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| 2. |
- Bale, S. D., et al.
(author)
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The FIELDS Instrument Suite for Solar Probe Plus
- 2016
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In: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 204:1-4, s. 49-82
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Research review (peer-reviewed)abstract
- NASA's Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.
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| 3. |
- De Leoz, M. L. A., et al.
(author)
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NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods
- 2020
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In: Molecular & Cellular Proteomics. - 1535-9476. ; 19:1, s. 11-30
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Journal article (peer-reviewed)abstract
- A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories. Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.
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| 4. |
- Fountoulakis, Konstantinos N., et al.
(author)
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Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia : an international multicenter study
- 2022
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In: CNS Spectrums. - : CAMBRIDGE UNIV PRESS. - 1092-8529 .- 2165-6509. ; 27:6, s. 716-723
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Journal article (peer-reviewed)abstract
- Background The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. Methods Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 +/- 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. Results There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. Discussion Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.
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| 5. |
- Fountoulakis, K.N., et al.
(author)
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Modeling psychological function in patients with schizophrenia with the PANSS : An international multi-center study
- 2021
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In: CNS Spectrums. - : Cambridge University Press. - 1092-8529 .- 2165-6509. ; 26:3, s. 290-298
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Journal article (peer-reviewed)abstract
- Background.The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model.Methods.Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed.Results.The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage.Conclusions.The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct “cores” of schizophrenia, the “Positive” and the “Negative,” while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.
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| 6. |
- Fountoulakis, Konstantinos N., et al.
(author)
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Staging of Schizophrenia With the Use of PANSS : An International Multi-Center Study
- 2019
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In: International Journal of Neuropsychopharmacology. - : Oxford University Press. - 1461-1457 .- 1469-5111. ; 22:11, s. 681-697
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Journal article (peer-reviewed)abstract
- IntroductionA specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method.MethodsTwenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed.ResultsExploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients.DiscussionThis study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.
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| 7. |
- Kaeufl, Hans Ulrich, et al.
(author)
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NEAR : New Earths in the Alpha Cen Region (bringing VISIR as a "visiting instrument" to ESO-VLT-UT4)
- 2018
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In: Ground-Based And Airborne Instrumentation For Astronomy VII. - : SPIE. - 9781510619586
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Conference paper (peer-reviewed)abstract
- ESO in collaboration with the Breakthrough Initiatives, is adding a dedicated coronagraph to the Very Large Telescope mid-IR imager (VISIR) to further boost the high dynamic range imaging capability of this instrument. After the VISIR upgrade in 2012, where coronagraphic masks were first added to VISIR, it became evident that coronagraphy at a ground-based 8m-class telescope, even at wavelengths as long as 10 mu m, critically needs adaptive optics. For VISIR, a work-horse observatory facility instrument in normal operations, this is "easiest" achieved by bringing VISIR as a visiting instrument to the ESO-VLT-UT4 having an adaptive M2. This "visit" enables a meaningful search for Earth-like planets in the habitable zone around both alpha-Cen(1) and alpha-Cen(2). Meaningful here means, achieving a contrast of approximate to 10(-6) within approximate to 0.8 arcsec from the star. Various measures to improve the sensitivity of VISIR will be applied, especially a dedicated filter, faster chopping and a Strehl-ratio close to 100% thanks to extreme adaptive optics. This should allow to detect a planet twice the diameter of Earth in 50 h on source integration time. Key components will be a diffractive coronagraphic mask, the annular groove phase mask (AGPM), optimized for the most sensitive spectral band-pass in the N-band, complemented by a sophisticated apodizer at the level of the Lyot stop. For VISIR noise filtering based on fast chopping is required. A novel internal chopper system will be integrated into the cryostat. This chopper is based on the standard technique from early radio astronomy, conceived by the microwave pioneer Robert Dicke in 1946, which was instrumental for the discovery of the 3K microwave background. For risk mitigation all components are being tested and quali fi ed under realistic conditions in the lab at ESO headquarters before integration into the instrument. The performance or suppression of the coronagraph is so good, that a non-thermal source (vulgo a laser) is needed on the test-bench. We will give an overview of the optical changes to VISIR, the implementation of wave front sensing, the Dicke switch design and laboratory testing, the AGPM design and laboratory testing, non common path error control with a ZELDA mask, sensitivity and contrast estimates, data flow and analysis, the overall project status, plan and outlook Needless to say that this project is of critical interest for future infrared instrumentation at the next generation of extremely large telescopes aiming at surveying the solar neighborhood for terrestrial planets by detecting and characterizing them based on their mid-IR fluxes.
