| 1. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 2. |
- Kruse, N., et al.
(författare)
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Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study
- 2015
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 36:9, s. 2587-2596
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Tidskriftsartikel (refereegranskat)abstract
- Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program -Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given. (C) 2015 Elsevier Inc. All rights reserved.
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| 3. |
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| 6. |
- Abdelnour, C., et al.
(författare)
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Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia
- 2016
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 31:8, s. 1203-1208
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionAlzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. MethodsFrom a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. ResultsThe Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. ConclusionsReduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. (c) 2016 International Parkinson and Movement Disorder Society
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| 7. |
- Abdelnour, C, et al.
(författare)
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Erratum
- 2019
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Ingår i: Movement disorders : official journal of the Movement Disorder Society. - : Wiley. - 1531-8257. ; 34:4, s. 593-593
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Tidskriftsartikel (refereegranskat)
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| 8. |
- Gottlob, H. D. B., et al.
(författare)
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Gentle FUSI NiSi metal gate process for high-k dielectric screening
- 2008
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 85:10, s. 2019-2021
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, a process flow well suited for screening of novel high-k dielectrics is presented. In vacuo silicon capping of the dielectrics excludes process and handling induced influences especially if hygroscopic materials are investigated. A gentle, low thermal budget process is demonstrated to form metal gate electrodes by turning the silicon capping into a fully silicided nickel silicide. This process enables the investigation of rare earth oxide based high-k dielectrics and specifically their intrinsic material properties using metal oxide semiconductor (MOS) capacitors. We demonstrate the formation of nickel monosilicide electrodes which show smooth interfaces to the lanthanum- and gadolinium-based high-k oxide films. The dielectrics have equivalent oxide thicknesses of EOT = 0.95 nm (lanthanum silicate) and EOT = 0.6 nm (epitaxial gadolinium oxide).
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| 12. |
- Lerche, S, et al.
(författare)
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Methods in Neuroepidemiology Characterization of European Longitudinal Cohort Studies in Parkinson's Disease--Report of the JPND Working Group BioLoC-PD
- 2015
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 45:4, s. 282-297
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Enormous effort is being put into the identification and characterization of symptoms that may be used as predictive and progression markers in Parkinson's disease (PD). An impressive number of PD patients and individuals at risk for or in the prodromal stage of PD are currently followed in longitudinal studies; however, there does not exist an overview on the kind of markers evaluated and the assessments used. <b><i>Methods:</i></b> Information on the design, sample size, evaluated markers and assessments of 21 studies of the Joint Programme - Neurodegenerative Disease Research BioLoC-PD working group were collected by questionnaire. The studies were classified into at risk/prodromal or clinical PD cohorts. The assessments were grouped into quantitative assessments, investigator-rated assessments, investigator interviews, patient-rated questionnaires and caregiver-rated questionnaires. <b><i>Results:</i></b> Compilation of these data revealed an interesting consensus on evaluated markers, but there was an enormous variability of assessments. Furthermore, there is a remarkable similarity in the markers assessed and evaluation methods applied in the risk/prodromal and clinical PD cohorts. <b><i>Conclusions:</i></b> The inventory of the longitudinal cohorts that are part of the BioLoC-PD consortium reveals that there is a growing consensus on the markers that should be assessed in longitudinal cohort studies in PD. However, controversy still exists on the specific type of assessment. To allow comparison of data and common analyses it will be essential to harmonize scales and assessment outcomes.
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| 13. |
- Luk, C., et al.
