurity content. In contrast to the smooth surface of the inner AlN layer, outer BN coating showed a highly rough 3D morphology in the form of BN nano-needle crystallites. It is shown that the combination of electrospinning and plasma-assisted low-temperature ALD/CVD can produce highly controlled multi-layered bishell nitride ceramic hollow nanostructures. While electrospinning enables easy fabrication of nanofibrous template, self-limiting reactions of plasma-assisted ALD and sequential CVD provide control over the wall thicknesses of AlN and BN layers with sub-nanometer accuracy.

  2. Properties of atomic layer deposited dielectrics for AlGaN/GaN device passivation

    NASA Astrophysics Data System (ADS)

    Ramanan, Narayanan; Lee, Bongmook; Kirkpatrick, Casey; Suri, Rahul; Misra, Veena

    2013-07-01

    In order to minimize ac-dc dispersion, reduce gate leakage and maximize ac transconductance, there is a critical need to identify optimal interfaces, low-k passivation dielectrics and high-k gate dielectrics. In this paper, an investigation of different atomic layer deposited (ALD) passivation dielectrics on AlGaN/GaN-based hetero-junction field effect transistors (HFETs) was performed. Angle-resolved x-ray photoelectron spectroscopy revealed that HCl/HF and NH4OH cleans resulted in a reduction of native oxide and carbon levels at the GaN surface. The role of high temperature anneals, following the ALD, on the effectiveness of passivation was also explored. Gate-lag measurements on HFETs passivated with a thin ALD high-k Al2O3 or HfAlO layer capped with a thick plasma enhanced chemical vapor deposited (PECVD) low-k SiO2 layer, annealed at 600-700 °C, were found to be as good as or even better than those with conventional PECVD silicon nitride passivation. Further, it was observed that different passivation dielectric stacks required different anneal temperatures for improved gate-lag behavior compared to the as-deposited case.

  3. Deposition and Oxidation of Oxide-Dispersed CoNiCrAlY Bondcoats

    NASA Astrophysics Data System (ADS)

    Okada, Mitsutoshi; Vassen, Robert; Karger, Matthias; Sebold, Doris; Mack, Daniel; Jarligo, Maria Ophelia; Bozza, Francesco

    2014-01-01

    CoNiCrAlY powder and nano-size alumina powder were milled by a high-energy-attrition ball-mill, and an oxide-dispersed powder was produced with a mixed structure of metal and alumina in each particle. The oxide-dispersed bond coat powder was deposited by HVOF. Pores, however, were observed in the coating since the alumina was deposited without sufficient melting. Isothermal oxidation tests were carried out for the bond coat specimens at a temperature of 1373 K up to 1000 h in air. As a result, oxidation proceeded inside the coating, since oxygen penetrated through pores formed in the dispersed alumina. However, the authors find that another deposition using higher power levels led to a bond coat without pores. A commercially available oxide-dispersed CoNiCrAlY powder was also deposited by HVOF and VPS, and isothermal oxidation tests were performed. The analysis clarifies that the HVOF bond coat exhibited the thinnest thermally grown oxide than those of the VPS bond coat and conventional metallic bond coat. Furnace cycling tests were conducted using the specimens with an additional ceramic thermal-barrier coating. The specimen with the bond coat sprayed by VPS using commercial oxide-dispersed powder showed almost same number of cycles to delamination compared with the specimen with the conventional metal bond coat.

  4. Manufacturing Ti-6Al-4V Components by Shaped Metal Deposition: Microstructure and Mechanical Properties

    NASA Astrophysics Data System (ADS)

    Baufeld, Bernd; van der Biest, Omer; Gault, Rosemary; Ridgway, Keith

    2011-12-01

    The urge in aeronautics to reduce cost and time to flight of components without compromising safety and performance stimulates the investigation of novel manufacturing routes. Shaped Metal Deposition (SMD) is an innovative time-compression technology, which creates near-net shaped components layer by layer by weld deposition. Especially for Ti alloys, which are difficult to shape by traditional methods such as forging, machining and casting and for which the loss of material during the shaping process is also very expensive, SMD promises great advantages. Applying preliminary SMD parameter, four different tubular components with a square cross section and wall thicknesses of about 9 mm were built. The microstructure of the Ti-6Al-4V components consists of large prior β grains, elongated along the temperature gradient during welding, which transform into a lamellar α/β substructure at room temperature. The ultimate tensile strength was between 880 and 1054 MPa. The strain at failure was between 3.0 and 11.3 % for tensile testing parallel to the deposition plane and between 9.1 and 16.4 % perpendicular to the deposition plane. The micro-hardness (3.1 - 3.4 GPa), the Young's modulus (117 - 121 GPa) and the oxygen and nitrogen content are comparable to cast Ti-6Al-4V material.

  5. Influence of Pre-Heated Al 6061 Substrate Temperature on the Residual Stresses of Multipass Al Coatings Deposited by Cold Spray

    NASA Astrophysics Data System (ADS)

    Rech, Silvano; Trentin, Andrea; Vezzù, Simone; Legoux, Jean-Gabriel; Irissou, Eric; Guagliano, Mario

    2011-01-01

    In this work, the influence of the substrate temperature on the deposition efficiency, on the coating properties and residual stress was investigated. Pure Al coatings were deposited on Al 6061 alloy substrates using a CGT Kinetics 3000 cold spray system. The substrate temperature was in a range between 20 (room temperature) and 375 °C and was kept nearly constant during a given deposition while all the other deposition parameters were unchanged. The deposited coatings were quenched in water (within 1 min from the deposition) and then characterized. The residual stress was determined by Almen gage method, Modified Layer Removal Method, and XRD in order to identify both the mean coating stress and the stress profile through the coating thickness from the surface to the coating-substrate interface. The residual stress results obtained by these three methods were compared and discussed. The coating morphology and porosity were investigated using optical and scanning electron microscopy.

  6. Self-forming Al oxide barrier for nanoscale Cu interconnects created by hybrid atomic layer deposition of Cu–Al alloy

    SciTech Connect

    Park, Jae-Hyung; Han, Dong-Suk; Kang, You-Jin; Shin, So-Ra; Park, Jong-Wan

    2014-01-15

    The authors synthesized a Cu–Al alloy by employing alternating atomic layer deposition (ALD) surface reactions using Cu and Al precursors, respectively. By alternating between these two ALD surface chemistries, the authors fabricated ALD Cu–Al alloy. Cu was deposited using bis(1-dimethylamino-2-methyl-2-butoxy) copper as a precursor and H{sub 2} plasma, while Al was deposited using trimethylaluminum as the precursor and H{sub 2} plasma. The Al atomic percent in the Cu–Al alloy films varied from 0 to 15.6 at. %. Transmission electron microscopy revealed that a uniform Al-based interlayer self-formed at the interface after annealing. To evaluate the barrier properties of the Al-based interlayer and adhesion between the Cu–Al alloy film and SiO{sub 2} dielectric, thermal stability and peel-off adhesion tests were performed, respectively. The Al-based interlayer showed similar thermal stability and adhesion to the reference Mn-based interlayer. Our results indicate that Cu–Al alloys formed by alternating ALD are suitable seed layer materials for Cu interconnects.

  7. Synthesis of Vertically-Aligned Carbon Nanotubes from Langmuir-Blodgett Films Deposited Fe Nanoparticles on Al2O3/Al/SiO2/Si Substrate.

    PubMed

    Takagiwa, Shota; Kanasugi, Osamu; Nakamura, Kentaro; Kushida, Masahito

    2016-04-01

    In order to apply vertically-aligned carbon nanotubes (VA-CNTs) to a new Pt supporting material of polymer electrolyte fuel cell (PEFC), number density and outer diameter of CNTs must be controlled independently. So, we employed Langmuir-Blodgett (LB) technique for depositing CNT growth catalysts. A Fe nanoparticle (NP) was used as a CNT growth catalyst. In this study, we tried to thicken VA-CNT carpet height and inhibit thermal aggregation of Fe NPs by using Al2O3/Al/SiO2/Si substrate. Fe NP LB films were deposited on three typed of substrates, SiO2/Si, as-deposited Al2O3/Al/SiO2/Si and annealed Al2O3/Al/SiO2/Si at 923 K in Ar atmosphere of 16 Pa. It is known that Al2O3/Al catalyzes hydrocarbon reforming, inhibits thermal aggregation of CNT growth catalysts and reduces CNT growth catalysts. It was found that annealed Al2O3/Al/SiO2/Si exerted three effects more strongly than as-deposited Al2O3/Al/SiO2/Si. VA-CNTs were synthesized from Fe NPs-C16 LB films by thermal chemical vapor deposition (CVD) method. As a result, at the distance between two nearest CNTs 28 nm or less, VA-CNT carpet height on annealed Al2O3/Al/SiO2/Si was about twice and ten times thicker than that on SiO2/Si and that on as-deposited Al2O3/Al/SiO2/Si, respectively. Moreover, distribution of CNT outer diameter on annealed Al2O3/Al/SiO2/Si was inhibited compared to that on SiO2/Si. These results suggest that since thermal aggregation of Fe NPs is inhibited, catalyst activity increases and distribution of Fe NP size is inhibited. PMID:27451619

  8. Characteristics of Al-doped ZnO films grown by atomic layer deposition for silicon nanowire photovoltaic device.

    PubMed

    Oh, Byeong-Yun; Han, Jin-Woo; Seo, Dae-Shik; Kim, Kwang-Young; Baek, Seong-Ho; Jang, Hwan Soo; Kim, Jae Hyun

    2012-07-01

    We report the structural, electrical, and optical characteristics of Al-doped ZnO (ZnO:Al) films deposited on glass by atomic layer deposition (ALD) with various Al2O3 film contents for use as transparent electrodes. Unlike films fabricated by a sputtering method, the diffraction peak position of the films deposited by ALD progressively moved to a higher angle with increasing Al2O3 film content. This indicates that Zn sites were effectively replaced by Al, due to layer-by-layer growth mechanism of ALD process which is based on alternate self-limiting surface chemical reactions. By adjusting the Al2O3 film content, a ZnO:Al film with low electrical resistivity (9.84 x 10(-4) Omega cm) was obtained at an Al2O3 film content of 3.17%, where the Al concentration, carrier mobility, optical transmittance, and bandgap energy were 2.8 wt%, 11.20 cm2 V(-1) s(-1), 94.23%, and 3.6 eV, respectively. Moreover, the estimated figure of merit value of our best sample was 8.2 m7Omega(-1). These results suggest that ZnO:Al films deposited by ALD could be useful for electronic devices in which especially require 3-dimensional conformal deposition of the transparent electrode and surface passivation. PMID:22966566

  9. Age-dependent inverse correlations in CSF and plasma amyloid-β(1-42) concentrations prior to amyloid plaque deposition in the brain of 3xTg-AD mice.

    PubMed

    Cho, Soo Min; Lee, Sejin; Yang, Seung-Hoon; Kim, Hye Yun; Lee, Michael Jisoo; Kim, Hyunjin Vincent; Kim, Jiyoon; Baek, Seungyeop; Yun, Jin; Kim, Dohee; Kim, Yun Kyung; Cho, Yakdol; Woo, Jiwan; Kim, Tae Song; Kim, YoungSoo

    2016-01-01

    Amyloid-β (Aβ) plays a critical role as a biomarker in Alzheimer's disease (AD) diagnosis. In addition to its diagnostic potential in the brain, recent studies have suggested that changes of Aβ level in the plasma can possibly indicate AD onset. In this study, we found that plasma Aβ(1-42) concentration increases with age, while the concentration of Aβ(1-42) in the cerebrospinal fluid (CSF) decreases in APPswe, PS1M146V and TauP301L transgenic (3xTg-AD) mice, if measurements were made before formation of ThS-positive plaques in the brain. Our data suggests that there is an inverse correlations between the plasma and CSF Aβ(1-42) levels until plaques form in transgenic mice's brains and that the plasma Aβ concentration possesses the diagnostic potential as a biomarker for diagnosis of early AD stages. PMID:26830653

  10. Age-dependent inverse correlations in CSF and plasma amyloid-β(1–42) concentrations prior to amyloid plaque deposition in the brain of 3xTg-AD mice

    PubMed Central

    Cho, Soo Min; Lee, Sejin; Yang, Seung-Hoon; Kim, Hye Yun; Lee, Michael Jisoo; Kim, Hyunjin Vincent; Kim, Jiyoon; Baek, Seungyeop; Yun, Jin; Kim, Dohee; Kim, Yun Kyung; Cho, Yakdol; Woo, Jiwan; Kim, Tae Song; Kim, YoungSoo

    2016-01-01

    Amyloid-β (Aβ) plays a critical role as a biomarker in Alzheimer’s disease (AD) diagnosis. In addition to its diagnostic potential in the brain, recent studies have suggested that changes of Aβ level in the plasma can possibly indicate AD onset. In this study, we found that plasma Aβ(1–42) concentration increases with age, while the concentration of Aβ(1–42) in the cerebrospinal fluid (CSF) decreases in APPswe, PS1M146V and TauP301L transgenic (3xTg-AD) mice, if measurements were made before formation of ThS-positive plaques in the brain. Our data suggests that there is an inverse correlations between the plasma and CSF Aβ(1–42) levels until plaques form in transgenic mice’s brains and that the plasma Aβ concentration possesses the diagnostic potential as a biomarker for diagnosis of early AD stages. PMID:26830653

  11. Self limiting atomic layer deposition of Al2O3 on perovskite surfaces: a reality?

    NASA Astrophysics Data System (ADS)

    Choudhury, Devika; Rajaraman, Gopalan; Sarkar, Shaibal K.

    2016-03-01

    The feasibility of self-saturated atomic layer deposition of Al2O3 on an organolead halide perovskite (MAPbI3-xClx) surface through a well known trimethylaluminium (TMA)-water (H2O) chemistry is studied. Though the sequential dosages of reactants form films on the perovskite surfaces, a self saturated growth is never observed. Self-saturation leads to the degradation of the material. Both experimental and density functional theory calculations are carried out for complete understanding of the growth mechanism of self-limiting Al2O3 on the perovskite surface.The feasibility of self-saturated atomic layer deposition of Al2O3 on an organolead halide perovskite (MAPbI3-xClx) surface through a well known trimethylaluminium (TMA)-water (H2O) chemistry is studied. Though the sequential dosages of reactants form films on the perovskite surfaces, a self saturated growth is never observed. Self-saturation leads to the degradation of the material. Both experimental and density functional theory calculations are carried out for complete understanding of the growth mechanism of self-limiting Al2O3 on the perovskite surface. Electronic supplementary information (ESI) available: Additional QCM results, FTIR spectra and DFT results. See DOI: 10.1039/c5nr06974b

  12. Mechanical Characterization of CrN/CrAlN Multilayer Coatings Deposited by Magnetron Sputtering System

    NASA Astrophysics Data System (ADS)

    Kaouther, Khlifi; Hafedh, Dhiflaoui; Lassaad, Zoghlami; Ahmed, Ben Cheikh Larbi

    2015-10-01

    Chromium-based coatings are deposited on a 100Cr6 (AISI 52100) substrate by a physical vapor deposition magnetron sputtering system. The coatings have different structures, such as a CrN monolayer and CrAlN multilayer. The structural and morphological compositions of the coatings were evaluated using glow discharge optical emission spectroscopy, atomic force microscopy, and cross-sectional scanning electron microscopy. Nano-indentation tests were performed to investigate the mechanical properties. Domes and craters are shown to be uniformly distributed over the entire surfaces of the two coatings. Additionally, the CrN/CrAlN multilayer coating exhibits a rough surface, attractive mechanical properties, a high compressive stress, and a high plastic and elastic deformation resistance. The improvement of the mechanical properties of the CrN/CrAlN coating is mainly attributed to a reduction in the crystallite size. We found that this reduction was related to three factors: (1) the compositional change resulting from the substitution of aluminum for chromium, which can produce a decrease in the interatomic distance; (2) the structure of CrN/CrAlN, which was characterized by grain size refinement; and (3) the high number of interfaces, which explains the widely accepted concept of dislocation blocking by the layer interfaces.

  13. Correlation of dark mantle deposits with high Mg/Al ratios. [from orbital X-ray fluorescence experiment on moon

    NASA Technical Reports Server (NTRS)

    Schonfeld, E.; Bielefeld, M. J.

    1978-01-01

    The Mg/Al concentration ratios from the orbital fluorescence X-ray experiment were used to characterize dark mantle deposits on the moon. The areas studied included the regions of Sulpicius Gallus, Taurus-Littrow, Hadley Rille, Mare Crisium (craters Picard and Pierce), and NE Mare Fecunditatis. In all these cases these deposits exhibit high Mg/Al ratios which suggest the presence of orange, black, and green pyroclastic glasses. The highest concentration of glasses was inferred in the Sulpicius Gallus Formation at about 35%. The depth of the initial pyroclastic deposits was estimated at 3 to 4 meters. Central Mare Serenitatis exhibits high Mg/Al values but does not possess dark mantle deposits. Orbital Al and Mg/Al data for this region is similar to the very low titanium mare basalts.

  14. Optimization of the chemical vapor deposition process for fabrication of carbon nanotube/Al composite powders

    SciTech Connect

    He, C.N.; Zhao, N.Q.; Shi, C.S.; Song, S.Z.

    2010-09-15

    In order to optimize the chemical vapor deposition process for fabrication of carbon nanotube/Al composite powders, the effect of different reaction conditions (such as reaction temperature, reaction time, and reaction gas ratio) on the morphological and structural development of the powder and dispersion of CNTs in Al powder was investigated using transmission electron microscope. The results showed that low temperatures (500-550 {sup o}C) give rise to herringbone-type carbon nanofibers and high temperatures (600-630 {sup o}C) lead to multi-walled CNTs. Long reaction times broaden the CNT size distribution and increase the CNT yield. Appropriate nitrogen flow is preferred for CNT growth, but high and low nitrogen flow result in carbon nanospheres and CNTs with coarse surfaces, respectively. Above results show that appropriate parameters are effective in dispersing the nanotubes in the Al powder which simultaneously protects the nanotubes from damage.

  15. Islet amyloid polypeptide-induced membrane leakage involves uptake of lipids by forming amyloid fibers.

    PubMed

    Sparr, Emma; Engel, Maarten F M; Sakharov, Dmitri V; Sprong, Mariette; Jacobs, Jet; de Kruijff, Ben; Höppener, Jo W M; Killian, J Antoinette

    2004-11-01

    Fibril formation of islet amyloid polypeptide (IAPP) is associated with cell death of the insulin-producing pancreatic beta-cells in patients with Type 2 Diabetes Mellitus. A likely cause for the cytotoxicity of human IAPP is that it destroys the barrier properties of the cell membrane. Here, we show by fluorescence confocal microscopy on lipid vesicles that the process of hIAPP amyloid formation is accompanied by a loss of barrier function, whereby lipids are extracted from the membrane and taken up in the forming amyloid deposits. No membrane interaction was observed when preformed fibrils were used. It is proposed that lipid uptake from the cell membrane is responsible for amyloid-induced membrane damage and that this represents a general mechanism underlying the cytotoxicity of amyloid forming proteins. PMID:15527771

  16. Hot Corrosion Performance of AlO-CrO/NiCoCrAlYTa and AlO/NiCoCrAlYTa Coatings Deposited by Atmospheric Plasma Spraying

    NASA Astrophysics Data System (ADS)

    Tao, Chong; Wang, Lei; Cheng, Nailiang; Hu, Hengfa; Liu, Yang; Song, Xiu

    2016-04-01

    AlO-CrO/NiCoCrAlYTa and AlO/NiCoCrAlYTa coatings were deposited on 316L stainless steel substrate using atmospheric plasma spraying, respectively, in order to improve the oxidation and corrosion resistance. The hot corrosion performance of the coatings at 700 and 900 °C were studied, and the detailed microstructures and phase composition of the coatings were analyzed using x-ray diffraction, scanning electron microscope with energy dispersive spectrometer, and transmission electron microscope. The results show that both coatings are structurally featured by slatted layers, consisting of amorphous phase, Cr2O3, Ni3Al, and Al2O3. The hot corrosion resistance of AlO-CrO/NiCoCrAlYTa coating is better than that of AlO/NiCoCrAlYTa coating. This improvement is attributed to lower porosity and more compact Cr2O3 in AlO-CrO/NiCoCrAlYTa coating which performs better than Al2O3 in blocking further inward progress of corrosion and oxidization.

  17. Nano-Al{sub 2}O{sub 3} multilayer film deposition on cotton fabrics by layer-by-layer deposition method

    SciTech Connect

    Ugur, Sule S.; Sariisik, Merih; Aktas, A. Hakan

    2011-08-15

    Highlights: {yields} Cationic charges were created on the cotton fibre surfaces with 2,3-epoxypropyltrimethylammonium chloride. {yields} Al{sub 2}O{sub 3} nanoparticles were deposited on the cotton fabrics by layer-by-layer deposition. {yields} The fabrics deposited with the Al{sub 2}O{sub 3} nanoparticles exhibit better UV-protection and significant flame retardancy properties. {yields} The mechanical properties were improved after surface film deposition. -- Abstract: Al{sub 2}O{sub 3} nanoparticles were used for fabrication of multilayer nanocomposite film deposition on cationic cotton fabrics by electrostatic self-assembly to improve the mechanical, UV-protection and flame retardancy properties of cotton fabrics. Cotton fabric surface was modified with a chemical reaction to build-up cationic charge known as cationization. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy, X-ray Photoelectron Spectroscopy and Scanning Electron Microscopy were used to verify the presence of deposited nanolayers. Air permeability, whiteness value, tensile strength, UV-transmittance and Limited Oxygen Index properties of cotton fabrics were analyzed before and after the treatment of Al{sub 2}O{sub 3} nanoparticles by electrostatic self-assemblies. It was proved that the flame retardancy, tensile strength and UV-transmittance of cotton fabrics can be improved by Al{sub 2}O{sub 3} nanoparticle additive through electrostatic self-assembly process.

  18. A novel approach to the identification and quantitative elemental analysis of amyloid deposits-Insights into the pathology of Alzheimer's disease

    SciTech Connect

    Rajendran, Reshmi; Minqin, Ren; Ynsa, Maria Dolores; Casadesus, Gemma; Smith, Mark A.; Perry, George; Halliwell, Barry; Watt, Frank

    2009-04-24

    There is considerable interest in the role of metals such as iron, copper, and zinc in amyloid plaque formation in Alzheimer's disease. However to convincingly establish their presence in plaques in vivo, a sensitive technique is required that is both quantitatively accurate and avoids isolation of plaques or staining/fixing brain tissue, since these processes introduce contaminants and redistribute elements within the tissue. Combining the three ion beam techniques of scanning transmission ion microscopy, Rutherford back scattering spectrometry and particle induced X-ray emission in conjunction with a high energy (MeV) proton microprobe we have imaged plaques in freeze-dried unstained brain sections from CRND-8 mice, and simultaneously quantified iron, copper, and zinc. Our results show increased metal concentrations within the amyloid plaques compared with the surrounding tissue: iron (85 ppm compared with 42 ppm), copper (16 ppm compared to 6 ppm), and zinc (87 ppm compared to 34 ppm).

  19. Deposition of ultrathin AlN films for high frequency electroacoustic devices

    SciTech Connect

    Felmetsger, Valery V.; Laptev, Pavel N.; Graham, Roger J.

    2011-03-15

    The authors investigate the microstructure, crystal orientation, and residual stress of reactively sputtered aluminum nitride (AlN) films having thicknesses as low as 200 down to 25 nm. A two-step deposition process by the dual cathode ac (40 kHz) powered S-gun magnetron enabling better conditions for AlN nucleation on the surface of the molybdenum (Mo) bottom electrode was developed to enhance crystallinity of ultrathin AlN films. Using the two-step process, the residual in-plane stress as well as the stress gradient through the film thickness can be effectively controlled. X-ray rocking curve measurements have shown that ultrathin films grown on Mo using this technology are highly c-axis oriented with full widths at half maximum of 1.8 deg. and 3.1 deg. for 200- and 25-nm-thick films, respectively, which are equal to or even better than the results previously reported for relatively thick AlN films. High-resolution transmission electron microscopy and fast Fourier transform analyses have confirmed strong grain orientation in 25-100-nm-thick films. A fine columnar texture and a continuous lattice microstructure within a single grain from the interface with the Mo substrate through to the AlN surface have been elicited even in the 25-nm-thick film.

  20. Electrophoretic deposition of double-layer HA/Al composite coating on NiTi.

    PubMed

    Karimi, Esmaeil; Khalil-Allafi, Jafar; Khalili, Vida

    2016-01-01

    In order to improve the bioactivity of NiTi alloys, which are being known as the suitable materials for biomedical applications, numerous NiTi disks were electrophoretically coated by hetero-coagulated hydroxyapatite/aluminum composite coatings in three main voltages from suspensions with different Al concentrations. In this paper, the amount of Ni ions release and bioactivity of prepared samples as well as bonding strength of the coating to substrate were investigated. The surface characterization of the coating by XRD, EDX, SEM, and FTIR showed that HA particles bonded by Al particles. It caused the formation of a free crack coating on NiTi disks. Moreover, the bonding strength of HA/Al coatings to NiTi substrate were improved by two times as compared to that of the pure HA coatings. Immersing of coated samples in SBF for 1 week showed that apatite formation ability was improved on HA/Al composite coating and Ni ions release from the surface of composite coating decreased. These results induce the appropriate bioactivity and biocompatibility of the deposited HA/Al composite coatings on NiTi disks. PMID:26478383

  1. Structural, electrical, and optical properties of atomic layer deposition Al-doped ZnO films

    SciTech Connect

    Banerjee, P; Lee, W. J.; Bae, K. R.; Lee, Sang Bok; Rubloff, Gary W

    2010-01-01

    Al-doped ZnO (AZO) films of ∼100 nm thickness with various Aldoping were prepared at 150 °C by atomic layer deposition on quartz substrates. At low Aldoping, the films were strongly textured along the [100] direction, while at higher Aldoping the films remained amorphous. Atomic force microscopy results showed that Al–O cycles when inserted in a ZnOfilm, corresponding to a few atomic percent Al, could remarkably reduce the surface roughness of the films. Hall measurements revealed a maximum mobility of 17.7 cm{sup 2} /V s . Film resistivity reached a minima of 4.4×10{sup −3}  Ω cm whereas the carrier concentration reached a maxima of 1.7×10{sup 20}  cm{sup −3} , at 3 at. % Al. The band gap of AZO films varied from 3.23 eV for undoped ZnOfilms to 3.73 eV for AZO films with 24.6 at. % Al. Optical transmittance over 80% was obtained in the visible region. The detrimental impact of increased Al resulting in decreased conductivity due to doping past 3.0 at. % is evident in the x-ray diffraction data, as an abrupt increase in the optical band gap and as a deviation from the Burstein–Moss effect.

  2. Impact of Al2O3 on the aggregation and deposition of graphene oxide.

    PubMed

    Ren, Xuemei; Li, Jiaxing; Tan, Xiaoli; Shi, Weiqun; Chen, Changlun; Shao, Dadong; Wen, Tao; Wang, Longfei; Zhao, Guixia; Sheng, Guoping; Wang, Xiangke

    2014-05-20

    To assess the environmental behavior and impact of graphene oxide (GO) on living organisms more accurately, the aggregation of GO and its deposition on Al2O3 particles were systematically investigated using batch experiments across a wide range of solution chemistries. The results indicated that the aggregation of GO and its deposition on Al2O3 depended on the solution pH and the types and concentrations of electrolytes. MgCl2 and CaCl2 destabilized GO because of their effective charge screening and neutralization, and the presence of NaH2PO4 and poly(acrylic acid) (PAA) improved the stability of GO with the increase in pH values as a result of electrostatic interactions and steric repulsion. Specifically, the dissolution of Al2O3 contributed to GO aggregation at relatively low pH or high pH values. Results from this study provide critical information for predicting the fate of GO in aquatic-terrestrial transition zones, where aluminum (hydro)oxides are present. PMID:24754235

  3. Polymorphism of Amyloid Fibrils In Vivo.

    PubMed

    Annamalai, Karthikeyan; Gührs, Karl-Heinz; Koehler, Rolf; Schmidt, Matthias; Michel, Henri; Loos, Cornelia; Gaffney, Patricia M; Sigurdson, Christina J; Hegenbart, Ute; Schönland, Stefan; Fändrich, Marcus

    2016-04-01

    Polymorphism is a wide-spread feature of amyloid-like fibrils formed in vitro, but it has so far remained unclear whether the fibrils formed within a patient are also affected by this phenomenon. In this study we show that the amyloid fibrils within a diseased individual can vary considerably in their three-dimensional architecture. We demonstrate this heterogeneity with amyloid fibrils deposited within different organs, formed from sequentially non-homologous polypeptide chains and affecting human or animals. Irrespective of amyloid type or source, we found in vivo fibrils to be polymorphic. These data imply that the chemical principles of fibril assembly that lead to such polymorphism are fundamentally conserved in vivo and in vitro. PMID:26954430

  4. Systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency.

    PubMed

    Taniyama, H; Yamamoto, S; Sako, T; Hirayama, K; Higuchi, H; Nagahata, H

    2000-01-01

    Histopathologic and immunohistochemical examinations were conducted on a 5-year-old Holstein-Friesian cow with systemic kappaAL amyloidosis associated with bovine leukocyte adhesion deficiency. Amyloid deposits were present in the perivascular and intercellular spaces of the visceral organs, such as the liver, kidneys, pancreas, adrenal glands, and upper alimentary tract. Amyloid was stained positively with Congo red with or without 5% potassium permanganate pretreatment and had green birefringence observed under polarized light. Immunohistochemically, amyloid reacted strongly against anti-bovine IgG (H+L) and anti-bovine kappa-light chain and reacted weakly against bovine X-light chain antibodies but was negative for anti-human amyloid AA antibody. This is the first description of AL amyloidosis immunohistochemically related to immunoglobulin kappa-light chains of precursor protein in cattle. PMID:10643989

  5. Heparan Sulfate Proteoglycans Are Important for Islet Amyloid Formation and Islet Amyloid Polypeptide-induced Apoptosis*

    PubMed Central

    Oskarsson, Marie E.; Singh, Kailash; Wang, Jian; Vlodavsky, Israel; Li, Jin-ping; Westermark, Gunilla T.

    2015-01-01

    Deposition of β cell toxic islet amyloid is a cardinal finding in type 2 diabetes. In addition to the main amyloid component islet amyloid polypeptide (IAPP), heparan sulfate proteoglycan is constantly present in the amyloid deposit. Heparan sulfate (HS) side chains bind to IAPP, inducing conformational changes of the IAPP structure and an acceleration of fibril formation. We generated a double-transgenic mouse strain (hpa-hIAPP) that overexpresses human heparanase and human IAPP but is deficient of endogenous mouse IAPP. Culture of hpa-hIAPP islets in 20 mm glucose resulted in less amyloid formation compared with the amyloid load developed in cultured islets isolated from littermates expressing human IAPP only. A similar reduction of amyloid was achieved when human islets were cultured in the presence of heparin fragments. Furthermore, we used CHO cells and the mutant CHO pgsD-677 cell line (deficient in HS synthesis) to explore the effect of cellular HS on IAPP-induced cytotoxicity. Seeding of IAPP aggregation on CHO cells resulted in caspase-3 activation and apoptosis that could be prevented by inhibition of caspase-8. No IAPP-induced apoptosis was seen in HS-deficient CHO pgsD-677 cells. These results suggest that β cell death caused by extracellular IAPP requires membrane-bound HS. The interaction between HS and IAPP or the subsequent effects represent a possible therapeutic target whose blockage can lead to a prolonged survival of β cells. PMID:25922077

  6. Cold spray deposition of Ti2AlC coatings for improved nuclear fuel cladding

    NASA Astrophysics Data System (ADS)

    Maier, Benjamin R.; Garcia-Diaz, Brenda L.; Hauch, Benjamin; Olson, Luke C.; Sindelar, Robert L.; Sridharan, Kumar

    2015-11-01

    Coatings of Ti2AlC MAX phase compound have been successfully deposited on Zircaloy-4 (Zry-4) test flats, with the goal of enhancing the accident tolerance of LWR fuel cladding. Low temperature powder spray process, also known as cold spray, has been used to deposit coatings ∼90 μm in thickness using powder particles of <20 μm. X-ray diffraction analysis showed the phase-content of the deposited coatings to be identical to the powders indicating that no phase transformation or oxidation had occurred during the coating deposition process. The coating exhibited a high hardness of about 800 HK and pin-on-disk wear tests using abrasive ruby ball counter-surface showed the wear resistance of the coating to be significantly superior to the Zry-4 substrate. Scratch tests revealed the coatings to be well-adhered to the Zry-4 substrate. Such mechanical integrity is required for claddings from the standpoint of fretting wear resistance and resisting wear handling and insertion. Air oxidation tests at 700 °C and simulated LOCA tests at 1005 °C in steam environment showed the coatings to be significantly more oxidation resistant compared to Zry-4 suggesting that such coatings can potentially provide accident tolerance to nuclear fuel cladding.

  7. Cold spray deposition of Ti2AlC coatings for improved nuclear fuel cladding

    NASA Astrophysics Data System (ADS)

    Maier, Benjamin R.; Garcia-Diaz, Brenda L.; Hauch, Benjamin; Olson, Luke C.; Sindelar, Robert L.; Sridharan, Kumar

    2015-11-01

    Coatings of Ti2AlC MAX phase compound have been successfully deposited on Zircaloy-4 (Zry-4) test flats, with the goal of enhancing the accident tolerance of LWR fuel cladding. Low temperature powder spray process, also known as cold spray, has been used to deposit coatings ˜90 μm in thickness using powder particles of <20 μm. X-ray diffraction analysis showed the phase-content of the deposited coatings to be identical to the powders indicating that no phase transformation or oxidation had occurred during the coating deposition process. The coating exhibited a high hardness of about 800 HK and pin-on-disk wear tests using abrasive ruby ball counter-surface showed the wear resistance of the coating to be significantly superior to the Zry-4 substrate. Scratch tests revealed the coatings to be well-adhered to the Zry-4 substrate. Such mechanical integrity is required for claddings from the standpoint of fretting wear resistance and resisting wear handling and insertion. Air oxidation tests at 700 °C and simulated LOCA tests at 1005 °C in steam environment showed the coatings to be significantly more oxidation resistant compared to Zry-4 suggesting that such coatings can potentially provide accident tolerance to nuclear fuel cladding.

  8. CoFe2/Al2O3/PMNPT multiferroic heterostructures by atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Zhou, Ziyao; Grocke, Garrett; Yanguas-Gil, Angel; Wang, Xinjun; Gao, Yuan; Sun, Nianxiang; Howe, Brandon; Chen, Xing

    2016-05-01

    Multiferroic materials and applications allow electric bias control of magnetism or magnetic bias control of polarization, enabling fast, compact, energy-efficient devices in RF/microwave communication systems such as filters, shifters, and antennas; electronics devices such as inductors and capacitors; and other magnetic material related applications including sensors and memories. In this manuscript, we utilize atomic layer deposition technology to grow magnetic CoFe metallic thin films onto PMNPT, with a ˜110 Oe electric field induced ferromagnetic resonance field shift in the CoFe/Al2O3/PMNPT multiferroic heterostructure. Our work demonstrates an atomic layer deposition fabricated multiferroic heterostructure with significant tunability and shows that the unique thin film growth mechanism will benefit integrated multiferroic application in near future.

  9. Sputtering deposition of Al-doped zinc oxide thin films using mixed powder targets

    NASA Astrophysics Data System (ADS)

    Ohshima, Tamiko; Maeda, Takashi; Tanaka, Yuki; Kawasaki, Hiroharu; Yagyu, Yoshihito; Ihara, Takeshi; Suda, Yoshiaki

    2016-01-01

    Sputtering deposition generally uses high-density bulk targets. Such a fabrication process has various problems including deterioration of the material during heating and difficulty in mixing a large number of materials in precise proportions. However, these problems can be solved by using a powder target. In this study, we prepared Al-doped ZnO (AZO) as transparent conductive thin films by radio-frequency magnetron sputtering with powder and bulk targets. Both the powder and bulk targets formed crystalline structures. The ZnO (002) peak was observed in the X-ray diffraction measurements. The mean transparency and resistivity of the films prepared with the powder target were 82% and 0.548 Ω · cm, respectively. The deposition rate with the powder target was lower than that with the bulk target.

  10. Impact of post-deposition annealing on interfacial chemical bonding states between AlGaN and ZrO{sub 2} grown by atomic layer deposition

    SciTech Connect

    Ye, Gang; Arulkumaran, Subramaniam; Ng, Geok Ing; Li, Yang; Ang, Kian Siong; Wang, Hong; Liu, Zhi Hong

    2015-03-02

    The effect of post-deposition annealing on chemical bonding states at interface between Al{sub 0.5}Ga{sub 0.5}N and ZrO{sub 2} grown by atomic layer deposition (ALD) is studied by angle-resolved x-ray photoelectron spectroscopy and high-resolution transmission electron microscopy. It has been found that both of Al-O/Al 2p and Ga-O/Ga 3d area ratio decrease at annealing temperatures lower than 500 °C, which could be attributed to “clean up” effect of ALD-ZrO{sub 2} on AlGaN. Compared to Ga spectra, a much larger decrease in Al-O/Al 2p ratio at a smaller take-off angle θ is observed, which indicates higher effectiveness of the passivation of Al-O bond than Ga-O bond through “clean up” effect near the interface. However, degradation of ZrO{sub 2}/AlGaN interface quality due to re-oxidation at higher annealing temperature (>500 °C) is also found. The XPS spectra clearly reveal that Al atoms at ZrO{sub 2}/AlGaN interface are easier to get oxidized as compared with Ga atoms.

  11. In situ study of atomic layer deposition Al2O3 on GaP (100)

    NASA Astrophysics Data System (ADS)

    Dong, H.; Brennan, B.; Qin, X.; Zhernokletov, D. M.; Hinkle, C. L.; Kim, J.; Wallace, R. M.

    2013-09-01

    The interfacial chemistry of atomic layer deposition (ALD) of Al2O3 on chemically treated GaP (100) has been studied using in situ X-ray photoelectron spectroscopy. A "self-cleaning" effect for Ga-oxide upon exposure to trimethylaluminum is seen to be efficient on the native oxide and chemically treated surfaces. The phosphorus oxide chemical states are seen to change during the ALD process, but the total concentration of P-oxides is seen to remain constant throughout the ALD process.

  12. Immunohistochemical characterization of amyloid proteins in sural nerves and clinical associations in amyloid neuropathy.

    PubMed Central

    Li, K.; Kyle, R. A.; Dyck, P. J.

    1992-01-01

    To test whether immunohistochemical characterization of proteins in amyloid deposits in biopsied sural nerves gives reliable and useful diagnostic information using commercially available reagents, biopsy specimens of sural nerves from 38 patients with amyloid neuropathy were studied. Transthyretin (TTR) was detected in the amyloid deposits of 11 nerves, lambda light chains (LC) in 8 nerves, kappa LC in 7 nerves, and both lambda and kappa LC in 3 nerves. In 9 nerves, the amyloid deposits were too small to allow adequate immunohistochemical characterization of amyloid proteins in serial sections. Evidence that immunohistochemical characterization was correct came from: 1) evaluation of kin, 2) search for monoclonal proteins in the plasma, and 3) sequencing of the gene abnormalities in TTR+ cases. In 9 of 11 TTR+ cases, in which DNA could be obtained, sequencing of the gene showed that each of the 9 cases was heterozygous for a gene mutation; 7 had previously described mutations and 2 undescribed mutations. Therefore, in the nine sporadic cases without plasma monoclonal light chains, the immunohistochemical characterization correctly identified the protein in amyloid as transthyretin. Likewise, there was a high concordance between immunoglobulin light chains in plasma and light chains in amyloid in primary amyloidosis. Evaluation of the type, distribution, and severity of the neurologic symptoms and deficits showed: 1) the sensorimotor and autonomic neuropathy of amyloidosis characteristically affects proximal as well as distal limbs, and 2) the type of amyloidosis probably cannot be determined from the characteristics or severity of the neuropathy alone or from the location or size of amyloid deposits in nerve. Images Figure 1 PMID:1321563

  13. Properties of AlN films deposited by reactive ion-plasma sputtering

    SciTech Connect

    Bert, N. A.; Bondarev, A. D.; Zolotarev, V. V.; Kirilenko, D. A.; Lubyanskiy, Ya. V.; Lyutetskiy, A. V.; Slipchenko, S. O.; Petrunov, A. N.; Pikhtin, N. A. Ayusheva, K. R.; Arsentyev, I. N.; Tarasov, I. S.