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| 8. |
- Karlsson, Dennis, et al.
(author)
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Structure and Hydrogenation Properties of a HfNbTiVZr High-Entropy Alloy
- 2018
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In: Inorganic Chemistry. - : AMER CHEMICAL SOC. - 0020-1669 .- 1520-510X. ; 57:4, s. 2103-2110
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Journal article (peer-reviewed)abstract
- A high-entropy alloy (HEA) of HfNbTiVZr was synthesized using an arc furnace followed by ball milling. The hydrogen absorption mechanism was studied by in situ X-ray diffraction at different temperatures and by in situ and ex situ neutron diffraction experiments. The body centered cubic (BCC) metal phase undergoes a phase transformation to a body centered tetragonal (BCT) hydride phase with hydrogen occupying both tetrahedral and octahedral interstitial sites in the structure. Hydrogen cycling of the alloy at 500 degrees C is stable. The large lattice strain in the HEA seems favorable for absorption in both octahedral and tetrahedral sites. HEAs therefore have potential as hydrogen storage materials because of favorable absorption in all interstitial sites within the structure.
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| 9. |
- Karlsson, Kasper
(author)
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Counting molecules in cell-free DNA and single cells RNA
- 2016
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Doctoral thesis (other academic/artistic)abstract
- The field of Molecular Biology got started in earnest with the discovery of the molecular structure of DNA. This lead to a surge of interest into the relationships between DNA, RNA and proteins, and to the development of fundamental tools for manipulating those substances, such as cutting, ligating, amplifying, visualizing and size-selecting DNA. With these tools at hand it was possible to begin sequencing DNA, a process that took a leap forward in 2005 with the advent of Next Generation Sequencing (NGS). An inherent problem with NGS is that both the sequencing process and the library preparation introduce errors and biases. The massive amount of data generated by NGS, and the use of NGS in clinical settings, has created a demand for methods that can account for this and thereby making the sequencing data correct and reproducible. Part 1 of this thesis briefly describes the development of Molecular Biology from the discovery of the molecular structure of DNA until today. Part 2 describes the development of error correcting and molecule counting methods, and part 3 describes the results of the papers of the thesis. Paper I introduces the concept of Unique Molecular Identifiers (UMI) for reducing noise in molecular karyotyping and RNA sequencing data. Paper II compares the use of UMIs, a novel amplification-free method, and standard library preparation in Non-Invasive Prenatal Testing (NIPT) of fetal karyotype. Paper III uses the UMI concept together with single-cell tagged reverse transcription (STRT) to examine promoter preference in single cells. Finally paper IV use UMIs combined with PacBio sequencing to examine the full-length transcriptome in single cells.
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| 10. |
- Kasper, M., et al.
(author)
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NEAR: : Low-mass Planets in α Cen with VISIR
- 2017
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In: The Messenger. ; 169, s. 16-20
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Journal article (peer-reviewed)abstract
- ESO, in collaboration with the Breakthrough Initiatives, is working to modify the Very Large Telescope mid-IR imager (VISIR) to greatly enhance its ability to search for potentially habitable planets around both components of the binary Alpha Centauri, part of the closest stellar system to the Earth. Much of the funding for the NEAR (New Earths in the Alpha Cen Region) project is provided by the Breakthrough Initiatives, and ESO mostly provides staff and observing time. The concept combines adaptive optics using the deformable secondary mirror at Unit Telescope 4, a new annular groove phase mask (AGPM) coronagraph optimised for the most sensitive spectral bandpass in the N-band, and a novel internal chopper system for noise filtering based on a concept for longer wavelengths invented by the microwave pioneer Robert Dicke. The NEAR experiment is relevant to the mid-infrared METIS instrument on the Extremely Large Telescope, as the knowledge gained and proof of concept will be transferable.
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| 14. |
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| 15. |
- Mawet, Dimitri, et al.
