Publications by authors named "Peter Werner"

83 Publications

Novel Symmetrical Cage Compounds as Inhibitors of the Symmetrical MRP4-Efflux Pump for Anticancer Therapy.

Int J Mol Sci 2021 May 12;22(10). Epub 2021 May 12.

Research Group of Drug Development, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.

Within the last decades cancer treatment improved by the availability of more specifically acting drugs that address molecular target structures in cancer cells. However, those target-sensitive drugs suffer from ongoing resistances resulting from mutations and moreover they are affected by the cancer phenomenon of multidrug resistance. A multidrug resistant cancer can hardly be treated with the common drugs, so that there have been long efforts to develop drugs to combat that resistance. Transmembrane efflux pumps are the main cause of the multidrug resistance in cancer. Early inhibitors disappointed in cancer treatment without a proof of expression of a respective efflux pump. Recent studies in efflux pump expressing cancer show convincing effects of those inhibitors. Based on the molecular symmetry of the efflux pump multidrug resistant protein (MRP) 4 we synthesized symmetric inhibitors with varied substitution patterns. They were evaluated in a MRP4-overexpressing cancer cell line model to prove structure-dependent effects on the inhibition of the efflux pump activity in an uptake assay of a fluorescent MRP4 substrate. The most active compound was tested to resentisize the MRP4-overexpressing cell line towards a clinically relevant anticancer drug as proof-of-principle to encourage for further preclinical studies.
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http://dx.doi.org/10.3390/ijms22105098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150856PMC
May 2021

Tunable Magnetic Antiskyrmion Size and Helical Period from Nanometers to Micrometers in a D Heusler Compound.

Adv Mater 2020 Jul 2;32(28):e2002043. Epub 2020 Jun 2.

Max Planck Institute of Microstructure Physics, Weinberg 2, Halle (Saale), D-06120, Germany.

Skyrmions and antiskyrmions are magnetic nano-objects with distinct chiral, noncollinear spin textures that are found in various magnetic systems with crystal symmetries that give rise to specific Dzyaloshinskii-Moriya exchange vectors. These magnetic nano-objects are associated with closely related helical spin textures that can form in the same material. The skyrmion size and the period of the helix are generally considered as being determined, in large part, by the ratio of the magnitude of the Heisenberg to that of the Dzyaloshinskii-Moriya exchange interaction. In this work, it is shown by real-space magnetic imaging that the helix period λ and the size of the antiskyrmion d in the D compound Mn PtSn can be systematically tuned by more than an order of magnitude from ≈100 nm to more than 1.1 µm by varying the thickness of the lamella in which they are observed. The chiral spin texture is verified to be preserved even up to micrometer-thick layers. This extreme size tunability is shown to arise from long-range magnetodipolar interactions, which typically play a much less important role for B20 skyrmions. This tunability in size makes antiskyrmions very attractive for technological applications.
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http://dx.doi.org/10.1002/adma.202002043DOI Listing
July 2020

Characterisation of barley landraces from Syria and Jordan for resistance to rhynchosporium and identification of diagnostic markers for Rrs1.

Theor Appl Genet 2020 Apr 22;133(4):1243-1264. Epub 2020 Jan 22.

The James Hutton Institute, Invergowrie, Dundee, DD2 5DA, Scotland, UK.

Key Message: Diagnostic markers for Rrs1 have been identified by testing for associations between SNPs within the Rrs1 interval in 150 barley genotypes and their resistance to Rhynchosporium commune isolates recognised by lines containing Rrs1. Rhynchosporium or barley scald, caused by the destructive fungal pathogen Rhynchosporium commune, is one of the most economically important diseases of barley in the world. Barley landraces from Syria and Jordan demonstrated high resistance to rhynchosporium in the field. Genotyping of a wide range of barley cultivars and landraces, including known sources of different Rrs1 genes/alleles, across the Rrs1 interval, followed by association analysis of this genotypic data with resistance phenotypes to R. commune isolates recognised by Rrs1, allowed the identification of diagnostic markers for Rrs1. These markers are specific to Rrs1 and do not detect other Rrs1 genes/alleles. The Rrs1 diagnostic markers represent a resource that can be exploited by breeders for the sustainable deployment of varietal resistance in new cultivars. Thirteen out of the 55 most resistant Syrian and Jordanian landraces were shown to contain markers specific to Rrs1. One of these lines came from Jordan, with the remaining 12 lines from different locations in Syria. One of the Syrian landraces containing Rrs1 was also shown to have Rrs2. The remaining landraces that performed well against rhynchosporium in the field are likely to contain other resistance genes and represent an important novel resource yet to be exploited by European breeders.
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http://dx.doi.org/10.1007/s00122-020-03545-9DOI Listing
April 2020

Observation of Magnetic Antiskyrmions in the Low Magnetization Ferrimagnet MnRhIrSn.