(författare)
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Development and assessment of sensitive immuno-PCR assays for the quantification of cerebrospinal fluid three- and four-repeat tau isoforms in tauopathies
- 2012
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; 123:3, s. 396-405
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Tidskriftsartikel (refereegranskat)abstract
- Characteristic tau isoform composition of the insoluble fibrillar tau inclusions define tauopathies, including Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and frontotemporal dementia with parkinsonism linked to chromosome 17/frontotemporal lobar degeneration-tau (FTDP-17/FTLD-tau). Exon 10 splicing mutations in the tau gene, MAPT, in familial FTDP-17 cause elevation of tau isoforms with four microtubule-binding repeat domains (4R-tau) compared to those with three repeats (3R-tau). On the basis of two well-characterised monoclonal antibodies against 3R- and 4R-tau, we developed novel, sensitive immuno-PCR assays for measuring the trace amounts of these isoforms in CSF. This was with the aim of assessing if CSF tau isoform changes reflect the pathological changes in tau isoform homeostasis in the degenerative brain and if these would be relevant for differential clinical diagnosis. Initial analysis of clinical CSF samples of PSP (n = 46), corticobasal syndrome (CBS; n = 22), AD (n = 11), Parkinson's disease with dementia (PDD; n = 16) and 35 controls revealed selective decreases of immunoreactive 4R-tau in CSF of PSP and AD patients compared with controls, and lower 4R-tau levels in AD compared with PDD. These decreases could be related to the disease-specific conformational masking of the RD4-binding epitope because of abnormal folding and/or aggregation of the 4R-tau isoforms in tauopathies or increased sequestration of the 4R-tau isoforms in brain tau pathology.
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| 14. |
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| 15. |
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| 16. |
- Miller, A. M., et al.
(författare)
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Multicenter immunoassay validation of cerebrospinal fluid neurofilament light: a biomarker for neurodegeneration
- 2016
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Ingår i: Bioanalysis. - : Future Science Ltd. - 1757-6180 .- 1757-6199. ; 8:21, s. 2243-2254
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Neurofilament light (NfL) chain, a putative cerebrospinal fluid biomarker, can support neurodegenerative disease diagnosis and indicate disease severity and prognosis. Universal validation protocols when used to measure biomarkers can reduce pre and analytical laboratory variation, thus increasing end-user confidence in the consistency of validation data across sites. Methodology: Here, a commercially available NfL ELISA (UmanDiagnostics, Ume dagger, Sweden) was validated in a multicentered setting using comprehensive newly developed standard operating procedures. Results: The data showed good assay sensitivity and intra and interassay precision. Interlaboratory precision was, however, suboptimal. Conclusion: The UmanDiagnostics assay is suitable for the quantification of NfL in human cerebrospinal fluid. However, sources of interlaboratory variation in the data require further investigation.
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| 17. |
- Mollenhauer, B., et al.
(författare)
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Validation of Serum Neurofilament Light Chain as a Biomarker of Parkinson's Disease Progression
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 35:11, s. 1999-2008
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Tidskriftsartikel (refereegranskat)abstract
- Background The objective of this study was to assess neurofilament light chain as a Parkinson's disease biomarker. Methods We quantified neurofilament light chain in 2 independent cohorts: (1) longitudinal cerebrospinal fluid samples from the longitudinal de novo Parkinson's disease cohort and (2) a large longitudinal cohort with serum samples from Parkinson's disease, other cognate/neurodegenerative disorders, healthy controls, prodromal conditions, and mutation carriers. Results In the Parkinson's Progression Marker Initiative cohort, mean baseline serum neurofilament light chain was higher in Parkinson's disease patients (13 +/- 7.2 pg/mL) than in controls (12 +/- 6.7 pg/mL),P= 0.0336. Serum neurofilament light chain increased longitudinally in Parkinson's disease patients versus controls (P< 0.01). Motor scores were positively associated with neurofilament light chain, whereas some cognitive scores showed a negative association. Conclusions Neurofilament light chain in serum samples is increased in Parkinson's disease patients versus healthy controls, increases over time and with age, and correlates with clinical measures of Parkinson's disease severity. Although the specificity of neurofilament light chain for Parkinson's disease is low, it is the first blood-based biomarker candidate that could support disease stratification of Parkinson's disease versus other cognate/neurodegenerative disorders, track clinical progression, and possibly assess responsiveness to neuroprotective treatments. However, use of neurofilament light chain as a biomarker of response to neuroprotective interventions remains to be assessed. (c) 2020 The Authors.Movement Disorderspublished by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.
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| 18. |
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| 19. |
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| 20. |
- Diaz-Lucena, D., et al.
(författare)
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TREM2 expression in the brain and biological fluids in prion diseases
- 2021
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 141, s. 841-859
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Tidskriftsartikel (refereegranskat)abstract
- Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78-0.90) and neurological controls (AUC = 0.73-0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer's disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring.
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| 21. |
- Echtermeyer, T., et al.