(author)
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L '-band AGPM vector vortex coronagraph's first light on VLT/NACO Discovery of a late-type companion at two beamwidths from an F0V star
- 2013
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 552, s. L13-
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Journal article (peer-reviewed)abstract
- Context. High contrast imaging has thoroughly combed through the limited search space accessible with first-generation ground-based adaptive optics instruments and the Hubble Space Telescope. Only a few objects were discovered, and many non-detections reported and statistically interpreted. The field is now in need of a technological breakthrough. Aims. Our aim is to open a new search space with first-generation systems such as NACO at the Very Large Telescope, by providing ground-breaking inner working angle (IWA) capabilities in the L' band. The L' band is a sweet spot for high contrast coronagraphy since the planet-to-star brightness ratio is favorable, while the Strehl ratio is naturally higher. Methods. An annular groove phase mask (AGPM) vector vortex coronagraph optimized for the L' band made from diamond subwavelength gratings was manufactured and qualified in the lab. The AGPM enables high contrast imaging at very small IWA, potentially being the key to unexplored discovery space. Results. Here we present the installation and successful on-sky tests of an L'-band AGPM coronagraph on NACO. Using angular differential imaging, which is well suited to the rotational symmetry of the AGPM, we demonstrated a Delta L' > 7.5 mag contrast from an IWA similar or equal to 0 ''.09 onwards, during average seeing conditions, and for total integration times of a few hundred seconds.
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| 17. |
- Neddermeyer, Anne, et al.
(author)
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A new mutant NPM1/IDH2R140- and PML-RARA-associated lncRNA MALNC plays a role in AML biology, prognosis and drug response
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Other publication (other academic/artistic)abstract
- Acute myeloid leukemia (AML) is a hematopoietic malignancy characterized by poor prognosis that requires better understanding of its disease biology and new tools for suitable risk stratification and effective treatments. Long non-coding RNAs (lncRNAs) are involved in numerous molecular mechanisms, are implicated in tumor biology and can serve as clinical biomarkers, yet their role remains mostly unclear in AML. In this study, the aim was to discover and characterize lncRNAs implicated in AML and to describe their role in AML biology. Further aims were to explore their use as prognostic or predictive biomarkers. Using whole-transcriptome analysis, a novel lncRNA, here named MALNC, was identified. MALNC had elevated expression in two large AML cohorts compared to normal CD34+ cells. Clinical correlation analyses indicated that MALNC was almost uniquely expressed in patients with PML-RARA fusion gene and with co-mutated isocitrate dehydrogenase-2 R140 and nucleophosmin-1 (IDH2R140/NPM1). MALNC expression was specifically high at the promyelocytic stage and decreased with maturation in leukemic and normal cells. High MALNC expression associated independently with better overall survival. CRISPR-Cas9-knockout in promyelocytic cell lines impaired proliferation, colony formation and all-trans retinoic acid (ATRA)-induced differentiation. Also, MALNC-knockout dramatically sensitized cells to arsenic trioxide (ATO), ATO-ATRA combinatorial and Bcl-2-inhibitor venetoclax treatment as well as associated with cyclin-dependent kinase (Cdk)-inhibitor resistance. In conclusion, MALNC is overexpressed in certain subgroups of AML and could play a role during normal and leukemic hematopoietic maturation. Furthermore, it correlates with response to anti-leukemic drugs, which suggests a role as a predictive marker to drug response and survival in AML.
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| 18. |
- Palkopoulou, Eleftheria, et al.
(author)
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A comprehensive genomic history of extinct and living elephants
- 2018
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In: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 115:11, s. E2566-E2574
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Journal article (peer-reviewed)abstract
- Elephantids are the world's most iconic megafaunal family, yet there is no comprehensive genomic assessment of their relationships. We report a total of 14 genomes, including 2 from the American mastodon, which is an extinct elephantid relative, and 12 spanning all three extant and three extinct elephantid species including an similar to 120,000-y-old straight-tusked elephant, a Columbian mammoth, and woolly mammoths. Earlier genetic studies modeled elephantid evolution via simple bifurcating trees, but here we show that interspecies hybridization has been a recurrent feature of elephantid evolution. We found that the genetic makeup of the straight-tusked elephant, previously placed as a sister group to African forest elephants based on lower coverage data, in fact comprises three major components. Most of the straight-tusked elephant's ancestry derives from a lineage related to the ancestor of African elephants while its remaining ancestry consists of a large contribution from a lineage related to forest elephants and another related to mammoths. Columbian and woolly mammoths also showed evidence of interbreeding, likely following a latitudinal cline across North America. While hybridization events have shaped elephantid history in profound ways, isolation also appears to have played an important role. Our data reveal nearly complete isolation between the ancestors of the African forest and savanna elephants for similar to 500,000 y, providing compelling justification for the conservation of forest and savanna elephants as separate species.