    2015-10-15

    The properties of SiO{sub 2}, Al{sub 2}O{sub 3}, and AlN dielectric coatings deposited by reactive ion-plasma sputtering are studied. The refractive indices of the dielectric coatings are determined by optical ellipsometry. It is shown that aluminum nitride is the optimal material for achieving maximum illumination of the output mirror of a semiconductor laser. A crystalline phase with a hexagonal atomic lattice and oxygen content of up to 10 at % is found by transmission electron microscopy in the aluminum-nitride films. It is found that a decrease in the concentration of residual oxygen in the chamber of the reactive ion-plasma sputtering installation makes it possible to eliminate the appearance of vertical pores in the bulk of the aluminum-nitride film.

  14. ECR plasma-assisted deposition of Al{sub 2}O{sub 3} and dispersion-strengthened AlO{sub 2}

    SciTech Connect

    Barbour, J.C.; Follstaedt, D.M.; Myers, S.M.

    1995-03-01

    Electron cyclotron resonance (ECR) O{sub 2} plasmas, in conjunction with electron-beam evaporation of Al, were used to grow thick AlO{sub x} films were varying but controlled composition and microstructure. The ion energy was varied from 30 to 190 eV, and growth temperatures varied from 35{degrees}C to 400{degrees}C. The ECR-film compositions were varied from AlO{sub 0.1} to Al{sub 2}O{sub 3} by controlling the plasma parameters and Al deposition rate. The Al-rich alloys exhibited a fine-grain (10-100 nm) fcc Al microstructure with {gamma}-Al{sub 2}O{sub 3} precipitates ({approximately}1 nm), similar to that found in the gigapascal-strength O-implanted Al. The measured hardness of the ECR Al-O alloys ({approximately}3 GPa) was also similar to the ion-implanted alloys which implies that the yield strength of the ECR material is {approximately}1 GPa. Moreover, the Al-O alloys retain much of the elasticity of the Al metal matrix. As-deposited stoichiometric Al{sub 2}O{sub 3} samples grown with an applied bias of -140 to -160 V at 400{degrees}C were fine-grain polycrystalline {gamma}-Al{sub 2}O{sub 3}. The amorphous films crystallized into the {gamma}-Al{sub 2}O{sub 3} phase upon vacuum annealing to 800{degrees}C.

  15. A comparative study of AlN and Al2O3 based gate stacks grown by atomic layer deposition on InGaAs

    NASA Astrophysics Data System (ADS)

    Krylov, Igor; Pokroy, Boaz; Ritter, Dan; Eizenberg, Moshe

    2016-02-01

    Thermal activated atomic layer deposited (t) (ALD) and plasma enhanced (p) ALD (PEALD) AlN films were investigated for gate applications of InGaAs based metal-insulator-semiconductor devices and compared to the well-known Al2O3 based system. The roles of post-metallization annealing (PMA) and the pre-deposition treatment (PDT) by either trimethylaluminium (TMA) or NH3 were studied. In contrast to the case of Al2O3, in the case of AlN, the annealing temperature reduced interface states density. In addition, improvement of the AlN film stoichiometry and a related border traps density reduction were observed following PMA. The lowest interface states density (among the investigated gate stacks) was found for PEALD AlN/InGaAs stacks after TMA PDT. At the same time, higher values of the dispersion in accumulation were observed for AlN/InGaAs gate stacks compared to those with Al2O3 dielectric. No indium out-diffusion and the related leakage current degradation due to annealing were observed at the AlN/InGaAs stack. In light of these findings, we conclude that AlN is a promising material for InGaAs based gate stack applications.

  16. Texture of Al thin films deposited by magnetron sputtering onto epitaxial W(001)

    SciTech Connect

    Madsen, Lynnette D.; Svedberg, Erik B.; Bergstrom, Daniel B.; Petrov, Ivan; Greene, Joseph E.

    2000-01-01

    Highly textured epitaxial metallizations will be required for the next generation of devices with the main driving force being a reduction in electromigration. Herein a model system of 190 nm of Al on a 140 nm layer of W grown on MgO <00l> substrates was studied. The W layer was <00l> oriented and rotated 45 degree sign with respect to the MgO substrate to minimize the misfit; the remaining strain was accommodated by dislocations, evident in transmission electron microscopy images. From high-resolution x-ray diffraction (XRD) measurements, the out-of-plane lattice parameter was determined to be 3.175 Aa, and the in-plane parameter was 3.153 Aa, i.e., the W film sustained a strain resulting in a tetragonal distortion of the lattice. XRD pole figures showed that the Al had four fold symmetry and two dominant orientations, <016> and <3 9 11>, which were twinned with multiple placements on the epitaxial W layer. The driving force for the tilted <001> and <011> orientations of Al on W is due to strain minimization through lattice matching. These results show that <00l> Al deposited at ambient conditions onto W is difficult to achieve and implies that electromigration difficulties are inherent. (c) 2000 American Institute of Physics.

  17. Ion-beam-assisted deposition of Al films with strong preferential orientation

    NASA Astrophysics Data System (ADS)

    Susumu, Masaki; Hiroshi, Kobayashi; Hiroshi, Morisaki

    1991-07-01

    Preferential crystal orientation of Al films deposited under simultaneous argon-ion irradiation has been investigated by changing both the ion-to-atom arrival rate ratio (ion-atom ratio) and the ion energy. The intensity of the <111> reflection, I(111), obtained from X-ray diffraction shows a drastic increase with ion irradiation, although the effect on other reflection peaks such as I(200) is only slight. The intensity ratio I(111)/I(200), a parameter for the electromigration resistance of Al films, has shown the highest value at a certain optimum ion-atom ratio. This optimum ion-atom ratio for each ion energy is found to shift toward lower values with increasing ion energy. Under the optimum conditions, the average ion energy per neutral atom after cascade collisions is found to be about 1.2 eV irrespective of the primary ion energy, which is comparable with the energy for the self-diffusion of Al (1.4 eV). The electrical measurements have shown that the resistivity of Al films increases considerably with simultaneous ion irradiation, however, it recovers to a level comparable with that of unassisted films by annealing at 400° C.

  18. An in vivo model for the neurodegenerative effects of beta amyloid and protection by substance P.

    PubMed Central

    Kowall, N W; Beal, M F; Busciglio, J; Duffy, L K; Yankner, B A

    1991-01-01

    Deposition of the beta-amyloid protein in senile plaques is a pathologic hallmark of Alzheimer disease (AD). Focal deposition of beta amyloid in the adult rat cerebral cortex caused profound neurodegenerative changes, including neuronal loss and degenerating neurons and neurites. Chronic induction of the Alz-50 antigen appeared in neurons around focal cortical deposits of beta amyloid. Immunoblot analysis showed that beta amyloid induced Alz-50-immunoreactive proteins in rat cerebral cortex that were very similar to the proteins induced in human cerebral cortex from patients with AD. The neuropeptide substance P prevented beta-amyloid-induced neuronal loss and expression of Alz-50 proteins when coadministered into the cerebral cortex. Systemic administration of substance P also provided protection against the effects of intracerebral beta amyloid. Thus, beta amyloid is a potent neurotoxin in the adult brain in vivo, and its effects can be blocked by substance P. Images PMID:1714596

  19. Bapineuzumab Alters Aβ Composition: Implications for the Amyloid Cascade Hypothesis and Anti-Amyloid Immunotherapy

    PubMed Central

    Roher, Alex E.; Cribbs, David H.; Kim, Ronald C.; Maarouf, Chera L.; Whiteside, Charisse M.; Kokjohn, Tyler A.; Daugs, Ian D.; Head, Elizabeth; Liebsack, Carolyn; Serrano, Geidy; Belden, Christine; Sabbagh, Marwan N.; Beach, Thomas G.

    2013-01-01

    The characteristic neuropathological changes associated with Alzheimer’s disease (AD) and other lines of evidence support the amyloid cascade hypothesis. Viewing amyloid deposits as the prime instigator of dementia has now led to clinical trials of multiple strategies to remove or prevent their formation. We performed neuropathological and biochemical assessments of 3 subjects treated with bapineuzumab infusions. Histological analyses were conducted to quantify amyloid plaque densities, Braak stages and the extent of cerebral amyloid angiopathy (CAA). Amyloid-β (Aβ) species in frontal and temporal lobe samples were quantified by ELISA. Western blots of amyloid-β precursor protein (AβPP) and its C-terminal (CT) fragments as well as tau species were performed. Bapineuzumab-treated (Bapi-AD) subjects were compared to non-immunized age-matched subjects with AD (NI-AD) and non-demented control (NDC) cases. Our study revealed that Bapi-AD subjects exhibited overall amyloid plaque densities similar to those of NI-AD cases. In addition, CAA was moderate to severe in NI-AD and Bapi-AD patients. Although histologically-demonstrable leptomeningeal, cerebrovascular and neuroparenchymal-amyloid densities all appeared unaffected by treatment, Aβ peptide profiles were significantly altered in Bapi-AD subjects. There was a trend for reduction in total Aβ42 levels as well as an increase in Aβ40 which led to a corresponding significant decrease in Aβ42:Aβ40 ratio in comparison to NI-AD subjects. There were no differences in the levels of AβPP, CT99 and CT83 or tau species between Bapi-AD and NI-AD subjects. The remarkable alteration in Aβ profiles reveals a dynamic amyloid production in which removal and depositional processes were apparently perturbed by bapineuzumab therapy. Despite the alteration in biochemical composition, all 3 immunized subjects exhibited continued cognitive decline. PMID:23555764

  20. Reactivity and morphology of vapor-deposited Al/polymer interfaces for organic semiconductor devices

    NASA Astrophysics Data System (ADS)

    Demirkan, K.; Mathew, A.; Weiland, C.; Reid, M.; Opila, R. L.

    2008-02-01

    The chemistry and the morphology of metal-deposited organic semiconductor interfaces play a significant role in determining the performance and reliability of organic semiconductor devices. We investigated the aluminum metallization of poly(2-methoxy-5,2'-ethyl-hexyloxy-phenylene vinylene) (MEH-PPV), polystyrene, and ozone-treated polystyrene surfaces by chemical (x-ray and ultraviolet photoelectron spectroscopy) and microscopic [atomic force microscopy, scanning electron microscopy (SEM), focused ion beam (FIB)] analyses. Photoelectron spectroscopy showed the degree of chemical interaction between Al and each polymer; for MEH-PPV, the chemical interactions were mainly through the C-O present in the side chain of the polymer structure. The chemical interaction of aluminum with polystyrene was less significant, but it showed a dramatic increase after ozone treatment of the polystyrene surface (due to the formation of exposed oxygen sites). Results showed a strong relationship between the surface reactivity and the condensation/sticking of the aluminum atoms on the surface. SEM analysis showed that, during the initial stages of the metallization, a significant clustering of aluminum takes place. FIB analysis showed that such clustering yields a notably porous structure. The chemical and the morphological properties of the vapor-deposited Al on organic semiconductor surfaces makes such electrical contacts more complicated. The possible effects of surface chemistry and interface morphology on the electrical properties and reliability of organic semiconductor devices are discussed in light of the experimental findings.

  1. The influence of process parameters and pulse ratio of precursors on the characteristics of La1 - x Al x O3 films deposited by atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Fei, Chenxi; Liu, Hongxia; Wang, Xing; Fan, Xiaojiao

    2015-04-01

    The influence of processing parameters of aluminum oxide (Al2O3) and lanthanum oxide (La2O3) gate dielectric is investigated. Trimethylaluminum (TMA) and tris(isopropylcyclopentadienyl) lanthanum [La(iPrCp)3] were used as precursors separately, and H2O was used as oxidant. The ultra-thin La1 - x Al x O3 gate dielectric films are deposited on p-type silicon substrates by atom layer deposition (ALD) for different pulse ratios of precursors. Effects of different La/Al precursor pulse ratios on the physical properties and electrical characteristics of La1 - x Al x O3 films are studied. The preliminary testing results indicate that the increase of La precursor pulse can improve the characteristics of film, which has significant effects on the dielectric constant, equivalent oxide thickness (EOT), electrical properties, and stability of film.

  2. Influences of different structures on the characteristics of H2O-based and O3-based La x Al y O films deposited by atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Chen-Xi, Fei; Hong-Xia, Liu; Xing, Wang; Dong-Dong, Zhao; Shu-Long, Wang; Shu-Peng, Chen

    2016-05-01

    H2O-based and O3-based La x Al y O nanolaminate films were deposited on Si substrates by atomic layer deposition (ALD). Structures and performances of the films were changed by different barrier layers. The effects of different structures on the electrical characteristics and physical properties of the La x Al y O films were studied. Chemical bonds in the La x Al y O films grown with different structures and different oxidants were also investigated with x-ray photoelectron spectroscopy (XPS). The preliminary testing results indicate that the La x Al y O films with different structures and different oxidants show different characteristics, including dielectric constant, equivalent oxide thickness (EOT), electrical properties, and stability. Project supported supported by the National Natural Science Foundation of China (Grant Nos. 61376099 and 61434007).

  3. The influence of process parameters and pulse ratio of precursors on the characteristics of La1 - x Al x O3 films deposited by atomic layer deposition.

    PubMed

    Fei, Chenxi; Liu, Hongxia; Wang, Xing; Fan, Xiaojiao

    2015-01-01

    The influence of processing parameters of aluminum oxide (Al2O3) and lanthanum oxide (La2O3) gate dielectric is investigated. Trimethylaluminum (TMA) and tris(isopropylcyclopentadienyl) lanthanum [La(iPrCp)3] were used as precursors separately, and H2O was used as oxidant. The ultra-thin La1 - x Al x O3 gate dielectric films are deposited on p-type silicon substrates by atom layer deposition (ALD) for different pulse ratios of precursors. Effects of different La/Al precursor pulse ratios on the physical properties and electrical characteristics of La1 - x Al x O3 films are studied. The preliminary testing results indicate that the increase of La precursor pulse can improve the characteristics of film, which has significant effects on the dielectric constant, equivalent oxide thickness (EOT), electrical properties, and stability of film. PMID:25983672

  4. Enhancement of photoluminescence properties in ZnO/AlN bilayer heterostructures grown by atomic layer deposition

    SciTech Connect

    Zhu, Shang-Bin; Lu, Hong-Liang Zhang, Yuan; Sun, Qing-Qing; Zhou, Peng; Ding, Shi-Jin; Zhang, David Wei; Zhang, Qiu-Xiang

    2015-01-15

    The AlN/ZnO bilayer heterostructures were deposited on Si (100) substrate by thermal atomic layer deposition. X-ray diffraction results show that the crystallinity of polycrystalline ZnO layer is enhanced by amorphous AlN capping layer. Compared with ZnO thin film, ZnO/AlN bilayer with 10.7 nm AlN capping layer exhibits three times enhanced near band edge (NBE) emission from the photoluminescence measurements. In addition, the near band edge emission from the ZnO can be further increased by ∼10 times through rapid thermal annealing at 600 °C. The underlying mechanisms for the enhancement of the NBE emission after coating AlN capping layer and thermal treatment are discussed. These results suggest that coating of a thin AlN layer and sequential thermal treatments can effectively tailor the luminescence properties of ZnO film.

  5. Texture Evolution During Laser Direct Metal Deposition of Ti-6Al-4V

    NASA Astrophysics Data System (ADS)

    Sridharan, Niyanth; Chaudhary, Anil; Nandwana, Peeyush; Babu, Sudarsanam Suresh

    2016-03-01

    Titanium alloys are used in a wide variety of high-performance applications and hence the processing of titanium and the resulting microstructures after additive manufacturing has received significant attention. During additive manufacturing, the processing route involves the transition from a liquid to solid state. The addition of successive layers results in a complex microstructure due to solid-state transformations. The current study focuses on understanding the phase transformations and relate them to the transformation texture in Ti-6Al-4V to identify conditions leading to a strong alpha transformation texture. The as-deposited builds were characterized using optical microscopy and electron backscattered diffraction. The results showed columnar prior β grains with a martensitic structure after the deposition of a single layer. On subsequent depositions, the martensitic microstructure decomposed to a colony and basketweave microstructure with a stronger transformation texture. The alpha texture with a colony and basketweave microstructure showed a stronger transformation texture as a result of variant selection. Thus, by controlling the cooling rate of the build from the β transus, it is possible to control the alpha transformation texture.

  6. Texture Evolution During Laser Direct Metal Deposition of Ti-6Al-4V

    DOE PAGESBeta

    Sridharan, Niyanth; Chaudhary, Anil; Nandwana, Peeyush; Babu, Sudarsanam Suresh

    2016-01-20

    Titanium alloys are used in a wide variety of high performance applications and hence the processing of the titanium and the resulting microstructures after additive manufacturing has received significant attention. During additive manufacturing the processing route involves the transition from a liquid to solid state. The addition of successive layers results in a complex microstructure due to solid-state transformations. The current study focuses on understanding the phase transformations and relate it to the transformation texture in Ti-6Al-4V to identify conditions leading to a strong alpha transformation texture. The as deposited builds were characterized using optical microscopy and electron backscattered diffraction.more » The results showed columnar prior β grains with a martensitic structure after the deposition of a single layer. On subsequent depositions the martensitic microstructure decomposes to a colony and basketweave microstructure with a stronger transformation texture. The alpha texture with a colony and basketweave microstructure shows a stronger transformation texture as a result of variant selection. Thus by controlling the cooling rate of the build from the β transus it is possible to control the alpha transformation texture.« less

  7. Superhydrophobic hierarchical surfaces fabricated by anodizing of oblique angle deposited Al-Nb alloy columnar films

    NASA Astrophysics Data System (ADS)

    Fujii, Takashi; Aoki, Yoshitaka; Habazaki, Hiroki

    2011-07-01

    A combined process of oblique angle magnetron sputtering and anodizing has been developed to tailor superhydrophobic surfaces with hierarchical morphology. Isolated submicron columns of single-phase Al-Nb alloys are deposited by magnetron sputtering at several oblique deposition angles on a scalloped substrate surface, with the gaps between columns increasing with an increase in the deposition angle from 70° to 110°. Then, the columnar films have been anodized in hot phosphate-glycerol electrolyte to form a nanoporous anodic oxide layer on each column. Such surfaces with submicron-/nano-porous structure have been coated with a fluoroalkyl phosphate layer to reduce the surface energy. The porous surface before coating is superhydrophilic with a contact angle for water is less than 10°, while after coating the contact angles are larger than 150°, being superhydrophobic. The beneficial effect of dual-scale porosity to enhance the water repellency is found from the comparison of the contact angles of the submicron columnar films with and without nanoporous oxide layers. The larger submicron gaps between columns are also preferable to increase the water repellency.

  8. Fueling the Fire with Fibers: Bacterial Amyloids Promote Inflammatory Disorders.

    PubMed

    Spaulding, Caitlin N; Dodson, Karen W; Chapman, Matthew R; Hultgren, Scott J

    2015-07-01

    Bacterial infection is associated with increased morbidity in patients with systematic lupus erythematosus. In a recent Immunity paper, Gallo et al. (2015) report that extracellular DNA is bound tightly by bacterial amyloid fibrils during biofilm formation and that amyloid/DNA composites are immune stimulators when injected into mice, leading to autoimmunity. PMID:26159711

  9. Regional brain hypometabolism is unrelated to regional amyloid plaque burden.

    PubMed

    Altmann, Andre; Ng, Bernard; Landau, Susan M; Jagust, William J; Greicius, Michael D

    2015-12-01

    In its original form, the amyloid cascade hypothesis of Alzheimer's disease holds that fibrillar deposits of amyloid are an early, driving force in pathological events leading ultimately to neuronal death. Early clinicopathological investigations highlighted a number of inconsistencies leading to an updated hypothesis in which amyloid plaques give way to amyloid oligomers as the driving force in pathogenesis. Rather than focusing on the inconsistencies, amyloid imaging studies have tended to highlight the overlap between regions that show early amyloid plaque signal on positron emission tomography and that also happen to be affected early in Alzheimer's disease. Recent imaging studies investigating the regional dependency between metabolism and amyloid plaque deposition have arrived at conflicting results, with some showing regional associations and other not. We extracted multimodal neuroimaging data from the Alzheimer's disease neuroimaging database for 227 healthy controls and 434 subjects with mild cognitive impairment. We analysed regional patterns of amyloid deposition, regional glucose metabolism and regional atrophy using florbetapir ((18)F) positron emission tomography, (18)F-fluordeoxyglucose positron emission tomography and T1-weighted magnetic resonance imaging, respectively. Specifically, we derived grey matter density and standardized uptake value ratios for both positron emission tomography tracers in 404 functionally defined regions of interest. We examined the relation between regional glucose metabolism and amyloid plaques using linear models. For each region of interest, correcting for regional grey matter density, age, education and disease status, we tested the association of regional glucose metabolism with (i) cortex-wide florbetapir uptake; (ii) regional (i.e. in the same region of interest) florbetapir uptake; and (iii) regional florbetapir uptake while correcting in addition for cortex-wide florbetapir uptake. P-values for each setting

  10. Characteristics of the electromagnetic interference shielding effectiveness of Al-doped ZnO thin films deposited by atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Choi, Yong-June; Gong, Su Cheol; Johnson, David C.; Golledge, Stephen; Yeom, Geun Young; Park, Hyung-Ho

    2013-03-01

    The structural, optical, and electrical properties of Al-doped ZnO (ZnO:Al) thin films deposited by atomic layer deposition (ALD) with a modified precursor pulse sequence were investigated to evaluate the electromagnetic interference shielding effectiveness (EMI-SE). A Zn-Al-O precursor exposure sequence was used in a modified ALD procedure to result in better distribution of Al3+ ions in the ZnO matrix with the aim of reducing the formation of complete nano-laminated structures that may form in the typical alternating ZnO and Al2O3 deposition procedure. The ALD dopant concentration of the ZnO:Al films was varied by adjusting the dopant deposition intervals of the ZnO:Znsbnd Alsbnd O precursor pulse cycle ratios among 24:1, 19:1, 14:1, and 9:1. The lowest obtained resistivity and average transmittance in the visible region (380-780 nm) were 5.876 × 10-4 Ω cm (carrier concentration of 6.02 × 1020 cm-3 and Hall mobility of 17.65 cm2/V s) and 85.93% in the 131 nm thick ZnO:Al(19:1) film, respectively. The average value of the EMI-SE in the range of 30 MHz to 1.5 GHz increased from 1.1 dB for the 121 nm thick undoped ZnO film to 6.5 dB for the 131 nm thick ZnO:Al(19:1) film.

  11. Is amyloid beta-protein glycated in Alzheimer's disease?

    PubMed

    Tabaton, M; Perry, G; Smith, M; Vitek, M; Angelini, G; Dapino, D; Garibaldi, S; Zaccheo, D; Odetti, P

    1997-03-01

    Recent data suggest that protein glycation is involved in the process of amyloid formation in Alzheimer's disease (AD). To further investigate this issue, we analyzed the presence of advanced glycation end products (AGE) in soluble and insoluble forms of amyloid beta-protein (A beta) as well as in apolipoprotein E (apoE), a protein bound to amyloid deposits. Both proteins were extracted from cerebral cortex obtained from patients with AD and probed by immunoblotting with two antibodies specific for different AGE, already known to immunocytochemically label amyloid plaques. All the AGE antibodies failed to recognize either A beta or apoE, whereas they reacted with synthetic A beta glycated in vitro. These findings indicate that other proteins associated with amyloid deposits are candidates to be modified with AGE in Alzheimer's cerebral tissue. PMID:9141062

  12. Beyond amyloid: getting real about nonamyloid targets in Alzheimer's disease.

    PubMed

    Herrup, Karl; Carrillo, Maria C; Schenk, Dale; Cacace, Angela; Desanti, Susan; Fremeau, Robert; Bhat, Ratan; Glicksman, Marcie; May, Patrick; Swerdlow, Russell; Van Eldik, Linda J; Bain, Lisa J; Budd, Samantha

    2013-07-01

    For decades, researchers have focused primarily on a pathway initiated by amyloid beta aggregation, amyloid deposition, and accumulation in the brain as the key mechanism underlying the disease and the most important treatment target. However, evidence increasingly suggests that amyloid is deposited early during the course of disease, even prior to the onset of clinical symptoms. Thus, targeting amyloid in patients with mild to moderate Alzheimer's disease (AD), as past failed clinical trials have done, may be insufficient to halt further disease progression. Scientists are investigating other molecular and cellular pathways and processes that contribute to AD pathogenesis. Thus, the Alzheimer's Association's Research Roundtable convened a meeting in April 2012 to move beyond amyloid and explore AD as a complex multifactorial disease, with the goal of using a more inclusive perspective to identify novel treatment strategies. PMID:23809366

  13. Study of high In-content AlInN deposition on p-Si(111) by RF-sputtering

    NASA Astrophysics Data System (ADS)

    Núñez-Cascajero, Arántzazu; Monteagudo-Lerma, Laura; Valdueza-Felip, Sirona; Navío, Cristina; Monroy, Eva; González-Herráez, Miguel; Naranjo, Fernando B.

    2016-05-01

    In this work, we investigate the effects of deposition conditions on the structural and morphological properties of AlInN thin films deposited on p-doped Si(111) substrates by reactive radio-frequency sputtering. The aluminum composition can be tuned in the 0 to 0.36 range by changing the power applied to the aluminum target. Al incorporation leads to a change in the layer morphology and improvement of the rms surface roughness of the layers. The compact Al0.36In0.64N sample grown at 550 °C exhibits intense room-temperature photoluminescence centered at 1.75 eV.

  14. Functionally graded Ti6Al4V and Inconel 625 by Laser Metal Deposition

    NASA Astrophysics Data System (ADS)

    Pulugurtha, Syamala R.

    The objective of the current work was to fabricate a crack-free functionally graded Ti6Al4V and Inconel 625 thin wall structure by Laser Metal Deposition (LMD). One potential application for the current material system is the ability to fabricate a functionally graded alloy that can be used in a space heat exchanger. The two alloys, Inconel 625 and Ti6Al4V are currently used for aerospace applications. They were chosen as candidates for grading because functionally grading those combines the properties of high strength/weight ratio of Ti6Al4V and high temperature oxidation resistance of Inconel 625 into one multifunctional material for the end application. However, there were challenges associated with the presence of Ni-Ti intermetallic phases (IMPs). The study focused on several critical areas such as (1) understanding microstructural evolution, (2) reducing macroscopic cracking, and (3) reducing mixing between graded layers. Finite element analysis (FEA) was performed to understand the effect of process conditions on multilayer claddings for simplified material systems such as SS316L and Inconel 625 where complex microstructures did not form. The thermo-mechanical models were developed using Abaqus(TM) (and some of them experimentally verified) to predict temperature-gradients; remelt layer depths and residual stresses. Microstructure evolution along the functionally graded Ti6Al4V and Inconel 625 was studied under different processing and grading conditions. Thermodynamic modeling using Factsage (v 6.1) was used to construct phase diagrams and predict the possible equilibrium major/minor phases (verified experimentally by XRD) that may be present along the functionally graded Ti6Al4V and Inconel 625 thin wall structures.

  15. Impedance analysis of nano thickness layered AlGaN acoustic sensor deposited by thermionic vacuum arc

    NASA Astrophysics Data System (ADS)

    Özen, Soner; Bilgiç, Eyüp; Gülmez, Gülay; Şenay, Volkan; Pat, Suat; Korkmaz, Şadan; Mohammadigharehbagh, Reza

    2016-03-01

    In this study, AlGaN acoustic sensor was deposited on aluminum metal substrate by thermionic vacuum arc (TVA) method for the first time. Gallium materials are used in many applications for optoelectronic device and semiconductor technology. Thermionic vacuum arc is the deposition technology for the variously materials and applications field. The thickness of the acoustic sensor is in deposited as nano layer. Impedance analyses were realized. Also, TVA production parameters and some properties of the deposited layers were investigated. TVA is a fast deposition technology for the gallium compounds and doped gallium compounds. Obtained results show that AlGaN materials are very promising materials. Moreover, these acoustic sensors have been produced by TVA technology.

  16. High rate reactive magnetron sputter deposition of Al-doped ZnO with unipolar pulsing and impedance control system

    SciTech Connect

    Nishi, Yasutaka; Hirohata, Kento; Tsukamoto, Naoki; Sato, Yasushi; Oka, Nobuto; Shigesato, Yuzo

    2010-07-15

    Al-doped ZnO (AZO) films were deposited on quartz glass substrates, unheated and heated to 200 deg. C, using reactive sputtering with a special feedback system of discharge impedance combined with midfrequency pulsing. A planar Zn-Al alloy target was connected to the switching unit, which was operated in a unipolar pulse mode. The oxidation of the target surface was precisely controlled by a feedback system for the entire O{sub 2} flow ratio including ''the transition region''. The deposition rate was about 10-20 times higher than that for films deposited by conventional sputtering using an oxide target. A deposition rate of AZO films of 390 nm/min with a resistivity of 3.8x10{sup -4} {Omega} cm and a transmittance in the visible region of 85% was obtained when the films were deposited on glass substrates heated to 200 deg. C with a discharge power of 4 kW.

  17. In situ study of e-beam Al and Hf metal deposition on native oxide InP (100)

    SciTech Connect

    Dong, H.; KC, Santosh; Azcatl, A.; Cabrera, W.; Qin, X.; Brennan, B.; Cho, K.; Wallace, R. M.; Zhernokletov, D.

    2013-11-28

    The interfacial chemistry of thin Al (∼3 nm) and Hf (∼2 nm) metal films deposited by electron beam (e-beam) evaporation on native oxide InP (100) samples at room temperature and after annealing has been studied by in situ angle resolved X-ray photoelectron spectroscopy and low energy ion scattering spectroscopy. The In-oxides are completely scavenged forming In-In/In-(Al/Hf) bonding after Al and Hf metal deposition. The P-oxide concentration is significantly decreased, and the P-oxide chemical states have been changed to more P-rich oxides upon metal deposition. Indium diffusion through these metals before and after annealing at 250 °C has also been characterized. First principles calculation shows that In has lower surface formation energy compared with Al and Hf metals, which is consistent with the observed indium diffusion behavior.

  18. Deposition of AlN Thin Films with Cubic Crystal Structures on Silicon Substrates at Room Temperature

    NASA Astrophysics Data System (ADS)

    Ren, Zhong-Min; Lu, Yong-Feng; Goh, Yeow-Whatt; Chong, Tow-Chong; Ng, Mei-Ling; Wang, Jian-Ping; Cheong, Boon-Aik; Liew, Yun-Fook

    2000-05-01

    Cubic AlN thin films were deposited at room temperature by nitrogen-ion-assisted pulsed laser ablation of a hexagonal AlN target. The full-width at half maximum (FWHM) of the X-ray diffraction peak in the θ˜ 2θ scan can reach a value of 0.27 degrees. In the Raman spectroscopy measurement, a new peak at 2333 cm-1 originating from cubic AlN polycrystalline was observed. Nitrogen ions not only effectively promote the formation of stable Al-N bonds but also improve the crystal properties of the deposited thin films. A nitrogen ion energy of 400 eV is proposed for the thin-film deposition.

  19. Structure of anodized Al-Zr sputter deposited coatings and effect on optical appearance

    NASA Astrophysics Data System (ADS)

    Gudla, Visweswara Chakravarthy; Canulescu, Stela; Shabadi, Rajashekhara; Rechendorff, Kristian; Dirscherl, Kai; Ambat, Rajan

    2014-10-01

    The mechanism of interaction of light with the microstructure of anodized layer giving specific optical appearance is investigated using Al-Zr sputter deposited coating as a model system on an AA6060 substrate. Differences in the oxidative nature of various microstructural components result in the evolution of typical features in the anodized layer, which are investigated as a function of microstructure and correlated with its optical appearance. The Zr concentration in the coating was varied from 6 wt.% to 23 wt.%. Heat treatment of the coated samples was carried out at 550 °C for 4 h in order to evolve Al-Zr based second phase precipitates in the microstructure. Anodizing was performed using 20 wt.% sulphuric acid at 18 °C with an intention to study the effect of anodizing on the Al-Zr based precipitates in the coating. Detailed microstructural characterization of the coating and anodized layer was carried out using high resolution scanning and transmission electron microscopy, grazing incidence X-ray diffraction analysis, glow discharge optical emission spectroscopy, and optical appearance using spectrophotometry. The evolution of microstructure in the anodized layer as a function of anodizing parameters and their influence on the interaction of light is investigated and the results in general are applicable to discolouration of anodized layer on recycled aluminium alloys due to intermetallics.

  20. Amyloid growth: combining experiment and kinetic theory

    NASA Astrophysics Data System (ADS)

    Knowles, Tuomas; Cohen, Samuel; Vendruscolo, Michele; Dobson, Christopher

    2012-02-01

    The conversion of proteins from their soluble forms into fibrillar amyloid nanostructures is a general type of behaviour encountered for many different proteins in the context of disease as well as for the generation of a select class of functional materials in nature. This talk focuses on the problem of defining the rates of the individual molecular level processes involved in the overall conversion reaction. A master equation approach is discussedootnotetextCohen et al, J Chem Phys 2011, 135, 065106 ootnotetextKnowles et al, Science, 2009, 326, 1533-1537 and used in combination with kinetic measurements to yield mechanistic insights into the amyloid growth phenomenon.

  1. Electrical properties of GaAs metal-oxide-semiconductor structure comprising Al2O3 gate oxide and AlN passivation layer fabricated in situ using a metal-organic vapor deposition/atomic layer deposition hybrid system

    NASA Astrophysics Data System (ADS)

    Aoki, Takeshi; Fukuhara, Noboru; Osada, Takenori; Sazawa, Hiroyuki; Hata, Masahiko; Inoue, Takayuki

    2015-08-01

    This paper presents a compressive study on the fabrication and optimization of GaAs metal-oxide-semiconductor (MOS) structures comprising a Al2O3 gate oxide, deposited via atomic layer deposition (ALD), with an AlN interfacial passivation layer prepared in situ via metal-organic chemical vapor deposition (MOCVD). The established protocol afforded self-limiting growth of Al2O3 in the atmospheric MOCVD reactor. Consequently, this enabled successive growth of MOCVD-formed AlN and ALD-formed Al2O3 layers on the GaAs substrate. The effects of AlN thickness, post-deposition anneal (PDA) conditions, and crystal orientation of the GaAs substrate on the electrical properties of the resulting MOS capacitors were investigated. Thin AlN passivation layers afforded incorporation of optimum amounts of nitrogen, leading to good capacitance-voltage (C-V) characteristics with reduced frequency dispersion. In contrast, excessively thick AlN passivation layers degraded the interface, thereby increasing the interfacial density of states (Dit) near the midgap and reducing the conduction band offset. To further improve the interface with the thin AlN passivation layers, the PDA conditions were optimized. Using wet nitrogen at 600 °C was effective to reduce Dit to below 2 × 1012 cm-2 eV-1. Using a (111)A substrate was also effective in reducing the frequency dispersion of accumulation capacitance, thus suggesting the suppression of traps in GaAs located near the dielectric/GaAs interface. The current findings suggest that using an atmosphere ALD process with in situ AlN passivation using the current MOCVD system could be an efficient solution to improving GaAs MOS interfaces.

  2. The influence of Cu /Al ratio on properties of chemical-vapor-deposition-grown p-type Cu-Al-O transparent semiconducting films

    NASA Astrophysics Data System (ADS)

    Cai, Jianling; Gong, Hao

    2005-08-01

    Transparent p-type copper aluminum oxide (Cu-Al-O) semiconducting thin films, with Cu /Al atomic ratios ranging from 1.0 to 4.3, were deposited by plasma-enhanced metal-organic chemical-vapor deposition. The films were grown on z-cut single-crystal quartz substrates, at a substrate temperature of 450°C. Crystalline CuAlO2 was found dominant in the films, including small amounts of CuAl2O4, Al2O3, and amorphous Cu2O. The effect of varying Cu /Al ratio on the structural, electrical, and optical properties of the films were studied by x-ray diffraction, energy dispersive x-ray spectroscopy, x-ray photoelectron spectroscopy, ultraviolet-visible spectroscopy, and Seebeck technique, and discussed. We were able to optimize the Cu /Al ratio for the p-type conductivity and transmittance in copper aluminum oxide thin films, and the best conductive film, with a room-temperature conductivity of 0.289Scm-1 and a transparency of 80%, was found to have a Cu /Al ratio of 1.4±0.3. In addition, the mechanism of the p-type conduction of copper aluminum oxide was discussed.

  3. Electrical and optical properties of Al-doped ZnO and ZnAl2O4 films prepared by atomic layer deposition

    PubMed Central

    2013-01-01

    ZnO/Al2O3 multilayers were prepared by alternating atomic layer deposition (ALD) at 150°C using diethylzinc, trimethylaluminum, and water. The growth process, crystallinity, and electrical and optical properties of the multilayers were studied with a variety of the cycle ratios of ZnO and Al2O3 sublayers. Transparent conductive Al-doped ZnO films were prepared with the minimum resistivity of 2.4 × 10−3 Ω·cm at a low Al doping concentration of 2.26%. Photoluminescence spectroscopy in conjunction with X-ray diffraction analysis revealed that the thickness of ZnO sublayers plays an important role on the priority for selective crystallization of ZnAl2O4 and ZnO phases during high-temperature annealing ZnO/Al2O3 multilayers. It was found that pure ZnAl2O4 film was synthesized by annealing the specific composite film containing alternative monocycle of ZnO and Al2O3 sublayers, which could only be deposited precisely by utilizing ALD technology. PMID:23537274

  4. Current-Voltage Characteristics and Deposition of AlTiN Thin Films by High Power Impulse Magnetron Sputtering Process

    NASA Astrophysics Data System (ADS)

    Wu, Wan-Yu; Su, Amei; Liu, Yawei; Yeh, Chi-Ming; Chen, Wei-Chih; Chang, Chi-Lung

    2015-09-01

    In this study, AlTiN thin films were deposited using a high power impulse magnetron sputtering (HiPIMS) process under a unipolar mode. The AlTi target had a composition of 70 at% Al and 30 at% Ti. Nitrogen was used as the reactive gas to deposite AlTiN thin films along with Ar gas at a working pressure of 1 ×10-3 torr. The target voltage and current were measured at different conditions including various duty cycles from 1 to 5%, pulse durations from 50 to 400 μs, target powers from 0.6 to 1.8 kW, and N2/Ar ratios from 0 to 1. Depending on the deposition condition, peak powers in the range of 104 to 105 W were observed. The effect of deposition conditions were discussed. For film deposition, the pulse duration and the duty cycle were fixed at 100 μs and 3%, respectively. A fixed bias of -150 V was applied to the substrates, including Si wafer, 304 stainless steel, and tungsten carbide.It was found that the nitrogen content increases with the N2/Ar ratio and then saturates. With increasing target power, a higher N2/Ar ratio was required for the AlTiN thin films to have a better mechanical properties. Meanwhile, the hardness of the AlTiN thin films also increases with the target power. The highest hardness of 41 GPa was observed as the N2/Ar ratio was 0.9 and the power was 1.8 kW. It was found that the amount Al-N bonding and the distribution of AlN phase within the AlTiN thin films play an important role in determining the mechanical properties.