Nano Lett 2020 Jan 13;20(1):59-65. Epub 2019 Dec 13.

Max Planck Institute of Microstructure Physics , Weinberg 2 , 06120 Halle (Saale) , Germany.

Recently, magnetic antiskyrmions were discovered in MnPtPdSn, an inverse tetragonal Heusler compound that is nominally a ferrimagnet, but which can only be formed with substantial Mn vacancies. The vacancies reduce considerably the compensation of the moments between the two expected antiferromagnetically coupled Mn sub-lattices so that the overall magnetization is very high and the compound is almost a "ferromagnet". Here, we report the observation of antiskyrmions in a second inverse tetragonal Heusler compound, MnRhIrSn, which can be formed stoichiometrically without any Mn vacancies and which thus exhibits a much smaller magnetization. Individual and lattices of antiskyrmions can be stabilized over a wide range of temperature from near room temperature to 100 K, the base temperature of the Lorentz transmission electron microscope used to image them. In low magnetic fields helical spin textures are found which evolve into antiskyrmion structures in the presence of small magnetic fields. A weaker Dzyaloshinskii-Moriya interaction (DMI), that stabilizes the antiskyrmions, is expected for the 4d element Rh as compared to the 5d element Pt, so that the observation of antiskyrmions in MnRhIrSn establishes the intrinsic stability of antiskyrmions in these Heusler compounds. Moreover, the finding of antiskyrmions with substantially lower magnetization promises, via chemical tuning, even zero moment antiskyrmions with important technological import.
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http://dx.doi.org/10.1021/acs.nanolett.9b02973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953472PMC
January 2020

Intrinsic stability of magnetic anti-skyrmions in the tetragonal inverse Heusler compound MnPtPdSn.

Nat Commun 2019 11 22;10(1):5305. Epub 2019 Nov 22.

Max Planck Institute of Microstructure Physics, Weinberg 2, 06120, Halle (Saale), Germany.

Magnetic anti-skyrmions are one of several chiral spin textures that are of great current interest both for their topological characteristics and potential spintronic applications. Anti-skyrmions were recently observed in the inverse tetragonal Heusler material MnPtPdSn. Here we show, using Lorentz transmission electron microscopy, that anti-skyrmions are found over a wide range of temperature and magnetic fields in wedged lamellae formed from single crystals of MnPtPdSn for thicknesses ranging up to ~250 nm. The temperature-field stability window of the anti-skyrmions varies little with thickness. Using micromagnetic simulations we show that this intrinsic stability of anti-skyrmions can be accounted for by the symmetry of the crystal lattice which is imposed on that of the Dzyaloshinskii-Moriya exchange interaction. These distinctive behaviors of anti-skyrmions makes them particularly attractive for spintronic applications.
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http://dx.doi.org/10.1038/s41467-019-13323-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874587PMC
November 2019

Extremely high conductivity observed in the triple point topological metal MoP.

Nat Commun 2019 06 6;10(1):2475. Epub 2019 Jun 6.

Max Planck Institute for Chemical Physics of Solids, 01187, Dresden, Germany.

Weyl and Dirac fermions have created much attention in condensed matter physics and materials science. Recently, several additional distinct types of fermions have been predicted. Here, we report ultra-high electrical conductivity in MoP at low temperature, which has recently been established as a triple point fermion material. We show that the electrical resistivity is 6 nΩ cm at 2 K with a large mean free path of 11 microns. de Haas-van Alphen oscillations reveal spin splitting of the Fermi surfaces. In contrast to noble metals with similar conductivity and number of carriers, the magnetoresistance in MoP does not saturate up to 9 T at 2 K. Interestingly, the momentum relaxing time of the electrons is found to be more than 15 times larger than the quantum coherence time. This difference between the scattering scales shows that momentum conserving scattering dominates in MoP at low temperatures.
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http://dx.doi.org/10.1038/s41467-019-10126-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554310PMC
June 2019

Exome sequences and multi-environment field trials elucidate the genetic basis of adaptation in barley.