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| 19. |
- Qu, Ying, et al.
(author)
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Cancer specific changes in DNA methylation reveal aberrant silencing and activation of enhancers in leukemia
- 2017
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 129:7, s. e13-e25
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Journal article (peer-reviewed)abstract
- Acute myeloid leukemia (AML) is characterized by an impaired differentiation process leading to an accumulation of immature blasts in the blood. One feature of cytogenetically normal AML is alterations to the DNA methylome. Here we have analyzed 57 AML patients with normal karyotype using Illuminas 450 k array and show that aberrant DNA methylation is significantly altered at enhancer regions and that the methylation levels at specific enhancers predict overall survival of AML patients. The majority of sites that become differentially methylated in AML occur in regulatory elements of the human genome. Hypermethylation associates with enhancer silencing. In addition, ChIP-seq analyses showed that a subset of hypomethylated sites correlate with enhancer activation, indicated by increased H3K27 acetylation. DNA hypomethylation is not therefore sufficient for enhancer activation. Some sites of hypomethylation occur at weak / poised enhancers marked with H3K4 monomethylation in hematopoietic progenitor cells. Other hypomethylated regions occur at sites inactive in progenitors and reflect the de novo acquisition of AML specific enhancers. Altered enhancer dynamics are reflected in the gene expression of enhancer target genes including genes involved in oncogenesis and blood cell development. This study demonstrates that histone variants and different histone modifications interact with aberrant DNA methylation, causing perturbed enhancer activity in CN-AML that contributes to a leukemic transcriptome.
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| 20. |
- Rydin, Emil, et al.
(author)
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Contrasting distribution and speciation of sedimentary organic phosphorus among different basins of the Baltic Sea
- 2023
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In: Limnology and Oceanography. - : John Wiley & Sons. - 0024-3590 .- 1939-5590. ; 68:4, s. 767-779
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Journal article (peer-reviewed)abstract
- Recycling of phosphorus (P) from deoxygenated sediments perpetuates eutrophic conditions in parts of the Baltic Sea. Sedimentary organic P is a major source of dissolved P to the water column, but also a sink for permanent P burial. The mechanisms behind these two pathways are, however, largely unknown. Using new methods, we determined P in DNA and phospholipids, which are both found in all organisms. We also identified inositol phosphates that are particularly important in eukaryotes. Sediment cores were collected from contrasting basins in the Baltic Sea to study their relative contribution to the total P pool. We found high DNA-P/phospholipid-P ratios in surface sediments from the Bothnian Bay and Bothnian Sea. However, these ratios were low throughout profiles in euxinic Baltic Proper sediments. The elevated ratios present in sediments overlain by oxic bottom waters might indicate the presence of a microbial community stimulated by bioturbation, whereas the low DNA-P/phospholipid-P ratios in Baltic Proper sediments likely indicate an energy-limited microbial community, typical to the "deep biosphere" environment. Inositol-P was almost absent in euxinic Baltic Proper sediments that had a low total P amount compared to those in the other basins. We suggest that variability in the composition of sedimentary microbial communities among the Baltic Sea basins might cause differences in organic P forms that in turn affects its turnover.
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| 21. |
- Wagner, Kevin, et al.
(author)
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Imaging low-mass planets within the habitable zone of α Centauri
- 2021
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Giant exoplanets on wide orbits have been directly imaged around young stars. If the thermal background in the mid-infrared can be mitigated, then exoplanets with lower masses can also be imaged. Here we present a ground-based mid-infrared observing approach that enables imaging low-mass temperate exoplanets around nearby stars, and in particular within the closest stellar system, alpha Centauri. Based on 75-80% of the best quality images from 100h of cumulative observations, we demonstrate sensitivity to warm sub-Neptune-sized planets throughout much of the habitable zone of alpha Centauri A. This is an order of magnitude more sensitive than state-of-the-art exoplanet imaging mass detection limits. We also discuss a possible exoplanet or exozodiacal disk detection around alpha Centauri A. However, an instrumental artifact of unknown origin cannot be ruled out. These results demonstrate the feasibility of imaging rocky habitable-zone exoplanets with current and upcoming telescopes. Imaging of low-mass exoplanets can be achieved once the thermal background in the mid-infrared (MIR) wavelengths can be mitigated. Here, the authors present a ground-based MIR observing approach enabling imaging low-mass temperate exoplanets around nearby stars.
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