  5. High temperature oxidation of ZrO2/Al2O3 thin films deposited on steel.

    PubMed

    Lee, Jae Chun; Kim, Sun Kyu; Van Trung, Trinh; Lee, Dong Bok

    2013-11-01

    Thin ZrO2/Al2O3 films that consisted of alternating monoclinic ZrO2 nanolayers and amorphous Al2O3 nanolayers were deposited on a tool steel substrate using Zr and Al cathodes in a cathodic arc plasma deposition system, and then oxidized at 600-900 degrees C in air for up to 50 h. The ZrO2/Al2O3 films effectively suppressed the oxidation of the substrate up to 800 degrees C by acting as a barrier layer against the outward diffusion of the substrate elements and inward diffusion of oxygen. However, rapid oxidation occurred at 900 degrees C due mainly to the increased diffusion and subsequent oxidation of steel as well as the crystallization of amorphous Al2O3. PMID:24245292

  6. Amyloid goes global

    PubMed Central

    Bezprozvanny, Ilya

    2016-01-01

    The brains of Alzheimer’s disease (AD) patients contain abundant amyloid plaques composed of Aβ peptides. It is generally assumed that amyloid plaques and soluble Aβ oligomers induce neuronal pathology in AD. The mechanism of amyloid-mediated pathological effects is not clearly understood. Recent in vivo calcium (Ca2+) imaging studies with AD mouse models provide novel insights into changes in brain function resulting from accumulation of amyloid plaques. The unexpected lesson from these studies is that amyloid plaques result in both localized and global changes in brain function. The amyloid-induced effects include “short-range” changes in neuronal Ca2+ levels, “medium-range” changes in neuronal activity and ‘long-range” changes in astrocytic Ca2+ signaling and induction of intracellular Ca2+ waves spreading via astrocytic network. These results have potential implications for understanding synaptic and neuronal network dysfunction in AD brains. PMID:19318622

  7. Pt-Al2O3 dual layer atomic layer deposition coating in high aspect ratio nanopores

    NASA Astrophysics Data System (ADS)

    Pardon, Gaspard; Gatty, Hithesh K.; Stemme, Göran; van der Wijngaart, Wouter; Roxhed, Niclas

    2013-01-01

    Functional nanoporous materials are promising for a number of applications ranging from selective biofiltration to fuel cell electrodes. This work reports the functionalization of nanoporous membranes using atomic layer deposition (ALD). ALD is used to conformally deposit platinum (Pt) and aluminum oxide (Al2O3) on Pt in nanopores to form a metal-insulator stack inside the nanopore. Deposition of these materials inside nanopores allows the addition of extra functionalities to nanoporous materials such as anodic aluminum oxide (AAO) membranes. Conformal deposition of Pt on such materials enables increased performances for electrochemical sensing applications or fuel cell electrodes. An additional conformal Al2O3 layer on such a Pt film forms a metal-insulator-electrolyte system, enabling field effect control of the nanofluidic properties of the membrane. This opens novel possibilities in electrically controlled biofiltration. In this work, the deposition of these two materials on AAO membranes is investigated theoretically and experimentally. Successful process parameters are proposed for a reliable and cost-effective conformal deposition on high aspect ratio three-dimensional nanostructures. A device consisting of a silicon chip supporting an AAO membrane of 6 mm diameter and 1.3 μm thickness with 80 nm diameter pores is fabricated. The pore diameter is reduced to 40 nm by a conformal deposition of 11 nm Pt and 9 nm Al2O3 using ALD.

  8. Oxidation precursor dependence of atomic layer deposited Al2O3 films in a-Si:H(i)/Al2O3 surface passivation stacks.

    PubMed

    Xiang, Yuren; Zhou, Chunlan; Jia, Endong; Wang, Wenjing

    2015-01-01

    In order to obtain a good passivation of a silicon surface, more and more stack passivation schemes have been used in high-efficiency silicon solar cell fabrication. In this work, we prepared a-Si:H(i)/Al2O3 stacks on KOH solution-polished n-type solar grade mono-silicon(100) wafers. For the Al2O3 film deposition, both thermal atomic layer deposition (T-ALD) and plasma enhanced atomic layer deposition (PE-ALD) were used. Interface trap density spectra were obtained for Si passivation with a-Si films and a-Si:H(i)/Al2O3 stacks by a non-contact corona C-V technique. After the fabrication of a-Si:H(i)/Al2O3 stacks, the minimum interface trap density was reduced from original 3 × 10(12) to 1 × 10(12) cm(-2) eV(-1), the surface total charge density increased by nearly one order of magnitude for PE-ALD samples and about 0.4 × 10(12) cm(-2) for a T-ALD sample, and the carrier lifetimes increased by a factor of three (from about 10 μs to about 30 μs). Combining these results with an X-ray photoelectron spectroscopy analysis, we discussed the influence of an oxidation precursor for ALD Al2O3 deposition on Al2O3 single layers and a-Si:H(i)/Al2O3 stack surface passivation from field-effect passivation and chemical passivation perspectives. In addition, the influence of the stack fabrication process on the a-Si film structure was also discussed in this study. PMID:25852428

  9. Sputter deposition of Al-doped ZnO films with various incident angles

    SciTech Connect

    Sato, Yasushi; Yanagisawa, Kei; Oka, Nobuto; Nakamura, Shin-ichi; Shigesato, Yuzo

    2009-09-15

    Al-doped ZnO (AZO) films were sputter deposited on glass substrates heated at 200 degree sign C under incident angles of sputtered particles at 0 degree sign (incidence normal to substrate), 20 deg., 40 deg., 60 deg., and 80 deg. In the case of normal incidence, x-ray diffraction pole figures show a strong [001] preferred orientation normal to the film surface. In contrast, in the case wherein the incident angles were higher than 60 degree sign , the [001] orientation inclined by 25 deg. - 35 deg. toward the direction of sputtered particles. Transmission electron microscopy revealed that the tilt angle of the [001] orientation increased with increasing angle of the incident sputtered particles, whereas the columnar structure did not show any sign of inclination with respect to the substrate plane.

  10. High performance ZnO:Al films deposited on PET substrates using facing target sputtering

    NASA Astrophysics Data System (ADS)

    Guo, Tingting; Dong, Guobo; Gao, Fangyuan; Xiao, Yu; Chen, Qiang; Diao, Xungang

    2013-10-01

    ZnO:Al (ZAO) thin films have been deposited on flexible PET substrates using a plasma damage-free facing target sputtering system at room temperature. The structure, surface morphology, electrical and optical properties were investigated as a function of working power. All the samples have a highly preferred orientation of the c-axis perpendicular to the PET substrate and have a high quality surface. With increased working power, the carrier concentration changes slightly, the mobility increases at the beginning and decreases after it reaches a maximum value, in line with electrical conductivity. The figure of merit has been significantly improved with increasing of the working power. Under the optimized condition, the lowest resistivity of 1.3 × 10-3 Ω cm with a sheet resistance of 29 Ω/□ and the relative visible transmittance above 93% in the visible region were obtained.

  11. Copper(II) ions and the Alzheimer's amyloid-β peptide: Affinity and stoichiometry of binding

    NASA Astrophysics Data System (ADS)

    Tõugu, Vello; Friedemann, Merlin; Tiiman, Ann; Palumaa, Peep

    2014-10-01

    Deposition of amyloid beta (Aβ) peptides into amyloid plaques is the hallmark of Alzheimer's disease. According to the amyloid cascade hypothesis this deposition is an early event and primary cause of the disease, however, the mechanisms that cause this deposition remain elusive. An increasing amount of evidence shows that the interactions of biometals can contribute to the fibrillization and amyloid formation by amyloidogenic peptides. From different anions the copper ions deserve the most attention since it can contribute not only toamyloid formation but also to its toxicity due to the generation of ROS. In this thesis we focus on the affinity and stoichiometry of copper(II) binding to the Aβ molecule.

  12. Prions, amyloids, and RNA: Pieces of a puzzle.

    PubMed

    Nizhnikov, Anton A; Antonets, Kirill S; Bondarev, Stanislav A; Inge-Vechtomov, Sergey G; Derkatch, Irina L

    2016-05-01

    Amyloids are protein aggregates consisting of fibrils rich in β-sheets. Growth of amyloid fibrils occurs by the addition of protein molecules to the tip of an aggregate with a concurrent change of a conformation. Thus, amyloids are self-propagating protein conformations. In certain cases these conformations are transmissible / infectious; they are known as prions. Initially, amyloids were discovered as pathological extracellular deposits occurring in different tissues and organs. To date, amyloids and prions have been associated with over 30 incurable diseases in humans and animals. However, a number of recent studies demonstrate that amyloids are also functionally involved in a variety of biological processes, from biofilm formation by bacteria, to long-term memory in animals. Interestingly, amyloid-forming proteins are highly overrepresented among cellular factors engaged in all stages of mRNA life cycle: from transcription and translation, to storage and degradation. Here we review rapidly accumulating data on functional and pathogenic amyloids associated with mRNA processing, and discuss possible significance of prion and amyloid networks in the modulation of key cellular functions. PMID:27248002

  13. Interface engineering for the passivation of c-Si with O3-based atomic layer deposited AlOx for solar cell application

    NASA Astrophysics Data System (ADS)

    Lee, Hyunju; Tachibana, Tomihisa; Ikeno, Norihiro; Hashiguchi, Hiroki; Arafune, Koji; Yoshida, Haruhiko; Satoh, Shin-ichi; Chikyow, Toyohiro; Ogura, Atsushi

    2012-04-01

    We have investigated the effects of deposition temperature and post-annealing on the passivation performance of AlOx films deposited by O3-based atomic layer deposition for crystalline Si. We found that the dramatic enhancement in the passivation performance of room-temperature deposited AlOx films by post-annealing is due to the phase transformation of aluminum silicate to mullite in an AlOx interlayer and the resulting self-aligned AlOx/SiOx interface. This result is interesting for the fabrication of high-performance silicon solar cells with AlOx passivation layers.

  14. Epitaxial growth and orientation of AlN thin films on Si(001) substrates deposited by reactive magnetron sputtering

    SciTech Connect

    Valcheva, E.; Birch, J.; Persson, P. O. A ring .; Tungasmita, S.; Hultman, L.

    2006-12-15

    Epitaxial domain formation and textured growth in AlN thin films deposited on Si(001) substrates by reactive magnetron sputtering was studied by transmission electron microscopy and x-ray diffraction. The films have a wurtzite type structure with a crystallographic orientation relationship to the silicon substrate of AlN(0001)(parallel sign)Si(001). The AlN film is observed to nucleate randomly on the Si surface and grows three dimensionally, forming columnar domains. The in-plane orientation reveals four domains with their a axes rotated by 15 deg. with respect to each other: AlN<1120>(parallel sign)Si[110], AlN<0110>(parallel sign)Si[110], AlN<1120>(parallel sign)Si[100], and AlN<0110>(parallel sign)Si[100] An explanation of the growth mode based on the large lattice mismatch and the topology of the substrate surface is proposed.

  15. 650-nm AlGaInP multiple-quantum-well lasers grown by metalorganic chemical vapor deposition using tertiarybutylphosphine

    NASA Astrophysics Data System (ADS)

    Dong, Jian-Rong; Teng, Jing-Hua; Chua, Soo-Jin; Foo, Boon-Chin; Wang, Yan-Jun; Yuan, Hai-Rong; Yuan, Shu

    2003-07-01

    Using tertiarybutylphosphine (TBP) as phosphorus precursor, high-quality AlGaInP epilayers and AlGaInP/GaInP multiple-quantum-well (MQW) structures have been grown by metalorganic chemical vapor deposition. The photoluminescence results indicate that the AlGaInP materials are as good as those grown using PH3 in terms of optical quality. Finally, AlGaInP MQW red laser structures have been grown, and the electrically pumped AlGaInP red lasers grown by TBP have been demonstrated with the emission wavelength of 647 nm, indicating that TBP can be used to grow high-quality AlGaInP epilayers and AlGaInP-based red lasers, which presently is dominated by the highly toxic gas source PH3.

  16. Structure of amyloid oligomers and their mechanisms of toxicities: Targeting amyloid oligomers using novel therapeutic approaches.

    PubMed

    Salahuddin, Parveen; Fatima, Munazza Tamkeen; Abdelhameed, Ali Saber; Nusrat, Saima; Khan, Rizwan Hasan

    2016-05-23

    Protein misfolding is one of the leading causes of amyloidoses. Protein misfolding occurs from changes in environmental conditions and host of other factors, including errors in post-translational modifications, increase in the rate of degradation, error in trafficking, loss of binding partners and oxidative damage. Misfolding gives rise to the formation of partially unfolded or misfolded intermediates, which have exposed hydrophobic residues and interact with complementary intermediates to form oligomers and consequently protofibrils and fibrils. The amyloid fibrils accumulate as amyloid deposits in the brain and central nervous system in Alzheimer's disease (AD), Prion disease and Parkinson's disease (PD). Initial studies have shown that amyloid fibrils were the main culprit behind toxicity that cause neurodegenerative diseases. However, attention shifted to the cytotoxicity of amyloid fibril precursors, notably amyloid oligomers, which are the major cause of toxicity. The mechanism of toxicity triggered by amyloid oligomers remains elusive. In this review, we have focused on the current knowledge of the structures of different aggregated states, including amyloid fibril, protofibrils, annular aggregates and oligomers. Based on the studies on the mechanism of toxicities, we hypothesize two major possible mechanisms of toxicities instigated by oligomers of Aβ (amyloid beta), PrP (prion protein) (106-126), and α-Syn (alpha-synuclein) including direct formation of ion channels and neuron membrane disruption by the increase in membrane conductance or leakage in the presence of small globulomers to large prefibrillar assemblies. Finally, we have discussed various novel innovative approaches that target amyloid oligomers in Alzheimer's diseases, Prion disease and Parkinson's disease. PMID:26974374

  17. Helium-Charged La-Ni-Al Thin Films Deposited by Magnetron Sputtering

    SciTech Connect

    Shi Liqun; Chen Deming; Xu Shilin; Liu Chaozhu; Hao Wanli; Zhou Zhuyin

    2005-07-15

    An advanced implantation of low energy helium-4 atoms during the La-Ni-Al film growth by adopting magnetron sputtering with Ar/He mixture gases is discussed. Both proton backscattering spectroscopy (PBS) and elastic recoil detection (ERD) analyses were adopted to measure helium concentration of the films and distribution in the near-surface region. Helium atoms with a high concentration incorporate evenly in deposited film. The introduction of the helium with no extra irradiation damage is expected by choosing suitable deposition conditions. It was found that amorphous and crystalline LaNi{sub 5}-type structures can be achieved when sputtered with pure Ar and Ar/He mixture gases at room temperature, respectively. Thermal desorption experiments proposes that a part of hydrogen atoms are bound to trapped helium at crystal and releases together with helium. Only a small fraction of helium is released from the helium-vacancy clusters in lower temperature range and most of helium is released from small size helium bubbles in the high temperature range.

  18. Amyloid in the islets of Langerhans: thoughts and some historical aspects.

    PubMed

    Westermark, Per

    2011-05-01

    Deposition of amyloid, derived from the polypeptide hormone islet amyloid polypeptide (IAPP; 'amylin') is the single most typical islet alteration in type 2 diabetes. Islet amyloid was described as hyalinization already in 1901, but not until 1986 was it understood that it is a polymerization product of a novel β-cell regulatory product. The subject of this focused review deals with the pathogenesis and importance of the islet amyloid itself, not with the biological effect of the polypeptide. Similar to the situation in Alzheimer's disease, it has been argued that the amyloid may not be of importance since there is no strict correlation between the degree of islet amyloid infiltration and the disease. However, it is hardly discussable that the amyloid is important in subjects where islets have been destroyed by pronounced islet amyloid deposits. Even when there is less islet amyloid the deposits are widely spread, and β-cells show ultrastructural signs of cell membrane destruction. It is suggested that type 2 diabetes is heterogeneous and that in one major subtype aggregation of IAPP into amyloid fibrils is determining the progressive loss of β-cells. Interestingly, development of islet amyloid may be an important event in the loss of β-cell function after islet transplantation into type 1 diabetic subjects. PMID:21486192

  19. Amyloid in the islets of Langerhans: Thoughts and some historical aspects

    PubMed Central

    2011-01-01

    Deposition of amyloid, derived from the polypeptide hormone islet amyloid polypeptide (IAPP; ‘amylin’) is the single most typical islet alteration in type 2 diabetes. Islet amyloid was described as hyalinization already in 1901, but not until 1986 was it understood that it is a polymerization product of a novel β-cell regulatory product. The subject of this focused review deals with the pathogenesis and importance of the islet amyloid itself, not with the biological effect of the polypeptide. Similar to the situation in Alzheimer's disease, it has been argued that the amyloid may not be of importance since there is no strict correlation between the degree of islet amyloid infiltration and the disease. However, it is hardly discussable that the amyloid is important in subjects where islets have been destroyed by pronounced islet amyloid deposits. Even when there is less islet amyloid the deposits are widely spread, and β-cells show ultrastructural signs of cell membrane destruction. It is suggested that type 2 diabetes is heterogeneous and that in one major subtype aggregation of IAPP into amyloid fibrils is determining the progressive loss of β-cells. Interestingly, development of islet amyloid may be an important event in the loss of β-cell function after islet transplantation into type 1 diabetic subjects. PMID:21486192

  20. Uniaxial magnetic anisotropy in Pd/Fe bilayers on Al2O3 (0001) induced by oblique deposition

    NASA Astrophysics Data System (ADS)

    Chi, Chiao-Sung; Wang, Bo-Yao; Pong, Way-Faung; Ho, Tsung-Ying; Tsai, Cheng-Jui; Lo, Fang-Yuh; Chern, Ming-Yau; Lin, Wen-Chin

    2012-06-01

    This study reports the preparation of self-organized 1-dimensional magnetic structures of Fe on Al2O3 (0001) by oblique deposition. The x-ray diffraction (XRD) results in this study show the preferred (110) texture of the Fe films. XRD and extended x-ray adsorption fine structure measurements indicate larger oblique deposition angle (65°) leads to more disorder in the Fe crystalline structure. After capping with a Pd overlayer, the Pd/Fe/Al2O3 (0001) still exhibits uniaxial magnetic anisotropy induced by the underlying 1-dimensional Fe nanostructure. This uniaxial magnetic anisotropy changes with the variation in Fe thickness and oblique deposition angle. These results clearly indicate the feasibility of manipulating uniaxial magnetic anisotropy and crystalline order through the oblique deposition of magnetic materials.

  1. Experimental Study of Direct Laser Deposition of Ti-6Al-4V and Inconel 718 by Using Pulsed Parameters

    PubMed Central

    Shah, Kamran; Haq, Izhar Ul; Shah, Shaukat Ali; Khan, Farid Ullah; Khan, Sikander

    2014-01-01

    Laser direct metal deposition (LDMD) has developed from a prototyping to a single metal manufacturing tool. Its potential for creating multimaterial and functionally graded structures is now beginning to be explored. This work is a first part of a study in which a single layer of Inconel 718 is deposited on Ti-6Al-4V substrate. Single layer tracks were built at a range of powder mass flow rates using a coaxial nozzle and 1.5 kW diode laser operating in both continuous and pulsed beam modes. This part of the study focused on the experimental findings during the deposition of Inconel 718 powder on Ti-6Al-4V substrate. Scanning electron microscopy (SEM) and X-ray diffraction analysis were performed for characterization and phase identification. Residual stress measurement had been carried out to ascertain the effects of laser pulse parameters on the crack development during the deposition process. PMID:24592190

  2. Sputter deposition of stress-controlled piezoelectric AlN and AlScN films for ultrasonic and energy harvesting applications.

    PubMed

    Barth, Stephan; Bartzsch, Hagen; Gloess, Daniel; Frach, Peter; Herzog, Thomas; Walter, Susan; Heuer, Henning

    2014-08-01

    This paper reports on the deposition and characterization of piezoelectric AlN and AlXSc1-XN layers. Characterization methods include XRD, SEM, active thermo probe, pulse echo, and piezometer measurements. A special focus is on the characterization of AlN regarding the mechanical stress in the films. The stress in the films changed between -2.2 GPa (compressive) and 0.2 GPa (tensile) and showed a significant dependence on film thickness. The cause of this behavior is presumed to be the different mean grain sizes at different film thicknesses, with bigger mean grain sizes at higher thicknesses. Other influences on film stress such as the sputter pressure or the pulse mode are presented. The deposition of gradient layers using those influences allowed the adjustment of film stress while retaining the piezoelectric properties. PMID:25073140

  3. Growth dynamics of reactive-sputtering-deposited AlN films

    SciTech Connect

    Auger, M.A.; Vazquez, L.; Sanchez, O.; Jergel, M.; Cuerno, R.; Castro, M.

    2005-06-15

    We have studied the surface kinetic roughening of AlN films grown on Si(100) substrates by dc reactive sputtering within the framework of the dynamic scaling theory. Films deposited under the same experimental conditions for different growth times were analyzed by atomic force microscopy and x-ray diffraction. The AlN films display a (002) preferred orientation. We have found two growth regimes with a crossover time of 36 min. In the first regime, the growth dynamics is unstable and the films present two types of textured domains, well textured and randomly oriented, respectively. In contrast, in the second regime the films are homogeneous and well textured, leading to a relative stabilization of the surface roughness characterized by a growth exponent {beta}=0.37{+-}0.03. In this regime a superrough scaling behavior is found with the following exponents: (i) Global exponents: roughness exponent {alpha}=1.2{+-}0.2 and {beta}=0.37{+-}0.03 and coarsening exponent 1/z=0.32{+-}0.05; (ii) local exponents: {alpha}{sub loc}=1, {beta}{sub loc}=0.32{+-}0.01. The differences between the growth modes are found to be related to the different main growth mechanisms dominating their growth dynamics: sticking anisotropy and shadowing, respectively.

  4. Glycosaminoglycans in extracts of cardiac amyloid fibrils from familial amyloid cardiomyopathy of Danish origin related to variant transthyretin Met 111.

    PubMed

    Magnus, J H; Stenstad, T; Kolset, S O; Husby, G

    1991-07-01

    We have previously demonstrated an association between secondary AA type amyloid fibrils and glycosaminoglycans (GAGs) in human liver. The present study was aimed at investigating whether a similar association could be demonstrated in isolated cardiac amyloid fibrils from a unique Danish family with amyloid cardiomyopathy related to variant transthyretin (TTR) with a single amino acid substitution of a methionin for leucine at position 111 (TTR Met 111). Using gel filtration and ion exchange chromatography, significant amounts of GAGs were detected in close association with purified myocardial amyloid fibrils, whereas only trace amounts of polysaccharides were present in the corresponding normal preparation. The GAGs were identified as 50% chondroitin sulfate, 33% heparin/heparan sulfate, and 17% hyaluronan. With the methods used the amyloid associated GAGs appeared as high molecular weight free polysaccharide chains, and not as part of intact proteoglycans (PGs) in the fibril extracts. We conclude that the association between purified amyloid fibrils and GAGs may be a general feature of amyloid deposits. Also, we suggest that the proportion of different GAGs in the amyloid deposits may depend both on the organ or tissues affected and the type of proteins making up the fibrils. PMID:2068532

  5. Investigation of thermal atomic layer deposited TiAlX (X = N or C) film as metal gate

    NASA Astrophysics Data System (ADS)

    Xiang, Jinjuan; Zhang, Yanbo; Li, Tingting; Wang, Xiaolei; Gao, Jianfeng; Yin, Huaxiang; Li, Junfeng; Wang, Wenwu; Ding, Yuqiang; Xu, Chongying; Zhao, Chao

    2016-08-01

    TiAlX (X = N or C) films are developed by thermal atomic layer deposition (ALD) technique as metal gate. The TiAlX films are deposited by using four different combinations of precursors: A: TiCl4-NH3-TMA-NH3, B: TiCl4-TMA-NH3, C: TiCl4-NH3-TMA and D: TiCl4-TMA. The physical characteristics of the TiAlX films such as chemical composition, growth rate, resistivity and surface roughness are estimated by X-ray photoemission spectroscopy, scanning electron microscope, four point probe method and atomic force microscopy respectively. Additionally, the electrical characteristics of the TiAlX films are investigated by using metal-oxide-semiconductor (MOS) capacitor structure. It is shown that NH3 presence in the reaction makes the film more like TiAlN(C) while NH3 absence makes the film more like TiAlC. The TiAlC film deposited by TiCl4-TMA has effective work function close to mid-gap of Si, which is rather potential for low power FinFET device application.

  6. Properties of Ultrathin Al2O3-TiO2 Nanolaminate Films for Gate Dielectric Applications Deposited by Plasma-Assisted Atomic Layer Deposition

    NASA Astrophysics Data System (ADS)

    Garces, Nelson; Meyer, David; Nepal, Neeraj; Wheeler, Virginia; Eddy, Charles

    2012-02-01

    High permittivity dielectrics such as Al2O3, HfO2, Ta2O5, TiO2, etc., are an essential component of aggressively-scaled III-V and graphene field effect transistors (FETs) where insulators are necessary to reduce gate leakage current while maintaining high gate capacitance and charge control of the channel. Atomic layer deposition (ALD) has the capability to deposit hybrid films, or nanolaminates, of two or more dielectrics that have unique properties. Thin [Al2O3+TiO2] nanolaminates with varying TiO2 and Al2O3 content were deposited on n-Si substrates at ˜225-300 C using ALD. A nanolaminate is composed of bilayers, defined as the sum of (x)Al2O3 and (y)TiO2, where x, and y indicate the number of times a component monolayer is repeated. While the overall thickness of the dielectric was held at ˜ 17-20 nm, the relative ratio of Al2O3 to TiO2 in the bilayer stack was varied to evaluate changes in the material properties and electrical performance of the oxides. C-V and I-V measurements on various [(x)TiO2+(y)Al2O3] MOS capacitors were taken. The high-TiO2-content films show limited evidence of oxide charge trapping and relatively large dielectric constants (κ˜15), whereas the high-Al2O3-content films offer a larger optical bandgap and improved suppression of leakage current. We will discuss the properties of very thin nanolaminates and their possible use as gate oxides. Morphological, electrical, and XPS composition assessments will be presented.

  7. Al{sub 2}O{sub 3} multi-density layer structure as a moisture permeation barrier deposited by radio frequency remote plasma atomic layer deposition

    SciTech Connect

    Jung, Hyunsoo; Jeon, Heeyoung; Choi, Hagyoung; Ham, Giyul; Shin, Seokyoon; Jeon, Hyeongtag

    2014-02-21

    Al{sub 2}O{sub 3} films deposited by remote plasma atomic layer deposition have been used for thin film encapsulation of organic light emitting diode. In this study, a multi-density layer structure consisting of two Al{sub 2}O{sub 3} layers with different densities are deposited with different deposition conditions of O{sub 2} plasma reactant time. This structure improves moisture permeation barrier characteristics, as confirmed by a water vapor transmission rate (WVTR) test. The lowest WVTR of the multi-density layer structure was 4.7 × 10{sup −5} gm{sup −2} day{sup −1}, which is one order of magnitude less than WVTR for the reference single-density Al{sub 2}O{sub 3} layer. This improvement is attributed to the location mismatch of paths for atmospheric gases, such as O{sub 2} and H{sub 2}O, in the film due to different densities in the layers. This mechanism is analyzed by high resolution transmission electron microscopy, elastic recoil detection, and angle resolved X-ray photoelectron spectroscopy. These results confirmed that the multi-density layer structure exhibits very good characteristics as an encapsulation layer via location mismatch of paths for H{sub 2}O and O{sub 2} between the two layers.

  8. Experimental manipulations of microglia in mouse models of Alzheimer’s pathology. Activation reduces amyloid but hastens tau pathology

    PubMed Central

    Lee, Daniel C.; Rizer, Justin; Hunt, Jerry B.; Selenica, Maj-Linda B.; Gordon, Marcia N.; Morgan, Dave

    2015-01-01

    The inflammation hypothesis of Alzheimer’s pathogenesis has directed much scientific effort towards ameliorating this disease. The development of mouse models of amyloid deposition permitted direct tests of the proposal that amyloid-activated microglia could cause neurodegeneration in vivo. Many approaches to manipulating microglial activation have been applied to these mouse models, and are the subject of this review. In general, these results do not support a direct neuricidal action of microglia in mouse amyloid models under any activation state. Some of the manipulations cause both a reduction in pathology, and a reduction in microglial activation. However, at least for agents like ibuprofen, this outcome may result from a direct action on amyloid production, and a reduction in the microglial provoking amyloid deposits, rather than from reduced microglial activation leading to a decline in amyloid deposition. Instead, a surprising number of the experimental manipulations which increase microglial activation lead to enhanced clearance of the amyloid deposits. Both the literature and new data presented here suggest that either classical or alternative activation of microglia can lead to enhanced amyloid clearance. However, a limited number of studies comparing the same treatments in amyloid-depositing vs tau-depositing mice find the opposite effects. Treatments that benefit amyloid pathology accelerate tau pathology. This observation argues strongly that potential treatments be tested for impact on both amyloid and tau pathology before consideration of testing in humans. PMID:23171029

  9. Demonstration of InAlN/AlGaN high electron mobility transistors with an enhanced breakdown voltage by pulsed metal organic chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Xue, JunShuai; Zhang, JinCheng; Hao, Yue

    2016-01-01

    In this work, InAlN/AlGaN heterostructures employing wider bandgap AlGaN instead of conventional GaN channel were grown on sapphire substrate by pulsed metal organic chemical vapor deposition, where the nominal Al composition in InAlN barrier and AlGaN channel were chosen to be 83% and 5%, respectively, to achieve close lattice-matched condition. An electron mobility of 511 cm2/V s along with a sheet carrier density of 1.88 × 1013 cm-2 were revealed in the prepared heterostructures, both of which were lower compared with lattice-matched InAlN/GaN due to increased intrinsic alloy disorder scattering resulting from AlGaN channel and compressively piezoelectric polarization in barrier, respectively. While the high electron mobility transistor (HEMT) processed on these structures not only exhibited a sufficiently high drain output current density of 854 mA/mm but also demonstrated a significantly enhanced breakdown voltage of 87 V, which is twice higher than that of reported InAlN/GaN HEMT with the same device dimension, potential characteristics for high-voltage operation of GaN-based electronic devices.

  10. Finding of vascular amyloid TTR in inferior nasal concha in a patient with FAP TTRVal30Met.

    PubMed

    Munar-Ques, Miguel; Martinez-Nadal, Jacinto; Torres-Rovira, Jose Juan; Sole, Manel; Zabay-Becerril, Jose Maria; Mulet-Ferrer, Juana Maria

    2008-12-01

    We report the case of a female patient with familial amyloid polyneuropathy (FAP) who demonstrated TTR amyloid deposition in the inferior nasal conchal vessels. To our knowledge this location has not been described previously in FAP; in addition, it was detected in a patient who had undergone successful liver transplantation (LTX) 4 years earlier. The amyloid deposition was found incidentally during examination of a right nasal obstruction caused by a nonspecific inflammatory polyp. Small focal deposits of amyloid TTR were observed on deep thick walled vessels, contrasting with the massive deposition reported in neoformed vessels in amyloidomas. This amyloid was clearly deposited between the onset of FAP and LTX and had probably decreased since the graft. If amyloid deposition is frequent in inferior nasal concha in FAP, this location could be a suitable biopsy site. PMID:19065300

  11. Current progress in the characterization of atomic layer deposited AlF3 for future astronomical ultraviolet mirror coatings

    NASA Astrophysics Data System (ADS)

    Moore, Christopher Samuel; Hennessy, John; Kersgaard, Eliot; Jewell, April D.; Nikzad, Shouleh; France, Kevin

    2015-08-01

    Reflective aluminum (Al) mirrors for astronomical telescopes are traditionally protected by a transmissive overcoat. The optical, mechanical and chemical properties of this overcoat material strongly affect the spectral reflective properties and durability of the mirror system. We are developing atomic layer deposited metal fluorides and assessing their applicability for future astronomical space missions in the ultraviolet and visible wavelengths. We are currently performing depositions on silicon wafers to serve as a basis for the metal-fluoride on Al depositions. In this paper we present reflectance, surface roughness, environmental storage and polarization sensitivity results of thin layers of AlF3 on silicon. Atomic layer deposited coatings of AlF3 grown at 100 and 200 °C yield good optical characteristics deduced from reflectance measurements from 90 - 800 nm and spectroscopic ellipsometry measurements from 200 - 800 nm, which are consistent with calculations from optical constants derived by our group and from the literature. Atomic force microscopy (AFM) measurements demonstrate a 15% increase in surface roughness for a ~25 nm film with respect to a silicon reference. Temporary storage in a gN2 box minimally affects the UV reflectance of ~30 nm of AlF3 on Si. Overall, these coatings have proven to be versatile and optically stable in the early phases of development.

  12. Electrochemical deposition and microstructural characterization of AlCrFeMnNi and AlCrCuFeMnNi high entropy alloy thin films

    NASA Astrophysics Data System (ADS)

    Soare, V.; Burada, M.; Constantin, I.; Mitrică, D.; Bădiliţă, V.; Caragea, A.; Târcolea, M.

    2015-12-01

    Al-Cr-Fe-Mn-Ni and Al-Cr-Cu-Fe-Mn-Ni high entropy alloy thin films were prepared by potentiostatic electrodeposition and the microstructure of the deposits was investigated. The thin films were co-deposited in an electrolyte based on a DMF (N,N-dimethylformamide)-CH3CN (acetonitrile) organic compound. The energy dispersive spectrometry investigation (EDS) indicated that all the five respectively six elements were successfully co-deposited. The scanning electron microscopy (SEM) analysis revealed that the film consists of compact and uniform particles with particle sizes of 500 nm to 4 μm. The X-ray diffractometry (XRD) patterns indicated that the as-deposited thin films were amorphous. Body-centered-cubic (BCC) structures were identified by XRD after the films were annealed at various temperatures under inert Ar atmosphere. The alloys adhesion on the substrate was determined by the scratch-testing method, with higher values obtained for the Al-Cr-Cu-Fe-Mn-Ni alloy.

  13. Adenoviral expression of murine serum amyloid A proteins to study amyloid fibrillogenesis.

    PubMed

    Kindy, M S; King, A R; Yu, J; Gerardot, C; Whitley, J; de Beer, F C

    1998-06-15

    Serum amyloid A (SAA) proteins are one of the most inducible acute-phase reactants and are precursors of secondary amyloidosis. In the mouse, SAA1 and SAA2 are induced in approximately equal quantities in response to amyloid induction models. These two isotypes differ in only 9 of 103 amino acid residues; however, only SAA2 is selectively deposited into amyloid fibrils. SAA expression in the CE/J mouse species is an exception in that gene duplication did not occur and the CE/J variant is a hybrid molecule sharing features of SAA1 and SAA2. However, even though it is more closely related to SAA2 it is not deposited as amyloid fibrils. We have developed an adenoviral vector system to overexpress SAA proteins in cell culture to determine the ability of these proteins to form amyloid fibrils, and to study the structural features in relation to amyloid formation. Both the SAA2 and CE/J SAA proteins were synthesized in large quantities and purified to homogeneity. Electron microscopic analysis of the SAA proteins revealed that the SAA2 protein was capable of forming amyloid fibrils, whereas the CE/J SAA was incapable. Radiolabelled SAAs were associated with normal or acute-phase high-density lipoproteins (HDLs); we examined them for their clearance from the circulation. In normal mice, SAA2 had a half-life of 70 min and CE/J SAA had a half-life of 120 min; however, in amyloid mice 50% of the SAA2 cleared in 55 min, compared with 135 min for the CE/J protein. When the SAA proteins were associated with acute-phase HDLs, SAA2 clearance was decreased to 60 min in normal mice compared with 30 min in amyloidogenic mice. Both normal and acute-phase HDLs were capable of depositing SAA2 into preformed amyloid fibrils, whereas the CE/J protein did not become associated with amyloid fibrils. This established approach opens the doors for large-scale SAA production and for the examination of specific amino acids involved in the fibrillogenic capability of the SAA2 molecule in vitro

  14. Plasticity of amyloid fibrils†

    PubMed Central

    Wetzel, Ronald; Shivaprasad, Shankaramma; Williams, Angela D.

    2008-01-01

    In experiments designed to characterize the basis of amyloid fibril stability through mutational analysis of the Aβ(1-40) molecule, fibrils exhibit consistent, significant structural malleability. In these results, and in other properties, amyloid fibrils appear to more resemble plastic materials generated from synthetic polymers than they do globular proteins. Thus, like synthetic polymers and plastics, amyloid fibrils exhibit both polymorphism, the ability of one polypeptide to form aggregates of different morphologies, and isomorphism, the ability of different polypeptides to grow into a fibrillar amyloid morphology. This view links amyloid with the prehistorical and 20th Century use of proteins as starting materials to make films, fibers, and plastics, and with the classic protein fiber stretching experiments of the Astbury group. Viewing amyloid from the point of view of the polymer chemist may shed new light on issues such as the role of protofibrils in the mechanism of amyloid formation, the biological potency of fibrils, and the prospects for discovering inhibitors of amyloid fibril formation. PMID:17198370

  15. Growth of highly oriented γ- and α-Al2O3 thin films by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Balakrishnan, G.; Babu, R. Venkatesh; Shin, K. S.; Song, J. I.

    2014-03-01

    Highly oriented aluminum oxide (Al2O3) thin films were grown on SrTiO3 (100), α-Al2O3 (11¯02), α-Al2O3 (0001) and MgO (100) single crystal substrates at an optimized oxygen partial pressure of 3.5×10-3 mbar and 700 °C by pulsed laser deposition. The films were characterized by X-ray diffraction and atomic force microscopy. The X-ray diffraction studies indicated the highly oriented growth of γ-Al2O3 (400) ǁ SrTiO3 (100), α-Al2O3 (024) ǁ α-Al2O3 (11¯02), α-Al2O3 (006) ǁ α-Al2O3 (0001) and α-Al2O3 (006) ǁ MgO (100). Formation of nanostructures with dense and smooth surface morphology was observed using atomic force microscopy. The root mean square surface roughness of the films were 0.2 nm, 0.5 nm, 0.7 nm and 0.3 nm on SrTiO3 (100), α-Al2O3 (11¯02), α-Al2O3 (0001) and MgO (100) substrates, respectively.

  16. Raft lipids as common components of human extracellular amyloid fibrils

    PubMed Central

    Gellermann, Gerald P.; Appel, Thomas R.; Tannert, Astrid; Radestock, Anja; Hortschansky, Peter; Schroeckh, Volker; Leisner, Christian; Lütkepohl, Tim; Shtrasburg, Shmuel; Röcken, Christoph; Pras, Mordechai; Linke, Reinhold P.; Diekmann, Stephan; Fändrich, Marcus

    2005-01-01

    Amyloid fibrils are fibrillar polypeptide aggregates from several degenerative human conditions, including Alzheimer's and Creutzfeldt-Jakob diseases. Analysis of amyloid fibrils derived from various human diseases (AA, ATTR, Aβ2M, ALλ, and ALκ amyloidosis) shows that these are associated with a common lipid component that has a conserved chemical composition and that is specifically rich in cholesterol and sphingolipids, the major components of cellular lipid rafts. This pattern is not notably affected by the purification procedure, and no tight lipid interactions can be detected when preformed fibrils are mixed with lipids. By contrast, the early and prefibrillar aggregates formed in an AA amyloid-producing cell system interact with the raft marker ganglioside-1, and amyloid formation is impaired by addition of cholesterol-reducing agents. These data suggest the existence of common cellular mechanisms in the generation of different types of clinical amyloid deposits. PMID:15851687

  17. Amyloid-Like Protein Inclusions in Tobacco Transgenic Plants

    PubMed Central

    Villar-Piqué, Anna; Sabaté, Raimon; Lopera, Oriol; Gibert, Jordi; Torne, Josep Maria; Santos, Mireya; Ventura, Salvador

    2010-01-01

    The formation of insoluble protein deposits in human tissues is linked to the onset of more than 40 different disorders, ranging from dementia to diabetes. In these diseases, the proteins usually self-assemble into ordered β-sheet enriched aggregates known as amyloid fibrils. Here we study the structure of the inclusions formed by maize transglutaminase (TGZ) in the chloroplasts of tobacco transplastomic plants and demonstrate that they have an amyloid-like nature. Together with the evidence of amyloid structures in bacteria and fungi our data argue that amyloid formation is likely a ubiquitous process occurring across the different kingdoms of life. The discovery of amyloid conformations inside inclusions of genetically modified plants might have implications regarding their use for human applications. PMID:21049018

  18. Rational design of potent human transthyretin amyloid disease inhibitors.

    PubMed

    Klabunde, T; Petrassi, H M; Oza, V B; Raman, P; Kelly, J W; Sacchettini, J C

    2000-04-01

    The human amyloid disorders, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and senile systemic amyloidosis, are caused by insoluble transthyretin (TTR) fibrils, which deposit in the peripheral nerves and heart tissue. Several nonsteroidal anti-inflammatory drugs and structurally similar compounds have been found to strongly inhibit the formation of TTR amyloid fibrils in vitro. These include flufenamic acid, diclofenac, flurbiprofen, and resveratrol. Crystal structures of the protein-drug complexes have been determined to allow detailed analyses of the protein-drug interactions that stabilize the native tetrameric conformation of TTR and inhibit the formation of amyloidogenic TTR. Using a structure-based drug design approach ortho-trifluormethylphenyl anthranilic acid and N-(meta-trifluoromethylphenyl) phenoxazine 4, 6-dicarboxylic acid have been discovered to be very potent and specific TTR fibril formation inhibitors. This research provides a rationale for a chemotherapeutic approach for the treatment of TTR-associated amyloid diseases. PMID:10742177

  19. Is in vivo amyloid distribution asymmetric in primary progressive aphasia?

    PubMed

    Martersteck, Adam; Murphy, Christopher; Rademaker, Alfred; Wieneke, Christina; Weintraub, Sandra; Chen, Kewei; Mesulam, M-Marsel; Rogalski, Emily

    2016-03-01

    We aimed to determine whether (18) F-florbetapir amyloid positron emission tomography imaging shows a clinically concordant, left-hemisphere-dominant pattern of deposition in primary progressive aphasia (PPA). Elevated cortical amyloid (Aβ(+) ) was found in 19 of 32 PPA patients. Hemispheric laterality of amyloid burden was compared between Aβ(+) PPA and an Aβ(+) amnestic dementia groups (n = 22). The parietal region showed significantly greater left lateralized amyloid uptake in the PPA group than the amnestic group (p < 0.007), consistent with the left lateralized pattern of neurodegeneration in PPA. These results suggest that the cortical distribution of amyloid may have a greater clinical concordance than previously reported. PMID:26600088

  20. Mechanistic Contributions of Biological Cofactors in Islet Amyloid Polypeptide Amyloidogenesis

    PubMed Central

    Nguyen, Phuong Trang; Andraka, Nagore; De Carufel, Carole Anne; Bourgault, Steve

    2015-01-01

    Type II diabetes mellitus is associated with the deposition of fibrillar aggregates in pancreatic islets. The major protein component of islet amyloids is the glucomodulatory hormone islet amyloid polypeptide (IAPP). Islet amyloid fibrils are virtually always associated with several biomolecules, including apolipoprotein E, metals, glycosaminoglycans, and various lipids. IAPP amyloidogenesis has been originally perceived as a self-assembly homogeneous process in which the inherent aggregation propensity of the peptide and its local concentration constitute the major driving forces to fibrillization. However, over the last two decades, numerous studies have shown a prominent role of amyloid cofactors in IAPP fibrillogenesis associated with the etiology of type II diabetes. It is increasingly evident that the biochemical microenvironment in which IAPP amyloid formation occurs and the interactions of the polypeptide with various biomolecules not only modulate the rate and extent of aggregation, but could also remodel the amyloidogenesis process as well as the structure, toxicity, and stability of the resulting fibrils. PMID:26576436

  1. Fibrillar dimer formation of islet amyloid polypeptides

    NASA Astrophysics Data System (ADS)

    Chiu, Chi-cheng; de Pablo, Juan J.