Plant J 2019 09 27;99(6):1172-1191. Epub 2019 Jun 27.

Biometris, Wageningen University and Research Centre, PO Box 16, 6700 AC, Wageningen, The Netherlands.

Broadening the genetic base of crops is crucial for developing varieties to respond to global agricultural challenges such as climate change. Here, we analysed a diverse panel of 371 domesticated lines of the model crop barley to explore the genetics of crop adaptation. We first collected exome sequence data and phenotypes of key life history traits from contrasting multi-environment common garden trials. Then we applied refined statistical methods, including some based on exomic haplotype states, for genotype-by-environment (G×E) modelling. Sub-populations defined from exomic profiles were coincident with barley's biology, geography and history, and explained a high proportion of trial phenotypic variance. Clear G×E interactions indicated adaptation profiles that varied for landraces and cultivars. Exploration of circadian clock-related genes, associated with the environmentally adaptive days to heading trait (crucial for the crop's spread from the Fertile Crescent), illustrated complexities in G×E effect directions, and the importance of latitudinally based genic context in the expression of large-effect alleles. Our analysis supports a gene-level scientific understanding of crop adaption and leads to practical opportunities for crop improvement, allowing the prioritisation of genomic regions and particular sets of lines for breeding efforts seeking to cope with climate change and other stresses.
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http://dx.doi.org/10.1111/tpj.14414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851764PMC
September 2019

A hydrated crystalline calcium carbonate phase: Calcium carbonate hemihydrate.

Science 2019 01;363(6425):396-400

Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.

As one of the most abundant materials in the world, calcium carbonate, CaCO, is the main constituent of the skeletons and shells of various marine organisms. It is used in the cement industry and plays a crucial role in the global carbon cycle and formation of sedimentary rocks. For more than a century, only three polymorphs of pure CaCO-calcite, aragonite, and vaterite-were known to exist at ambient conditions, as well as two hydrated crystal phases, monohydrocalcite (CaCO·1HO) and ikaite (CaCO·6HO). While investigating the role of magnesium ions in crystallization pathways of amorphous calcium carbonate, we unexpectedly discovered an unknown crystalline phase, hemihydrate CaCO·½HO, with monoclinic structure. This discovery may have important implications in biomineralization, geology, and industrial processes based on hydration of CaCO.
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http://dx.doi.org/10.1126/science.aav0210DOI Listing
January 2019

Electric Field Control of Phase Transition and Tunable Resistive Switching in SrFeO.

ACS Appl Mater Interfaces 2019 Feb 1;11(6):6581-6588. Epub 2019 Feb 1.

Key Laboratory of Advanced Materials (MOE), School of Materials Science and Engineering , Tsinghua University , Beijing 100084 , China.

SrFeO (SFO ) compounds exhibit ionic conduction and oxygen-related phase transformation, having potential applications in solid oxide fuel cells, smart windows, and memristive devices. The phase transformation in SFO typically requires a thermal annealing process under various pressure conditions, hindering their practical applications. Here, we have achieved a reversible phase transition from brownmillerite (BM) to perovskite (PV) in SrFeO (SFO) films through ionic liquid (IL) gating. The real-time phase transformation is imaged using in situ high-resolution transmission electron microscopy. The magnetic transition in SFO is identified by fabricating an assisted LaSrMnO (LSMO) bottom layer. The IL-gating-converted PV phase of a SrFeO (SFO) layer shows a ferromagnetic-like behavior but applies a huge pinning effect on LSMO magnetic moments, which consequently leads to a prominent exchange bias phenomenon, suggesting an uncompensated helical magnetic structure of SFO. On the other hand, the suppression of both magnetic and exchange coupling signals for a BM-phased SFO layer elucidates its fully compensated G-type antiferromagnetic nature. We also demonstrated that the phase transition by IL gating is an effective pathway to tune the resistive switching parameters, such as set, reset, and high/low-resistance ratio in SFO-based resistive random-access memory devices.
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http://dx.doi.org/10.1021/acsami.8b18251DOI Listing
February 2019

Direct imaging of structural changes induced by ionic liquid gating leading to engineered three-dimensional meso-structures.

