1. |
- Sweeney, M. D., et al.
(author)
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Vascular dysfunction-The disregarded partner of Alzheimer's disease
- 2019
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:1, s. 158-167
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Journal article (peer-reviewed)abstract
- Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts. (C) 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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2. |
- Hoenigl, M., et al.
(author)
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Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study
- 2023
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In: Lancet. Infectious Diseases. - : Elsevier BV. - 1473-3099 .- 1474-4457. ; 23:6, s. 751-761
-
Journal article (peer-reviewed)abstract
- Background The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes.Methods In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines.Findings 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1 & BULL;08 [95% CI 1 & BULL;04-1 & BULL;11; p<0 & BULL;0001] in patients with a central venous catheter and 1 & BULL;09 [1 & BULL;05-1 & BULL;13; p<0 & BULL;0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment with other antifungals.Interpretation Although overall mortality in patients with candidaemia was high, our study indicates that adherence to clinical guideline recommendations, reflected by higher EQUAL Candida scores, might increase survival. New antifungals, with similar activity as current echinocandins but with longer half-lives or oral bioavailability, are needed to reduce duration of hospital stay.
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5. |
- Wang, T, et al.
(author)
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Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4932-
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Journal article (peer-reviewed)abstract
- Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case–control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E−06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E−07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype–genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.
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8. |
- Ossenkoppele, R., et al.
(author)
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Tau PET patterns mirror clinical and neuroanatomical variability in Alzheimer's disease
- 2016
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 139, s. 1551-1567
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Journal article (peer-reviewed)abstract
- The PET tracer [F-18]-AV-1451 allows visualization of tau pathology in living subjects. Ossenkoppele et al. employ the tracer in patients with distinct Alzheimer's disease variants to investigate correlates of tau deposition. Pathological aggregation of tau, but not amyloid-beta, is linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.See Sarazin et al. (doi:10.1093/brain/aww041) for a scientific commentary on this article. The PET tracer [F-18]-AV-1451 allows visualization of tau pathology in living subjects. Ossenkoppele et al. employ the tracer in patients with distinct Alzheimer's disease variants to investigate correlates of tau deposition. Pathological aggregation of tau, but not amyloid-beta, is linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.The advent of the positron emission tomography tracer F-18-AV1451 provides the unique opportunity to visualize the regional distribution of tau pathology in the living human brain. In this study, we tested the hypothesis that tau pathology is closely linked to symptomatology and patterns of glucose hypometabolism in Alzheimer's disease, in contrast to the more diffuse distribution of amyloid-beta pathology. We included 20 patients meeting criteria for probable Alzheimer's disease dementia or mild cognitive impairment due to Alzheimer's disease, presenting with a variety of clinical phenotypes, and 15 amyloid-beta-negative cognitively normal individuals, who underwent F-18-AV1451 (tau), C-11-PiB (amyloid-beta) and F-18-FDG (glucose metabolism) positron emission tomography, apolipoprotein E (APOE) genotyping and neuropsychological testing. Voxel-wise contrasts against controls (at P < 0.05 family-wise error corrected) showed that F-18-AV1451 and F-18-FDG patterns in patients with posterior cortical atrophy ('visual variant of Alzheimer's disease', n = 7) specifically targeted the clinically affected posterior brain regions, while C-11-PiB bound diffusely throughout the neocortex. Patients with an amnestic-predominant presentation (n = 5) showed highest F-18-AV1451 retention in medial temporal and lateral temporoparietal regions. Patients with logopenic variant primary progressive aphasia ('language variant of Alzheimer's disease', n = 5) demonstrated asymmetric left greater than right hemisphere F-18-AV1451 uptake in three of five patients. Across 30 FreeSurfer-defined regions of interest in 16 Alzheimer's disease patients with all three positron emission tomography scans available, there was a strong negative association between F-18-AV1451 and F-18-FDG uptake (Pearson's r = -0.49 +/- 0.07, P < 0.001) and less pronounced positive associations between C-11-PiB and F-18-FDG (Pearson's r = 0.16 +/- 0.09, P < 0.001) and F-18-AV1451 and C-11-PiB (Pearson's r = 0.18 +/- 0.09, P < 0.001). Voxel-wise linear regressions thresholded at P < 0.05 (uncorrected) showed that, across all patients, younger age was associated with greater F-18-AV1451 uptake in wide regions of the neocortex, while older age was associated with increased F-18-AV1451 in the medial temporal lobe. APOE I mu 4 carriers showed greater temporal and parietal F-18-AV1451 uptake than non-carriers. Finally, worse performance on domain-specific neuropsychological tests was associated with greater F-18-AV1451 uptake in key regions implicated in memory (medial temporal lobes), visuospatial function (occipital, right temporoparietal cortex) and language (left > right temporoparietal cortex). In conclusion, tau imaging-contrary to amyloid-beta imaging-shows a strong regional association with clinical and anatomical heterogeneity in Alzheimer's disease. Although preliminary, these results are consistent with and expand upon findings from post-mortem, animal and cerebrospinal fluid studies, and suggest that the pathological aggregation of tau is closely linked to patterns of neurodegeneration and clinical manifestations of Alzheimer's disease.