    2015-09-01

    Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 - 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 - 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

  2. Fibrillar dimer formation of islet amyloid polypeptides

    SciTech Connect

    Chiu, Chi-cheng; de Pablo, Juan J.

    2015-05-08

    Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimental and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.

  3. Neuropsychological Effects of Cerebral Amyloid Angiopathy.

    PubMed

    Schrag, Matthew; Kirshner, Howard

    2016-08-01

    Cerebral amyloid angiopathy is a condition of the cerebral arterioles and to a lesser extent capillaries and veins, wherein beta-amyloid is deposited. In arterioles, this preferentially targets vascular smooth muscle cells and in the later stages undermines the stability of the vessel. This condition is frequently comorbid with Alzheimer's disease and its role in cognitive impairment and dementia is a topic of considerable recent research. This article reviews recent literature which confirms that CAA independently contributes to cognitive impairment by potentiating the neurodegeneration of Alzheimer's disease, by predisposing to microhemorrhagic and microischemic injury to the brain parenchyma, and by interfering with the autoregulation of CNS blood flow. In this review, we discuss the clinical presentation of cerebral amyloid angiopathy, with a focus on the neuropsychological manifestations of this vasculopathy. PMID:27357378

  4. Cerebral amyloid-β accumulation and deposition following traumatic brain injury-A narrative review and meta-analysis of animal studies.

    PubMed

    Bird, Sabine M; Sohrabi, Hamid R; Sutton, Thomas A; Weinborn, Michael; Rainey-Smith, Stephanie R; Brown, Belinda; Patterson, Leigh; Taddei, Kevin; Gupta, Veer; Carruthers, Malcolm; Lenzo, Nat; Knuckey, Neville; Bucks, Romola S; Verdile, Giuseppe; Martins, Ralph N

    2016-05-01

    Traumatic brain injury (TBI) increases the risk of neurodegenerative disorders many years post-injury. However, molecular mechanisms underlying the relationship between TBI and neurodegenerative diseases, such as Alzheimer's disease (AD), remain to be elucidated. Nevertheless, previous studies have demonstrated a link between TBI and increased amyloid-β (Aβ), a protein involved in AD pathogenesis. Here, we review animal studies that measured Aβ levels following TBI. In addition, from a pool of initially identified 1209 published papers, we examined data from 19 eligible animal model studies using a meta-analytic approach. We found an acute increase in cerebral Aβ levels ranging from 24h to one month following TBI (overall log OR=2.97±0.40, p<0.001). These findings may contribute to further understanding the relationship between TBI and future dementia risk. The methodological inconsistencies of the studies discussed in this review suggest the need for improved and more standardised data collection and study design, in order to properly elucidate the role of TBI in the expression and accumulation of Aβ. PMID:26899257

  5. Influence of Substrate Temperature on Structural Properties and Deposition Rate of AlN Thin Film Deposited by Reactive Magnetron Sputtering

    NASA Astrophysics Data System (ADS)

    Jin, Hao; Feng, Bin; Dong, Shurong; Zhou, Changjian; Zhou, Jian; Yang, Yi; Ren, Tianling; Luo, Jikui; Wang, Demiao

    2012-07-01

    Aluminum nitride (AlN) thin films with c-axis preferred orientation have been prepared by reactive direct-current (DC) magnetron sputtering. The degree of preferred crystal orientation, the cross-sectional structure, and the surface morphology of AlN thin films grown on Si (100) substrates at various substrate temperatures from 60°C to 520°C have been investigated by x-ray diffraction, scanning electron microscopy, and atomic force microscopy. Results show that the substrate temperature has a significant effect on the structural properties, such as the degree of c-axis preferred orientation, the full-width at half-maximum (FWHM) of the rocking curve, the surface morphology, and the cross-sectional structure as well as the deposition rate of the AlN thin films. The optimal substrate temperature is 430°C, with corresponding root-mean-square surface roughness ( R rms) of 1.97 nm, FWHM of AlN (002) diffraction of 2.259°, and deposition rate of 20.86 nm/min. The mechanisms behind these phenomena are discussed. Finally, film bulk acoustic resonators based on AlN films were fabricated; the corresponding typical electromechanical coupling coefficient ( k {t/2}) is 5.1% with series and parallel frequencies of 2.37 GHz and 2.42 GHz, respectively.

  6. Conduction mechanisms in thin atomic layer deposited Al{sub 2}O{sub 3} layers

    SciTech Connect

    Spahr, Holger; Montzka, Sebastian; Reinker, Johannes; Hirschberg, Felix; Kowalsky, Wolfgang; Johannes, Hans-Hermann

    2013-11-14

    Thin Al{sub 2}O{sub 3} layers of 2–135 nm thickness deposited by thermal atomic layer deposition at 80 °C were characterized regarding the current limiting mechanisms by increasing voltage ramp stress. By analyzing the j(U)-characteristics regarding ohmic injection, space charge limited current (SCLC), Schottky-emission, Fowler-Nordheim-tunneling, and Poole-Frenkel-emission, the limiting mechanisms were identified. This was performed by rearranging and plotting the data in a linear scale, such as Schottky-plot, Poole-Frenkel-plot, and Fowler-Nordheim-plot. Linear regression then was applied to the data to extract the values of relative permittivity from Schottky-plot slope and Poole-Frenkel-plot slope. From Fowler-Nordheim-plot slope, the Fowler-Nordheim-energy-barrier was extracted. Example measurements in addition to a statistical overview of the results of all investigated samples are provided. Linear regression was applied to the region of the data that matches the realistic values most. It is concluded that ohmic injection and therefore SCLC only occurs at thicknesses below 12 nm and that the Poole-Frenkel-effect is no significant current limiting process. The extracted Fowler-Nordheim-barriers vary in the range of up to approximately 4 eV but do not show a specific trend. It is discussed whether the negative slope in the Fowler-Nordheim-plot could in some cases be a misinterpreted trap filled limit in the case of space charge limited current.

  7. Oxide Charge Engineering of Atomic Layer Deposited AlOxNy/Al2O3 Gate Dielectrics: A Path to Enhancement Mode GaN Devices.

    PubMed

    Negara, M A; Kitano, M; Long, R D; McIntyre, P C

    2016-08-17

    Nitrogen incorporation to produce negative fixed charge in Al2O3 gate insulator layers is investigated as a path to achieve enhancement mode GaN device operation. A uniform distribution of nitrogen across the resulting AlOxNy films is obtained using N2 plasma enhanced atomic layer deposition (ALD). The flat band voltage (Vfb) increases to a significantly more positive value with increasing nitrogen concentration. Insertion of a 2 nm thick Al2O3 interlayer greatly decreases the trap density of the insulator/GaN interface, and reduces the voltage hysteresis and frequency dispersion of gate capacitance compared to single-layer AlOxNy gate insulators in GaN MOSCAPs. PMID:27459343

  8. Optical characteristics of nanocrystalline Al{sub x}Ga{sub 1−x}N thin films deposited by hollow cathode plasma-assisted atomic layer deposition

    SciTech Connect

    Goldenberg, Eda; Ozgit-Akgun, Cagla; Biyikli, Necmi; Kemal Okyay, Ali

    2014-05-15

    Gallium nitride (GaN), aluminum nitride (AlN), and Al{sub x}Ga{sub 1−x}N films have been deposited by hollow cathode plasma-assisted atomic layer deposition at 200 °C on c-plane sapphire and Si substrates. The dependence of film structure, absorption edge, and refractive index on postdeposition annealing were examined by x-ray diffraction, spectrophotometry, and spectroscopic ellipsometry measurements, respectively. Well-adhered, uniform, and polycrystalline wurtzite (hexagonal) GaN, AlN, and Al{sub x}Ga{sub 1−x}N films were prepared at low deposition temperature. As revealed by the x-ray diffraction analyses, crystallite sizes of the films were between 11.7 and 25.2 nm. The crystallite size of as-deposited GaN film increased from 11.7 to 12.1 and 14.4 nm when the annealing duration increased from 30 min to 2 h (800 °C). For all films, the average optical transmission was ∼85% in the visible (VIS) and near infrared spectrum. The refractive indices of AlN and Al{sub x}Ga{sub 1−x}N were lower compared to GaN thin films. The refractive index of as-deposited films decreased from 2.33 to 2.02 (λ = 550 nm) with the increased Al content x (0 ≤ x ≤ 1), while the extinction coefficients (k) were approximately zero in the VIS spectrum (>400 nm). Postdeposition annealing at 900 °C for 2 h considerably lowered the refractive index value of GaN films (2.33–1.92), indicating a significant phase change. The optical bandgap of as-deposited GaN film was found to be 3.95 eV, and it decreased to 3.90 eV for films annealed at 800 °C for 30 min and 2 h. On the other hand, this value increased to 4.1 eV for GaN films annealed at 900 °C for 2 h. This might be caused by Ga{sub 2}O{sub 3} formation and following phase change. The optical bandgap value of as-deposited Al{sub x}Ga{sub 1−x}N films decreased from 5.75 to 5.25 eV when the x values decreased from 1 to 0.68. Furthermore, postdeposition annealing did not

  9. Tribological and mechanical properties of Ti/TiAlN/TiAlCN nanoscale multilayer PVD coatings deposited on AISI H11 hot work tool steel

    NASA Astrophysics Data System (ADS)

    AL-Bukhaiti, M. A.; Al-hatab, K. A.; Tillmann, W.; Hoffmann, F.; Sprute, T.

    2014-11-01

    A new [Ti/TiAlN/TiAlCN]5 multilayer coatings were deposited onto polished substrate AISI H11 (DIN 1.2343) steel by an industrial magnetron sputtering device. The tribological performance of the coated system was investigated by a ball-on-disk tribometer against 100Cr6 steel and Al2O3 balls. The friction coefficients and specific wear rates were measured at various normal loads (2, 5, 8, and 10 N) and sliding velocities (0.2, 0.4, and 0.8 m/s) in ambient air and dry conditions. The phase structure, composition, wear tracks morphologies, hardness, and film/substrate adhesion of the coatings were characterized by light-microscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), 3D-surface analyzer, nanoindentation, and scratch tests. Results showed that the deposited coatings showed low wear rates in the scale of 10-15 m3/N m, low friction coefficients against 100Cr6 and Al2O3 balls in the range of 0.25-0.37, and good hardness in the range of 17-20 GPa. Results also revealed that the friction coefficients and disc wear rates decrease and increase, respectively with the increase in normal load and sliding velocity for both coating/Al2O3 and coating/100Cr6 sliding system. Compared with the uncoated-H11 substrate, the deposited coating exhibited superior tribological and mechanical properties. The dominant wear mechanism was abrasive wear for coating/Al2O3 pair, while for coating/100Cr6 pair, a combination of mild adhesive wear, severe adhesive wear, and abrasive wear (extensive plowing) were the dominant wear mechanisms at different applied normal loads.

  10. Amyloid Hypothesis: Is There a Role for Antiamyloid Treatment in Late-Life Depression?

    PubMed

    Mahgoub, Nahla; Alexopoulos, George S

    2016-03-01

    Antidepressants have modest efficacy in late-life depression (LLD), perhaps because various neurobiologic processes compromise frontolimbic networks required for antidepressant response. We propose that amyloid accumulation is an etiologic factor for frontolimbic compromise that predisposes to depression and increases treatment resistance in a subgroup of older adults. In patients without history of depression, amyloid accumulation during the preclinical phase of Alzheimer disease (AD) may result in the prodromal depression syndrome that precedes cognitive impairment. In patients with early-onset depression, pathophysiologic changes during recurrent episodes may promote amyloid accumulation, further compromise neurocircuitry required for antidepressant response, and increase treatment resistance during successive depressive episodes. The findings that support the amyloid hypothesis of LLD are (1) Depression is a risk factor, a prodrome, and a common behavioral manifestation of AD; (2) amyloid deposition occurs during a long predementia period when depression is prevalent; (3) patients with lifetime history of depression have significant amyloid accumulation in brain regions related to mood regulation; and (4) amyloid deposition leads to neurobiologic processes, including vascular damage, neurodegeneration, neuroinflammation, and disrupted functional connectivity, that impair networks implicated in depression. The amyloid hypothesis of LLD is timely because availability of ligands allows in vivo assessment of amyloid in the human brain, a number of antiamyloid agents are relatively safe, and there is evidence that some antidepressants may reduce amyloid production. A model of LLD introducing the role of amyloid may guide the design of studies aiming to identify novel antidepressant approaches and prevention strategies of AD. PMID:26946981

  11. Bottom-gate coplanar graphene transistors with enhanced graphene adhesion on atomic layer deposition Al2O3

    NASA Astrophysics Data System (ADS)

    Park, Dong-Wook; Mikael, Solomon; Chang, Tzu-Hsuan; Gong, Shaoqin; Ma, Zhenqiang

    2015-03-01

    A graphene transistor with a bottom-gate coplanar structure and an atomic layer deposition (ALD) aluminum oxide (Al2O3) gate dielectric is demonstrated. Wetting properties of ALD Al2O3 under different deposition conditions are investigated by measuring the surface contact angle. It is observed that the relatively hydrophobic surface is suitable for adhesion between graphene and ALD Al2O3. To achieve hydrophobic surface of ALD Al2O3, a methyl group (CH3)-terminated deposition method has been developed and compared with a hydroxyl group (OH)-terminated deposition. Based on this approach, bottom-gate coplanar graphene field-effect transistors are fabricated and characterized. A post-thermal annealing process improves the performance of the transistors by enhancing the contacts between the source/drain metal and graphene. The fabricated transistor shows an Ion/Ioff ratio, maximum transconductance, and field-effect mobility of 4.04, 20.1 μS at VD = 0.1 V, and 249.5 cm2/V.s, respectively.

  12. Novel silicon surface passivation by Al2O3/ZnO/Al2O3 films deposited by thermal atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Jeong, Kwang-Seok; Oh, Sung-Kwen; Shin, Hong-Sik; Yun, Ho-Jin; Kim, Seong-Hyeon; Lee, Ho-Ryeong; Han, Kyu-Min; Park, Ho-Yun; Lee, Hi-Deok; Lee, Ga-Won

    2014-01-01

    In this paper, a novel Al2O3/ZnO/Al2O3 stack is proposed as the silicon passivation layer for c-Si solar cell application. Recently, the Al2O3 film has been proved to be effective for passivating the p-type c-Si surface by forming the negative fixed oxide charge. It is confirmed by this experiment that the amount of negative fixed oxide charge can be controlled by inserting a ZnO interlayer (IL), which is explained by acceptor-like defect (VZn, Oi, and OZn) formation determined by the room-temperature photoluminescence (RTPL) analysis. The effect of ZnO IL is investigated using Al2O3 bottom layers of various thicknesses by electrical and physical analyses. The effective lifetime measurement shows that the electronic recombination losses at the silicon surface are reduced effectively by optimizing the Al2O3/ZnO/Al2O3 stack.

  13. Structural and electrical properties of ternary Ru-AlN thin films prepared by plasma-enhanced atomic layer deposition

    SciTech Connect

    Shin, Yu-Ri; Kwack, Won-Sub; Park, Yun Chang; Kim, Jin-Hyock; Shin, Seung-Yong; Moon, Kyoung Il; Lee, Hyung-Woo; Kwon, Se-Hun

    2012-03-15

    Highlights: Black-Right-Pointing-Pointer Ru-AlN thin films were grown by plasma-enhanced atomic layer deposition (PEALD). Black-Right-Pointing-Pointer Structural properties were systematically investigated by XRD, BF-STEM and EDX. Black-Right-Pointing-Pointer A drastic decrease in resistivity was due to the microstructural change of the films. -- Abstract: Ruthenium-aluminum-nitride (Ru-AlN) thin films were grown by plasma-enhanced atomic layer deposition (PEALD) at 300 Degree-Sign C. The Ru intermixing ratio of Ru-AlN thin films was controlled by the number of Ru unit cycles, while the number of AlN unit cycles was fixed to one cycle. The electrical resistivity of Ru-AlN thin film decreased with increasing the Ru intermixing ratio, but a drastic decrease in electrical resistivity was observed when the Ru intermixing ratio was around 0.58-0.78. Bright-field scanning transmission electron microscope (BF-STEM) and energy-dispersive X-ray spectroscopy (EDX) element mapping analysis revealed that the electrical resistivity of Ru-AlN thin film was strongly dependent on the microstructures as well as on the Ru intermixing ratio. Although the electrical resistivity of Ru-AlN thin films decreased with increasing the Ru intermixing ratio, a drastic decrease in electrical resistivity occurred where the electrical paths formed as a result of the coalescence of Ru nanocrystals.

  14. Principal component analysis with pre-normalization improves the signal-to-noise ratio and image quality in positron emission tomography studies of amyloid deposits in Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Razifar, Pasha; Engler, Henry; Blomquist, Gunnar; Ringheim, Anna; Estrada, Sergio; Långström, Bengt; Bergström, Mats

    2009-06-01

    This study introduces a new approach for the application of principal component analysis (PCA) with pre-normalization on dynamic positron emission tomography (PET) images. These images are generated using the amyloid imaging agent N-methyl [11C]2-(4'-methylaminophenyl)-6-hydroxy-benzothiazole ([11C]PIB) in patients with Alzheimer's disease (AD) and healthy volunteers (HVs). The aim was to introduce a method which, by using the whole dataset and without assuming a specific kinetic model, could generate images with improved signal-to-noise and detect, extract and illustrate changes in kinetic behavior between different regions in the brain. Eight AD patients and eight HVs from a previously published study with [11C]PIB were used. The approach includes enhancement of brain regions where the kinetics of the radiotracer are different from what is seen in the reference region, pre-normalization for differences in noise levels and removal of negative values. This is followed by slice-wise application of PCA (SW-PCA) on the dynamic PET images. Results obtained using the new approach were compared with results obtained using reference Patlak and summed images. The new approach generated images with good quality in which cortical brain regions in AD patients showed high uptake, compared to cerebellum and white matter. Cortical structures in HVs showed low uptake as expected and in good agreement with data generated using kinetic modeling. The introduced approach generated images with enhanced contrast and improved signal-to-noise ratio (SNR) and discrimination power (DP) compared to summed images and parametric images. This method is expected to be an important clinical tool in the diagnosis and differential diagnosis of dementia.

  15. Effects of Al interlayer coating and thermal treatment on electron emission characteristics of carbon nanotubes deposited by electrophoretic method

    PubMed Central

    2014-01-01

    The effects of aluminum (Al) interlayer coating and thermal post-treatment on the electron emission characteristics of carbon nanotubes (CNTs) were investigated. These CNTs were deposited on conical-shaped tungsten (W) substrates using an electrophoretic method. The Al interlayers were coated on the W substrates via magnetron sputtering prior to the deposition of CNTs. Compared with the as-deposited CNTs, the thermally treated CNTs revealed significantly improved electron emission characteristics, such as the decrease of turn-on electric fields and the increase of emission currents. The observations of Raman spectra confirmed that the improved emission characteristics of the thermally treated CNTs were ascribed to their enhanced crystal qualities. The coating of Al interlayers played a role in enhancing the long-term emission stabilities of the CNTs. The thermally treated CNTs with Al interlayers sustained stable emission currents without any significant degradation even after continuous operation of 20 h. The X-ray photoelectron spectroscopy (XPS) study suggested that the cohesive forces between the CNTs and the underlying substrates were strengthened by the coating of Al interlayers. PMID:24959105

  16. Growth of crystalline Al{sub 2}O{sub 3} via thermal atomic layer deposition: Nanomaterial phase stabilization

    SciTech Connect

    Prokes, S. M. Katz, M. B.; Twigg, M. E.

    2014-03-01

    We report the growth of crystalline Al{sub 2}O{sub 3} thin films deposited by thermal Atomic Layer Deposition (ALD) at 200 °C, which up to now has always resulted in the amorphous phase. The 5 nm thick films were deposited on Ga{sub 2}O{sub 3}, ZnO, and Si nanowire substrates 100 nm or less in diameter. The crystalline nature of the Al{sub 2}O{sub 3} thin film coating was confirmed using Transmission Electron Microscopy (TEM), including high-resolution TEM lattice imaging, selected area diffraction, and energy filtered TEM. Al{sub 2}O{sub 3} coatings on nanowires with diameters of 10 nm or less formed a fully crystalline phase, while those with diameters in the 20–25 nm range resulted in a partially crystalline coating, and those with diameters in excess of 50 nm were fully amorphous. We suggest that the amorphous Al{sub 2}O{sub 3} phase becomes metastable with respect to a crystalline alumina polymorph, due to the nanometer size scale of the film/substrate combination. Since ALD Al{sub 2}O{sub 3} films are widely used as protective barriers, dielectric layers, as well as potential coatings in energy materials, these findings may have important implications.

  17. High Rate Deposition of High Quality ZnO:Al by Filtered Cathodic Arc

    SciTech Connect

    Mendelsberg, Rueben J.; Lim, S.H.N.; Milliron, D.J.; Anders, Andre

    2010-11-18

    High quality ZnO:Al (AZO) thin films were prepared on glass substrates by direct current filtered cathodic arc deposition. Substrate temperature was varied from room temperature to 425oC, and samples were grown with and without the assistance of low power oxygen plasma (75W). For each growth condition, at least 3 samples were grown to give a statistical look at the effect of the growth environment on the film properties and to explore the reproducibility of the technique. Growth rate was in the 100-400 nm/min range but was apparently random and could not be easily traced to the growth conditions explored. For optimized growth conditions, 300-600 nm AZO films had resistivities of 3-6 x 10-4 ?Omega cm, carrier concentrations in the range of 2-4 x 1020 cm3, Hall mobility as high as 55 cm2/Vs, and optical transmittance greater than 90percent. These films are also highly oriented with the c-axis perpendicular to the substrate and a surface roughness of 2-4 nm.

  18. Effect of ozone concentration on silicon surface passivation by atomic layer deposited Al2O3

    NASA Astrophysics Data System (ADS)

    von Gastrow, Guillaume; Li, Shuo; Putkonen, Matti; Laitinen, Mikko; Sajavaara, Timo; Savin, Hele

    2015-12-01

    We study the impact of ozone-based Al2O3 Atomic Layer Deposition (ALD) on the surface passivation quality of crystalline silicon. We show that the passivation quality strongly depends on the ozone concentration: the higher ozone concentration results in lower interface defect density and thereby improved passivation. In contrast to previous studies, our results reveal that too high interface hydrogen content can be detrimental to the passivation. The interface hydrogen concentration can be optimized by the ozone-based process; however, the use of pure ozone increases the harmful carbon concentration in the film. Here we demonstrate that low carbon and optimal hydrogen concentration can be achieved by a single process combining the water- and ozone-based reactions. This process results in an interface defect density of 2 × 1011 eV-1 cm-2, and maximum surface recombination velocities of 7.1 cm/s and 10 cm/s, after annealing and after an additional firing at 800 °C, respectively. In addition, our results suggest that the effective oxide charge density can be optimized in a simple way by varying the ozone concentration and by injecting water to the ozone process.

  19. Effect of Al Enrichment by Pack Cementation of FeCr Coatings Deposited by HVOF

    NASA Astrophysics Data System (ADS)

    Bellucci, A.; Bellini, S.; Pileggi, R.; Stocchi, D.; Tuurna, S.

    2015-01-01

    A great contribution to CO2 emissions comes from coal fired power generation. Combination of carbon capture sequestering technologies with sustainable biomass conversion constitutes a decisive boost in limiting rise in global temperature. Co-firing alternative materials with pulverized coal and using oxy-fuel combustion conditions (oxy-fuel co-combustion) is a very attractive process for power industry. Materials with both high mechanical properties and high environmental resistance are required by such advanced combustion systems. One approach to improve high-temperature oxidation/corrosion resistance is to apply protective coatings. In the present work, low and high Cr content Fe-based alloys have been deposited in order to investigate the influence of Cr content on coating protective performance in oxy-fuel co-combustion conditions. Grade 91 steel has been assumed as reference substrate. Effect of Al enrichment on coating environmental resistance has also been analyzed. Activities have been performed within the framework of Macplus Project (Integrated Project co-founded by the European Commission under the 7th Framework Program in the Energy area).

  20. High temperature stability, interface bonding, and mechanical behavior in (beta)-NiAl and Ni3Al matrix composites with reinforcements modified by ion beam enhanced deposition

    NASA Astrophysics Data System (ADS)

    Grummon, D. S.

    1993-01-01

    Diffusion-bonded NiAl-Al2O3 and Ni3Al-Al2O3 couples were thermally fatigued at 900 C for 1500 and 3500 cycles. The fiber-matrix interface weakened after 3500 cycles for the Saphikon fibers, while the Altex, PRD-166, and FP fibers showed little, if any, degradation. Diffusion bonding of fibers to Nb matrix is being studied. Coating the fibers slightly increases the tensile strength and has a rule-of-mixtures effect on elastic modulus. Push-out tests on Sumitomo and FP fibers in Ni aluminide matrices were repeated. Al2O3 was evaporated directly from pure oxide rod onto acoustically levitated Si carbide particles, using a down-firing, rod-fed electron beam hearth; superior coatings were subsequently produced using concurrent irradiation with 200-eV argon ion-assist beam. The assist beam produced adherent films with reduced tensile stresses. In diffusion bonding in B-doped Ni3Al matrices subjected to compressive bonding at 40 MPa at 1100 C for 1 hr, the diffusion barriers failed to prevent catastrophic particle-matrix reaction, probably because of inadequate film quality. AlN coatings are currently being experimented with, produced by both reactive evaporation and by N(+)-ion enhanced deposition. A 3-kW rod-fed electron-beam-heated evaporation source has been brought into operation.

  1. High-reliability passivation of hydrogen-terminated diamond surface by atomic layer deposition of Al2O3

    NASA Astrophysics Data System (ADS)

    Daicho, Akira; Saito, Tatsuya; Kurihara, Shinichiro; Hiraiwa, Atsushi; Kawarada, Hiroshi

    2014-06-01

    Although the two-dimensional hole gas (2DHG) of a hydrogen-terminated diamond surface provides a unique p-type conducting layer for high-performance transistors, the conductivity is highly sensitive to its environment. Therefore, the surface must be passivated to preserve the 2DHG, especially at high temperature. We passivated the surface at high temperature (450 °C) without the loss of C-H surface bonds by atomic layer deposition (ALD) and investigated the thermal reliability of the Al2O3 film. As a result, C-H bonds were preserved, and the hole accumulation effect appeared after the Al2O3 deposition by ALD with H2O as an oxidant. The sheet resistivity and hole density were almost constant between room temperature and 500 °C by the passivation with thick Al2O3 film thicker than 38 nm deposited by ALD at 450 °C. After the annealing at 550 °C in air The sheet resistivity and hole density were preserved. These results indicate the possibility of high-temperature application of the C-H surface diamond device in air. In the case of lower deposition temperatures, the sheet resistivity increased after air annealing, suggesting an insufficient protection capability of these films. Given the result of sheet resistivity after annealing, the increase in the sheet resistivity of these samples was not greatly significant. However, bubble like patterns were observed in the Al2O3 films formed from 200 to 400 °C by air annealing at 550 °C for 1 h. On the other hand, the patterns were no longer observed at 450 °C deposition. Thus, this 450 °C deposition is the sole solution to enabling power device application, which requires high reliability at high temperatures.

  2. AlN nanorod and nanoneedle arrays prepared by chloride assisted chemical vapor deposition for field emission applications.

    PubMed

    Song, Xubo; Guo, Zhigang; Zheng, Jie; Li, Xingguo; Pu, Yikang

    2008-03-19

    Hexagonal AlN nanorod and nanoneedle arrays were synthesized through the direct reaction of AlCl(3) and NH(3) by chemical vapor deposition at about 750 °C. Both the AlN nanoneedle and nanorod samples were of wurtzite structure and grew preferentially along the c-axis. With an increase in the ratio of NH(3) to Ar, an evolution from nanorods to nanoneedles was observed. A growth model was proposed to explain the possible growth mechanism. Measurements in field emission show that AlN nanoneedle arrays have a much lower turn-on field (3.1 V µm(-1)) compared to nanorod arrays (15.3 V µm(-1)), due to their large curvature geometry. The AlN nanoneedle arrays have potential applications in many fields, such as electron-emitting nanodevices and field-emission-based flat-panel displays. PMID:21730560

  3. Imaging of experimental amyloidosis with /sup 131/I-labeled serum amyloid P component

    SciTech Connect

    Caspi, D.; Zalzman, S.; Baratz, M.; Teitelbaum, Z.; Yaron, M.; Pras, M.; Baltz, M.L.; Pepys, M.B.

    1987-11-01

    /sup 131/I-labeled human serum amyloid P component, which was injected into mice with experimentally induced systemic AA amyloidosis and into controls, became specifically localized and was retained in amyloidotic organs. In comparison, it was rapidly and completely eliminated from unaffected tissues and from control animals. Distinctive images of this amyloid-specific deposition of labeled serum amyloid P component were derived from whole body scanning, in vivo, of amyloidotic mice. These findings suggest that such imaging may have applications for the diagnosis and quantitation of amyloid deposits in humans.

  4. Microstructure, thermo-physical and mechanical properties of spray-deposited Si-30Al alloy for electronic packaging application

    SciTech Connect

    Wang Feng Xiong Baiqing; Zhang Yongan; Zhu Baohong; Liu Hongwei; Wei Yanguang

    2008-10-15

    In this study, Si-30Al alloy was synthesized by the spray atomization and deposition technique. The microstructure and properties of the alloy were studied using optical microscopy, scanning electron microscopy, coefficient of thermal expansion (CTE) and thermal conductivity (TC) measurements, and 3-point bending tests. It was found that the microstructure of the alloy after hot pressing is composed of a continuous network of globular primary Si and interpenetrating secondary Al-rich phase. The property measurements results indicate that the spray-deposited 70Si30Al alloy has advantageous physical and mechanical characteristics, including low coefficient of thermal expansion (6.8 x 10{sup -6}/K), high thermal conductivity (118 W/mK), low density (2.42 g cm{sup -3}), high ultimate flexural strength (180 MPa) and Brinell hardness (261)

  5. Electrowetting properties of atomic layer deposited Al{sub 2}O{sub 3} decorated silicon nanowires

    SciTech Connect

    Rajkumar, K.; Rajavel, K.; Cameron, D. C.; Mangalaraj, D.; Rajendrakumar, R. T.

    2015-06-24

    This paper reports the electrowetting properties of liquid droplet on superhydrophobic silicon nanowires with Atomic layer deposited (ALD) Al{sub 2}O{sub 3} as dielectric layer. Silicon wafer were etched by metal assisted wet chemical etching with silver as catalyst. ALD Al{sub 2}O{sub 3} films of 10nm thickness were conformally deposited over silicon nanowires. Al{sub 2}O{sub 3} dielectric film coated silicon nanowires was chemically modified with Trichloro (1H, 1H, 2H, 2H-perfluorooctyl) silane to make it superhydrophobic(SHP). The contact angle was measured and all the samples exhibited superhydrophobic nature with maximum contact angles of 163° and a minimum contact angle hysteresis of 6°. Electrowetting induced a maximum reversible decrease of the contact angle of 20°at 150V in air.

  6. Characterization of plasma-enhanced atomic layer deposition of Al{sub 2}O{sub 3} using dimethylaluminum isopropoxide

    SciTech Connect

    Yang, Jialing; Eller, Brianna S.; Nemanich, Robert J.; Kaur, Manpuneet

    2014-03-15

    In this research, Al{sub 2}O{sub 3} films were grown by remote plasma-enhanced atomic layer deposition using a nonpyrophoric precursor, dimethylaluminum isopropoxide (DMAI), and oxygen plasma. After optimization, the growth rate was determined to be ∼1.5 Å/cycle within a growth window of 25–220 °C; the higher growth rate than reported for thermal atomic layer deposition was ascribed to the higher reactivity of the plasma species compared with H{sub 2}O and the adsorption of active oxygen at the surface, which was residual from the oxygen plasma exposure. Both effects enhance DMAI chemisorption and increase the saturation density. In addition, a longer oxygen plasma time was required at room temperature to complete the reaction and decrease the carbon contamination below the detection limit of x-ray photoemission spectroscopy. The properties of the subsequent Al{sub 2}O{sub 3} films were measured for different temperatures. When deposited at 25 °C and 200 °C, the Al{sub 2}O{sub 3} films demonstrated a single Al-O bonding state as measured by x-ray photoemission spectroscopy, a similar band gap of 6.8±0.2 eV as determined by energy loss spectroscopy, a similar index of refraction of 1.62±0.02 as determined by spectroscopic ellipsometry, and uniform growth with a similar surface roughness before and after growth as confirmed by atomic force microscopy. However, the room temperature deposited Al{sub 2}O{sub 3} films had a lower mass density (2.7 g/cm{sup 3} compared with 3.0 g/cm{sup 3}) and a higher atomic ratio of O to Al (2.1 compared with 1.6) as indicated by x-ray reflectivity and Rutherford backscattering spectroscopy, respectively.

  7. Tunable optoelectronic properties of pulsed dc sputter-deposited ZnO:Al thin films: Role of growth angle

    NASA Astrophysics Data System (ADS)

    Kumar, Mohit; Singh, Ranveer; Nandy, Suman; Ghosh, Arnab; Rath, Satchidananda; Som, Tapobrata

    2016-07-01

    In this paper, we investigate the role of deposition angle on the physical properties and work function of pulsed dc sputter-deposited Al-doped zinc oxide (AZO) thin films. It is observed that average grain size and crystal quality increase with higher angle of deposition, yielding improved optical properties. A systematic blue shift as well as a decrease in the resistivity takes place with the increasing growth angle up to 70°, while an opposite trend is observed beyond that. In addition, the work function of AZO films is also measured using Kelvin probe force microscopy, which corroborates well with the optical and structural properties. The observed results are explained in the framework of growth angle induced diffusion and shadowing effects. The films deposited at higher angles will be important for rapid incorporation into new technological applications that require a transparent conductive oxide.

  8. Influence of Bond Coats on the Microstructure and Mechanical Behaviors of HVOF-Deposited TiAlNb Coatings

    NASA Astrophysics Data System (ADS)

    Zeng, H. J.; Zhang, L. Q.; Lin, J. P.; He, X. Y.; Zhang, Y. C.; Jia, P.

    2012-12-01

    Hot dip galvanizing has been extensively employed for corrosion protection of steel structures. However, during the process of galvanization, the corrosion in molten zinc brings many problems to galvanization industry. In this study, as a material of corrosion resistance to molten zinc intended for application in Hot-dip galvanization, HVOF Ti28.15Al63.4Nb8.25Y (at.%) coatings with different bond coats (NiCr5Al, NiCoCrAlY, CoCrAlYTaSi, and NiCr80/20) were deposited onto 316L stainless steel substrate, respectively. The influences of different bond coats on HVOF Ti28.15Al63.4Nb8.25Y coatings were investigated. The results showed that bond coat had an obvious influence on improving the mechanical properties of HVOF Ti28.15Al63.4Nb8.25Y coatings. HVOF Ti28.15Al63.4Nb8.25Y coatings with NiCoCrAlY bond coat displayed the best mechanical properties. However, bond coats had no obvious effects on the microstructure, porosity, and hardness of HVOF Ti28.15Al63.4Nb8.25Y top coatings. The effects of as-received powder morphology and grain size on the characteristics of coatings were also discussed.

  9. Elementary surface chemistry during CuO/Al nanolaminate-thermite synthesis: copper and oxygen deposition on aluminum (111) surfaces.

    PubMed

    Lanthony, Cloé; Guiltat, Mathilde; Ducéré, Jean Marie; Verdier, Agnes; Hémeryck, Anne; Djafari-Rouhani, Mehdi; Rossi, Carole; Chabal, Yves J; Estève, Alain

    2014-09-10

    The surface chemistry associated with the synthesis of energetic nanolaminates controls the formation of the critical interfacial layers that dominate the performances of nanothermites. For instance, the interaction of Al with CuO films or CuO with Al films needs to be understood to optimize Al/CuO nanolaminates. To that end, the chemical mechanisms occurring during early stages of molecular CuO adsorption onto crystalline Al(111) surfaces are investigated using density functional theory (DFT) calculations, leading to the systematic determination of their reaction enthalpies and associated activation energies. We show that CuO undergoes dissociative chemisorption on Al(111) surfaces, whereby the Cu and O atoms tend to separate from each other. Both Cu and O atoms form islands with different properties. Copper islanding fosters Cu insertion (via surface site exchange mechanism) into the subsurface, while oxygen islands remain stable at the surface. Above a critical local oxygen coverage, aluminum atoms are extracted from the Al surface, leading to oxygen-aluminum intermixing and the formation of aluminum oxide (γ-alumina). For Cu and O co-deposition, copper promotes oxygen-aluminum interaction by oxygen segregation and separates the resulting oxide from the Al substrate by insertion into Al and stabilization below the oxide front, preventing full mixing of Al, Cu, and O species. PMID:25089744

  10. Fibrillar Amyloid Plaque Formation Precedes Microglial Activation

    PubMed Central

    Steinbach, Sonja; Blazquez-Llorca, Lidia; Herms, Jochen

    2015-01-01

    In Alzheimer’s disease (AD), hallmark β-amyloid deposits are characterized by the presence of activated microglia around them. Despite an extensive characterization of the relation of amyloid plaques with microglia, little is known about the initiation of this interaction. In this study, the detailed investigation of very small plaques in brain slices in AD transgenic mice of the line APP-PS1(dE9) revealed different levels of microglia recruitment. Analysing plaques with a diameter of up to 10 μm we find that only the half are associated with clear morphologically activated microglia. Utilizing in vivo imaging of new appearing amyloid plaques in double-transgenic APP-PS1(dE9)xCX3CR1+/- mice further characterized the dynamic of morphological microglia activation. We observed no correlation of morphological microglia activation and plaque volume or plaque lifetime. Taken together, our results demonstrate a very prominent variation in size as well as in lifetime of new plaques relative to the state of microglia reaction. These observations might question the existing view that amyloid deposits by themselves are sufficient to attract and activate microglia in vivo. PMID:25799372

  11. Comparison in mechanical and tribological properties of CrTiAlMoN and CrTiAlN nano-multilayer coatings deposited by magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Wang, Tao; Zhang, Guojun; Jiang, Bailing

    2016-02-01

    CrTiAlN and CrTiAlMoN nano-multilayer coatings were deposited by closed field unbalanced magnetron sputtering. TiMoN and CrTiMoN nano-multilayer coatings with same Mo2N layer thickness were also prepared for comparison. The structure of these coatings is investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The mechanical and tribological properties were characterized and compared by nano-indentation and ball-on-disc test. It was found that these coatings were structured by fcc metal nitride phases (including CrN, TiN, AlN and Mo2N) and the preferred orientation changed from (1 1 1) to (2 0 0) with the increase of Mo content. The TEM results showed that the coatings exhibited typical columnar structure and nano-multilayer structure with modulation periods ranged from 3.2 nm to 7.6 nm. Among these coatings, CrTiAlMoN coatings presented the highest hardness, lowest coefficient of friction (COF) and wear rate. The hardness of these nano-multilayer coatings were determined by layer interfaces: TiN/Mo2N and AlN/Mo2N layer interface showed benefit on hardness enhancement while CrN/Mo2N layer interface led to a great hardness decrement. In comparison with the other as-deposited coatings, the low COF of CrTiAlMoN coatings was not only affected by Mo addition but also related to its oxidation behaviors.