Nat Commun 2018 08 3;9(1):3055. Epub 2018 Aug 3.

Max Planck Institute for Microstructure Physics, Halle, 06120, Germany.

The controlled transformation of materials, both their structure and their physical properties, is key to many devices. Ionic liquid gating can induce the transformation of thin-film materials over long distances from the gated surface. Thus, the mechanism underlying this process is of considerable interest. Here we directly image, using in situ, real-time, high-resolution transmission electron microscopy, the reversible transformation between the oxygen vacancy ordered phase brownmillerite SrCoO and the oxygen ordered phase perovskite SrCoO. We show that the phase transformation boundary moves at a velocity that is highly anisotropic, traveling at speeds ~30 times faster laterally than through the thickness of the film. Taking advantage of this anisotropy, we show that three-dimensional metallic structures such as cylinders and rings can be realized. Our results provide a roadmap to the construction of complex meso-structures from their exterior surfaces.
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http://dx.doi.org/10.1038/s41467-018-05330-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076294PMC
August 2018

Dissecting the complex regulation of lodging resistance in .

Mol Breed 2018 21;38(3):30. Epub 2018 Feb 21.

1John Innes Centre, Norwich Research Park, Norwich, NR4 7UH UK.

Lodging continues to be a major cause of yield loss in important crop species such as Understanding the genetic regulation of lodging resistance is therefore of key interest to breeders worldwide. Current strategies aimed at minimising lodging risk involve the incorporation of dwarfing genes or the application of plant growth regulators. However, despite these efforts, lodging continues to be a persistent problem and it is therefore of high interest that novel, complimentary strategies for lodging control are implemented. One approach would be to focus on understanding the genetic properties underlying stem mechanical strength. With this in mind, we screened a training genetic diversity panel of . accession for variation in stem mechanical strength and related traits. Using Associative Transcriptomics, we identified molecular markers for a suite of valuable traits. Using an independent test genetic diversity panel, we show that the methods employed are robust for identification of predictive markers. Furthermore, based on conserved synteny with , we are able to provide a biological context to the marker associations detected and provide evidence for a role in pectin methylesterification in contributing to stem mechanical strength in
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http://dx.doi.org/10.1007/s11032-018-0781-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842258PMC
February 2018

Magnetic antiskyrmions above room temperature in tetragonal Heusler materials.

Nature 2017 08 23;548(7669):561-566. Epub 2017 Aug 23.

Max Planck Institute of Microstructure Physics, Weinberg 2, 06120 Halle, Germany.

Magnetic skyrmions are topologically stable, vortex-like objects surrounded by chiral boundaries that separate a region of reversed magnetization from the surrounding magnetized material. They are closely related to nanoscopic chiral magnetic domain walls, which could be used as memory and logic elements for conventional and neuromorphic computing applications that go beyond Moore's law. Of particular interest is 'racetrack memory', which is composed of vertical magnetic nanowires, each accommodating of the order of 100 domain walls, and that shows promise as a solid state, non-volatile memory with exceptional capacity and performance. Its performance is derived from the very high speeds (up to one kilometre per second) at which chiral domain walls can be moved with nanosecond current pulses in synthetic antiferromagnet racetracks. Because skyrmions are essentially composed of a pair of chiral domain walls closed in on themselves, but are, in principle, more stable to perturbations than the component domain walls themselves, they are attractive for use in spintronic applications, notably racetrack memory. Stabilization of skyrmions has generally been achieved in systems with broken inversion symmetry, in which the asymmetric Dzyaloshinskii-Moriya interaction modifies the uniform magnetic state to a swirling state. Depending on the crystal symmetry, two distinct types of skyrmions have been observed experimentally, namely, Bloch and Néel skyrmions. Here we present the experimental manifestation of another type of skyrmion-the magnetic antiskyrmion-in acentric tetragonal Heusler compounds with D crystal symmetry. Antiskyrmions are characterized by boundary walls that have alternating Bloch and Néel type as one traces around the boundary. A spiral magnetic ground-state, which propagates in the tetragonal basal plane, is transformed into an antiskyrmion lattice state under magnetic fields applied along the tetragonal axis over a wide range of temperatures. Direct imaging by Lorentz transmission electron microscopy shows field-stabilized antiskyrmion lattices and isolated antiskyrmions from 100 kelvin to well beyond room temperature, and zero-field metastable antiskyrmions at low temperatures. These results enlarge the family of magnetic skyrmions and pave the way to the engineering of complex bespoke designed skyrmionic structures.
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http://dx.doi.org/10.1038/nature23466DOI Listing
August 2017

Organic crystal lattices in the axial filament of silica spicules of Demospongiae.