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9. |
- Mattsson, Niklas, 1979, et al.
(author)
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Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
- 2012
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In: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 409-17
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
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13. |
- Ginsburg, Adam, et al.
(author)
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astroquery: An Astronomical Web-querying Package in Python
- 2019
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In: Astronomical Journal. - : American Astronomical Society. - 1538-3881 .- 0004-6256. ; 157:3
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Journal article (peer-reviewed)abstract
- Astroquery is a collection of tools for requesting data from databases hosted on remote servers with interfaces exposed on the Internet, including those with web pages but without formal application program interfaces. These tools are built on the Python requests package, which is used to make HTTP requests, and astropy, which provides most of the data parsing functionality. astroquery modules generally attempt to replicate the web page interface provided by a given service as closely as possible, making the transition from browser-based to command-line interaction easy. astroquery has received significant contributions from throughout the astronomical community, including several from telescope archives. astroquery enables the creation of fully reproducible workflows from data acquisition through publication. This paper describes the philosophy, basic structure, and development model of the astroquery package. The complete documentation for astroquery can be found at http://astroquery.readthedocs.io/.
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17. |
- Lockhart, K. E., et al.
(author)
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A Slowly Precessing Disk in the Nucleus of M31 as the Feeding Mechanism for a Central Starburst
- 2018
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 854:2
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Journal article (peer-reviewed)abstract
- We present a kinematic study of the nuclear stellar disk in M31 at infrared wavelengths using high spatial resolution integral field spectroscopy. The spatial resolution achieved, FWHM = 0.'' 12 (0.45 pc at the distance of M31), has only previously been equaled in spectroscopic studies by space-based long-slit observations. Using adaptive optics-corrected integral field spectroscopy from the OSIRIS instrument at the W. M. Keck Observatory, we map the line-of-sight kinematics over the entire old stellar eccentric disk orbiting the supermassive black hole (SMBH) at a distance of r<4 pc. The peak velocity dispersion is 381 +/- 55 km/s(-1), offset by 0.'' 13 +/- 0.'' 03 from the SMBH, consistent with previous high-resolution long-slit observations. There is a lack of near-infrared (NIR) emission at the position of the SMBH and young nuclear cluster, suggesting a spatial separation between the young and old stellar populations within the nucleus. We compare the observed kinematics with dynamical models from Peiris & Tremaine (2003). The best-fit disk orientation to the NIR flux is [theta(l), theta(i), theta(a)] = [-33 +/- 4 degrees, 44 +/- 2 degrees, -15 +/- 15 degrees}], which is tilted with respect to both the larger-scale galactic disk and the best-fit orientation derived from optical observations. The precession rate of the old disk is Omega(P) = 0.0 +/- 3.9 km/s(-1)pc(-1), lower than the majority of previous observations. This slow precession rate suggests that stellar winds from the disk will collide and shock, driving rapid gas inflows and fueling an episodic central starburst as suggested in Chang et al.
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19. |
- Bacchus, E., et al.
(author)
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Project 1640 observations of the white dwarf HD 114174 B
- 2017
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In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 469:4, s. 4796-4805
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Journal article (peer-reviewed)abstract
- We present the first near infrared spectrum of the faint white dwarf companion HD 114174 B, obtained with Project 1640. Our spectrum, covering the Y, J and H bands, combined with previous TaRgetting bENchmark-objects with Doppler Spectroscopy (TRENDS) photometry measurements, allows us to place further constraints on this companion. We suggest two possible scenarios; either this object is an old, low-mass, cool H atmosphere white dwarf with T-eff similar to 3800 K or a high-mass white dwarf with T-eff > 6000 K, potentially with an associated cool (T-eff similar to 700 K) brown dwarf or debris disc resulting in an infrared excess in the L' band. We also provide an additional astrometry point for 2014 June 12 and use the modelled companion mass combined with the radial velocity and direct imaging data to place constraints on the orbital parameters for this companion.
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20. |
- Brailo, V., et al.