  12. Stoichiometry of LaAlO3 films grown on SrTiO3 by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Golalikhani, M.; Lei, Q. Y.; Chen, G.; Spanier, J. E.; Ghassemi, H.; Johnson, C. L.; Taheri, M. L.; Xi, X. X.

    2013-07-01

    We have studied the stoichiometry of epitaxial LaAlO3 thin films on SrTiO3 substrate grown by pulsed laser deposition as a function of laser energy density and oxygen pressure during the film growth. Both x-ray diffraction (θ-2θ scan and reciprocal space mapping) and transmission electron microscopy (geometric phase analysis) revealed a change of lattice constant in the film with the distance from the substrate. Combined with composition analysis using x-ray fluorescence we found that the nominal unit-cell volume expanded when the LaAlO3 film was La-rich, but remained near the bulk value when the film was La-poor or stoichiometric. La excess was found in all the films deposited in oxygen pressures lower than 10-2 Torr. We conclude that the discussion of LaAlO3/SrTiO3 interfacial properties should include the effects of cation off-stoichiometry in the LaAlO3 films when the deposition is conducted under low oxygen pressures.

  13. Atomic layer deposition of AlN for thin membranes using trimethylaluminum and H2/N2 plasma

    NASA Astrophysics Data System (ADS)

    Goerke, Sebastian; Ziegler, Mario; Ihring, Andreas; Dellith, Jan; Undisz, Andreas; Diegel, Marco; Anders, Solveig; Huebner, Uwe; Rettenmayr, Markus; Meyer, Hans-Georg

    2015-05-01

    Aluminum nitride (AlN) thin films with thicknesses from 20 to 100 nm were deposited on silicon, amorphous silica, silicon nitride, and vitreous carbon by plasma enhanced atomic layer deposition (PE-ALD). Trimethylaluminum (TMA) and a H2/N2 plasma mixture were used as precursors. We investigated the influence of deposition temperature and plasma parameters on the growth characteristics and the film properties of AlN. Stable PE-ALD growth conditions were obtained from 150 °C to the highest tested temperature of 300 °C. The growth rate, refractive index, and thickness homogeneity on 4″ wafers were determined by spectroscopic ellipsometry. X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM) and Rutherford backscattering spectrometry (RBS) were carried out to analyze crystallinity and composition of the films. Furthermore, the thermal conductivity and the film stress were determined. The stress was sufficiently low to fabricate mechanically stable free-standing AlN membranes with lateral dimensions of up to 2.2 × 2.2 mm2. The membranes were patterned with focused ion beam etching. Thus, these AlN membranes qualify as dielectric support material for a variety of potential applications.

  14. Tribological characterization of zirconia coatings deposited on Ti6Al4V components for orthopedic applications.

    PubMed

    Berni, M; Lopomo, N; Marchiori, G; Gambardella, A; Boi, M; Bianchi, M; Visani, A; Pavan, P; Russo, A; Marcacci, M

    2016-05-01

    One of the most important issues leading to the failure of total joint arthroplasty is related to the wear of the plastic components, which are generally made of ultra high molecular weight polyethylene (UHMWPE). Therefore, the reduction of joint wear represents one of the main challenges the research in orthopedics is called to address nowadays. Surface treatments and coatings have been recognized as innovative methods to improve tribological properties, also in the orthopedic field. This work investigated the possibility to realize hard ceramic coatings on the metal component of a prosthesis, by means of Pulsed Plasma Deposition, in order to reduce friction and wear in the standard coupling against UHMWPE. Ti6Al4V substrates were coated with a 2 μm thick yttria-stabilized zirconia (YSZ) layer. The mechanical properties of the YSZ coatings were assessed by nanoindentation tests performed on flat Ti6Al4V substrates. Tribological performance was evaluated using a ball-on-disk tribometer in dry and lubricated (i.e. with fetal bovine serum) highly-stressing conditions, up to an overall distance of 10 km. Tribology was characterized in terms of coefficient of friction (CoF) and wear rate of the UHMWPE disk. After testing, specimens were analyzed through optical microscopy and SEM images, in order to check the wear degradation mechanisms. Progressive loading scratch tests were also performed in dry and wet conditions to determine the effects of the environment on the adhesion of the coating. Our results supported the beneficial effect of YSZ coating on metal components. In particular, the proposed solution significantly reduced UHMWPE wear rate and friction. At 10 km of sliding distance, a wear rate reduction of about 18% in dry configuration and of 4% in presence of serum, was obtained by the coated group compared to the uncoated group. As far as friction in dry condition is concerned, the coating allowed to maintain low CoF values until the end of the tests, with an

  15. Oxygen vacancy defect engineering using atomic layer deposited HfAlOx in multi-layered gate stack

    NASA Astrophysics Data System (ADS)

    Bhuyian, M. N.; Sengupta, R.; Vurikiti, P.; Misra, D.

    2016-05-01

    This work evaluates the defects in high quality atomic layer deposited (ALD) HfAlOx with extremely low Al (<3% Al/(Al + Hf)) incorporation in the Hf based high-k dielectrics. The defect activation energy estimated by the high temperature current voltage measurement shows that the charged oxygen vacancies, V+/V2+, are the primary source of defects in these dielectrics. When Al is added in HfO2, the V+ type defects with a defect activation energy of Ea ˜ 0.2 eV modify to V2+ type to Ea ˜ 0.1 eV with reference to the Si conduction band. When devices were stressed in the gate injection mode for 1000 s, more V+ type defects are generated and Ea reverts back to ˜0.2 eV. Since Al has a less number of valence electrons than do Hf, the change in the co-ordination number due to Al incorporation seems to contribute to the defect level modifications. Additionally, the stress induced leakage current behavior observed at 20 °C and at 125 °C demonstrates that the addition of Al in HfO2 contributed to suppressed trap generation process. This further supports the defect engineering model as reduced flat-band voltage shifts were observed at 20 °C and at 125 °C.

  16. Radio frequency plasma power dependence of the moisture permeation barrier characteristics of Al{sub 2}O{sub 3} films deposited by remote plasma atomic layer deposition

    SciTech Connect

    Jung, Hyunsoo; Samsung Display Co. Ltd., Tangjeong, Chungcheongnam-Do 336-741 ; Choi, Hagyoung; Lee, Sanghun; Jeon, Heeyoung; Jeon, Hyeongtag; Department of Nano-scale Semiconductor Engineering, Hanyang University, Seoul 133-791

    2013-11-07

    In the present study, we investigated the gas and moisture permeation barrier properties of Al{sub 2}O{sub 3} films deposited on polyethersulfone films (PES) by capacitively coupled plasma (CCP) type Remote Plasma Atomic Layer Deposition (RPALD) at Radio Frequency (RF) plasma powers ranging from 100 W to 400 W in 100 W increments using Trimethylaluminum [TMA, Al(CH{sub 3}){sub 3}] as the Al source and O{sub 2} plasma as the reactant. To study the gas and moisture permeation barrier properties of 100-nm-thick Al{sub 2}O{sub 3} at various plasma powers, the Water Vapor Transmission Rate (WVTR) was measured using an electrical Ca degradation test. WVTR decreased as plasma power increased with WVTR values for 400 W and 100 W of 2.6 × 10{sup −4} gm{sup −2}day{sup −1} and 1.2 × 10{sup −3} gm{sup −2}day{sup −1}, respectively. The trends for life time, Al-O and O-H bond, density, and stoichiometry were similar to that of WVTR with improvement associated with increasing plasma power. Further, among plasma power ranging from 100 W to 400 W, the highest power of 400 W resulted in the best moisture permeation barrier properties. This result was attributed to differences in volume and amount of ion and radical fluxes, to join the ALD process, generated by O{sub 2} plasma as the plasma power changed during ALD process, which was determined using a plasma diagnosis technique called the Floating Harmonic Method (FHM). Plasma diagnosis by FHM revealed an increase in ion flux with increasing plasma power. With respect to the ALD process, our results indicated that higher plasma power generated increased ion and radical flux compared with lower plasma power. Thus, a higher plasma power provides the best gas and moisture permeation barrier properties.

  17. Microstructure and mechanical properties of sputter deposited Ni/Ni3Al multilayer films at elevated temperature

    NASA Astrophysics Data System (ADS)

    Zhang, Chao; Feng, Kai; Li, Zhuguo; Lu, Fenggui; Huang, Jian; Wu, Yixiong

    2016-08-01

    Nano-structured Ni/Ni3Al multilayer was prepared by magnetron sputtering, with individual layer thicknesses h varying from 10 to 160 nm. The microstructure and hardness of Ni/Ni3Al multilayer were investigated by X-ray diffraction, transmission electron microscopy and nanoindentation. The results show that the hardness increases with decreasing h for as-deposited and 500 °C annealed multilayers. When annealed at 700 °C, the hardness approach a peak value at h = 40 nm with followed by softening at smaller h. The influence of individual layer thickness, grain size as well as formation of ordered Ni3Al on strengthening mechanisms of Ni/Ni3Al multilayers at elevated temperature are discussed.

  18. Metalorganic chemical vapor deposition and characterization of (Al,Si)O dielectrics for GaN-based devices

    NASA Astrophysics Data System (ADS)

    Chan, Silvia H.; Tahhan, Maher; Liu, Xiang; Bisi, Davide; Gupta, Chirag; Koksaldi, Onur; Li, Haoran; Mates, Tom; DenBaars, Steven P.; Keller, Stacia; Mishra, Umesh K.

    2016-02-01

    In this paper, we report on the growth and electrical characterization of (Al,Si)O dielectrics grown by metalorganic chemical vapor deposition (MOCVD) using trimethylaluminum, oxygen, and silane as precursors. The growth rates, refractive indices, and composition of (Al,Si)O films grown on Si(001) were determined from ellipsometry and XPS measurements. Crystallinity and electrical properties of (Al,Si)O films grown in situ on c-plane GaN were characterized using grazing incidence X-ray diffraction and capacitance-voltage with current-voltage measurements, respectively. Si concentration in the films was found to be tunable by varying the trimethylaluminum and/or oxygen precursor flows. The Si incorporation suppressed the formation of crystalline domains, leading to amorphous films that resulted in reduced interfacial trap density, low gate leakage and ultra-low hysteresis in (Al,Si)O/n-GaN MOS-capacitors.

  19. Surface chemistry of plasma-assisted atomic layer deposition of Al2O3 studied by infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Langereis, E.; Keijmel, J.; van de Sanden, M. C. M.; Kessels, W. M. M.

    2008-06-01

    The surface groups created during plasma-assisted atomic layer deposition (ALD) of Al2O3 were studied by infrared spectroscopy. For temperatures in the range of 25-150°C, -CH3 and -OH were unveiled as dominant surface groups after the Al(CH3)3 precursor and O2 plasma half-cycles, respectively. At lower temperatures more -OH and C-related impurities were found to be incorporated in the Al2O3 film, but the impurity level could be reduced by prolonging the plasma exposure. The results demonstrate that -OH surface groups rule the surface chemistry of the Al2O3 process and likely that of plasma-assisted ALD of metal oxides from organometallic precursors in general.

  20. Metalorganic chemical vapor deposition and characterization of (Al,Si)O dielectrics for GaN–based devices

    DOE PAGESBeta

    Chan, Silvia; Mishra, Umesh K.; Tahhan, Maher; Liu, Xiang; Bisi, David; Gupta, Chirag; Koksaldi, Onur; Li, Haoran; Mates, Tom; DenBaars, Steven P.; et al

    2016-01-20

    In this study, we report on the growth and electrical characterization of (Al,Si)O dielectrics grown by metalorganic chemical vapor deposition (MOCVD) using trimethylaluminum, oxygen, and silane as precursors. The growth rates, refractive indices, and composition of (Al,Si)O films grown on Si(001) were determined from ellipsometry and XPS measurements. Crystallinity and electrical properties of (Al,Si)O films grown in situ on c-plane GaN were characterized using grazing incidence X-ray diffraction and capacitance–voltage with current–voltage measurements, respectively. Si concentration in the films was found to be tunable by varying the trimethylaluminum and/or oxygen precursor flows. The Si incorporation suppressed the formation of crystallinemore » domains, leading to amorphous films that resulted in reduced interfacial trap density, low gate leakage and ultra-low hysteresis in (Al,Si)O/n-GaN MOS-capacitors.« less

  1. Agglomeration, sputtering, and carbon monoxide adsorption behavior for Au/Al(2)O(3) prepared by Au(n)(+) deposition on Al(2)O(3)/NiAl(110).

    PubMed

    Lee, Sungsik; Fan, Chaoyang; Wu, Tianpin; Anderson, Scott L

    2005-06-01

    Size-selected gold clusters, Au(n)(+) (n = 1, 3, 4), were deposited on an ordered Al(2)O(3) film grown on NiAl(110), and changes in morphology and electronic properties with deposition/annealing temperature and cluster size were investigated by X-ray photoelectron spectroscopy (XPS) and ion-scattering spectroscopy (ISS). Extensive agglomeration was observed by ISS for annealing temperatures above 300 K, accompanied by large shifts in the Au XPS binding energy. Agglomeration is more extensive in room-temperature deposition, compared to samples prepared by low-temperature deposition, then annealed to room temperature. Agglomeration is also observed to be dependent on deposited cluster size. CO adsorption was studied by ISS and temperature-programmed desorption, and we looked for CO oxidation under conditions where substantial activity is seen for Au(n)/TiO(2). No activity was observed for Au(n)/Al(2)O(3). The differences between the two systems are interpreted in terms of the nature of the metal-support interactions. PMID:16852385

  2. Characterization and oxidation behavior of NiCoCrAlY coating fabricated by electrophoretic deposition and vacuum heat treatment

    NASA Astrophysics Data System (ADS)

    Li, Zhiming; Qian, Shiqiang; Wang, Wei

    2011-03-01

    Electrophoretic deposition (EPD) was showed to be a feasible and convenient method to fabricate NiCoCrAlY coatings on nickel based supperalloys. The microstructure and composition of the NiCoCrAlY coatings after vacuum heat treatment were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive X-ray analysis (EDAX). Isothermal-oxidation test was performed at 1100 °C in static air for 100 h. The results show that the major phases in electrophoretic deposited and vacuum heat treated NiCoCrAlY coating are γ-Ni and γ‧-Ni3Al phases, also there is an extremely small quantity of Al2O3 in the coating. Composition fluctuations occur in the coating and a certain amount of titanium diffuse from the superalloy substrate to the top of the coating during vacuum heat treatment. The oxidation test results exhibit that the oxidation kinetics of this coating has two typical stages. The protective oxide layer is mainly formed in the initial linear growth stage and then the oxide layer hinders further oxidation of the coating in the subsequent parabolic growth stage. The coating can effectively protect the superalloy substrate from oxidation. A certain amount of rutile TiO2 is formed in the coating during oxidation and it is adverse to the oxidation resistance of the coating.

  3. Characterization and Wear Behavior of Heat-treated Ni3Al Coatings Deposited by Air Plasma Spraying

    NASA Astrophysics Data System (ADS)

    Mehmood, K.; Rafiq, M. A.; Nusair Khan, A.; Ahmed, F.; Mudassar Rauf, M.

    2016-07-01

    Air plasma spraying was utilized to deposit Ni3Al coatings on AISI-321 steel substrate. The deposited coatings were isothermally heat-treated at various temperatures from 500 to 800 °C for 10, 30, 60, and 100 h. The x-ray diffraction analysis revealed NiO formation in Ni3Al at 500 °C after 100 h, and the percentage of NiO increased with increasing exposure time and temperature. The hardness of the coating increased with the formation of NiO. The DSC test showed the formation of minor phases, Al3Ni and Al3Ni2, within the coating along with the major phase Ni3Al. TGA revealed a slowing down of the oxidation rate upon surface oxide formation. The pin-on-disk wear test on the as-sprayed and heat-treated coatings showed that wear rate and coefficient of friction decreased with an increase in the NiO phase content.

  4. Characterization and Wear Behavior of Heat-treated Ni3Al Coatings Deposited by Air Plasma Spraying

    NASA Astrophysics Data System (ADS)

    Mehmood, K.; Rafiq, M. A.; Nusair Khan, A.; Ahmed, F.; Mudassar Rauf, M.

    2016-05-01

    Air plasma spraying was utilized to deposit Ni3Al coatings on AISI-321 steel substrate. The deposited coatings were isothermally heat-treated at various temperatures from 500 to 800 °C for 10, 30, 60, and 100 h. The x-ray diffraction analysis revealed NiO formation in Ni3Al at 500 °C after 100 h, and the percentage of NiO increased with increasing exposure time and temperature. The hardness of the coating increased with the formation of NiO. The DSC test showed the formation of minor phases, Al3Ni and Al3Ni2, within the coating along with the major phase Ni3Al. TGA revealed a slowing down of the oxidation rate upon surface oxide formation. The pin-on-disk wear test on the as-sprayed and heat-treated coatings showed that wear rate and coefficient of friction decreased with an increase in the NiO phase content.

  5. On performance limitations and property correlations of Al-doped ZnO deposited by radio-frequency sputtering

    NASA Astrophysics Data System (ADS)

    Crovetto, Andrea; Sand Ottsen, Tobias; Stamate, Eugen; Kjær, Daniel; Schou, Jørgen; Hansen, Ole

    2016-07-01

    The electrical properties of RF-sputtered Al-doped ZnO are often spatially inhomogeneous and strongly dependent on deposition parameters. In this work, we study the mechanisms that limit the minimum resistivity achievable under different deposition regimes. In a low- and intermediate-pressure regime, we find a generalized dependence of the electrical properties, grain size, texture, and Al content on compressive stress, regardless of sputtering pressure or position on the substrate. In a high-pressure regime, a porous microstructure limits the achievable resistivity and causes it to increase over time as well. The primary cause of inhomogeneity in the electrical properties is identified as energetic particle bombardment. Inhomogeneity in oxygen content is also observed, but its effect on the electrical properties is small and limited to the carrier mobility.

  6. Investigation of the HA film deposited on the porous Ti6Al4V alloy prepared via additive manufacturing

    NASA Astrophysics Data System (ADS)

    Surmeneva, M.; Chudinova, E.; Syrtanov, M.; Koptioug, A.; Surmenev, R.

    2015-11-01

    This study is focused on the use of radio frequency magnetron sputtering to modify the surface of porous Ti6Al4V alloy fabricated via additive manufacturing technology. The hydroxyapatite (HA) coated porous Ti6Al4V alloy was studied in respect with its chemical and phase composition, surface morphology, water contact angle and hysteresis, and surface free energy. Thin nanocrystalline HA film was deposited while its structure with diamond-shaped cells remained unchanged. Hysteresis and water contact angle measurements revealed an effect of the deposited HA films, namely an increased water contact angle and contact angle hysteresis. The increase of the contact angle of the coating-substrate system compared to the uncoated substrate was attributed to the multiscale structure of the resulted surfaces.

  7. Electrochemical promotion of propane oxidation on Pt deposited on a dense β"-Al2O3 ceramic Ag+ conductor

    NASA Astrophysics Data System (ADS)

    Tsampas, Michail; Kambolis, Anastasios; Obeid, Emil; Lizarraga, Leonardo; Sapountzi, Foteini; Vernoux, Philippe

    2013-08-01

    A new kind of electrochemical catalyst based on a Pt porous catalyst film deposited on a β"-Al2O3 ceramic Ag+ conductor was developed and evaluated during propane oxidation. It was observed that upon anodic polarization, the rate of propane combustion was significantly electropromoted up to 400%. Moreover, for the first time, exponential increase of the catalytic rate was evidenced during galvanostatic transient experiment in excellent agreement with EPOC equation.

  8. High quality ZnO:Al transparent conducting oxide films synthesized by pulsed filtered cathodic arc deposition

    SciTech Connect

    Anders, Andre; Lim, Sunnie H.N.; Yu, Kin Man; Andersson, Joakim; Rosen, Johanna; McFarland, Mike; Brown, Jeff

    2009-04-24

    Aluminum-doped zinc oxide, ZnO:Al or AZO, is a well-known n-type transparent conducting oxide with great potential in a number of applications currently dominated by indium tin oxide (ITO). In this study, the optical and electrical properties of AZO thin films deposited on glass and silicon by pulsed filtered cathodic arc deposition are systematically studied. In contrast to magnetron sputtering, this technique does not produce energetic negative ions, and therefore ion damage can be minimized. The quality of the AZO films strongly depends on the growth temperature while only marginal improvements are obtained with post-deposition annealing. The best films, grown at a temperature of about 200?C, have resistivities in the low to mid 10-4 Omega cm range with a transmittance better than 85percent in the visible part of the spectrum. It is remarkable that relatively good films of small thickness (60 nm) can be fabricated using this method.

  9. Effect of substrate pretreatments on the atomic layer deposited Al{sub 2}O{sub 3} passivation quality

    SciTech Connect

    Bao, Yameng; Li, Shuo Gastrow, Guillaume von; Repo, Päivikki; Savin, Hele; Putkonen, Matti

    2015-01-15

    The authors show here that the passivation quality of Al{sub 2}O{sub 3} is highly sensitive to the surface condition prior to the atomic layer deposition, affecting especially the thermal stability of the film. Pretreatments like diluted HCl bath or preheating at 200 °C both improved significantly the passivation quality and thermal stability of the films. In addition, the authors observed that a thin chemical SiO{sub 2} layer resulting from diluted HCl solves the blistering problem often encountered in H{sub 2}O based atomic layer deposited process. Finally, the authors show that the chemical oxide protects the surface from contaminants, enabling long storage times in a dirty ambient between the cleaning and the film deposition.

  10. A Novel liposomal nanoparticle for the imaging of amyloid plaque by MRI

    PubMed Central

    Tanifum, Eric A.; Ghaghada, Ketan; Vollert, Craig; Head, Elizabeth; Eriksen, Jason L.; Annapragada, Ananth

    2016-01-01

    Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid deposits in dog brain and human brain tissue ex vivo. The ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. The preparation was tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates and Indocyanine green were included in the particles for visualization by MRI and near-infrared microscopy. Upon intravenous injection, the particles successfully traversed the blood-brain barrier in these mice, and bound to the plaques. Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated elevated signal in the brains of mice with amyloid plaques present. No signal was observed in amyloid-negative mice, or in amyloid-positive mice injected with an untargeted version of the same agent. The MRI results were confirmed by immunohistochemical and fluorescent microscopic examination of mouse brain sections, showing colocalization of the fluorescent tags and amyloid deposits. PMID:27031484

  11. Wear resistance and microstructural properties of Ni–Al/h-BN/WC–Co coatings deposited using plasma spraying

    SciTech Connect

    Hsiao, W.T.; Su, C.Y.; Huang, T.S.; Liao, W.H.

    2013-05-15

    Hexagonal boron nitride (h-BN) and tungsten carbide cobalt (WC–Co) were added to nickel aluminum alloy (Ni–Al) and deposited as plasma sprayed coatings to improve their tribological properties. The microstructure of the coatings was analyzed using a scanning electron microscope (SEM). Following wear test, the worn surface morphologies of the coatings were analyzed using a SEM to identify their fracture modes. The results of this study demonstrate that the addition of h-BN and WC–Co improved the properties of the coatings. Ni–Al/h-BN/WC–Co coatings with high hardness and favorable lubrication properties were deposited. - Highlights: • We mixed Ni–Al, h-BN and WC–Co powders and deposited them as composite coatings. • Adding WC–Co was found to increase the hardness and reduce the wear volume loss. • Adding h-BN was found to decrease the hardness and reduce the friction coefficient. • This composite coating was shown to have improved wear properties at 850 °C.

  12. Performance of NiCrAlY Coatings Deposited by Oxyfuel Thermal Spraying in High Temperature Chlorine Environment

    NASA Astrophysics Data System (ADS)

    Habib, K. A.; Damra, M. S.; Carpio, J. J.; Cervera, I.; Saura, J. J.

    2014-10-01

    A microcrystalline Ni-22Cr-10Al-1Y (wt.%) coating was deposited on AISI 304 stainless steel by the oxyfuel thermal spray technique. The deposited coating was subjected to heat treatment to improve the microstructure characteristics and its corresponding high-temperature properties. The isothermal high-temperature corrosion behavior at 650 and 700 °C in synthetic air and in the presence of 1% Cl2 was investigated using thermogravimetric analysis, x-ray diffraction, and scanning electron microscopy with energy-dispersive x-ray spectroscopy. The results indicated that the deposited NiCrAlY coating possessed acceptable oxidation-corrosion resistance at 650 °C owing to the formation of extensive amounts of the protective oxide of Cr2O3; NiO and a lesser amount of a Cr1.12 Ni2,88 metallic phase are also formed. At 700 °C, the coating lost its protective characteristic because of the excessive consumption of thermodynamically stable phases by oxidation-chlorination process. In this case, the steel base and the coating were attacked by chlorine during the exposure time; the mass gain of the NiCrAlY coating was slightly higher and provided only a limited protection up to 11 h; thereafter, breakdown of the layer of oxides occurred and this is attributed to the formation of non-protective oxides mainly β-Fe2O3 and Fe21.33O32 and the depletion of chromium.

  13. Initial growth, refractive index, and crystallinity of thermal and plasma-enhanced atomic layer deposition AlN films

    SciTech Connect

    Van Bui, Hao Wiggers, Frank B.; Gupta, Anubha; Nguyen, Minh D.; Aarnink, Antonius A. I.; Jong, Michel P. de; Kovalgin, Alexey Y.

    2015-01-01

    The authors have studied and compared the initial growth and properties of AlN films deposited on Si(111) by thermal and plasma-enhanced atomic layer deposition (ALD) using trimethylaluminum and either ammonia or a N{sub 2}-H{sub 2} mixture as precursors. In-situ spectroscopic ellipsometry was employed to monitor the growth and measure the refractive index of the films during the deposition. The authors found that an incubation stage only occurred for thermal ALD. The linear growth for plasma-enhanced ALD (PEALD) started instantly from the beginning due to the higher nuclei density provided by the presence of plasma. The authors observed the evolution of the refractive index of AlN during the growth, which showed a rapid increase up to a thickness of about 30 nm followed by a saturation. Below this thickness, higher refractive index values were obtained for AlN films grown by PEALD, whereas above that the refractive index was slightly higher for thermal ALD films. X-ray diffraction characterization showed a wurtzite crystalline structure with a (101{sup ¯}0) preferential orientation obtained for all the layers with a slightly better crystallinity for films grown by PEALD.

  14. Amyloid imaging in cognitively normal individuals, at-risk populations and preclinical Alzheimer's disease☆

    PubMed Central

    Chételat, Gaël; La Joie, Renaud; Villain, Nicolas; Perrotin, Audrey; de La Sayette, Vincent; Eustache, Francis; Vandenberghe, Rik

    2013-01-01

    Recent developments of PET amyloid ligands have made it possible to visualize the presence of Aβ deposition in the brain of living participants and to assess the consequences especially in individuals with no objective sign of cognitive deficits. The present review will focus on amyloid imaging in cognitively normal elderly, asymptomatic at-risk populations, and individuals with subjective cognitive decline. It will cover the prevalence of amyloid-positive cases amongst cognitively normal elderly, the influence of risk factors for AD, the relationships to cognition, atrophy and prognosis, longitudinal amyloid imaging and ethical aspects related to amyloid imaging in cognitively normal individuals. Almost ten years of research have led to a few consensual and relatively consistent findings: some cognitively normal elderly have Aβ deposition in their brain, the prevalence of amyloid-positive cases increases in at-risk populations, the prognosis for these individuals is worse than for those with no Aβ deposition, and significant increase in Aβ deposition over time is detectable in cognitively normal elderly. More inconsistent findings are still under debate; these include the relationship between Aβ deposition and cognition and brain volume, the sequence and cause-to-effect relations between the different AD biomarkers, and the individual outcome associated with an amyloid positive versus negative scan. Preclinical amyloid imaging also raises important ethical issues. While amyloid imaging is definitely useful to understand the role of Aβ in early stages, to define at-risk populations for research or for clinical trial, and to assess the effects of anti-amyloid treatments, we are not ready yet to translate research results into clinical practice and policy. More researches are needed to determine which information to disclose from an individual amyloid imaging scan, the way of disclosing such information and the impact on individuals and on society. PMID

  15. LaAlO3/Si capacitors: Comparison of different molecular beam deposition conditions and their impact on electrical properties

    NASA Astrophysics Data System (ADS)

    Pelloquin, Sylvain; Saint-Girons, Guillaume; Baboux, Nicolas; Albertini, David; Hourani, Waël; Penuelas, Jose; Grenet, Geneviève; Plossu, Carole; Hollinger, Guy

    2013-01-01

    A study of the structural and electrical properties of amorphous LaAlO3 (LAO)/Si thin films fabricated by molecular beam deposition (MBD) is presented. Two substrate preparation procedures have been explored namely a high temperature substrate preparation technique—leading to a step and terraces surface morphology—and a chemical HF-based surface cleaning. The LAO deposition conditions were improved by introducing atomic plasma-prepared oxygen instead of classical molecular O2 in the chamber. An Au/Ni stack was used as the top electrode for its electrical characteristics. The physico-chemical properties (surface topography, thickness homogeneity, LAO/Si interface quality) and electrical performance (capacitance and current versus voltage and TunA current topography) of the samples were systematically evaluated. Deposition conditions (substrate temperature of 550 °C, oxygen partial pressure settled at 10-6 Torr, and 550 W of power applied to the O2 plasma) and post-depositions treatments were investigated to optimize the dielectric constant (κ) and leakage currents density (JGate at |VGate| = |VFB - 1|). In the best reproducible conditions, we obtained a LAO/Si layer with a dielectric constant of 16, an equivalent oxide thickness of 8.7 Å, and JGate ≈ 10-2A/cm2. This confirms the importance of LaAlO3 as an alternative high-κ for ITRS sub-22 nm technology node.

  16. Electrophoretic deposition and mechanistic studies of nano-Al/CuO thermites

    NASA Astrophysics Data System (ADS)

    Sullivan, K. T.; Kuntz, J. D.; Gash, A. E.

    2012-07-01

    Electrophoretic deposition was used to deposit thin films (˜10-200 μm) of nano-aluminum/copper oxide thermites, with a density of 29% the theoretical maximum. The reaction propagation velocity was examined using fine-patterned electrodes (0.25 × 20 mm), and the optimum velocity was found to correspond to a fuel-rich equivalence ratio of 1.7. This value did not correlate with the calculated maximum in gas production or temperature, and it is suggested that it is a result of enhanced condensed-phase transport, which is speculated to increase for fuel-rich conditions. A ˜25% drop in propagation velocity occurred above an equivalence ratio of 2.0, where Al2O3 is predicted to undergo a phase change from liquid to solid. This is expected to hinder the kinetics by decreasing the mobility of condensed-phase reacting species. The effect of film thickness on propagation velocity was investigated, using the optimum equivalence ratio. The velocity was seen to exhibit a two-plateau behavior, with one plateau between 13 and 50 μm film thickness, and the other above ˜120 μm. The latter had nearly an order of magnitude faster velocity than the former, 36 m/s vs. 4 m/s, respectively. For film thicknesses in the 50-120 μm range, a linear transitional regime was observed. Images from the combustion studies showed an increase in forward-transported particles as the film thickness increased, along with more turbulent behavior of the flame. It was suggested that the two-plateau behavior indicated a shift in the energy transport mechanism. While nanocomposite thermites have been traditionally thought to exhibit convective energy transport, we find in this work that particle advection may also be important. The velocity of particles ejected through a thin slit mounted above a thermite strip was measured, and was found to be even faster (˜2-3×) than the flame propagation velocity. The morphology of captured particles was examined with an electron microscope, and indicated that

  17. Structural requirements of glycosaminoglycans for facilitating amyloid fibril formation of human serum amyloid A.

    PubMed

    Takase, Hiroka; Tanaka, Masafumi; Yamamoto, Aki; Watanabe, Shiori; Takahashi, Sanae; Nadanaka, Satomi; Kitagawa, Hiroshi; Yamada, Toshiyuki; Mukai, Takahiro

    2016-06-01

    Serum amyloid A (SAA) is a precursor protein of amyloid fibrils. Given that heparan sulfate (HS), a glycosaminoglycan (GAG), is detected in amyloid deposits, it has been suggested that GAG is a key component of amyloid fibril formation. We previously reported that heparin (an analog of HS) facilitates the fibril formation of SAA, but the structural requirements remain unknown. In the present study, we investigated the structural requirements of GAGs for facilitating the amyloid fibril formation of SAA. Spectroscopic analyses using structurally diverse GAG analogs suggested that the fibril formation of SAA was facilitated irrespective of the backbone structure of GAGs; however, the facilitating effect was strongly correlated with the degree of sulfation. Microscopic analyses revealed that the morphologies of SAA aggregates were modulated by the GAGs. The HS molecule, which is less sulfated than heparin but contains highly sulfated domains, exhibited a relatively high potential to facilitate fibril formation compared to other GAGs. The length dependence of fragmented heparins on the facilitating effect suggested that a high density of sulfate groups is also required. These results indicate that not only the degree of sulfation but also the lengths of sulfated domains in GAG play important roles in fibril formation of SAA. PMID:27097047

  18. Immunoglobulin light chains, glycosaminoglycans and amyloid.

    SciTech Connect

    Stevens, F. J.; Kisilevsky, R.; Biosciences Division; Queen's Univ.

    2000-03-01

    Immunoglobulin light chains are the precursor proteins for fibrils that are formed during primary amyloidosis and in amyloidosis associated with multiple myeloma. As found for the approximately 20 currently described forms of focal, localized, or systemic amyloidoses, light chain-related fibrils extracted from physiological deposits are invariably associated with glycosaminoglycans, predominantly heparan sulfate. Other amyloid-related proteins are either structurally normal, such as g2-microglobulin and islet amyloid polypeptide, fragments of normal proteins such as serum amyloid A protein or the precursor protein of the g peptide involved in Alzheimer's disease, or are inherited forms of single amino acid variants of a normal protein such as found in the familial forms of amyloid associated with transthyretin. In contrast, the primary structures of light chains involved in fibril formation exhibit extensive mutational diversity rendering some proteins highly amyloidogenic and others non-pathological. The interactions between light chains and glycosaminoglycans are also affected by amino acid variation and may influence the clinical course of disease by enhancing fibril stability and contributing to resistance to protease degradation. Relatively little is currently known about the mechanisms by which glycosaminoglycans interact with light chains and light-chain fibrils. It is probable that future studies of this uniquely diverse family of proteins will continue o shed light on the processes of amyloidosis, and contribute as well to a greater understanding of the normal physiological roles of glycosaminoglycans.

  19. Defects in semipolar (1122) ZnO grown on (112) LaAlO3/(La,Sr)(Al,Ta)O3 substrate by pulsed laser deposition.

    PubMed

    Tian, Jr-Sheng; Wu, Yue-Han; Peng, Chun-Yen; Chiu, Kun-An; Shih, Yi-Sen; Do, Hien; Lin, Pei-Yin; Ho, Yen-Teng; Chu, Ying-Hao; Chang, Li

    2013-03-27

    The microstructure of semipolar [Formula: see text] ZnO deposited on (112) LaAlO3/(La,Sr)(Al,Ta)O3 was investigated by transmission electron microscopy. The ZnO shows an in-plane epitaxial relationship of [Formula: see text] with oxygen-face sense polarity. The misfit strain along [Formula: see text] and [Formula: see text] is relieved through the formation of misfit dislocations with the Burgers vectors [Formula: see text] and [Formula: see text], respectively. The line defects in the semipolar ZnO are predominantly perfect dislocations, and the dislocation density decreases with increasing ZnO thickness as a result of dislocation reactions. Planar defects were observed to lie in the M-plane and extend along 〈0001〉, whereas basal stacking faults were rarely found. PMID:23449009

  20. Properties of the c-Si/Al2O3 interface of ultrathin atomic layer deposited Al2O3 layers capped by SiNx for c-Si surface passivation

    NASA Astrophysics Data System (ADS)

    Schuldis, D.; Richter, A.; Benick, J.; Saint-Cast, P.; Hermle, M.; Glunz, S. W.

    2014-12-01

    This work presents a detailed study of c-Si/Al2O3 interfaces of ultrathin Al2O3 layers deposited with atomic layer deposition (ALD), and capped with SiNx layers deposited with plasma-enhanced chemical vapor deposition. A special focus was the characterization of the fixed charge density of these dielectric stacks and the interface defect density as a function of the Al2O3 layer thickness for different ALD Al2O3 deposition processes (plasma-assisted ALD and thermal ALD) and different thermal post-deposition treatments. Based on theoretical calculations with the extended Shockley-Read-Hall model for surface recombination, these interface properties were found to explain well the experimentally determined surface recombination. Thus, these interface properties provide fundamental insights into to the passivation mechanisms of these Al2O3/SiNx stacks, a stack system highly relevant, particularly for high efficiency silicon solar cells. Based on these findings, it was also possible to improve the surface passivation quality of stacks with thermal ALD Al2O3 by oxidizing the c-Si surface prior to the Al2O3 deposition.

  1. Amyloid fibril protein nomenclature: 2012 recommendations from the Nomenclature Committee of the International Society of Amyloidosis.

    PubMed

    Sipe, Jean D; Benson, Merrill D; Buxbaum, Joel N; Ikeda, Shu-ichi; Merlini, Giampaolo; Saraiva, Maria J M; Westermark, Per

    2012-12-01

    The Nomenclature Committee of the International Society of Amyloidosis (ISA) met during the XIIIth International Symposium, May 6-10, 2012, Groningen, The Netherlands, to formulate recommendations on amyloid fibril protein nomenclature and to consider newly identified candidate amyloid fibril proteins for inclusion in the ISA Amyloid Fibril Protein Nomenclature List. The need to promote utilization of consistent and up to date terminology for both fibril chemistry and clinical classification of the resultant disease syndrome was emphasized. Amyloid fibril nomenclature is based on the chemical identity of the amyloid fibril forming protein; clinical classification of the amyloidosis should be as well. Although the importance of fibril chemistry to the disease process has been recognized for more than 40 years, to this day the literature contains clinical and histochemical designations that were used when the chemical diversity of amyloid diseases was poorly understood. Thus, the continued use of disease classifications such as familial amyloid neuropathy and familial amyloid cardiomyopathy generates confusion. An amyloid fibril protein is defined as follows: the protein must occur in body tissue deposits and exhibit both affinity for Congo red and green birefringence when Congo red stained deposits are viewed by polarization microscopy. Furthermore, the chemical identity of the protein must have been unambiguously characterized by protein sequence analysis when so is practically possible. Thus, in nearly all cases, it is insufficient to demonstrate mutation in the gene of a candidate amyloid protein; the protein itself must be identified as an amyloid fibril protein. Current ISA Amyloid Fibril Protein Nomenclature Lists of 30 human and 10 animal fibril proteins are provided together with a list of inclusion bodies that, although intracellular, exhibit some or all of the properties of the mainly extracellular amyloid fibrils. PMID:23113696

  2. Adolescent exposure to MDMA induces dopaminergic toxicity in substantia nigra and potentiates the amyloid plaque deposition in the striatum of APPswe/PS1dE9 mice.