J Struct Biol 2017 06 18;198(3):186-195. Epub 2017 Mar 18.

Institut für Chemie - Institute of Anorganic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120 Halle (Saale), Germany.

The skeletal system of Demospongiae consists of siliceous spicules, which are composed of an axial channel containing an organic axial filament (AF) surrounded by a compact layer of hydrated amorphous silica. Here we report the ultrastructural investigations of the AF of siliceous spicules from two Demospongiae: Suberites domuncula and Tethya aurantium. Electron microscopy, electron diffraction and elemental mapping analyses on both longitudinal and transversal cross-sections yield that spicules's AF consist of a three-dimensional crystal lattice of six-fold symmetry. Its structure, which is the result of a biological growth process, is a crystalline assembly characterized by a lattice of organic cages (periodicity in the range of 6nm) filled with enzymatically-produced silica. In general, the six-fold lattice symmetry is reflected by the morphology of the AF, which is characterized by six-fold facets. This seems to be the result of a lattice energy minimization process similar to the situation found during the growth of inorganic crystals. Our structural exploitation of three-dimensional organic lattices generated by biological systems is expected to contribute for explaining the relation between axial filament's ultrastructure and spicule's ultimate morphology.
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http://dx.doi.org/10.1016/j.jsb.2017.03.005DOI Listing
June 2017

Feasibility of in vivo F-florbetaben PET/MR imaging of human carotid amyloid-β.

Eur J Nucl Med Mol Imaging 2017 Jul 21;44(7):1119-1128. Epub 2017 Mar 21.

Department of Nuclear Medicine, Leipzig University Medical Centre, Leipzig, Germany.

Purpose: Amyloid-beta (Aβ) peptides are involved in the inflammatory pathology of atherosclerosis. F-Florbetaben is a PET tracer for clinical imaging of cerebral Aβ plaques in Alzheimer's disease (AD). We sought to determine whether specific uptake of F-florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors.

Methods: Carotid F-florbetaben uptake was quantified as the mean of the maximum target-to-background ratio (TBR) in 40 cognitively impaired subjects (age 68.2 ± 9.5 years) undergoing F-florbetaben PET/MRI to diagnose AD. Associations between carotid F-florbetaben uptake and several CVD risk factors were assessed by univariate analysis followed by a multivariate linear regression analysis. Furthermore, carotid F-florbetaben uptake was compared between patients with and without a positive cerebral Aβ PET scan.

Results: F-Florbetaben uptake was clearly visualized in the carotid arteries. Values of TBR corrected for the blood pool activity of the tracer showed specific F-florbetaben uptake in the carotid wall. Male gender was associated with carotid F-florbetaben uptake in the univariate analysis, and was found to be an independent predictor of F-florbetaben uptake in the multivariate regression analysis (standardized regression coefficient β = 0.407, p = 0.009). Carotid F-florbetaben TBR in patients with a positive cerebral Aβ scan did not differ from that in patients without cerebral Aβ deposits.

Conclusion: Specific F-florbetaben uptake in human carotid arteries was detected. Male gender was identified as an independent clinical risk factor. Therefore, F-florbetaben PET/MRI might provide new insights into the pathophysiological process in atherosclerosis.
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http://dx.doi.org/10.1007/s00259-017-3651-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434137PMC
July 2017

Weyl Semimetals as Hydrogen Evolution Catalysts.

Adv Mater 2017 May 15;29(19). Epub 2017 Mar 15.

Chemistry and Physics Materials Unit, New Chemistry Unit and International Centre for Materials Science, Sheik Saqr Laboratory, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur P. O., Bangalore, 560064, India.