(författare)
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Investigation of MOS capacitors and SOI-MOSFETs with epitaxial gadolinium oxide (Gd2O3) and titanium nitride (TiN) electrodes
- 2007
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Ingår i: Solid-State Electronics. - : Elsevier BV. - 0038-1101 .- 1879-2405. ; 51:4, s. 617-621
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Tidskriftsartikel (refereegranskat)abstract
- Electrical properties of metal oxide semiconductor (MOS) capacitors with gate stacks of epitaxial gadolinium oxide (Gd2O3) and titanium nitride (TiN) are studied. The influence of CMOS compatible rapid thermal annealing on these gate stacks is examined. Finally, n- and p-type MOS-field effect transistors (MOSFETs) on silicon on insulator (SOI) material with epitaxial Gd2O3 and TiN gate electrodes are presented.
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| 22. |
- Efavi, J K, et al.
(författare)
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Investigation of NiAlN as gate-material for submicron CMOS technology
- 2004
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 76:1-4, s. 354-359
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Tidskriftsartikel (refereegranskat)abstract
- Nickel-Aluminium-Nitride (NiAlN) is investigated as gate material for submicron CMOS technology for the first time. The MAIN films have been reactively sputtered from a Ni0.5Al0.5 target in a mixture of argon and nitrogen gas. The influence of the reactive gas content and process temperatures on the work function is presented. Electrical properties are extracted from high and low frequency capacitance-voltage measurements (QSCV, HFCV). Resistivity measurements are shown for various process conditions. Interface properties are observed by transmission electron microscopy. Primarily results show NiAlN's suitability for use as gate material in a CMOS replacement gate technology. Fabrication of n-type metal-oxide-semiconductor field effect transistors with a MAIN gates activated at 900 degreesC is demonstrated.
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| 23. |
- Efavi, J K, et al.
(författare)
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Tungsten work function engineering for dual metal gate nano-CMOS
- 2005
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Ingår i: Journal of materials science. Materials in electronics. - : Springer Science and Business Media LLC. - 0957-4522 .- 1573-482X. ; 16:7, s. 433-436
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Tidskriftsartikel (refereegranskat)abstract
- A buffer layer technology for work function engineering of tungsten for dual metal gate Nano-CMOS is investigated. For the first time, tungsten is used as a p-type gate material using 1 nm of sputtered Aluminum Nitride (AlNx) as a buffer layer on silicon dioxide (SiO2) gate dielectric. A tungsten work function of 5.12 eV is realized using this technology in contrast to a mid-gap value of 4.6 eV without a buffer layer. Device characteristics of a p-MOSFET on silicon-on-insulator (SOI) substrate fabricated with this technology are presented.
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| 24. |
- Fuchs, A., et al.
(författare)
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Nanowire fin field effect transistors via UV-based nanoimprint lithography
- 2006
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Ingår i: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567. ; 24:6, s. 2964-2967
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Tidskriftsartikel (refereegranskat)abstract
- A triple step alignment process for UV nanoimprint lithography (UV-NIL) for the fabrication of nanoscale fin field effect transistors (FinFETs) is presented. An alignment accuracy is demonstrated between two functional layers of less than 20 nm (3 sigma). The electrical characterization of the FinFETs fabricated by a full NIL process demonstrates the potential of UV-NIL for future nanoelectronic devices.
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| 25. |
- Gottlob, H. D. B., et al.
(författare)
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0.86-nm CET gate stacks with epitaxial Gd2O3 high-k dielectrics and FUSINiSi metal electrodes
- 2006
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Ingår i: IEEE Electron Device Letters. - 0741-3106 .- 1558-0563. ; 27:10, s. 814-816
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Tidskriftsartikel (refereegranskat)abstract
- In this letter, ultrathin gadolinium oxide (Gd2O3) high-kappa gate dielectrics with complementary-metal-oxide-semiconductor (CMOS)-compatible fully silicided nickel-silicide metal gate electrodes are reported for the first time. MOS capacitors with a Gd2O3 thickness of 3.1 nm yield a capacitance equivalent oxide thickness of CET = 0.86 nm. The extracted dielectric constant is kappa =-13-14. Leakage currents and equivalent oxide thicknesses of this novel gate stack meet the International Technology Roadmap for Semiconductors targets for the near term schedule and beyond.
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