    PubMed

    Abad, Sonia; Ramon, Carla; Pubill, David; Camarasa, Jorge; Camins, Antonio; Escubedo, Elena

    2016-09-01

    MDMA is one of the most used drugs by adolescents and its consumption has been associated with many psychobiological problems, among them psychomotor problems. Moreover, some authors described that early exposure to MDMA may render the dopaminergic neurons more vulnerable to the effects of future neurotoxic insults. Alzheimer disease (AD) is the main cause of dementia in the elderly and a percentage of the patients have predisposition to suffer nigrostriatal alterations, developing extrapyramidal signs. Nigrostriatal dysfunction in the brain of aged APPswe/PS1dE9 (APP/PS1), a mouse model of familiar AD (FAD), has also been described. The aim of the present study was to investigate the consequences of adolescent exposure to MDMA in APP/PS1 mice, on nigrostriatal function on early adulthood. We used a MDMA schedule simulating weekend binge abuse of this substance. Our MDMA schedule produced a genotype-independent decrease in dopaminergic neurons in the substantia nigra that remained at least 3months. Shortly after the injury, wild-type animals showed a decrease in the locomotor activity and apparent DA depletion in striatum, however in the APP/PS1 mice neither the locomotor activity nor the DA levels were modified, but a reduction in dopamine transporter (DAT) expression and a higher levels of oxidative stress were observed. We found that these disturbances are age-related characteristics that this APP/PS1 mice develops spontaneously much later. Therefore, MDMA administration seems to anticipate the striatal dopaminergic dysfunction in this FAD model. The most important outcome lies in a potentiation, by MDMA, of the amyloid beta deposition in the striatum. PMID:27344237

  3. Carbon Deposition from the CO2-Steam Reforming of Methane Over Modified Ni/γ-Al2O3 Catalysts.

    PubMed

    Choi, Bong Kwan; Ok, Hye Jeong; Moon, Dong Ju; Kim, Jong Ho; Park, Nam Cook; Kim, Young Chul

    2015-01-01

    The aim of this work is to study the catalytic activity and suppression of carbon deposition in the CO2-Steam reforming of methane (SCR) to develop a high performance catalyst for GTL-FPSO application which is required to high pressure (20 bar) for F-T synthesis. Ni/La-X(6)/Al2O3 (X = Ce, Mg, Zr) catalysts were prepared by the impregnation method. The catalytic reaction was studied in a fixed bed reactor system at high pressure. X-ray diffraction (XRD), BET specific surface area and H2-temperature programmed reduction (TPR) were used to observe the characteristics of the prepared catalysts. The carbon deposition and the carbon amount in the used catalysts were examined by SEM and TGA, respectively. As a result, it was found that the Ni/La-Mg(6)/Al2O3 catalyst showed the highest activity and high carbon resistance. The highest activity in Ni/La-Mg(6)/Al2O3 was attributed to the proper Mg loading. It also had the lowest Ni particle and formed relatively stable MgAl2O4, which have an effect on the catalytic activity. PMID:26328367

  4. Microwave Band-Pass Filter with Aerosol-Deposited Al2O3-Polytetrafluoroethylene Composite Thick Films.

    PubMed

    Lee, Ji-Won; Koh, Jung-Hyuk

    2015-03-01

    Fabrication of microwave band-pass filter with coplanar waveguide with ground structure was realized by employing Al2O3-polytetrafluoroethylene (Al2O3-PTFE) composite thick films for integrated substrates produced by aerosol deposition (AD). In order to predict the performance of the band-pass filter, 3-D electromagnetic simulations were performed by high-frequency structure analysis. The thick Al2O3-PTFE composite films prepared by the AD process had submicron-sized Al2O3 crystallites due to the shock-absorbing effect of PTFE during the film growth. The thick films were characterized by X-ray diffraction and scanning electron microscopy. The Cu transmission lines with the thickness of 300 nm were deposited by electron-beam evaporation to form the band-pass filter. The fabricated band-pass filter showed similar characteristics to the simulation results. The insertion loss and resonance frequency were 9.5 dB and 2.3 GHz, respectively. PMID:26413656

  5. Tribological behavior of Ti-Al-Si-C-N hard coatings deposited by hybrid arc-enhanced magnetron sputtering

    SciTech Connect

    Wu Guizhi; Ma Shengli; Xu Kewei; Chu, Paul K

    2012-03-15

    Ti-Al-Si-C-N hard coatings are deposited on high speed steel by hybrid arc-enhanced magnetron sputtering, and the hardness, adhesion, and tribological behavior are studied. On account of the nanocomposite structure, the coatings possess hardness of more than 30 GPa. Failure of the coating during the scratch test is due to the buckling and wedge spallation failure mechanism. Compared to Ti-Al-Si-N, the presence of C in the Ti-Al-Si-C-N coatings leads to reduced friction coefficient and wear rate, indicating effective lubrication rendered by amorphous C. According to the wear tracks examined by scanning electron microscopy, the wear mechanism can be explained by plowing abrasion.

  6. Phase-coherent electron transport in (Zn, Al)O{sub x} thin films grown by atomic layer deposition

    SciTech Connect

    Saha, D. E-mail: pmisra@rrcat.gov.in; Misra, P. E-mail: pmisra@rrcat.gov.in; Ajimsha, R. S.; Joshi, M. P.; Kukreja, L. M.

    2014-11-24

    A clear signature of disorder induced quantum-interference phenomena leading to phase-coherent electron transport was observed in (Zn, Al)O{sub x} thin films grown by atomic layer deposition. The degree of static-disorder was tuned by varying the Al concentration through periodic incorporation of Al{sub 2}O{sub 3} sub-monolayer in ZnO. All the films showed small negative magnetoresistance due to magnetic field suppressed weak-localization effect. The temperature dependence of phase-coherence length (l{sub φ}∝T{sup −3/4}), as extracted from the magnetoresistance measurements, indicated electron-electron scattering as the dominant dephasing mechanism. The persistence of quantum-interference at relatively higher temperatures up to 200 K is promising for the realization of ZnO based phase-coherent electron transport devices.

  7. Atomic layer deposition of Al-incorporated Zn(O,S) thin films with tunable electrical properties

    SciTech Connect

    Park, Helen Hejin; Jayaraman, Ashwin; Heasley, Rachel; Yang, Chuanxi; Hartle, Lauren; Gordon, Roy G.; Mankad, Ravin; Haight, Richard; Gunawan, Oki; Mitzi, David B.

    2014-11-17

    Zinc oxysulfide, Zn(O,S), films grown by atomic layer deposition were incorporated with aluminum to adjust the carrier concentration. The electron carrier concentration increased up to one order of magnitude from 10{sup 19} to 10{sup 20} cm{sup −3} with aluminum incorporation and sulfur content in the range of 0 ≤ S/(Zn+Al) ≤ 0.16. However, the carrier concentration decreased by five orders of magnitude from 10{sup 19} to 10{sup 14} cm{sup −3} for S/(Zn+Al) = 0.34 and decreased even further when S/(Zn+Al) > 0.34. Such tunable electrical properties are potentially useful for graded buffer layers in thin-film photovoltaic applications.

  8. Porous α-Al2O3 thermal barrier coatings with dispersed Pt particles prepared by cathode plasma electrolytic deposition

    NASA Astrophysics Data System (ADS)

    Wang, Peng; He, Ye-dong; Deng, Shun-jie; Zhang, Jin

    2016-01-01

    Porous α-Al2O3 thermal barrier coatings (TBCs) containing dispersed Pt particles were prepared by cathode plasma electrolytic deposition (CPED). The influence of the Pt particles on the microstructure of the coatings and the CPED process were studied. The prepared coatings were mainly composed of α-Al2O3. The average thickness of the coatings was approximately 100 μm. Such single-layer TBCs exhibited not only excellent high-temperature cyclic oxidation and spallation resistance, but also good thermal insulation properties. Porous α-Al2O3 TBCs inhibit further oxidation of alloy substrates because of their extremely low oxygen diffusion rate, provide good thermal insulation because of their porous structure, and exhibit excellent mechanical properties because of the toughening effect of the Pt particles and because of stress relaxation induced by deformation of the porous structure.

  9. Quantum Chemical Simulation of Carbon Nanotube Nucleation on Al2O3 Catalysts via CH4 Chemical Vapor Deposition.

    PubMed

    Page, Alister J; Saha, Supriya; Li, Hai-Bei; Irle, Stephan; Morokuma, Keiji

    2015-07-29

    We present quantum chemical simulations demonstrating how single-walled carbon nanotubes (SWCNTs) form, or "nucleate", on the surface of Al2O3 nanoparticles during chemical vapor deposition (CVD) using CH4. SWCNT nucleation proceeds via the formation of extended polyyne chains that only interact with the catalyst surface at one or both ends. Consequently, SWCNT nucleation is not a surface-mediated process. We demonstrate that this unusual nucleation sequence is due to two factors. First, the π interaction between graphitic carbon and Al2O3 is extremely weak, such that graphitic carbon is expected to desorb at typical CVD temperatures. Second, hydrogen present at the catalyst surface actively passivates dangling carbon bonds, preventing a surface-mediated nucleation mechanism. The simulations reveal hydrogen's reactive chemical pathways during SWCNT nucleation and that the manner in which SWCNTs form on Al2O3 is fundamentally different from that observed using "traditional" transition metal catalysts. PMID:26148208

  10. Temperature-dependent microstructural evolution of Ti2AlN thin films deposited by reactive magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Zhang, Zheng; Jin, Hongmei; Chai, Jianwei; Pan, Jisheng; Seng, Hwee Leng; Goh, Glen Tai Wei; Wong, Lai Mun; Sullivan, Michael B.; Wang, Shi Jie

    2016-04-01

    Ti2AlN MAX-phase thin films have been deposited on MgO (1 1 1) substrates between 500 and 750 °C using DC reactive magnetron sputtering of a Ti2Al compound target in a mixed N2/Ar plasma. The composition, crystallinity, morphology and hardness of the thin films have been characterized by X-ray photoelectron spectroscopy, X-ray diffraction, atomic force microscopy and nano-indentation, respectively. The film initially forms a mixture of Ti, Al and (Ti,Al)N cubic solid solution at 500 °C and nucleates into polycrystalline Ti2AlN MAX phases at 600 °C. Its crystallinity is further improved with an increase in the substrate temperature. At 750 °C, a single-crystalline Ti2AlN (0 0 0 2) thin film is formed having characteristic layered hexagonal surface morphology, high hardness, high Young's modulus and low electrical resistivity. The mechanism behind the evolution of the microstructure with growth temperature is discussed in terms of surface energies, lattice mismatch and enhanced adatom diffusion at high growth temperatures.

  11. Effect of the thickness on properties of Al{sub 2}O{sub 3} coatings deposited by plasma spraying

    SciTech Connect

    Yin Zhijian; Tao Shunyan; Zhou Xiaming

    2011-01-15

    Al{sub 2}O{sub 3} coatings with different thicknesses (160, 320, 480 and 640 {mu}m) were deposited on stainless steel substrate by plasma spraying. The variation in microstructural characteristics and properties of coatings with various thicknesses was investigated. Powders morphology and the microstructure of as-sprayed coatings were characterized by scanning electron microscopy and optical microscopy. The microhardness was measured using a Vickers' indentor. The corrosion behaviour of plasma-sprayed Al{sub 2}O{sub 3} coatings in 1 N H{sub 2}SO{sub 4} solution at a temperature of 25 deg. C was evaluated by electrochemistry method. Experimental results indicated that surface roughness showed no obvious dependence on the coating thickness. However, the porosity of Al{sub 2}O{sub 3} coating was increased with increased thickness. The enhanced coating thickness also resulted in decreasing microhardness and reduced corrosion resistance. In this study, the Al{sub 2}O{sub 3} coating with thickness of 160 {mu}m possesses the lowest porosity, the highest hardness and superior corrosion resistance. Research Highlights: {yields} Increase of coating thickness shows no obvious effect on phase composition and surface roughness of plasma sprayed Al{sub 2}O{sub 3} coatings. {yields} Variation of porosity and microhardness presents dependence on coating thickness parameter. {yields} Increasing coating thickness leads to reduced corrosion resistance of plasma sprayed Al{sub 2}O{sub 3} coating.

  12. Growth of epitaxial AlN films on (Mn,Zn)Fe 2O 4 substrates by pulsed laser deposition

    NASA Astrophysics Data System (ADS)

    Ohta, J.; Fujioka, H.; Takahashi, H.; Oshima, M.

    2002-09-01

    We have grown AlN on (Mn,Zn)Fe 2O 4 substrates by pulsed laser deposition (PLD) and investigated their structural properties using high resolution X-ray diffraction (HRXRD), reflection high energy electron diffraction (RHEED), and atomic force microscopy (AFM). We have observed the transition of the RHEED pattern from sharp streaks into clear spots at the early stage of the film growth, which indicates that the growth mode of AlN changed from the two-dimensional mode to the three-dimensional mode due to the stress buildup. RHEED and XRD observations have revealed that hexagonal AlN (0 0 0 1) grows on (Mn,Zn)Fe 2O 4 (1 1 1) with the in-plane epitaxial relationship of [1 1 -2 0]AlN//[0 1 -1](Mn,Zn)Fe 2O 4. The lattice mismatch for this alignment is calculated to be 6%. The FWHM value of the AlN (0 0 0 2) X-ray rocking curve is as low as 77 arcsec, which indicates that the density of the threading screw dislocations in the AlN film is quite low.

  13. ZnO/Al:ZnO Transparent Resistive Switching Devices Grown by Atomic Layer Deposition for Memristor Applications.

    PubMed

    Mundle, Rajeh; Carvajal, Christian; Pradhan, Aswini K

    2016-05-17

    ZnO has intrinsic semiconductor conductivity because of an unintentional doping mechanism resulting from the growth process that is mainly attributable to oxygen vacancies (VO) positioned in the bandgap. ZnO has multiple electronic states that depend on the number of vacancies and the charge state of each vacancy. In addition to the individual electron states, the vacancies have different vibrational states. We developed a high-temperature precursor vapor mask technique using Al2O3 to pattern the atomic layer deposition of ZnO and Al:ZnO layers on ZnO-based substrates. This technique was used to create a memristor device based on Al:ZnO thin films having metallic and semiconducting and insulating transport properties ZnO. We demonstrated that adding combination of Al2O3 and TiO2 barrier layers improved the resistive switching behavior. The change in the resistance between the high- and low-resistivity states of the memristor with a combination of Al2O3 and TiO2 was approximately 157%. The devices were exposed to laser light from three different laser diodes. The 450 nm laser diode noticeably affected the combined Al2O3 and TiO2 barrier, creating a high-resistivity state with a 2.9% shift under illumination. The high-resistivity state shift under laser illumination indicates defect shifts and the thermodynamic transition of ZnO defects. PMID:27124366

  14. Amyloid Beta Mediates Memory Formation

    ERIC Educational Resources Information Center

    Garcia-Osta, Ana; Alberini, Cristina M.

    2009-01-01

    The amyloid precursor protein (APP) undergoes sequential cleavages to generate various polypeptides, including the amyloid [beta] (1-42) peptide (A[beta][1-42]), which is believed to play a major role in amyloid plaque formation in Alzheimer's disease (AD). Here we provide evidence that, in contrast with its pathological role when accumulated,…

  15. Impaired fasting glucose is associated with increased regional cerebral amyloid.

    PubMed

    Morris, Jill K; Vidoni, Eric D; Wilkins, Heather M; Archer, Ashley E; Burns, Nicole C; Karcher, Rainer T; Graves, Rasinio S; Swerdlow, Russell H; Thyfault, John P; Burns, Jeffrey M

    2016-08-01

    The Alzheimer's disease risk gene apolipoprotein E epsilon 4 (APOE ε4) is associated with increased cerebral amyloid. Although impaired glucose metabolism is linked to Alzheimer's disease risk, the relationship between impaired glycemia and cerebral amyloid is unclear. To investigate the independent effects of APOE ε4 and impaired glycemia on cerebral amyloid, we stratified nondemented subjects (n = 73) into 4 groups: normal glucose, APOE ε4 noncarrier (control [CNT]; n = 31), normal glucose, APOE ε4 carrier (E4 only; n = 14) impaired glycemia, APOE ε4 noncarrier (IG only; n = 18), and impaired glycemia, APOE ε4 carrier (IG+E4; n = 10). Cerebral amyloid differed both globally (p = 0.023) and regionally; precuneus (p = 0.007), posterior cingulate (PCC; p = 0.020), superior parietal cortex (SPC; p = 0.029), anterior cingulate (p = 0.027), and frontal cortex (p = 0.018). Post hoc analyses revealed that E4 only subjects had increased cerebral amyloid versus CNT globally and regionally in the precuneus, PCC, SPC, anterior cingulate, and frontal cortex. In IG only subjects, increased cerebral amyloid compared with CNT was restricted to precuneus, PCC, and SPC. IG+E4 subjects exhibited higher cerebral amyloid only in the precuneus relative to CNT. These results indicate that impaired glycemia and APOE ε4 genotype are independent risk factors for regional cerebral amyloid deposition. However, APOE ε4 and impaired glycemia did not have an additive effect on cerebral amyloid. PMID:27318141

  16. Amyloid Fibril Solubility.

    PubMed

    Rizzi, L G; Auer, S

    2015-11-19

    It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain-side-chain interactions, backbone hydrogen bonding, and temperature affect amyloid fibril solubility, which might prove to be a powerful tool to design protein fibrils with desired solubility and aggregation properties in general. PMID:26496385

  17. c-axis orientation and piezoelectric coefficients of AlN thin films sputter-deposited on titanium bottom electrodes

    NASA Astrophysics Data System (ADS)

    Ababneh, A.; Alsumady, M.; Seidel, H.; Manzaneque, T.; Hernando-García, J.; Sánchez-Rojas, J. L.; Bittner, A.; Schmid, U.

    2012-10-01

    Aluminum nitride (AlN) reactively sputter deposited from an aluminum target is an interesting compound material due to its CMOS compatible fabrication process and its piezoelectric properties. To obtain high piezoelectric coefficients it is a necessary pre-request to synthesize films with c-axis orientation. Besides the influence of sputter conditions on the microstructure of AlN thin films the condition of the substrate surface is another important factor of utmost importance. In this study, the influence of 350 nm thick titanium metallization DC sputter-deposited on SiO2/Si substrates at varying back pressure levels bp,Ti in the range of 2 × 10-3 to 14 × 10-3 mbar on the c-axis orientation and the piezoelectric coefficients of 600 nm thick AlN thin films is investigated. Besides the plasma power for Ti deposition (Pp,Ti = 100 W) the parameters for AlN synthetization are fixed to Pp = 1000 W and bp,AlN = 4 × 10-3 mbar in 100% N2 atmosphere. Basically, the surface roughness of the Ti bottom layer is the dominating factor resulting either in a high degree of c-axis orientation (i.e. at low bp,Ti values) or in an amorphous AlN microstructure (i.e. at high bp,Ti values). Under low pressure conditions, a smooth and dense surface characteristics is achieved due to a higher kinetic energy associated with the adatoms what is especially important at nominally unheated substrate conditions. The piezoelectric coefficient d33 decreases from 2.55 to 1.7 pm -1 when increasing the titanium sputter pressure from 2 × 10-3 to 14 × 10-3 mbar. When decreasing the Ti film thickness to 60 nm and hence, reducing the root mean square roughness by a factor of about 2, the intensity associated with the AlN (0 0 2) peak is increased by a factor of about 1.7 demonstrating the direct impact. Furthermore, the highest values for d33 and d31 (i.e. 3.15 pm V-1 and -1.28 pm V-1) are determined.

  18. Intravenous Delivery of Targeted Liposomes to Amyloid-β Pathology in APP/PSEN1 Transgenic Mice

    PubMed Central

    Tanifum, Eric A.; Dasgupta, Indrani; Srivastava, Mayank; Bhavane, Rohan C.; Sun, Li; Berridge, John; Pourgarzham, Hoda; Kamath, Rashmi; Espinosa, Gabriela; Cook, Stephen C.; Eriksen, Jason L.; Annapragada, Ananth

    2012-01-01

    Extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles constitute the major neuropathological hallmarks of Alzheimer’s disease (AD). It is now apparent that parenchymal Aβ plaque deposition precedes behavioral signs of disease by several years. The development of agents that can target these plaques may be useful as diagnostic or therapeutic tools. In this study, we synthesized an Aβ-targeted lipid conjugate, incorporated it in stealth liposomal nanoparticles and tested their ability to bind amyloid plaque deposits in an AD mouse model. The results show that the particles maintain binding profiles to synthetic Aβ aggregates comparable to the free ligand, and selectively bind Aβ plaque deposits in brain tissue sections of an AD mouse model (APP/PSEN1 transgenic mice) with high efficiency. When administered intravenously, these long circulating nanoparticles appear to cross the blood-brain barrier and bind to Aβ plaque deposits, labeling parenchymal amyloid deposits and vascular amyloid characteristic of cerebral amyloid angiopathy. PMID:23119043

  19. Atomic layer deposition of highly-doped Er:Al2O3 and Tm:Al2O3 for silicon-based waveguide amplifiers (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Roenn, John; Karvonen, Lasse; Pyymäki-Perros, Alexander; Peyghambarian, Nasser; Lipsanen, Harri; Säynätjoki, Antti; Sun, Zhipei

    2016-05-01

    Recently, rare-earth doped waveguide amplifiers (REDWAs) have drawn significant attention as a promising solution to on-chip amplification of light in silicon photonics and integrated optics by virtue of their high excited state lifetime (up to 10 ms) and broad emission spectrum (up to 200 nm) at infrared wavelengths. In the family of rare-earths, at least erbium, holmium, thulium, neodymium and ytterbium have been demonstrated to be good candidates for amplifier operation at moderate concentrations (< 0.1 %). However, efficient amplifier operation in REDWAs is a very challenging task because high concentration of ions (<0.1%) is required in order to produce reasonable amplification over short device length. Inevitably, high concentration of ions leads to energy-transfer between neighboring ions, which results as decreased gain and increased noise in the amplifier system. It has been shown that these energy-transfer mechanisms in highly-doped gain media are inversely proportional to the sixth power of the distance between the ions. Therefore, novel fabrication techniques with the ability to control the distribution of the rare-earth ions within the gain medium are urgently needed in order to fabricate REDWAs with high efficiency and low noise. Here, we show that atomic layer deposition (ALD) is an excellent technique to fabricate highly-doped (<1%) RE:Al2O3 gain materials by using its nanoscale engineering ability to delicately control the incorporation of RE ions during the deposition. In our experiment, we fabricated Er:Al2O3 and Tm:Al2O3 thin films with ALD by varying the concentration of RE ions from 1% to 7%. By measuring the photoluminescence response of the fabricated samples, we demonstrate that it is possible to incorporate up to 5% of either Er- or Tm-ions in Al2O3 host before severe quenching occurs. We believe that this technique can be extended to other RE ions as well. Therefore, our results show the exceptionality of ALD as a deposition technique for

  20. A subcutaneous cellular implant for passive immunization against amyloid-β reduces brain amyloid and tau pathologies.

    PubMed

    Lathuilière, Aurélien; Laversenne, Vanessa; Astolfo, Alberto; Kopetzki, Erhard; Jacobsen, Helmut; Stampanoni, Marco; Bohrmann, Bernd; Schneider, Bernard L; Aebischer, Patrick

    2016-05-01

    Passive immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. For effective immunotherapy against Alzheimer's disease, recent clinical data indicate that monoclonal antibodies directed against the amyloid-β peptide should be administered before the onset of symptoms associated with irreversible brain damage. It is therefore critical to develop technologies for continuous antibody delivery applicable to disease prevention. Here, we addressed this question using a bioactive cellular implant to deliver recombinant anti-amyloid-β antibodies in the subcutaneous tissue. An encapsulating device permeable to macromolecules supports the long-term survival of myogenic cells over more than 10 months in immunocompetent allogeneic recipients. The encapsulated cells are genetically engineered to secrete high levels of anti-amyloid-β antibodies. Peripheral implantation leads to continuous antibody delivery to reach plasma levels that exceed 50 µg/ml. In a proof-of-concept study, we show that the recombinant antibodies produced by this system penetrate the brain and bind amyloid plaques in two mouse models of the Alzheimer's pathology. When encapsulated cells are implanted before the onset of amyloid plaque deposition in TauPS2APP mice, chronic exposure to anti-amyloid-β antibodies dramatically reduces amyloid-β40 and amyloid-β42 levels in the brain, decreases amyloid plaque burden, and most notably, prevents phospho-tau pathology in the hippocampus. These results support the use of encapsulated cell implants for passive immunotherapy against the misfolded proteins, which accumulate in Alzheimer's disease and other neurodegenerative disorders. PMID:26956423

  1. AMYLOID FORMATION RESULTS IN RECURRENCE OF HYPERGLYCAEMIA FOLLOWING TRANSPLANTATION OF HUMAN ISLET AMYLOID POLYPEPTIDE TRANSGENIC MOUSE ISLETS

    PubMed Central

    Udayasankar, J.; Kodama, K.; Hull, R.L.; Zraika, S.; Aston-Mourney, K.; Subramanian, S.L.; Tong, J.; Faulenbach, M.V.; Vidal, J.; Kahn, S.E.

    2016-01-01

    Aims/Hypothesis Islet transplantation is a potential cure for diabetes; however, rates of graft failure remain high. We sought to determine whether amyloid deposition is associated with reduced beta cell volume in islet grafts and the recurrence of hyperglycaemia following islet transplantation. Methods We transplanted streptozotocin-diabetic mice with 100 islets from human islet amyloid polypeptide transgenic mice that have the propensity to form islet amyloid (n=8–12) or from non-transgenic mice that do not develop amyloid (n=6–10) in sets of studies that lasted one or six weeks. Results Plasma glucose before and for one week after transplantation was similar in mice that received transgenic or non-transgenic islets, and at that time amyloid was detected in all transgenic grafts and, as expected, in none of the non-transgenic grafts. However, over six weeks following transplantation, plasma glucose increased in transgenic but remained stable in non-transgenic islet graft recipients (p<0.05). At six weeks, amyloid was present in 92% of the transgenic grafts and in none of the non-transgenic grafts. Beta cell volume was reduced by 30% (p<0.05), beta cell apoptosis was two-fold higher (p<0.05), while beta cell replication was reduced by 50% (p<0.001) in transgenic compared to non-transgenic grafts. In summary, amyloid deposition in islet grafts occurs prior to the recurrence of hyperglycaemia and its accumulation over time is associated with beta cell loss. Conclusion/Interpretation Islet amyloid formation may explain in part the non-immune loss of beta cells and recurrence of hyperglycaemia following clinical islet transplantation. PMID:19002432

  2. Unwinding fibril formation of medin, the peptide of the most common form of human amyloid

    SciTech Connect

    Larsson, Annika; Soederberg, Linda; Westermark, Gunilla T.; Sletten, Knut; Engstroem, Ulla; Tjernberg, Lars O.; Naeslund, Jan; Westermark, Per

    2007-10-05

    Medin amyloid affects the medial layer of the thoracic aorta of most people above 50 years of age. The consequences of this amyloid are not completely known but the deposits may contribute to diseases such as thoracic aortic aneurysm and dissection or to the general diminished elasticity of blood vessels seen in elderly people. We show that the 50-amino acid residue peptide medin forms amyloid-like fibrils in vitro. With the use of Congo red staining, Thioflavin T fluorescence, electron microscopy, and a solid-phase binding assay on different synthetic peptides, we identified the last 18-19 amino acid residues to constitute the amyloid-promoting region of medin. We also demonstrate that the two C-terminal phenylalanines, previously suggested to be of importance for amyloid formation, are not required for medin amyloid formation.

  3. Mutation of the Alzheimer's Disease Amyloid Gene in Hereditary Cerebral Hemorrhage, Dutch Type

    NASA Astrophysics Data System (ADS)

    Levy, Efrat; Carman, Mark D.; Fernandez-Madrid, Ivan J.; Power, Michael D.; Lieberburg, Ivan; van Duinen, Sjoerd G.; Bots, Gerard Th. A. M.; Luyendijk, Willem; Frangione, Blas

    1990-06-01

    An amyloid protein that precipitates in the cerebral vessel walls of Dutch patients with hereditary cerebral hemorrhage with amyloidosis is similar to the amyloid protein in vessel walls and senile plaques in brains of patients with Alzheimer's disease, Down syndrome, and sporadic cerebral amyloid angiopathy. Cloning and sequencing of the two exons that encode the amyloid protein from two patients with this amyloidosis revealed a cytosine-to-guanine transversion, a mutation that caused a single amino acid substitution (glutamine instead of glutamic acid) at position 22 of the amyloid protein. The mutation may account for the deposition of this amyloid protein in the cerebral vessel walls of these patients, leading to cerebral hemorrhages and premature death.

  4. Islet amyloid inhibitors improve glucose homeostasis in a transgenic mouse model of type 2 diabetes.

    PubMed

    Wijesekara, N; Ahrens, R; Wu, L; Ha, K; Liu, Y; Wheeler, M B; Fraser, P E

    2015-10-01

    Increasing evidence points to the cytotoxicity of islet amyloid polypeptide (IAPP) aggregates as a major contributor to the loss of β-cell mass in type 2 diabetes. Prevention of IAPP formation represents a potential treatment to increase β-cell survival and function. The IAPP inhibitory peptide, D-ANFLVH, has been previously shown to prevent islet amyloid accumulation in cultured human islets. To assess its activity in vivo, D-ANFLVH was administered by intraperitoneal injection into a human IAPP transgenic mouse model, which replicates type 2 diabetes islet amyloid pathology. The peptide was a potent inhibitor of islet amyloid deposition, resulting in reduced islet cell apoptosis and preservation of β-cell area leading to improved glucose tolerance. These findings provide support for a key role of islet amyloid in β-cell survival and validate the application of anti-amyloid compounds as therapeutic strategies to maintain normal insulin secretion in patients with type 2 diabetes. PMID:26095311

  5. Investigation on dielectric properties of atomic layer deposited Al{sub 2}O{sub 3} dielectric films

    SciTech Connect

    Yıldız, Dilber Esra; Yıldırım, Mert; Gökçen, Muharrem

    2014-05-15

    Al/Al{sub 2}O{sub 3}/p-Si Schottky barrier diodes (SBDs) were fabricated using atomic layer deposition technique in order to investigate dielectric properties of SBDs. For this purpose, admittance measurements were conducted at room temperature between −1 V and 3 V in the frequency range of 10 kHz and 1 MHz. In addition to the investigation of Al{sub 2}O{sub 3} morphology using atomic force microscope, dielectric parameters; such as dielectric constant (ε′), dielectric loss (ε″), dielectric loss tangent (tan δ), and real and imaginary parts of dielectric modulus (M′ and M″, respectively), were calculated and effect of frequency on these parameters of Al/Al{sub 2}O{sub 3}/p-Si SBDs was discussed. Variations in these parameters at low frequencies were associated with the effect of interface states in low frequency region. Besides dielectric parameters, ac electrical conductivity of these SBDs was also investigated.

  6. Passivation Effect of Atomic Layer Deposition of Al2O3 Film on HgCdTe Infrared Detectors

    NASA Astrophysics Data System (ADS)

    Zhang, Peng; Ye, Zhen-Hua; Sun, Chang-Hong; Chen, Yi-Yu; Zhang, Tian-Ning; Chen, Xin; Lin, Chun; Ding, Ring-Jun; He, Li

    2016-09-01

    The passivation effect of atomic layer deposition of (ALD) Al2O3 film on a HgCdTe infrared detector was investigated in this work. The passivation effect of Al2O3 film was evaluated by measuring the minority carrier lifetime, capacitance versus voltage ( C- V) characteristics of metal-insulator-semiconductor devices, and resistance versus voltage ( R- V) characteristics of variable-area photodiodes. The minority carrier lifetime, C- V characteristics, and R- V characteristics of HgCdTe devices passivated by ALD Al2O3 film was comparable to those of HgCdTe devices passivated by e-beam evaporation of ZnS/CdTe film. However, the baking stability of devices passivated by Al2O3 film is inferior to that of devices passivated by ZnS/CdTe film. In future work, by optimizing the ALD Al2O3 film growing process and annealing conditions, it may be feasible to achieve both excellent electrical properties and good baking stability.

  7. Passivation Effect of Atomic Layer Deposition of Al2O3 Film on HgCdTe Infrared Detectors

    NASA Astrophysics Data System (ADS)

    Zhang, Peng; Ye, Zhen-Hua; Sun, Chang-Hong; Chen, Yi-Yu; Zhang, Tian-Ning; Chen, Xin; Lin, Chun; Ding, Ring-Jun; He, Li

    2016-06-01

    The passivation effect of atomic layer deposition of (ALD) Al2O3 film on a HgCdTe infrared detector was investigated in this work. The passivation effect of Al2O3 film was evaluated by measuring the minority carrier lifetime, capacitance versus voltage (C-V) characteristics of metal-insulator-semiconductor devices, and resistance versus voltage (R-V) characteristics of variable-area photodiodes. The minority carrier lifetime, C-V characteristics, and R-V characteristics of HgCdTe devices passivated by ALD Al2O3 film was comparable to those of HgCdTe devices passivated by e-beam evaporation of ZnS/CdTe film. However, the baking stability of devices passivated by Al2O3 film is inferior to that of devices passivated by ZnS/CdTe film. In future work, by optimizing the ALD Al2O3 film growing process and annealing conditions, it may be feasible to achieve both excellent electrical properties and good baking stability.

  8. Surface Thiolation of Al Microspheres to Deposite Thin and Compact Ag Shells for High Conductivity.

    PubMed

    Wang, Yilong; Wen, Jianghong; Zhao, Suling; Chen, Zhihong; Ren, Ke; Sun, Jie; Guan, Jianguo

    2015-12-15

    In this work, we have demonstrated a method for controllable thiolated functionalization coupled with electroless silver plating to achieve aluminum@silver (Al@Ag) core-shell composite particles with thin and compact layers. First, Al microspheres were functionalized by a well-known polymerizable silane coupling agent, i.e., 3-mercaptopropyltrimethoxysilane (MPTMS). Decreasing the ethanol-to-water volume ratio (F) in silane solution produces modification films with high content of thiol groups on Al microspheres, owing to the dehydration of silane molecules with hydroxyl groups on Al microspheres and self-polymerization of silane molecules. Then, ethanol was used as one of the solvents to play a major role in the uniform dispersion of silane coupling agent in the solution, resulting in uniformly distributing and covalently attaching thiol groups on Al microspheres. In electroless silver plating, thiol groups being densely grafted on the surface of Al microspheres favor the heterogeneous nucleation of Ag, since the thiol group can firmly bind with Ag(+) and enable the in situ reduction by the reducing reagent. In this manner, dense Ag nuclei tend to produce thin and compact silver shells on the Al microspheres surfaces. The as-obtained Al@Ag core-shell composite particles show a resistivity as low as (8.58 ± 0.07) × 10(-5) Ω·cm even when the Ag content is as low as 15.46 wt %. Therefore, the as-obtained Al@Ag core-shell composite particles have advantages of low weight, low silver content and high conductivity, which could make it a promising candidate for application in conductive and electromagnetic shielding composite materials. PMID:26574653

  9. Epitaxial growth of aligned AlGalnN nanowires by metal-organic chemical vapor deposition

    DOEpatents

    Han, Jung; Su, Jie

    2008-08-05

    Highly ordered and aligned epitaxy of III-Nitride nanowires is demonstrated in this work. <1010> M-axis is identified as a preferential nanowire growth direction through a detailed study of GaN/AlN trunk/branch nanostructures by transmission electron microscopy. Crystallographic selectivity can be used to achieve spatial and orientational control of nanowire growth. Vertically aligned (Al)GaN nanowires are prepared on M-plane AlN substrates. Horizontally ordered nanowires, extending from the M-plane sidewalls of GaN hexagonal mesas or islands demonstrate new opportunities for self-aligned nanowire devices, interconnects, and networks.

  10. Direct Metal Deposition by Laser in TiNi-Al System for Graded Structure Fabrication

    NASA Astrophysics Data System (ADS)

    Shishkovsky, I.; Kakovkina, N.; Missemer, F.

    2016-07-01

    Intermetallic phase formation was studied in powdered TiNi-Al system under layerwise laser cladding with the aim of forming a gradient of properties due to a change in the concentration relation of Al in the NiTi powder mixture from one layer to another. The relationship between the laser cladding parameters and the intermetallic phase structures in consecutively cladded layers were determined. The structure of intermetallic compounds formed by laser synthesis was studied by optical microscopy, measurement of microhardness, SEM with EDX analysis. Microhardness doubling from 500 HV to 1000 HV was achieved due to nitinol matrix enrichment by Al, which is promising for aerospace applications.

  11. Reduced defect density at the CZTSSe/CdS interface by atomic layer deposition of Al2O3

    NASA Astrophysics Data System (ADS)

    Erkan, Mehmet Eray; Chawla, Vardaan; Scarpulla, Michael A.

    2016-05-01

    The greatest challenge for improving the power conversion efficiency of Cu2ZnSn(S,Se)4 (CZTSSe)/CdS/ZnO thin film solar cells is increasing the open circuit voltage (VOC). Probable leading causes of the VOC deficit in state-of-the-art CZTSSe devices have been identified as bulk recombination, band tails, and the intertwined effects of CZTSSe/CdS band offset, interface defects, and interface recombination. In this work, we demonstrate the modification of the CZTSSe absorber/CdS buffer interface following the deposition of 1 nm-thick Al2O3 layers by atomic layer deposition (ALD) near room temperature. Capacitance-voltage profiling and quantum efficiency measurements reveal that ALD-Al2O3 interface modification reduces the density of acceptor-like states at the heterojunction resulting in reduced interface recombination and wider depletion width. Indications of increased VOC resulting from the modification of the heterojunction interface as a result of ALD-Al2O3 treatment are presented. These results, while not conclusive for application to state-of-the-art high efficiency CZTSSe devices, suggest the need for further studies as it is probable that interface recombination contributes to reduced VOC even in such devices.

  12. ZnO:Al thin films deposited by RF-magnetron sputtering with tunable and uniform properties.

    PubMed

    Miorin, E; Montagner, F; Battiston, S; Fiameni, S; Fabrizio, M

    2011-03-01

    Nanostructured, high quality and large area Al-doped ZnO (ZnO:Al) thin films were obtained by radiofrequency (RF) magnetron sputtering. The sample rotation during deposition has resulted in excellent spatial distribution of thickness and electro-optical properties compared to that obtained under static conditions. ZnO:Al thin films are employed in a large number of devices, including thin film solar cells, where the uniformity of the properties is a key factor for a possible up-scaling of the research results to industrially relevant substrate sizes. A chemical post etching treatment was employed achieving tunable surface nanotextures to generate light scattering at the desired wavelength for improved cell efficiency. Since the film resistivity is only slightly increased by the etching, this post-deposition step allows separating the optimization of electro-optical properties from light scattering behavior. The thin films were characterized by FE-SEM, XRD, UV-VIS spectroscopy, four probe and van der Paw techniques. PMID:21449368

  13. Tantalum coating on porous Ti6Al4V scaffold using chemical vapor deposition and preliminary biological evaluation.

    PubMed

    Li, Xiang; Wang, Lin; Yu, Xiaoming; Feng, Yafei; Wang, Chengtao; Yang, Ke; Su, Daniel

    2013-07-01

    Porous tantalum (Ta), produced via chemical vapor deposition (CVD) of commercially pure Ta onto a vitreous carbon, is currently available for use in orthopedic applications. However, the relatively high manufacturing cost and the incapability to produce customized implant using medical image data have limited its application to gain widespread acceptance. In this study, Ta film was deposited on porous Ti6Al4V scaffolds using CVD technique. Digital microscopy and scanning electron microscopy indicated that the Ta coating evenly covered the entire scaffold structure. X-ray diffraction analysis showed that the coating consisted of α and β phases of Ta. Goat mesenchymal stem cells were seeded and cultured on the Ti6Al4V scaffolds with and without coating. The tetrazolium-based colorimetric assay exhibited better cell adhesion and proliferation on Ta-coated scaffolds compared with uncoated scaffolds. The porous scaffolds were subsequently implanted in goats for 12weeks. Histological analysis revealed similar bone formation around the periphery of the coated and uncoated implants, but bone ingrowth is better within the Ta-coated scaffolds. To demonstrate the ability of producing custom implant for clinical applications via this technology, we designed and fabricated a porous Ti6Al4V scaffold with segmental mandibular shape derived from patient computerized tomography data. PMID:23623123

  14. Analysis of the co-deposition of Al2O3 particles with nickel by an electrolytic route: The influence of organic additives presence and Al2O3 concentration

    NASA Astrophysics Data System (ADS)

    Temam, H. B.; Temam, E. G.

    2016-04-01

    Alloy coatings were prepared by co-deposition of Al2O3 particles in Ni matrix on carbon steel substrate from nickel chloride bath in which metallic powders were held in suspension. The influence of metal powder amount in the bath on chemical composition, morphology, thickness, microhardness and corrosion behavior of obtained coatings, has been investigated. It was shown that the presence of Al2O3 particles in deposit greatly improves the hardness and the wear resistance of alloy coatings. Characterization by microanalysis (EDX) of the various deposits elaborated confirms that the rate of particles incorporated increases as the concentration of solid particles increasing. The results showed that the presence of organic additives in Ni-Al2O3 electrolyte deposition led to an increase in the hardness and corrosion resistance of the deposits.