(author)
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World Workshop on Oral Medicine VI: Utilization of Oral Medicine-specific software for support of clinical care, research, and education: current status and strategy for broader implementation
- 2015
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In: Oral Surgery Oral Medicine Oral Pathology Oral Radiology. - : Elsevier BV. - 2212-4403. ; 120:2, s. 172-184
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Journal article (peer-reviewed)abstract
- Objectives. To assess the current scope and status of Oral Medicine-specific software (OMSS) utilized to support clinical care, research, and education in Oral Medicine and to propose a strategy for broader implementation of OMSS within the global Oral Medicine community. Study Design. An invitation letter explaining the objectives was sent to the global Oral Medicine community. Respondents were interviewed to obtain information about different aspects of OMSS functionality. Results. Ten OMSS tools were identified. Four were being used for clinical care, one was being used for research, two were being used for education, and three were multipurpose. Clinical software was being utilized as databases developed to integrate of different type of clinical information. Research software was designed to facilitate multicenter research. Educational software represented interactive, case-orientated technology designed for clinical training in Oral Medicine. Easy access to patient data was the most commonly reported advantage. Difficulty of use and poor integration with other software was the most commonly reported disadvantage. Conclusions. The OMSS presented in this paper demonstrate how information technology (IT) can have an impact on the quality of patient care, research, and education in the field of Oral Medicine. A strategy for broader implementation of OMSS is proposed.
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22. |
- Follert, R., et al.
(author)
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CRIRES plus : a cross-dispersed high-resolution infrared spectrograph for the ESO VLT
- 2014
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
-
Conference paper (peer-reviewed)abstract
- High-resolution infrared spectroscopy plays an important role in astrophysics from the search for exoplanets to cosmology. Yet, many existing infrared spectrographs are limited by a rather small simultaneous wavelength coverage. The AO assisted CRIRES instrument, installed at the ESO VLT on Paranal, is one of the few IR (0.92-5.2 mu m) high-resolution spectrographs in operation since 2006. However it has a limitation that hampers its efficient use: the wavelength range covered in a single exposure is limited to similar to 15 nanometers. The CRIRES Upgrade project (CRIRES+) will transform CRIRES into a cross-dispersed spectrograph and will also add new capabilities. By introducing cross-dispersion elements the simultaneously covered wavelength range will be increased by at least a factor of 10 with respect to the present configuration, while the operational wavelength range will be preserved. For advanced wavelength calibration, new custom made absorption gas cells and etalons will be added. A spectro-polarimetric unit will allow one for the first time to record circularly polarized spectra at the highest spectral resolution. This will be all supported by a new data reduction software which will allow the community to take full advantage of the new capabilities of CRIRES+.
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23. |
- Gill, Dipender, et al.
(author)
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ACE inhibition and cardiometabolic risk factors, lung ACE2 and TMPRSS2 gene expression, and plasma ACE2 levels : a Mendelian randomization study
- 2020
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In: Royal Society Open Science. - : ROYAL SOC. - 2054-5703. ; 7:11
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Journal article (peer-reviewed)abstract
- Angiotensin-converting enzyme 2 (ACE2) and serine protease TMPRSS2 have been implicated in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). The expression of ACE2 and TMPRSS2 in the lung epithelium might have implications for the risk of SARS-CoV-2 infection and severity of COVID-19. We use human genetic variants that proxy angiotensin-converting enzyme (ACE) inhibitor drug effects and cardiovascular risk factors to investigate whether these exposures affect lung ACE2 and TMPRSS2 gene expression and circulating ACE2 levels. We observed no consistent evidence of an association of genetically predicted serum ACE levels with any of our outcomes. There was weak evidence for an association of genetically predicted serum ACE levels with ACE2 gene expression in the Lung eQTL Consortium (p = 0.014), but this finding did not replicate. There was evidence of a positive association of genetic liability to type 2 diabetes mellitus with lung ACE2 gene expression in the Gene-Tissue Expression (GTEx) study (p = 4 x 10(-4)) and with circulating plasma ACE2 levels in the INTERVAL study (p = 0.03), but not with lung ACE2 expression in the Lung eQTL Consortium study (p = 0.68). There were no associations of genetically proxied liability to the other cardiometabolic traits with any outcome. This study does not provide consistent evidence to support an effect of serum ACE levels (as a proxy for ACE inhibitors) or cardiometabolic risk factors on lung ACE2 and TMPRSS2 expression or plasma ACE2 levels.
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25. |
- Gronqvist, Raoul, et al.