  15. Atomic-layer-deposited Al2O3-HfO2-Al2O3 dielectrics for metal-insulator-metal capacitor applications

    NASA Astrophysics Data System (ADS)

    Ding, Shi-Jin; Zhu, Chunxiang; Li, Ming-Fu; Zhang, David Wei

    2005-08-01

    Atomic-layer-deposited Al2O3-HfO2-Al2O3 dielectrics have been investigated to replace conventional silicon oxide and nitride for radio frequency and analog metal-insulator-metal capacitors applications. In the case of 1-nm-Al2O3, sufficiently good electrical performances are achieved, including a high dielectric constant of ˜17, a small dissipation factor of 0.018 at 100kHz, an extremely low leakage current of 7.8×10-9A/cm2 at 1MV/cm and 125°C, perfect voltage coefficients of capacitance (74ppm/V2 and 10ppm/V). The quadratic voltage coefficient of capacitance decreases with the applied frequency due to the change of relaxation time with different carrier mobility in insulator, and correlates with the dielectric composition and thickness, which is of intrinsic property owing to electric field polarization. Furthermore, the conduction mechanism of the AHA dielectrics is also discussed, indicating the Schottky emission dominated at room temperature.

  16. Preparation of epitaxial AlN films by electron cyclotron resonance plasma-assisted chemical vapor deposition on Ir- and Pt-coated sapphire substrates

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Vargas, Roberto; Goto, Takashi; Someno, Yoshihiro; Hirai, Toshio

    1994-03-01

    AlN epitaxial films have been fabricated on Ir- and Pt-coated α-Al2O3 substrates via electron cyclotron resonance plasma-assisted chemical vapor deposition (ECRPACVD) using an AlBr3-N2-H2-Ar gas system at substrate temperatures ranging from 500 to 700 °C. The epitaxial relationships between AlN films and substrates were determined by x-ray diffraction, x-ray pole figure, and reflection high-energy electron diffraction. The results are useful in practical applications, such as AlN/metal/α-Al2O3 structure in surface acoustic wave (SAW) devices.

  17. A Human Monoclonal IgG That Binds Aβ Assemblies and Diverse Amyloids Exhibits Anti-Amyloid Activities In Vitro and In Vivo

    PubMed Central

    O'Nuallain, Brian; Puligedda, Rama Devudu; Ondrejcak, Tomas; Adekar, Sharad P.; Chen, Cindy; Cruz, Pedro E.; Rosario, Awilda M.; Macy, Sallie; Mably, Alexandra J.; Walsh, Dominic M.; Vidal, Ruben; Solomon, Alan; Brown, Daniel; Rowan, Michael J.; Golde, Todd E.

    2015-01-01

    Alzheimer's disease (AD) and familial Danish dementia (FDD) are degenerative neurological diseases characterized by amyloid pathology. Normal human sera contain IgG antibodies that specifically bind diverse preamyloid and amyloid proteins and have shown therapeutic potential in vitro and in vivo. We cloned one of these antibodies, 3H3, from memory B cells of a healthy individual using a hybridoma method. 3H3 is an affinity-matured IgG that binds a pan-amyloid epitope, recognizing both Aβ and λ Ig light chain (LC) amyloids, which are associated with AD and primary amyloidosis, respectively. The pan-amyloid-binding properties of 3H3 were demonstrated using ELISA, immunohistochemical studies, and competition binding assays. Functional studies showed that 3H3 inhibits both Aβ and LC amyloid formation in vitro and abrogates disruption of hippocampal synaptic plasticity by AD-patient-derived soluble Aβ in vivo. A 3H3 single-chain variable fragment (scFv) retained the binding specificity of the 3H3 IgG and, when expressed in the brains of transgenic mice using an adeno-associated virus (AAV) vector, decreased parenchymal Aβ amyloid deposition in TgCRND8 mice and ADan (Danish Amyloid) cerebral amyloid angiopathy in the mouse model of FDD. These data indicate that naturally occurring human IgGs can recognize a conformational, amyloid-specific epitope and have potent anti-amyloid activities, providing a rationale to test their potential as antibody therapeutics for diverse neurological and other amyloid diseases. PMID:25904780

  18. Growing LaAlO{sub 3}/SrTiO{sub 3} interfaces by sputter deposition

    SciTech Connect

    Dildar, I. M.; Neklyudova, M.; Xu, Q.; Zandbergen, H. W.; Harkema, S.; Boltje, D.; Aarts, J.

    2015-06-15

    Sputter deposition of oxide materials in a high-pressure oxygen atmosphere is a well-known technique to produce thin films of perovskite oxides in particular. Also interfaces can be fabricated, which we demonstrated recently by growing LaAlO{sub 3} on SrTiO{sub 3} substrates and showing that the interface showed the same high degree of epitaxy and atomic order as is made by pulsed laser deposition. However, the high pressure sputtering of oxides is not trivial and number of parameters are needed to be optimized for epitaxial growth. Here we elaborate on the earlier work to show that only a relatively small parameter window exists with respect to oxygen pressure, growth temperature, radiofrequency power supply and target to substrate distance. In particular the sensitivity to oxygen pressure makes it more difficult to vary the oxygen stoichiometry at the interface, yielding it insulating rather than conducting.

  19. Alzheimer's silent partner: cerebral amyloid angiopathy.

    PubMed

    Cupino, Tanya L; Zabel, Matthew K

    2014-06-01

    Alzheimer's disease (AD) is the most common form of dementia, which completely lacks a viable, long-term therapeutic intervention. This is partly due to an incomplete understanding of AD etiology and the possible confounding factors associated with its genotypic and phenotypic heterogeneity. Cerebral amyloid angiopathy (CAA) is a common, yet frequently overlooked, pathology associated with AD. CAA manifests with deposition amyloid-beta (Aβ) within the smooth muscle layer of cerebral arteries and arterioles. The role of Aβ in AD and CAA pathophysiology has long been controversial. Although it has demonstrated toxicity at super-physiological levels in vitro, Aβ load does not necessarily correlate with cognitive demise in humans. In this review, we describe the contributions of CAA to AD pathophysiology and important pathomechanisms that may lead to vascular fragility and hemorrhages. Additionally, we discuss the effect of Aβ on smooth muscle cell phenotype and viability, especially in terms of the complement cascade. PMID:24323728

  20. Enhancement mode AlGaN/GaN MOS high-electron-mobility transistors with ZrO2 gate dielectric deposited by atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Anderson, Travis J.; Wheeler, Virginia D.; Shahin, David I.; Tadjer, Marko J.; Koehler, Andrew D.; Hobart, Karl D.; Christou, Aris; Kub, Francis J.; Eddy, Charles R., Jr.

    2016-07-01

    Advanced applications of AlGaN/GaN high-electron-mobility transistors (HEMTs) in high-power RF and power switching are driving the need for insulated gate technology. We present a metal–oxide–semiconductor (MOS) gate structure using atomic-layer-deposited ZrO2 as a high-k, high-breakdown gate dielectric for reduced gate leakage and a recessed barrier structure for enhancement mode operation. Compared to a Schottky metal-gate HEMT, the recessed MOS-HEMT structure demonstrated a reduction in the gate leakage current by 4 orders of magnitude and a threshold voltage shift of +6 V to a record +3.99 V, enabled by a combination of a recessed barrier structure and negative oxide charge.

  1. Chronic imaging of amyloid plaques in the live mouse brain using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Bacskai, Brian J.; Kajdasz, Stephen T.; Christie, R. H.; Zipfel, Warren R.; Williams, Rebecca M.; Kasischke, Karl A.; Webb, Watt W.; Hyman, B. T.

    2001-04-01

    Transgenic mice expressing the human Amyloid Precursor Protein (APP) develop amyloid plaques as they age. These plaques resemble those found in the human disease. Multiphoton laser scanning microscopy combined with a novel surgical approach was used to measure amyloid plaque dynamics chronically in the cortex of living transgenic mice. Thioflavine S (thioS) was used as a fluorescent marker of amyloid deposits. Multiphoton excitation allowed visualization of amyloid plaques up to 200 micrometers deep into the brain. The surgical site could be imaged repeatedly without overt damage to the tissue, and individual plaques within this volume could be reliably identified over periods of several days to several months. On average, plaque sizes remained constant over time, supporting a model of rapid deposition, followed by relative stability. Alternative reporters for in vivo histology include thiazine red, and FITC-labeled amyloid-(Beta) peptide. We also present examples of multi-color imaging using Hoechst dyes and FITC-labeled tomato lectin. These approaches allow us to observe cell nuclei or microglia simultaneously with amyloid-(Beta) deposits in vivo. Chronic imaging of a variety of reporters in these transgenic mice should provide insight into the dynamics of amyloid-(Beta) activity in the brain.

  2. Microwave assisted apatite coating deposition on Ti6Al4V implants.

    PubMed

    Zhou, Huan; Nabiyouni, Maryam; Bhaduri, Sarit B

    2013-10-01

    In this work we report a novel microwave assisted technology to deposit a uniform, ultra-thin apatite coating without any cracks on titanium implants in minutes. This method comprises of conventional biomimetic coating in synergism with microwave irradiation to result in alkaline earth phosphate nucleation. The microwave assisted coating process mainly follows the initial stages of biomimetic coating until the step of the Ca-P nuclei formation. After that, due to microwave irradiation more Ca-P nuclei are formed to cover the whole surface of the implant instead of the growth of deposited Ca-P nuclei to Ca-P globules and coatings. It is interesting to note the doping of Mg(2+) to Ca-P apatite coating can significantly change the properties and performances of as-deposited coatings. The hydrophilicity, physical properties, bioactivity, cell adhesion, and growth capability of as-deposited microwave assisted coatings were investigated. The study shows that this coating technology has great potential in biomedical applications. Additionally, since biomimetic coating can be applied to series of implant materials such as polymer, metals and glass, it is expected this microwave assisted coating technology can also be applied to these materials if they can remains stable at 100 °C, the boiling point of water. PMID:23910363

  3. Antireflective conducting nanostructures with an atomic layer deposited an AlZnO layer on a transparent substrate

    NASA Astrophysics Data System (ADS)

    Park, Hyun-Woo; Ji, Seungmuk; Herdini, Diptya Suci; Lim, Hyuneui; Park, Jin-Seong; Chung, Kwun-Bum

    2015-12-01

    The antireflective conducting nanostructures on a transparent substrate were shown to have enhanced optical and electrical properties via colloidal lithography and atomic layer deposition. The conformal AlZnO layer on a transparent nanostructured substrate exhibited 5.52 × 10-4 Ω cm in resistivity and 88% in average visible transmittance, both of which were superior to those of a flat transparent conducting substrate. The improvement of transparency was explained by the gradual changes of the refractive index in the film depth direction. The decrease in electrical resistivity is strongly correlated to the increased surface area with the nanostructure and the change of chemical bonding states.

  4. Identification and spatial distribution of light-toned deposits enriched in Al-phyllosilicates on the plateaus around Valles Marineris, Mars

    NASA Astrophysics Data System (ADS)

    Le Deit, L.; Flahaut, J.; Quantin, C.; Allemand, P.

    2009-12-01

    The plateaus around Valles Marineris consist in series of mafic rocks suggested to be flood basalts (McEwen et al., 1998), lavas interbedded with sediments (Malin and Edgett, 2000), layered intrusive rocks (Williams et al., 2003), or lava flows dated from the Noachian to the late Hesperian epochs (Scott and Carr, 1978). Recent studies show the occurrence of light layered deposits of hundred meters thick cropping out on plateaus near Ius Chasma, Melas Chasma, Candor Chasma, Juventae Chasma and Ganges Chasma deposited during the Hesperian epoch by fluvio-lacustrine processes (Weitz et al., 2009), or by air-fall processes (Le Deit et al., 2009). These layered deposits are enriched in hydrated minerals including opaline silica (Milliken et al., 2008), hydroxylated ferric sulfates (Bishop et al., 2009), and possibly Al-rich phyllosilicates (Le Deit et al., 2009). We identified another type of formation corresponding to light-toned massive deposits cropping out around Valles Marineris. It appears that these light-toned deposits are associated to bright, rough, and highly cratered terrains, located beneath a dark and thin capping unit. Previous studies report the occurrence of phyllosilicates on few locations around Valles Marineris based on OMEGA data analyses (Gondet et al., 2007; Carter et al., 2009). The analysis of CRISM data show that the light-toned deposits are associated with spectra displaying absorption bands at 1.4 μm, 1.9 μm, and a narrow band at 2.2 μm. These spectral characteristics are consistent with the presence of Al-rich phyllosilicates such as montmorillonite, or illite in the light-toned deposits. They constitute dozens of outcrops located on the plateaus south and east of Coprates Chasma and Capri Chasma, and west of Ganges Chasma. All outcrops investigated so far are present over Noachian terrains mapped as the unit Npl2 by Scott and Tanaka (1986), and Witbeck et al. (1991). These light-toned deposits could result from in situ aqueous alteration

  5. Fleeting Amyloid-like Forms of Rim4 Ensure Meiotic Fidelity

    PubMed Central

    Ford, Alice Flynn; Shorter, James

    2015-01-01

    Berchowitz et al. establish that transient amyloid-like forms of Rim4, a yeast RNA-binding protein with a predicted prion domain, translationally repress cyclin CLB3 in meiosis I, thereby ensuring homologous chromosome segregation. These findings suggest that prion domains might enable formation of tightly regulated amyloid-like effectors in diverse functional settings. PMID:26451477

  6. Atomic Layer Deposited Al{sub 2}O{sub 3} as Characterized Reference Samples for Nanolayer Metrology

    SciTech Connect

    Nutsch, A.; Lemberger, M.; Petrik, P.

    2011-11-10

    Plasma assisted Atomic Layer Deposition Al{sub 2}O{sub 3} samples were studied using an approach of complementary metrology using Ellipsometry, X-Ray Reflectivity, Atomic Force Microscopy, and Total Reflection X-Ray Fluorescence. For modeling the samples, an interfacial rough SiO{sub 2} layer has to be assumed. The excellent linearity of the ALD process was used to cross check Ellipsometry and X-Ray Reflectivity. In contrast to Ellipsometry, X-Ray Reflectivity showed a residual surface layer, identified as chlorine contaminated layer by TXRF. The samples are shown to be ideal candidates for calibration of X-ray fluorescence as the Al signal linearly depends on the film thickness or ALD cycles. Furthermore, the impact of self-absorption of thick layers for TXRF was shown by the samples.

  7. Fabrication and Electrical Characterization of the Si/ZnO/ZnO:Al Structure Deposited by RF-Magnetron Sputtering

    NASA Astrophysics Data System (ADS)

    Alaya, A.; Djessas, K.; El Mir, L.; Khirouni, K.

    2016-06-01

    The electrical transport properties of the structures of Si(p)/ZnO(i)/ZnO: Al(3%) and Si(p)/PS/ZnO(i)/ZnO: Al(3%) deposited by radio-frequency-magnetron sputtering were investigated and compared by using current-voltage and impedance spectroscopy measurements in a wide temperature range of 80-300 K. Aluminum-doped ZnO is considered to be one of the most important transparent conducting oxide materials due to its high conductivity, good transparency and low cost. From the current-voltage-temperature (I-V-T) characteristics, it was found that both structures had a good rectifying behavior. This behavior decreases according to the porous silicon layer. The variation of the conductance with frequency indicates the semiconducting behavior and superposition of different conduction mechanisms. The insertion of the porous silicon layer results in a decrease of conductivity, which is attributed to reduced conductivity of defect-rich porous silicon.

  8. Microstructure and Properties of Laser-Deposited Ti6Al4V Metal Matrix Composites Using Ni-Coated Powder

    NASA Astrophysics Data System (ADS)

    Zheng, B.; Smugeresky, J. E.; Zhou, Y.; Baker, D.; Lavernia, E. J.

    2008-05-01

    As a layer additive rapid manufacturing process, laser engineered net shaping (LENS) can fabricate three-dimensional components directly from a computer-aided design (CAD) model. In this work, the LENS process was employed to fabricate Ti6Al4V metal matrix composites using powder mixtures of gas-atomized Ti6Al4V powder and varying volume fractions of Ni nanocoated TiC particles. The as-fabricated microstructures were studied using scanning electron microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), differential thermal analyzer (DTA), and transmission electron microscopy (TEM) techniques. The interfaces between the metal matrix and ceramic particles were examined. The presence of intermetallic phases and resolidified TiC particles was rationalized on the basis of the thermal field during deposition. The influence of LENS parameters on the microstructure evolution and mechanical behavior of the metal matrix composites (MMCs) was also discussed.

  9. Electrically conducting n-type AlGaN/GaN distributed Bragg reflectors grown by metalorganic chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Liu, Yuh-Shiuan; Haq, A. F. M. Saniul; Kao, Tsung-Ting; Mehta, Karan; Shen, Shyh-Chiang; Detchprohm, Theeradetch; Yoder, P. Douglas; Dupuis, Russell D.; Xie, Hongen; Ponce, Fernando A.

    2016-06-01

    We report an electrically conducting 40-pair silicon doped Al0.12Ga0.88N/GaN distributed Bragg reflector (DBR) grown by metalorganic chemical vapor deposition on a silicon doped n-type GaN template. Due to the relatively small lattice mismatch between AlGaN and GaN, strain managing layers are not required for crack-free n-DBR growth. The DBR demonstrates a peak reflectivity of 91.6% at 368 nm with stopband of 11 nm. In addition, the 40-pair n-DBR shows the vertical resistance of 5.5 Ω, which corresponds to bulk resistivity of 0.52 Ω cm, near the maximum measured current of 100 mA.

  10. In situ spectroscopic ellipsometry growth studies on the Al-doped ZnO films deposited by remote plasma-enhanced metalorganic chemical vapor deposition

    SciTech Connect

    Volintiru, I.; Creatore, M.; Sanden, M. C. M. van de

    2008-02-01

    In situ spectroscopic ellipsometry (SE) was applied to study the pyramidlike and pillarlike growth of Al doped ZnO (AZO) films deposited by means of remote plasma-enhanced metalorganic chemical vapor deposition for transparent conductive oxide applications. Real time SE studies in the visible region allowed discerning between the two growth modes by addressing the time evolution of the bulk and surface roughness layer thickness. While the pillarlike mode is characterized by a constant growth rate, a slower rate in the initial stage (up to 150-200 nm film thickness), compared to the bulk, is observed for the growth of pyramidlike AZO films. The two modes differ also in terms of surface roughness development: a saturation behavior is observed for film thickness above 150-200 nm in the case of the pyramidlike films, while a slow linear increase with film thickness characterizes the pillarlike mode. By extending the SE analysis of the AZO films to the near infrared region, valuable information about the in grain properties could be extracted: excellent in grain mobility values, i.e., larger than 100 and 50 cm{sup 2}/V s, are determined for the pyramidlike and pillarlike AZO layers, respectively. The comparison between the outcome of the in situ real time SE studies and the ex situ electrical and chemical characterization highlights the limitations in the electron transport occurring in both types of films and allows one to address routes toward further improvement in AZO conductivity.

  11. Generating local amyloidosis in mice by the subcutaneous injection of human insulin amyloid fibrils.

    PubMed

    Chinisaz, Maryam; Ebrahim-Habibi, Azadeh; Yaghmaei, Parichehreh; Parivar, Kazem; Dehpour, Ahmad-Reza

    2014-08-01

    Localized deposits of amyloid structures are observed in various pathological conditions. One example of when local amyloidosis occurs is following repeated insulin injections in diabetic patients. The present study aimed to simulate the same condition in mice. To obtain the amyloid structures, regular insulin was incubated at 57°C for 24 h. The subsequently formed amyloid fibrils were analyzed using the Congo red absorbance test, as well as transmission electron microscopy images, and then injected into mice once per day for 21 consecutive days. Firm waxy masses were developed following this period, which were excised, prepared as thin sections and stained with hematoxylin and eosin, Congo red and Sudan black. Histological examination revealed that these masses contained adipose cells and connective tissue, in which amyloid deposition was visible. Thus, localized amyloidosis was obtained by the subcutaneous injection of insulin fibrils. The present results may be of further use in the development of models of amyloid tumors. PMID:25009591

  12. Generating local amyloidosis in mice by the subcutaneous injection of human insulin amyloid fibrils

    PubMed Central

    CHINISAZ, MARYAM; EBRAHIM-HABIBI, AZADEH; YAGHMAEI, PARICHEHREH; PARIVAR, KAZEM; DEHPOUR, AHMAD-REZA

    2014-01-01

    Localized deposits of amyloid structures are observed in various pathological conditions. One example of when local amyloidosis occurs is following repeated insulin injections in diabetic patients. The present study aimed to simulate the same condition in mice. To obtain the amyloid structures, regular insulin was incubated at 57°C for 24 h. The subsequently formed amyloid fibrils were analyzed using the Congo red absorbance test, as well as transmission electron microscopy images, and then injected into mice once per day for 21 consecutive days. Firm waxy masses were developed following this period, which were excised, prepared as thin sections and stained with hematoxylin and eosin, Congo red and Sudan black. Histological examination revealed that these masses contained adipose cells and connective tissue, in which amyloid deposition was visible. Thus, localized amyloidosis was obtained by the subcutaneous injection of insulin fibrils. The present results may be of further use in the development of models of amyloid tumors. PMID:25009591

  13. Growth and characterisation of NiAl and N-doped NiAl films deposited by closed field unbalanced magnetron sputtering ion plating using elemental ni and Al targets.

    PubMed

    Said, R; Ahmed, W; Abuain, T; Abuazza, A; Gracio, J

    2010-04-01

    Closed Field Unbalanced Magnetron Sputtering Ion Plating (CFUBMSIP) has been used to deposit undoped and nitrogen doped NiAI thin films onto glass and stainless steel 316 substrates. These films have potential applications in tribological, electronic media and thermal barrier coatings. The surface characteristics, composition, mechanical and structural properties have been investigated using stylus profilometry, X-ray diffraction (XRD), Energy dispersive spectroscopy (EDAX), Atomic force microscopy (AFM) and nanoindentation. The average thickness of the films was approximately 1 microm. The X-ray diffraction spectra revealed the presence of the beta NiAl phase. The EDAX results revealed that all of the undoped and nitrogen doped NiAl thin films exhibited the near equiatomic NiAl composition with the best results being achieved using 300 Watts DC power for Ni and 400 Watts DC power for Al targets respectively. AFM results of both types of films deposited on glass samples exhibited a surface roughness of less than 100 nm. The nanoindenter results for coatings on glass substrates displayed hardness and elastic modulus of 7.7 GPa and 100 GPa respectively. The hardest coatings obtained were obtained at 10% of nitrogen. PMID:20355470

  14. Bioactivity of fluorapatite/alumina composite coatings deposited on Ti6Al4V substrates by laser cladding

    NASA Astrophysics Data System (ADS)

    Chien, C. S.; Liu, C. W.; Kuo, T. Y.; Wu, C. C.; Hong, T. F.

    2016-04-01

    Hydroxyapatite (HA) is one of the most commonly used coating materials for metal implants. However, following high-temperature deposition, HA easily decomposes into an unstable phase or forms an amorphous phase, and hence, the long-term stability of the implant is reduced. Accordingly, the present study investigates the use of fluorapatite (FA) fortified with 20 wt% alumina (α-Al2O3) as an alternative biomedical coating material. The coatings are deposited on Ti6Al4V substrates using a Nd:YAG laser cladding process performed with laser powers and travel speeds of 400 W/200 mm/min, 800 W/400 mm/min and 1200 W/600 mm/min, respectively. The results show that for all of the specimens, a strong metallurgical bond is formed at the interface between the coating layer and the transition layer due to melting and diffusion. The XRD analysis results reveal that the cladding layers in all of the specimens consist mainly of FA, β-TCP, CaF2, Ti and θ-Al2O3 phases. In addition, the cladding layers of the specimens prepared using laser powers of 400 and 800 W also contain CaTiO3 and CaAl2O4, while that of the specimen clad using a power of 1200 W contains TTCP and CaO. Following immersion in simulated body fluid for 14 days, all of the specimens precipitate dense bone-like apatite and exhibit excellent bioactivity. However, among all of the specimens, the specimen that is prepared with a laser power of 800 W shows the best biological activity due to the presence of residual FA, apatite-generating CaTiO3 and a rough cladding layer surface.

  15. Increased Brain Activity May Compensate for Amyloid Pathology in Older Brains

    MedlinePlus

    ... reported the findings online Sept. 14, 2014 in Nature Neuroscience . The work was funded by NIA and ... in older people with brain amyloiddeposition . Nature Neuroscience . Published online Sept. 14, 2014. doi:10. ...

  16. First effects of rising amyloid-β in transgenic mouse brain: synaptic transmission and gene expression

    PubMed Central

    Cummings, Damian M.; Liu, Wenfei; Portelius, Erik; Bayram, Sevinç; Yasvoina, Marina; Ho, Sui-Hin; Smits, Hélène; Ali, Shabinah S.; Steinberg, Rivka; Pegasiou, Chrysia-Maria; James, Owain T.; Matarin, Mar; Richardson, Jill C.; Zetterberg, Henrik; Blennow, Kaj; Hardy, John A.; Salih, Dervis A.

    2015-01-01

    Detecting and treating Alzheimer’s disease, before cognitive deficits occur, has become the health challenge of our time. The earliest known event in Alzheimer’s disease is rising amyloid-β. Previous studies have suggested that effects on synaptic transmission may precede plaque deposition. Here we report how relative levels of different soluble amyloid-β peptides in hippocampus, preceding plaque deposition, relate to synaptic and genomic changes. Immunoprecipitation-mass spectrometry was used to measure the early rise of different amyloid-β peptides in a mouse model of increasing amyloid-β (‘TASTPM’, transgenic for familial Alzheimer’s disease genes APP/PSEN1). In the third postnatal week, several amyloid-β peptides were above the limit of detection, including amyloid-β40, amyloid-β38 and amyloid-β42 with an intensity ratio of 6:3:2, respectively. By 2 months amyloid-β levels had only increased by 50% and although the ratio of the different peptides remained constant, the first changes in synaptic currents, compared to wild-type mice could be detected with patch-clamp recordings. Between 2 and 4 months old, levels of amyloid-β40 rose by ∼7-fold, but amyloid-β42 rose by 25-fold, increasing the amyloid-β42:amyloid-β40 ratio to 1:1. Only at 4 months did plaque deposition become detectable and only in some mice; however, synaptic changes were evident in all hippocampal fields. These changes included increased glutamate release probability (P < 0.001, n = 7–9; consistent with the proposed physiological effect of amyloid-β) and loss of spontaneous action potential-mediated activity in the cornu ammonis 1 (CA1) and dentate gyrus regions of the hippocampus (P < 0.001, n = 7). Hence synaptic changes occur when the amyloid-β levels and amyloid-β42:amyloid-β40 ratio are still low compared to those necessary for plaque deposition. Genome-wide microarray analysis revealed changes in gene expression at 2–4 months including synaptic genes being

  17. First effects of rising amyloid-β in transgenic mouse brain: synaptic transmission and gene expression.

    PubMed

    Cummings, Damian M; Liu, Wenfei; Portelius, Erik; Bayram, Sevinç; Yasvoina, Marina; Ho, Sui-Hin; Smits, Hélène; Ali, Shabinah S; Steinberg, Rivka; Pegasiou, Chrysia-Maria; James, Owain T; Matarin, Mar; Richardson, Jill C; Zetterberg, Henrik; Blennow, Kaj; Hardy, John A; Salih, Dervis A; Edwards, Frances A

    2015-07-01

    Detecting and treating Alzheimer's disease, before cognitive deficits occur, has become the health challenge of our time. The earliest known event in Alzheimer's disease is rising amyloid-β. Previous studies have suggested that effects on synaptic transmission may precede plaque deposition. Here we report how relative levels of different soluble amyloid-β peptides in hippocampus, preceding plaque deposition, relate to synaptic and genomic changes. Immunoprecipitation-mass spectrometry was used to measure the early rise of different amyloid-β peptides in a mouse model of increasing amyloid-β ('TASTPM', transgenic for familial Alzheimer's disease genes APP/PSEN1). In the third postnatal week, several amyloid-β peptides were above the limit of detection, including amyloid-β40, amyloid-β38 and amyloid-β42 with an intensity ratio of 6:3:2, respectively. By 2 months amyloid-β levels had only increased by 50% and although the ratio of the different peptides remained constant, the first changes in synaptic currents, compared to wild-type mice could be detected with patch-clamp recordings. Between 2 and 4 months old, levels of amyloid-β40 rose by ∼7-fold, but amyloid-β42 rose by 25-fold, increasing the amyloid-β42:amyloid-β40 ratio to 1:1. Only at 4 months did plaque deposition become detectable and only in some mice; however, synaptic changes were evident in all hippocampal fields. These changes included increased glutamate release probability (P < 0.001, n = 7-9; consistent with the proposed physiological effect of amyloid-β) and loss of spontaneous action potential-mediated activity in the cornu ammonis 1 (CA1) and dentate gyrus regions of the hippocampus (P < 0.001, n = 7). Hence synaptic changes occur when the amyloid-β levels and amyloid-β42:amyloid-β40 ratio are still low compared to those necessary for plaque deposition. Genome-wide microarray analysis revealed changes in gene expression at 2-4 months including synaptic genes being strongly

  18. Formation and Yield of Multi-Walled Carbon Nanotubes Synthesized via Chemical Vapour Deposition Routes Using Different Metal-Based Catalysts of FeCoNiAl, CoNiAl and FeNiAl-LDH

    PubMed Central

    Hussein, Mohd Zobir; Mohamad Jaafar, Adila; Hj. Yahaya, Asmah; Masarudin, Mas Jaffri; Zainal, Zulkarnain

    2014-01-01

    Multi-walled carbon nanotubes (MWCNTs) were prepared via chemical vapor deposition (CVD) using a series of different catalysts, derived from FeCoNiAl, CoNiAl and FeNiAl layered double hydroxides (LDHs). Catalyst-active particles were obtained by calcination of LDHs at 800 °C for 5 h. Nitrogen and hexane were used as the carrier gas and carbon source respectively, for preparation of MWCNTs using CVD methods at 800 °C. MWCNTs were allowed to grow for 30 min on the catalyst spread on an alumina boat in a quartz tube. The materials were subsequently characterized through X-ray diffraction, Fourier transform infrared spectroscopy, surface area analysis, field emission scanning electron microscopy and transmission electron microscopy. It was determined that size and yield of MWCNTs varied depending on the type of LDH catalyst precursor that is used during synthesis. MWCNTs obtained using CoNiAl-LDH as the catalyst precursor showed smaller diameter and higher yield compared to FeCoNiAl and FeNiAl LDHs. PMID:25380526

  19. Formation and yield of multi-walled carbon nanotubes synthesized via chemical vapour deposition routes using different metal-based catalysts of FeCoNiAl, CoNiAl and FeNiAl-LDH.

    PubMed

    Hussein, Mohd Zobir; Jaafar, Adila Mohamad; Yahaya, Asmah Hj; Masarudin, Mas Jaffri; Zainal, Zulkarnain

    2014-01-01

    Multi-walled carbon nanotubes (MWCNTs) were prepared via chemical vapor deposition (CVD) using a series of different catalysts, derived from FeCoNiAl, CoNiAl and FeNiAl layered double hydroxides (LDHs). Catalyst-active particles were obtained by calcination of LDHs at 800 °C for 5 h. Nitrogen and hexane were used as the carrier gas and carbon source respectively, for preparation of MWCNTs using CVD methods at 800 °C. MWCNTs were allowed to grow for 30 min on the catalyst spread on an alumina boat in a quartz tube. The materials were subsequently characterized through X-ray diffraction, Fourier transform infrared spectroscopy, surface area analysis, field emission scanning electron microscopy and transmission electron microscopy. It was determined that size and yield of MWCNTs varied depending on the type of LDH catalyst precursor that is used during synthesis. MWCNTs obtained using CoNiAl-LDH as the catalyst precursor showed smaller diameter and higher yield compared to FeCoNiAl and FeNiAl LDHs. PMID:25380526

  20. Determination of fracture toughness of calcium phosphate coatings deposited onto Ti6Al4V substrate by using indentation technique

    NASA Astrophysics Data System (ADS)

    Aydin, Ibrahim; Cetinel, Hakan; Pasinli, Ahmet

    2012-09-01

    In this study, fracture toughness values of calcium phosphate (CaP) coatings deposited onto Ti6Al4V substrate were determined by using Vickers indentation method. In this new patent holding method, the activation processes were performed with NaOH and NaOH+H2O2 on the Ti6Al4V material surface. Thicknesses of CaP coatings were measured from cross-sections of the samples by using optical microscopy. Vickers indentation tests were performed by using microhardness tester. Young's modulus values of the coatings were determined by using ultra microhardness tester. As a result, fracture toughness (K1C) values of the CaP coatings produced by using two different activation processes, were calculated by using experimental study results. These were found to be 0.43 MPa m1/2 and 0.39 MPa m1/2, respectively. It was determined that the CaP coating on Ti6Al4V activated by NaOH+H2O2 had higher fracture toughness than the CaP coating on Ti6Al4V activated by NaOH.

  1. Temperature dependence of the crystalline quality of AlN layer grown on sapphire substrates by metalorganic chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Li, Xiao-Hang; Wei, Yong O.; Wang, Shuo; Xie, Hongen; Kao, Tsung-Ting; Satter, Md. Mahbub; Shen, Shyh-Chiang; Douglas Yoder, P.; Detchprohm, Theeradetch; Dupuis, Russell D.; Fischer, Alec M.; Ponce, Fernando A.

    2015-03-01

    We studied temperature dependence of crystalline quality of AlN layers at 1050-1250 °C with a fine increment step of around 18 °C. The AlN layers were grown on c-plane sapphire substrates by metalorganic chemical vapor deposition (MOCVD) and characterized by X-ray diffraction (XRD) ω-scans and atomic force microscopy (AFM). At 1050-1068 °C, the templates exhibited poor quality with surface pits and higher XRD (002) and (102) full-width at half-maximum (FWHM) because of insufficient Al atom mobility. At 1086 °C, the surface became smooth suggesting sufficient Al atom mobility. Above 1086 °C, the (102) FWHM and thus edge dislocation density increased with temperatures which may be attributed to the shorter growth mode transition from three-dimension (3D) to two-dimension (2D). Above 1212 °C, surface macro-steps were formed due to the longer diffusion length of Al atoms than the expected step terrace width. The edge dislocation density increased rapidly above 1212 °C, indicating this temperature may be a threshold above which the impact of the transition from 3D to 2D is more significant. The (002) FWHM and thus screw dislocation density were insensitive to the temperature change. This study suggests that high-quality AlN/sapphire templates may be potentially achieved at temperatures as low as 1086 °C which is accessible by most of the III-nitride MOCVD systems.

  2. Microglial response to amyloid plaques in APPsw transgenic mice.

    PubMed Central

    Frautschy, S. A.; Yang, F.; Irrizarry, M.; Hyman, B.; Saido, T. C.; Hsiao, K.; Cole, G. M.

    1998-01-01

    Microglial activation is central to the inflammatory response in Alzheimer's Disease (AD). A recently described mouse line, Tg(HuAPP695.K670N/M671L)2576, expressing human amyloid precursor protein with a familial AD gene mutation, age-related amyloid deposits, and memory deficits, was found to develop a significant microglial response using Griffonia simplicifolia lectin or phosphotyrosine probe to identify microglia Both Griffonia simplicifolia lectin and phosphotyrosine staining showed increased numbers of intensely labeled, often enlarged microglia clustered in and around plaques, consistent with microglial activation related to beta-amyloid formation. Using quantitative image analysis of coronal phosphotyrosine-immunostained sections, transgene-positive 10- to 16-month-old, hemizygous, hybrid Tg2576 (APPsw) animals showed significantly increased microglial density and size in plaque-forming areas of hippocampus and frontal, entorhinal, and occipital cortex. Quantitative analysis of microglia as a function of distance from the center of plaques (double labeled for A beta peptide and microglia) revealed highly significant, two- to fivefold elevations in microglial number and area within plaques compared with neighboring regions. Tg2576 beta-amyloid-plaque-forming mice should be a useful system for assessing the consequences of the microglial-mediated inflammatory response to beta-amyloid and developing anti-inflammatory therapeutic strategies for Alzheimer's disease. These results provide the first quantitative link between beta-amyloid plaque formation and microglial activation in an animal model with neuritic plaques and memory deficits. Images Figure 1 Figure 2 PMID:9422548

  3. Isotope analysis of diamond-surface passivation effect of high-temperature H2O-grown atomic layer deposition-Al2O3 films

    NASA Astrophysics Data System (ADS)

    Hiraiwa, Atsushi; Saito, Tatsuya; Matsumura, Daisuke; Kawarada, Hiroshi

    2015-06-01

    The Al2O3 film formed using an atomic layer deposition (ALD) method with trimethylaluminum as Al precursor and H2O as oxidant at a high temperature (450 °C) effectively passivates the p-type surface conduction (SC) layer specific to a hydrogen-terminated diamond surface, leading to a successful operation of diamond SC field-effect transistors at 400 °C. In order to investigate this excellent passivation effect, we carried out an isotope analysis using D2O instead of H2O in the ALD and found that the Al2O3 film formed at a conventional temperature (100 °C) incorporates 50 times more CH3 groups than the high-temperature film. This CH3 is supposed to dissociate from the film when heated afterwards at a higher temperature (550 °C) and causes peeling patterns on the H-terminated surface. The high-temperature film is free from this problem and has the largest mass density and dielectric constant among those investigated in this study. The isotope analysis also unveiled a relatively active H-exchange reaction between the diamond H-termination and H2O oxidant during the high-temperature ALD, the SC still being kept intact. This dynamic and yet steady H termination is realized by the suppressed oxidation due to the endothermic reaction with H2O. Additionally, we not only observed the kinetic isotope effect in the form of reduced growth rate of D2O-oxidant ALD but found that the mass density and dielectric constant of D2O-grown Al2O3 films are smaller than those of H2O-grown films. This is a new type of isotope effect, which is not caused by the presence of isotopes in the films unlike the traditional isotope effects that originate from the presence of isotopes itself. Hence, the high-temperature ALD is very effective in forming Al2O3 films as a passivation and/or gate-insulation layer of high-temperature-operation diamond SC devices, and the knowledge of the aforementioned new isotope effect will be a basis for further enhancing ALD technologies in general.

  4. Deposition and Characterization of Al:ZnO Thin Films for Optoelectronic Applications

    NASA Astrophysics Data System (ADS)

    Pandey, R. K.; Mishra, Swati; Bajpai, P. K.

    2016-07-01

    Transparent aluminum-doped zinc oxide (Al:ZnO) thin films have been successfully synthesized on silicon substrates at room temperature using a sol-gel spin-coating method. The structural and optical properties and surface morphology of the synthesized films were characterized using x-ray diffraction (XRD) analysis, ultraviolet-visible (UV-Vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, micro-Raman spectroscopy, and atomic force microscopy (AFM). The prepared Al:ZnO retained the hexagonal wurtzite structure of ZnO. FTIR and Raman spectra clearly revealed a major peak at 437 cm-1, associated with the ZnO bond. UV-Vis spectra showed that the Al:ZnO films were transparent from the near-ultraviolet to near-infrared region. The effect of film thickness on the physical and optical properties of the Al:ZnO thin films for 2.0 at.% aluminum concentration was investigated. Measurements revealed that the film transparency, optical energy bandgap, Urbach energy, extinction coefficient, and porosity varied with the film thickness. The energy bandgap values for the prepared thin films increased in the range of 3.18 eV to 3.2 eV with increasing film thickness.

  5. Seeding-dependent maturation of beta2-microglobulin amyloid fibrils at neutral pH.

    PubMed

    Kihara, Miho; Chatani, Eri; Sakai, Miyo; Hasegawa, Kazuhiro; Naiki, Hironobu; Goto, Yuji

    2005-03-25

    Beta2-microglobulin (beta2-m) is a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Recent studies have focused on the mechanism by which amyloid fibrils are formed under physiological conditions, which had been difficult to reproduce quantitatively. Yamamoto et al. (Yamamoto, S., Hasegawa, K., Yamaguchi, I., Tsutsumi, S., Kardos, J., Goto, Y., Gejyo, F. & Naiki, H. (2004) Biochemistry 43, 11075-11082) showed that a combination of seed fibrils prepared under acidic conditions and a low concentration of sodium dodecyl sulfate below its critical micelle concentration enabled extensive fibril formation at pH 7.0. Here, we found that repeated self-seeding at pH 7.0 with fibrils formed at the same pH causes a marked acceleration of growth, indicating the maturation of fibrils. The observed maturation can be simulated by assuming the existence of two types of fibrils with different growth rates. Importantly, some mutations of beta2-m or the addition of a low concentration of urea, both destabilizing the native conformation, were not enough to extend the fibrils at pH 7.0, and a low concentration of sodium dodecyl sulfate (i.e. 0.5 mM) was essential. Thus, even though the first stage fibrils in patients are unstable and require stabilizing factors to remain at neutral pH, they can adapt to a neutral pH with repeated self-seeding, implying a mechanism of development of amyloid deposition after a long latent period in patients. PMID:15659393

  6. Vancomycin-chitosan composite deposited on post porous hydroxyapatite coated Ti6Al4V implant for drug controlled release.

    PubMed

    Yang, Chi-Chuan; Lin, Chien-Chung; Liao, Jiunn-Wang; Yen, Shiow-Kang

    2013-05-01

    Through the hydrogen bonds and the deprotonation, the vancomycin-chitosan composite has been originally deposited on Ti4Al4V by electrochemical technology. However, the rapid destruction of the hydrogen bonding between them by polar water molecules during immersion tests revealed 80% drug burst in a few hours. In this study, the post porous hydroxyapatite (HA) coated Ti4Al4V is prepared for the subsequent electrolytic deposition of vancomycin-chitosan composite to control the drug release. As expected, the initial burst is reduced to 55%, followed by a steady release about 20% from day 1 to day 5 and a slower release of the retained 25% after day 6, resulting in bacterial inhibition zone diameter of 30 mm which can last for more than a month in antibacterial tests, compared with the coated specimen without HA gradually loosing inhibition zone after 21 days. Besides, the cell culture indicates that the vancomycin-chitosan/HA composite coated has enhanced the proliferation, the differentiation and the mineralization of the osteoblast-like cell. In general, it is helpful for the osteointegration on permanent implants. Consistently, it effectively provides the prophylaxis and therapy of osteomyelitis according to the results of the rabbit infection animal model. PMID:23498249

  7. Amyloid formation in human islets is enhanced by heparin and inhibited by heparinase.

    PubMed

    Potter, K J; Werner, I; Denroche, H C; Montane, J; Plesner, A; Chen, Y; Lei, D; Soukhatcheva, G; Warnock, G L; Oberholzer, J; Fraser, P E; Verchere, C B

    2015-06-01

    Islet transplantation is a promising therapy for patients with diabetes, but its long-term success is limited by many factors, including the formation of islet amyloid deposits. Heparin is employed in clinical islet transplantation to reduce clotting but also promotes fibrillization of amyloidogenic proteins. We hypothesized that heparin treatment of islets during pre-transplant culture may enhance amyloid formation leading to beta cell loss and graft dysfunction. Heparin promoted the fibrillization of human islet amyloid polypeptide (IAPP) and enhanced its toxicity to INS-1 beta cells. Heparin increased amyloid deposition in cultured human islets, but surprisingly decreased islet cell apoptosis. Treatment of human islets with heparin prior to transplantation increased the likelihood of graft failure. Removal of islet heparan sulfate glycosaminoglycans, which localize with islet amyloid deposits in type 2 diabetes, by heparinase treatment decreased amyloid deposition and protected against islet cell death. These findings raise the possibility that pretransplant treatment of human islets with heparin could potentiate IAPP aggregation and amyloid formation and may be detrimental to subsequent graft function. PMID:25833002

  8. Transparent and conductive Al/F and In co-doped ZnO thin films deposited by spray pyrolysis

    NASA Astrophysics Data System (ADS)

    Hadri, A.; Taibi, M.; El hat, A.; Mzerd, A.

    2016-02-01

    In doped ZnO (IZO), In-Al co-doped ZnO (IAZO) and In-F co-doped ZnO (IFZO) were deposited on glass substrates at 350 °C by spray pyrolysis technique. The structural, optical and electrical properties of as-deposited thin films were investigated and compared. A polycrystalline and (002) oriented wurtzite crystal structure was confirmed by X-ray patterns for all films; and the full width at half -maximum (FWHM) of (002) diffraction peak increased after co-doping. The investigation of the optical properties was performed using Uv-vis spectroscopy. The average transmittances of all the films were between 70 and 85%. Hall Effect measurements showed that the electrical conductivity of co-doped films increased as compared with IZO thin film. The highest conductivity of about 16.39 Ω-1 cm-1 was obtained for as-deposited IFZO thin film. In addition, the thin films were annealed at 350 °C for two hour under Ar atmosphere and their optical, electrical properties and the associated photoluminescence (PL) responses of selected films were analysed. After annealing, the electrical conductivity of all thin films was improved and the optical transmittance remained above 70%. Room temperature PL revealed that the annealed IAZO thin film had a strong green emission than that of IZO film.

  9. Effect of pre-deposition RF plasma etching on wafer surface morphology and crystal orientation of piezoelectric AlN thin films.

    PubMed

    Felmetsger, V; Mikhov, M; Laptev, P

    2015-02-01

    In this work, we describe the design and operation of a planarized capacitively coupled RF plasma module and investigate the effects of non-reactive RF plasma etching on Si (100) wafer surface morphology and crystal orientation of Al bottom electrodes and subsequently deposited AlN films. To ensure formation of highly (111) textured Al electrode, a thin 25-nm AlN seed layer was grown before the Al deposition. The seed layer's orientation efficiency improved with increasing the RF power from 70 to 300 W and resulted in narrowing the Al (111) rocking curves. AFM and XRD data have shown that crystal orientations of both the electrode and reactively sputtered AlN film are considerably improved when the substrate micro roughness is reduced from an ordinary level of a few nanometers to atomic level corresponding to root mean square roughness as low as about 0.2 to 0.3 nm. The most perfectly crystallized film stacks of 100-nm Al and 500-nm AlN were obtained in this work using etching in Ar plasma optimized to create an atomically smooth, epi-ready Si surface morphology that enables superior AlN seed layer nucleation conditions. X-ray rocking curves around the Al (111) and AlN (0002) diffraction peaks exhibited extremely low FWHM values of 0.68° and 1.05°, respectively. PMID:25643087

  10. Imaging linear birefringence and dichroism in cerebral amyloid pathologies

    PubMed Central

    Jin, Lee-Way; Claborn, Kacey A.; Kurimoto, Miki; Geday, Morten A.; Maezawa, Izumi; Sohraby, Faranak; Estrada, Marcus; Kaminksy, Werner; Kahr, Bart

    2003-01-01

    New advances in polarized light microscopy were used to image Congo red-stained cerebral amyloidosis in sharp relief. The rotating-polarizer method was used to separate the optical effects of transmission, linear birefringence, extinction, linear dichroism, and orientation of the electric dipole transition moments and to display them as false-color maps. These effects are typically convolved in an ordinary polarized light microscope. In this way, we show that the amyloid deposits in Alzheimer's disease plaques contain structurally disordered centers, providing clues to mechanisms of crystallization of amyloid in vivo. Comparisons are made with plaques from tissues of subjects having Down's syndrome and a prion disease. In plaques characteristic of each disease, the Congo red molecules are oriented radially. The optical orientation in amyloid deposited in blood vessels from subjects having cerebral amyloid angiopathy was 90° out of phase from that in the plaques, suggesting that the fibrils run tangentially with respect to the circumference of the blood vessels. Our result supports an early model in which Congo red molecules are aligned along the long fiber axis and is in contrast to the most recent binding models that are based on computation. This investigation illustrates that the latest methods for the optical analysis of heterogeneous substances are useful for in situ study of amyloid. PMID:14668440

  11. Will PET amyloid imaging lead to overdiagnosis of Alzheimer dementia?

    PubMed

    Dubroff, Jacob G; Nasrallah, Ilya M

    2015-08-01

    Alzheimer disease (AD), a progressive neurodegenerative disease that causes dementia, affects millions of elderly Americans and represents a growing problem with the aging of the population. There has been an increasing effort for improved and earlier diagnosis for AD. Several newly developed radiolabeled compounds targeting β-amyloid plaques, one of the major pathologic biomarkers of AD, have recently become available for clinical use. These radiopharmaceuticals allow for in vivo noninvasive visualization of abnormal β-amyloid deposits in the brain using positron emission tomography (PET). Amyloid PET imaging has demonstrated high sensitivity for pathologic cerebral amyloid deposition in multiple studies. Principal drawbacks to this new diagnostic test are declining specificity in older age groups and uncertain clinical role given lack of disease-modifying therapy for AD. Although there is strong evidence for the utility of amyloid PET in certain situations, detailed in a set of guidelines for appropriate use from the Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging, the question of overdiagnosis, the diagnosis of a disease that would result in neither symptoms nor deaths, using this new medical tool needs to be carefully considered in light of efforts to secure reimbursement for the new technology that is already widely available for use as a clinical tool. PMID:26100192

  12. Silicon diffusion control in atomic-layer-deposited Al2O3/La2O3/Al2O3 gate stacks using an Al2O3 barrier layer.

    PubMed

    Wang, Xing; Liu, Hong-Xia; Fei, Chen-Xi; Yin, Shu-Ying; Fan, Xiao-Jiao

    2015-01-01

    In this study, the physical and electrical characteristics of Al2O3/La2O3/Al2O3/Si stack structures affected by the thickness of an Al2O3 barrier layer between Si substrate and La2O3 layer are investigated after a rapid thermal annealing (RTA) treatment. Time of flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron spectroscopy (XPS) tests indicate that an Al2O3 barrier layer (15 atomic layer deposition (ALD) cycles, approximately 1.5 nm) plays an important role in suppressing the diffusion of silicon atoms from Si substrate into the La2O3 layer during the annealing process. As a result, some properties of La2O3 dielectric degenerated by the diffusion of Si atoms are improved. Electrical measurements (C-V, J-V) show that the thickness of Al2O3 barrier layer can affect the shift of flat band voltage (V FB) and the magnitude of gate leakage current density. PMID:25897303

  13. Impacts of Thermal Atomic Layer-Deposited AlN Passivation Layer on GaN-on-Si High Electron Mobility Transistors.

    PubMed

    Zhao, Sheng-Xun; Liu, Xiao-Yong; Zhang, Lin-Qing; Huang, Hong-Fan; Shi, Jin-Shan; Wang, Peng-Fei

    2016-12-01

    Thermal atomic layer deposition (ALD)-grown AlN passivation layer is applied on AlGaN/GaN-on-Si HEMT, and the impacts on drive current and leakage current are investigated. The thermal ALD-grown 30-nm amorphous AlN results in a suppressed off-state leakage; however, its drive current is unchanged. It was also observed by nano-beam diffraction method that thermal ALD-amorphous AlN layer barely enhanced the polarization. On the other hand, the plasma-enhanced chemical vapor deposition (PECVD)-deposited SiN layer enhanced the polarization and resulted in an improved drive current. The capacitance-voltage (C-V) measurement also indicates that thermal ALD passivation results in a better interface quality compared with the SiN passivation. PMID:26964559

  14. Nucleation of amyloid fibrils

    NASA Astrophysics Data System (ADS)

    Kashchiev, Dimo; Auer, Stefan

    2010-06-01

    We consider nucleation of amyloid fibrils in the case when the process occurs by the mechanism of direct polymerization of practically fully extended protein segments, i.e., β-strands, into β-sheets. Applying the classical nucleation theory, we derive a general expression for the work to form a nanosized amyloid fibril (protofilament) constituted of successively layered β-sheets. Analysis of this expression reveals that with increasing its size, the fibril transforms from one-dimensional to two-dimensional aggregate in order to preserve the equilibrium shape corresponding to minimal formation work. We determine the size of the fibril nucleus, the fibril nucleation work, and the fibril nucleation rate as explicit functions of the concentration and temperature of the protein solution. The results obtained are applicable to homogeneous nucleation, which occurs when the solution is sufficiently pure and/or strongly supersaturated.

  15. Amyloid-β aggregation on model lipid membranes: an atomic force microscopy study.

    PubMed

    Hane, Francis; Drolle, Elizabeth; Gaikwad, Ravi; Faught, Erin; Leonenko, Zoya

    2011-01-01

    Amyloid fibril formation is generally associated with many neurodegenerative disorders, including Alzheimer's disease (AD). Although fibril plaque formation is associated with biological membranes in vivo, the role of the cell surfaces in amyloid fibril formation and the molecular mechanism of amyloid toxicity are not well understood. Understanding the details of amyloid interaction with lipid membrane may shed light on the mechanism of amyloid toxicity. Using atomic force microscopy, we investigated aggregation of amyloid-β1-42 (Aβ1-42) on model phospholipid membranes as a function of time and membrane composition. Neutral, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), anionic - 1,2-dioleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (sodium salt) (DOPG), and cationic - 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), were used to study the effect of lipid type on amyloid binding. We showed that both the charge on the lipid head group and lipid phase affect the interaction of amyloid oligomers with the membrane surface changing the rate of adsorption and causing changes in membrane structure and structure of amyloid deposits. We observed that amyloid aggregates progressively accumulate in a similar manner on the surface of neutral DPPC gel phase membrane and on the surface of fluid phase negatively charged DOPG membrane. In contrast to DPPC and DOPG, positively charged fluid DOTAP membrane and neutral fluid phase DOPC membrane contain amyloid deposits with reduced height, which suggests fusing of Aβ1-42 into the lipid membrane surface. PMID:21694459

  16. Observations of Guinier-Preston zones in an as-deposited Al-1wt.%Si-0.5wt.%Cu thin film

    SciTech Connect

    Tung, C.H.; Chiu, R.L.; Chang, P.H.

    1996-05-01

    Aluminum-copper (Al-Cu) and aluminum-silicon-copper (Al-Si-Cu) films are widely used as interconnects and contacts in contemporary very large scale integration (VLSI) technology. Cu alloying in Al results in the formation of intermetallic Al{sub 2}Cu precipitates, which increase corrosion susceptibility as well as process difficulty. Understanding the formation of Al2Cu theta-phase precipitates within Al alloy thin films is thus of great scientific and technical value. For the first time Guinier-Preston zones are observed by HRTEM to form on Al{l_brace}111{r_brace} planes in an as-deposited Al-1wt%Si-0.5wt%Cu thin films sputtered on oxidized Si substrate. At present time the chemical nature (Si or Cu) of the precipitation in the observed GP zones is still uncertain.

  17. Low substrate temperature deposition of transparent and conducting ZnO:Al thin films by RF magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Waykar, Ravindra; Amit, Pawbake; Kulkarni, Rupali; Jadhavar, Ashok; Funde, Adinath; Waman, Vaishali; Dewan, Rupesh; Pathan, Habib; Jadkar, Sandesh

    2016-04-01

    Transparent and conducting Al-doped ZnO (ZnO:Al) films were prepared on glass substrate using the RF sputtering method at different substrate temperatures from room temperature (RT) to 200 °C. The structural, morphological, electrical and optical properties of these films were investigated using a variety of characterization techniques such as low angle XRD, Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), Hall measurement and UV–visible spectroscopy. The electrical properties showed that films deposited at RT have the lowest resistivity and it increases with an increase in the substrate temperature whereas carrier mobility and concentration decrease with an increase in substrate temperature. Low angle XRD and Raman spectroscopy analysis reavealed that films are highly crystalline with a hexagonal wurtzite structure and a preferred orientation along the c-axis. The FE-SEM analysis showed that the surface morphology of films is strongly dependent on the substrate temperature. The band gap decreases from 3.36 to 3.29 eV as the substrate temperature is increased from RT to 200 °C. The fundamental absorption edge in the UV region shifts towards a longer wavelength with an increase in substrate temperature and be attributed to the Burstein-Moss shift. The synthesized films showed an average transmission (> 85%) in the visible region, which signifies that synthesized ZnO:Al films can be suitable for display devices and solar cells as transparent electrodes.

  18. Monoclonal antibodies to amyloid subunit proteins for in vivo radioimmunodetection of amyloid diseases

    SciTech Connect

    Srivastava, S.C.; Meinken, G.E.; Gorevic, P.; Atkins, H.L.; Fand, I.; Marshall, J.; McNally, W.; Muller, D.; Wood, D.

    1984-01-01

    Amyloid fibrils of systemic amyloidosis are low molecular weight subunit proteins with poor immunogenicity and a tendency to polymerize. Antibodies to these proteins are useful for the detection of amyloid deposits in-situ. The extracellular location of amyloid deposits and proximity to congophilic angiopathy suggest the potential of labeled monocional antibodies (MAb) for in vivo radioimmunodetection. The authors tested feasibility of this approach using two rat MAbs to mouse AA protein in casein-induced amyloidosis, a model system for human secondary amyloidosis. The antibodies were labeled with I-125, I-123, and In-111 with good specificity retention. Amyloidotic mice were pretreated with 50 ..mu..g colchicine ip 3 hr before receiving radioiodinated MAb via the tall vein. Controls included injection of MAb to normal mice and of labeled polyclonal normal rat IgG (pIg) into amyloidotic and control mice. Blood clearance of MAb was faster in amyloidotic than control groups. Fractionation studies showed that both MAb and pIg were uncomplexed. Studies up to 96 hr showed specific and high uptake at sites of amyloid deposition (saline perfused liver, spleen, kidney. Specific localization was confirmed by whole body autoradiography (I-125, 20 ..mu..Ci/animal; 50 ..mu..g MAb) and by external imaging (I-123, 200 ..mu..Ci/animal, 10-15 ..mu..g MAb) of amyloidotic mice studied at 4-72 hr. Amyloidotic animals showed perifollicular localization in spleen, periportal in liver, and glomerular in kidney; scans of controls showed diffuse early washout. These results document the feasibility of using MAbs to fibril subunit proteins for the in vivo detection and therapy of amyloidosis.

  19. Nitride passivation reduces interfacial traps in atomic-layer-deposited Al2O3/GaAs (001) metal-oxide-semiconductor capacitors using atmospheric metal-organic chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Aoki, T.; Fukuhara, N.; Osada, T.; Sazawa, H.; Hata, M.; Inoue, T.

    2014-07-01

    Using an atmospheric metal-organic chemical vapor deposition system, we passivated GaAs with AlN prior to atomic layer deposition of Al2O3. This AlN passivation incorporated nitrogen at the Al2O3/GaAs interface, improving the capacitance-voltage (C-V) characteristics of the resultant metal-oxide-semiconductor capacitors (MOSCAPs). The C-V curves of these devices showed a remarkable reduction in the frequency dispersion of the accumulation capacitance. Using the conductance method at various temperatures, we extracted the interfacial density of states (Dit). The Dit was reduced over the entire GaAs band gap. In particular, these devices exhibited Dit around the midgap of less than 4 × 1012 cm-2eV-1, showing that AlN passivation effectively reduced interfacial traps in the MOS structure.

  20. Targeting vascular amyloid in arterioles of Alzheimer disease transgenic mice with amyloid β protein antibody-coated nanoparticles.

    PubMed

    Poduslo, Joseph F; Hultman, Kristi L; Curran, Geoffry L; Preboske, Gregory M; Chamberlain, Ryan; Marjańska, Małgorzata; Garwood, Michael; Jack, Clifford R; Wengenack, Thomas M

    2011-08-01

    The relevance of cerebral amyloid angiopathy (CAA) to the pathogenesis of Alzheimer disease (AD) and dementia in general emphasizes the importance of developing novel targeting approaches for detecting and treating cerebrovascular amyloid (CVA) deposits. We developed a nanoparticle-based technology that uses a monoclonal antibody against fibrillar human amyloid-β42 that is surface coated onto a functionalized phospholipid monolayer. We demonstrate that this conjugated nanoparticle binds to CVA deposits in arterioles of AD transgenic mice (Tg2576) after infusion into the external carotid artery using 3 different approaches. The first 2 approaches use a blood vessel enrichment of homogenized brain and a leptomeningeal vessel preparation from thin tangential brain slices from the surface of the cerebral cortex. Targeting of CVA by the antibody-coated nanoparticle was visualized using fluorescent lissamine rhodamine-labeled phospholipids in the nanoparticles, which were compared with fluorescent staining of the endothelial cells and amyloid deposits using confocal laser scanning microscopy. The third approach used high-field strength magnetic resonance imaging of antibody-coated iron oxide nanoparticles after infusion into the external carotid artery. Dark foci of contrast enhancement in cortical arterioles were observed in T2*-weighted images of ex vivo AD mouse brains that correlated histologically with CVA deposits. The targeting ability of these nanoparticles to CVA provides opportunities for the prevention and treatment of CAA. PMID:21760540

  1. Are amyloid fibrils molecular spandrels?

    PubMed

    Hane, Francis

    2013-11-15

    Amyloid-β, the protein implicated in Alzheimer's disease, along with a number of other proteins, has been shown to form amyloid fibrils. Fibril forming proteins share no common primary structure and have little known function. Furthermore, all proteins have the ability to form amyloid fibrils under certain conditions as the fibrillar structure lies at the global free energy minimum of proteins. This raises the question of the mechanism of the evolution of the amyloid fibril structure. Experimental evidence supports the hypothesis that the fibril structure is a by-product of the forces of protein folding and lies outside the bounds of evolutionary pressures. PMID:24140343

  2. Amyloids: from Pathogenesis to Function.

    PubMed

    Nizhnikov, A A; Antonets, K S; Inge-Vechtomov, S G

    2015-09-01

    The term "amyloids" refers to fibrillar protein aggregates with cross-β structure. They have been a subject of intense scrutiny since the middle of the previous century. First, this interest is due to association of amyloids with dozens of incurable human diseases called amyloidoses, which affect hundreds of millions of people. However, during the last decade the paradigm of amyloids as pathogens has changed due to an increase in understanding of their role as a specific variant of quaternary protein structure essential for the living cell. Thus, functional amyloids are found in all domains of the living world, and they fulfill a variety of roles ranging from biofilm formation in bacteria to long-term memory regulation in higher eukaryotes. Prions, which are proteins capable of existing under the same conditions in two or more conformations at least one of which having infective properties, also typically have amyloid features. There are weighty reasons to believe that the currently known amyloids are only a minority of their real number. This review provides a retrospective analysis of stages in the development of amyloid biology that during the last decade resulted, on one hand, in reinterpretation of the biological role of amyloids, and on the other hand, in the development of systems biology of amyloids, or amyloidomics. PMID:26555466

  3. Partial Volume Correction in Quantitative Amyloid Imaging

    PubMed Central

    Su, Yi; Blazey, Tyler M.; Snyder, Abraham Z.; Raichle, Marcus E.; Marcus, Daniel S.; Ances, Beau M.; Bateman, Randall J.; Cairns, Nigel J.; Aldea, Patricia; Cash, Lisa; Christensen, Jon J.; Friedrichsen, Karl; Hornbeck, Russ C.; Farrar, Angela M.; Owen, Christopher J.; Mayeux, Richard; Brickman, Adam M.; Klunk, William; Price, Julie C.; Thompson, Paul M.; Ghetti, Bernardino; Saykin, Andrew J.; Sperling, Reisa A.; Johnson, Keith A.; Schofield, Peter R.; Buckles, Virginia; Morris, John C.; Benzinger, Tammie. LS.

    2014-01-01

    Amyloid imaging is a valuable tool for research and diagnosis in dementing disorders. As positron emission tomography (PET) scanners have limited spatial resolution, measured signals are distorted by partial volume effects. Various techniques have been proposed for correcting partial volume effects, but there is no consensus as to whether these techniques are necessary in amyloid imaging, and, if so, how they should be implemented. We evaluated a two-component partial volume correction technique and a regional spread function technique using both simulated and human Pittsburgh compound B (PiB) PET imaging data. Both correction techniques compensated for partial volume effects and yielded improved detection of subtle changes in PiB retention. However, the regional spread function technique was more accurate in application to simulated data. Because PiB retention estimates depend on the correction technique, standardization is necessary to compare results across groups. Partial volume correction has sometimes been avoided because it increases the sensitivity to inaccuracy in image registration and segmentation. However, our results indicate that appropriate PVC may enhance our ability to detect changes in amyloid deposition. PMID:25485714

  4. Partial volume correction in quantitative amyloid imaging.

    PubMed

    Su, Yi; Blazey, Tyler M; Snyder, Abraham Z; Raichle, Marcus E; Marcus, Daniel S; Ances, Beau M; Bateman, Randall J; Cairns, Nigel J; Aldea, Patricia; Cash, Lisa; Christensen, Jon J; Friedrichsen, Karl; Hornbeck, Russ C; Farrar, Angela M; Owen, Christopher J; Mayeux, Richard; Brickman, Adam M; Klunk, William; Price, Julie C; Thompson, Paul M; Ghetti, Bernadino; Saykin, Andrew J; Sperling, Reisa A; Johnson, Keith A; Schofield, Peter R; Buckles, Virginia; Morris, John C; Benzinger, Tammie L S

    2015-02-15

    Amyloid imaging is a valuable tool for research and diagnosis in dementing disorders. As positron emission tomography (PET) scanners have limited spatial resolution, measured signals are distorted by partial volume effects. Various techniques have been proposed for correcting partial volume effects, but there is no consensus as to whether these techniques are necessary in amyloid imaging, and, if so, how they should be implemented. We evaluated a two-component partial volume correction technique and a regional spread function technique using both simulated and human Pittsburgh compound B (PiB) PET imaging data. Both correction techniques compensated for partial volume effects and yielded improved detection of subtle changes in PiB retention. However, the regional spread function technique was more accurate in application to simulated data. Because PiB retention estimates depend on the correction technique, standardization is necessary to compare results across groups. Partial volume correction has sometimes been avoided because it increases the sensitivity to inaccuracy in image registration and segmentation. However, our results indicate that appropriate PVC may enhance our ability to detect changes in amyloid deposition. PMID:25485714

  5. Fibrillar dimer formation of islet amyloid polypeptides

    DOE PAGESBeta

    Chiu, Chi -cheng; de Pablo, Juan J.

    2015-05-08

    Amyloid deposits of human islet amyloid polypeptide (hIAPP), a 37-residue hormone co-produced with insulin, have been implicated in the development of type 2 diabetes. Residues 20 – 29 of hIAPP have been proposed to constitute the amyloidogenic core for the aggregation process, yet the segment is mostly unstructured in the mature fibril, according to solid-state NMR data. Here we use molecular simulations combined with bias-exchange metadynamics to characterize the conformational free energies of hIAPP fibrillar dimer and its derivative, pramlintide. We show that residues 20 – 29 are involved in an intermediate that exhibits transient β-sheets, consistent with recent experimentalmore » and simulation results. By comparing the aggregation of hIAPP and pramlintide, we illustrate the effects of proline residues on inhibition of the dimerization of IAPP. The mechanistic insights presented here could be useful for development of therapeutic inhibitors of hIAPP amyloid formation.« less

  6. Cooperative Hydrogen Bonding in Amyloid Formation.

    SciTech Connect

    Tsemekhman, Kiril L.; Goldschmidt, Lukasz; Eisenberg, Dvaid; Baker, David

    2007-04-01

    The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. Amyloid diseases, including Alzheimer's and prion diseases, are each associated with unbranched protein fibrils. Each fibril is made of a particular protein, yet they share common properties. One such property is nucleation-dependent fibril growth. Monomers of amyloid-forming proteins can remain in dissolved form for long periods, before rapidly assembly into fibrils. The lag before growth has been attributed to slow kinetics of formation of a nucleus, on which other molecules can deposit to form the fibril. We have explored the energetics of fibril formation, based on the known molecular structure of a fibril-forming peptide from the yeast prion, Sup35, using both classical and quantum (density functional theory) methods. We find that the energetics of fibril formation for the first three layers are cooperative using both methods. This cooperativity is consistent with the observation that formation of amyloid fibrils involves slow nucleation and faster growth.

  7. Toward the Molecular Mechanism(s) by which EGCG Treatment Remodels Mature Amyloid Fibrils

    PubMed Central

    Palhano, Fernando L.; Lee, Jiyong; Grimster, Neil P.; Kelly, Jeffery W.

    2013-01-01

    Protein misfolding and/or aggregation has been implicated in several human diseases, such as Alzheimer’s and Parkinson’s diseases and familial amyloid polyneuropathy. These maladies are referred to as amyloid diseases, because they are named after the cross-β-sheet amyloid fibril aggregates or deposits common to these diseases. Epigallocatechin-3-gallate (EGCG), the principal polyphenol present in green tea, has been shown to be effective at preventing aggregation and is able to remodel amyloid fibrils comprising different amyloidogenic proteins, although the mechanistic underpinnings are unclear. Herein, we work towards an understanding of the molecular mechanism(s) by which EGCG remodels mature amyloid fibrils made up of Aβ1–40, IAPP8–24, or Sup35NM7–16. We show that EGCG amyloid remodeling activity in vitro is dependent on auto-oxidation of the EGCG. Oxidized and unoxidized EGCG binds to amyloid fibrils, preventing the binding of thioflavin T. This engagement of the hydrophobic binding sites in Aβ1–40, IAPP8–24, or Sup35NM7–16 amyloid fibrils seems to be sufficient to explain the majority of the amyloid remodeling observed by EGCG treatment, although how EGCG oxidation drives remodeling remains unclear. Oxidized EGCG molecules react with free amines within the amyloid fibril through the formation of Schiff bases, cross-linking the fibrils, which may prevent dissociation and toxicity, but these aberrant post-translational modifications do not appear to be the major driving force for amyloid remodeling by EGCG treatment. These insights into the molecular mechanism of action of EGCG provide boundary conditions for exploring amyloid remodeling in more detail. PMID:23611538

  8. Hydrogen and Carbon Effects on Al2O3 Surface Phases and Metal Deposition

    NASA Astrophysics Data System (ADS)

    Wang, Xiao-Gang; Smith, John

    2005-03-01

    Effects of H and C impurities on α-Al2O3 (0001) surface stability and metal wetting behavior are determined from first principles[1]. The ab initio surface phase diagram for H and C on the alumina surface reveals six distinct surface phases. These different surface phases exhibit a variety of adhesion strengths with Cu and Co, and correspondingly different wetting behaviors. These results are consistent with the varied wetting characteristics observed experimentally. [1] Xiao-Gang Wang and John R. Smith, Phys. Rev. B70, Rapid communications, 081401 (2004).

  9. Characteristics of AZO thin films prepared at various Al target input current deposited on PET substrate

    NASA Astrophysics Data System (ADS)

    Kim, Yun-Hae; Park, Chang-Wook; Lee, Jin-Woo; Lee, Dong Myung

    2015-03-01

    Transparent conductive oxide is a thin film to be used in numerous applications throughout the industry in general. Transparent electrode materials used in these industries are in need of light transmittance with excellent high and low electrical characteristics, substances showing the most excellent physical properties while satisfying all the characteristics such as indium tin oxide film. However, reserves of indium are very small, there is an environmental pollution problem. So the study of zinc oxide (ZnO) is actively carried out in an alternative material. This study analyzed the characteristics by using a direct current (DC) magnetron sputtering system. The electric and optical properties of these films were studied by Hall measurement and optical spectroscopy, respectively. When the Al target input current is 2 mA and 4 mA, it demonstrates about 80% transmittance in the range of the visible spectrum. Also, when Al target input current was 6 mA, sheet resistance was the smallest on PET substrate. The minimum resistivity is 3.96×10-3 ohm/sq.

  10. Low-Temperature Process for Atomic Layer Chemical Vapor Deposition of an Al2O3 Passivation Layer for Organic Photovoltaic Cells.

    PubMed

    Kim, Hoonbae; Lee, Jihye; Sohn, Sunyoung; Jung, Donggeun

    2016-05-01

    Flexible organic photovoltaic (OPV) cells have drawn extensive attention due to their light weight, cost efficiency, portability, and so on. However, OPV cells degrade quickly due to organic damage by water vapor or oxygen penetration when the devices are driven in the atmosphere without a passivation layer. In order to prevent damage due to water vapor or oxygen permeation into the devices, passivation layers have been introduced through methods such as sputtering, plasma enhanced chemical vapor deposition, and atomic layer chemical vapor deposition (ALCVD). In this work, the structural and chemical properties of Al2O3 films, deposited via ALCVD at relatively low temperatures of 109 degrees C, 200 degrees C, and 300 degrees C, are analyzed. In our experiment, trimethylaluminum (TMA) and H2O were used as precursors for Al2O3 film deposition via ALCVD. All of the Al2O3 films showed very smooth, featureless surfaces without notable defects. However, we found that the plastic flexible substrate of an OPV device passivated with 300 degrees C deposition temperature was partially bended and melted, indicating that passivation layers for OPV cells on plastic flexible substrates need to be formed at temperatures lower than 300 degrees C. The OPV cells on plastic flexible substrates were passivated by the Al2O3 film deposited at the temperature of 109 degrees C. Thereafter, the photovoltaic properties of passivated OPV cells were investigated as a function of exposure time under the atmosphere. PMID:27483916

  11. An Alternative Low-Cost Process for Deposition of MCrAlY Bond Coats for Advanced Syngas/Hydrogen Turbine Applications

    SciTech Connect

    Zhang, Ying

    2015-09-11

    The objective of this project was to develop and optimize MCrAlY bond coats for syngas/hydrogen turbine applications using a low-cost electrolytic codeposition process. Prealloyed CrAlY-based powders were codeposited into a metal matrix of Ni, Co or Ni-Co during the electroplating process, and a subsequent post-deposition heat treatment converted it to the MCrAlY coating. Our research efforts focused on: (1) investigation of the effects of electro-codeposition configuration and parameters on the CrAlY particle incorporation in the NiCo-CrAlY composite coatings; (2) development of the post-deposition heat treating procedure; (3) characterization of coating properties and evaluation of coating oxidation performance; (4) exploration of a sulfurfree electroplating solution; (5) cost analysis of the present electrolytic codeposition process. Different electro-codeposition configurations were investigated, and the rotating barrel system demonstrated the capability of depositing NiCo-CrAlY composite coatings uniformly on the entire specimen surface, with the CrAlY particle incorporation in the range 37-42 vol.%. Post-deposition heat treatment at 1000-1200 °C promoted interdiffusion between the CrAlY particles and the Ni-Co metal matrix, resulting in β/γ’/γ or β/γ’ phases in the heat-treated coatings. The results also indicate that the post-deposition heat treatment should be conducted at temperatures ≤1100 °C to minimize Cr evaporation and outward diffusion of Ti. The electro-codeposited NiCrAlY coatings in general showed lower hardness and surface roughness than thermal spray MCrAlY coatings. Coating oxidation performance was evaluated at 1000-1100 °C in dry and wet air environments. The initial electro-codeposited NiCoCrAlY coatings containing relatively high sulfur did not show good oxidation resistance. After modifications of the coating process, the cleaner NiCoCrAlY coating exhibited good oxidation performance at 1000 °C during the 2,000 1-h cyclic

  12. Substrate Heating Effect on c-Axis Texture and Piezoelectric Properties of AlN Thin Films Deposited by Unbalanced Magnetron Sputtering

    NASA Astrophysics Data System (ADS)

    Hasheminiasari, Masood; Lin, Jianliang

    2016-03-01

    Aluminum nitride (AlN) thin films with highly preferred (002) orientations have been reactively deposited by a pulsed-closed field unbalanced magnetron sputtering system using TiN/Ti as the seed/adhesion layer with various substrate temperatures. The texture, orientation and piezoelectric properties of AlN films were characterized by means of x-ray diffraction, rocking curves and laser interferometry. A Michelson laser interferometer was designed and built to obtain the converse piezoelectric response of the deposited AlN thin films. It was found that a slight substrate temperature increase would significantly affect the (002) orientation and the piezoelectric coefficient of AlN thin films compared to the coating obtained with no intentional substrate heating, while higher temperature applications on substrate deteriorated the c-axis texture of the coatings without significant improvement in the piezoelectric response of AlN films.

  13. Relationship between passivation properties and band alignment in O3-based atomic-layer-deposited AlOx on crystalline Si for photovoltaic applications

    NASA Astrophysics Data System (ADS)

    Ikeno, Norihiro; Yamashita, Yoshihiro; Oji, Hiroshi; Miki, Shohei; Arafune, Koji; Yoshida, Haruhiko; Satoh, Shin-ichi; Hirosawa, Ichiro; Chikyow, Toyohiro; Ogura, Atsushi

    2015-08-01

    The passivation properties and band structures in aluminum oxide (AlOx) deposited by ozone-based atomic layer deposition (ALD) at room temperature on p-type crystalline silicon were investigated by X-ray photoelectron spectroscopy (XPS). The effective carrier lifetime depends on the thickness of AlOx films, since the field effects induced in the films by fixed charges depend on film thickness. The fixed charges are different by two orders of magnitude between films with thicknesses of 10 and 30 nm. At the 30-nm-thick AlOx/Si interface, the completely accumulated band bending of the Si surface was observed. On the other hand, a thin depletion layer was formed at the 10-nm-thick AlOx/Si interface. From the time-dependent XPS measurements, a hole trap was observed toward AlOx, in which trapping centers existed.

  14. Substrate Heating Effect on c-Axis Texture and Piezoelectric Properties of AlN Thin Films Deposited by Unbalanced Magnetron Sputtering

    NASA Astrophysics Data System (ADS)

    Hasheminiasari, Masood; Lin, Jianliang

    2016-06-01

    Aluminum nitride (AlN) thin films with highly preferred (002) orientations have been reactively deposited by a pulsed-closed field unbalanced magnetron sputtering system using TiN/Ti as the seed/adhesion layer with various substrate temperatures. The texture, orientation and piezoelectric properties of AlN films were characterized by means of x-ray diffraction, rocking curves and laser interferometry. A Michelson laser interferometer was designed and built to obtain the converse piezoelectric response of the deposited AlN thin films. It was found that a slight substrate temperature increase would significantly affect the (002) orientation and the piezoelectric coefficient of AlN thin films compared to the coating obtained with no intentional substrate heating, while higher temperature applications on substrate deteriorated the c-axis texture of the coatings without significant improvement in the piezoelectric response of AlN films.

  15. Amyloid imaging with PET in early Alzheimer disease diagnosis.

    PubMed

    Rowe, Christopher C; Villemagne, Victor L

    2013-05-01

    In vivo imaging of amyloid-β (Aβ) with positron emission tomography has moved from the research arena into clinical practice. Clinicians working with cognitive decline and dementia must become familiar with its benefits and limitations. Amyloid imaging allows earlier diagnosis of Alzheimer disease and better differential diagnosis of dementia and provides prognostic information for mild cognitive impairment. It also has an increasingly important role in therapeutic trial recruitment and for evaluation of anti-Aβ treatments. Longitudinal observations are required to elucidate the role of Aβ deposition in the course of Alzheimer disease and provide information needed to fully use the prognostic power of this investigation. PMID:23642577

  16. Reaction kinetics during the thermal activation of the silicon surface passivation with atomic layer deposited Al{sub 2}O{sub 3}

    SciTech Connect

    Richter, Armin Benick, Jan; Hermle, Martin; Glunz, Stefan W.

    2014-02-10

    The excellent surface passivation of crystalline silicon provided by Al{sub 2}O{sub 3} requires always an activation by a thermal post-deposition treatment. In this work, we present an indirect study of the reaction kinetics during such thermal activation treatments for Al{sub 2}O{sub 3} synthesized by atomic layer deposition. The study was performed for Al{sub 2}O{sub 3} deposited at varying temperatures, which results in different micro-structures of the films and, in particular, different hydrogen concentrations. The effective carrier lifetime was measured sequentially as a function of the annealing time and temperature. From these data, the reaction rate R{sub act} and the activation energy E{sub A} were extracted. The results revealed a rather constant E{sub A} in the range of 1.4 to 1.5 eV, independent of the deposition temperature. The reaction rate, however, was found to increase with decreasing deposition temperature, which correlates with an increasing amount of hydrogen being incorporated in the Al{sub 2}O{sub 3} films. This is a strong indication for an interface hydrogenation that takes place during the thermal activation, which is limited by the amount of hydrogen provided by the Al{sub 2}O{sub 3} layer.

  17. Effect of concurrent joule heat and charge trapping on RESET for NbAlO fabricated by atomic layer deposition

    PubMed Central

    2013-01-01

    The RESET process of NbAlO-based resistive switching memory devices fabricated by atomic layer deposition is investigated at low temperatures from 80 to 200 K. We observed that the conduction mechanism of high resistance state changed from hopping conduction to Frenkel-Poole conduction with elevated temperature. It is found that the conductive filament rupture in RRAM RESET process can be attributed not only to the Joule heat generated by internal current flow through a filament but also to the charge trap/detrapping effect. The RESET current decreases upon heating. Meanwhile, the energy consumption also decreases exponentially. This phenomenon indicates the temperature-related charge trap/detrapping process which contributes to the RESET besides direct Joule heat. PMID:23421401

  18. Bimodal substrate biasing to control γ-Al{sub 2}O{sub 3} deposition during reactive magnetron sputtering

    SciTech Connect

    Prenzel, Marina; Kortmann, Annika; Stein, Adrian; Keudell, Achim von; Nahif, Farwah; Schneider, Jochen M.

    2013-09-21

    Al{sub 2}O{sub 3} thin films have been deposited at substrate temperatures between 500 °C and 600 °C by reactive magnetron sputtering using an additional arbitrary substra