(author)
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Human-centred approaches in slipperiness measurement
- 2001
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In: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 44:13, s. 1167-1199
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Journal article (peer-reviewed)abstract
- A number of human-centred methodologies-subjective, objective, and combined-are used for slipperiness measurement. They comprise a variety of approaches from biomechanically-oriented experiments to psychophysical tests and subjective evaluations. The objective of this paper is to review some of the research done in the field, including such topics as awareness and perception of slipperiness, postural and balance control, rating scales for balance, adaptation to slippery conditions, measurement of unexpected movements, kinematics of slipping, and protective movements during falling. The role of human factors in slips and falls will be discussed. Strengths and weaknesses of human-centred approaches in relation to mechanical slip test methodologies are considered. Current friction-based criteria and thresholds for walking without slipping are reviewed for a number of work tasks. These include activities such as walking on a level or an inclined surface, running, stopping and jumping, as well as stair ascent and descent, manual exertion (pushing and pulling, load carrying, lifting) and particular concerns of the elderly and mobility disabled persons. Some future directions for slipperiness measurement and research in the field of slips and falls are outlined. Human-centred approaches for slipperiness measurement do have many applications. First, they are utilized to develop research hypotheses and models to predict workplace risks caused by slipping. Second, they are important alternatives to apparatus-based friction measurements and are used to validate such methodologies. Third, they are used as practical tools for evaluating and monitoring slip resistance properties of footwear, anti-skid devices and floor surfaces.
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27. |
- Lockhart de la Rosa, César Javier, 1987, et al.
(author)
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Frame assisted H2O electrolysis induced H2 bubbling transfer of large area graphene grown by chemical vapor deposition on Cu
- 2013
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 102:2
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Journal article (peer-reviewed)abstract
- An improved technique for transferring large area graphene grown by chemical vapor deposition on copper is presented. It is based on mechanical separation of the graphene/copper by H-2 bubbles during H2O electrolysis, which only takes a few tens of seconds while leaving the copper cathode intact. A semi-rigid plastic frame in combination with thin polymer layer span on graphene gives a convenient way of handling-and avoiding wrinkles and holes in graphene. Optical and electrical characterizations prove the graphene quality is better than that obtained by traditional wet etching transfer. This technique appears to be highly reproducible and cost efficient.
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28. |
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29. |
- Oliva, E., et al.
(author)
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Concept and optical design of the cross-disperser module for CRIRES
- 2014
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
-
Conference paper (peer-reviewed)abstract
- CRIRES, the ESO high resolution infrared spectrometer, is a unique instrument which allows astronomers to access a parameter space which up to now was largely uncharted. In its current setup, it consists of a single-order spectrograph providing long-slit, single-order spectroscopy with resolving power up to R=100,000 over a quite narrow spectral range. This has resulted in sub-optimal efficiency and use of telescope time for all the scientific programs requiring broad spectral coverage of compact objects (e.g. chemical abundances of stars and intergalactic medium, search and characterization of extra-solar planets). To overcome these limitations, a consortium was set-up for upgrading CRIRES to a cross-dispersed spectrometer, called CRIRES+. This paper presents the updated optical design of the cross-dispersion module for CRIRES+. This new module can be mounted in place of the current pre-disperser unit. The new system yields a factor of >10 increase in simultaneous spectral coverage and maintains a quite long slit (10"), ideal for observations of extended sources and for precise sky-background subtraction.
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30. |
- Schöll, Michael, 1980, et al.
(author)
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PET Imaging of Tau Deposition in the Aging Human Brain
- 2016
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In: Neuron. - : Elsevier BV. - 0896-6273. ; 89:5, s. 971-982
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Journal article (peer-reviewed)abstract
- Tau pathology is a hallmark of Alzheimer's disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent F-18-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and beta-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical b-amyloid and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and beta-amyloid deposition.
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31. |
- Seemann, U., et al.
(author)
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Wavelength calibration from 1-5 mu m for the CRIRES plus high-resolution spectrograph at the VLT
- 2014
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY V. - : SPIE. - 9780819496157
-
Conference paper (peer-reviewed)abstract
- CRIRES at the VLT is one of the few adaptive optics enabled instruments that offer a resolving power of 10 5 from 1 - 5 mu m. An instrument upgrade (CRIRES+) is proposed to implement cross-dispersion capabilities, spectro-polarimetry modes, a new detector mosaic, and a new gas absorption cell. CRIRES+ will boost the simultaneous wavelength coverage of the current instrument (similar to lambda/70 in a single-order) by a factor of greater than or similar to 10 in the cross-dispersed configuration, while still retaining a 10 arcsec slit suitable for long-slit spectroscopy. CRIRES+ dramatically enhances the instrument's observing efficiency, and opens new scientific opportunities. These include high-precision radial-velocity studies on the 3m/s level to characterize extra-solar planets and their athmospheres, which demand for specialized, highly accurate wavelength calibration techniques. In this paper, we present a newly developed absorption gas-cell to enable high-precision wavelength calibration for CRIRES+. We also discuss the strategies and developments to cover the full operational spectral range (1-5 mu m), employing hollow-cathode emission lamps, Fabry-Perot etalons, and absorption gas-cells.
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