The search for highly efficient and low-cost catalysts is one of the main driving forces in catalytic chemistry. Current strategies for the catalyst design focus on increasing the number and activity of local catalytic sites, such as the edge sites of molybdenum disulfides in the hydrogen evolution reaction (HER). Here, the study proposes and demonstrates a different principle that goes beyond local site optimization by utilizing topological electronic states to spur catalytic activity. For HER, excellent catalysts have been found among the transition-metal monopnictides-NbP, TaP, NbAs, and TaAs-which are recently discovered to be topological Weyl semimetals. Here the study shows that the combination of robust topological surface states and large room temperature carrier mobility, both of which originate from bulk Dirac bands of the Weyl semimetal, is a recipe for high activity HER catalysts. This approach has the potential to go beyond graphene based composite photocatalysts where graphene simply provides a high mobility medium without any active catalytic sites that have been found in these topological materials. Thus, the work provides a guiding principle for the discovery of novel catalysts from the emerging field of topological materials.
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http://dx.doi.org/10.1002/adma.201606202DOI Listing
May 2017

Test-retest measurements of dopamine D-type receptors using simultaneous PET/MRI imaging.

Eur J Nucl Med Mol Imaging 2017 Jun 14;44(6):1025-1032. Epub 2017 Feb 14.

Department of Nuclear Medicine, University of Leipzig, Liebigstrasse 18, D-04103, Leipzig, Germany.

Purpose: The role of dopamine D-type receptor (DR)-expressing neurons in the regulation of motivated behavior and reward prediction has not yet been fully established. As a prerequisite for future research assessing D-mediated neuronal network regulation using simultaneous PET/MRI and DR-selective [C]SCH23390, this study investigated the stability of central DR measurements between two independent PET/MRI sessions under baseline conditions.

Methods: Thirteen healthy volunteers (7 female, age 33 ± 13 yrs) underwent 90-min emission scans, each after 90-s bolus injection of 486 ± 16 MBq [C]SCH23390, on two separate days within 2-4 weeks using a PET/MRI system. Parametric images of DR distribution volume ratio (DVR) and binding potential (BP) were generated by a multi-linear reference tissue model with two parameters and the cerebellar cortex as receptor-free reference region. Volume-of-interest (VOI) analysis was performed with manual VOIs drawn on consecutive transverse MRI slices for brain regions with high and low DR density.

Results: The DVR varied from 2.5 ± 0.3 to 2.9 ± 0.5 in regions with high DR density (e.g. the head of the caudate) and from 1.2 ± 0.1 to 1.6 ± 0.2 in regions with low DR density (e.g. the prefrontal cortex). The absolute variability of the DVR ranged from 2.4% ± 1.3% to 5.1% ± 5.3%, while Bland-Altman analyses revealed very low differences in mean DVR (e.g. 0.013 ± 0.17 for the nucleus accumbens). Intraclass correlation (one-way, random) indicated very high agreement (0.93 in average) for both DVR and BP values. Accordingly, the absolute variability of BP ranged from 7.0% ± 4.7% to 12.5% ± 10.6%; however, there were regions with very low DR content, such as the occipital cortex, with higher mean variability.

Conclusion: The test-retest reliability of DR measurements in this study was very high. This was the case not only for DR-rich brain areas, but also for regions with low DR density. These results will provide a solid base for future joint PET/MRI data analyses in stimulation-dependent mapping of DR-containing neurons and their effects on projections in neuronal circuits that determine behavior.
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http://dx.doi.org/10.1007/s00259-017-3645-0DOI Listing
June 2017

Process analytical approaches for the coil-to-globule transition of poly(N-isopropylacrylamide) in a concentrated aqueous suspension.

Anal Bioanal Chem 2017 Jan 9;409(3):807-819. Epub 2016 Nov 9.

Physical Chemistry - innoFSPEC, University of Potsdam, Am Mühlenberg 3, 14476, Potsdam-Golm, Germany.

The coil-to-globule transition of poly(N-isopropylacrylamide) (PNIPAM) microgel particles suspended in water has been investigated in situ as a function of heating and cooling rate with four optical process analytical technologies (PAT), sensitive to structural changes of the polymer. Photon Density Wave (PDW) spectroscopy, Focused Beam Reflectance Measurements (FBRM), turbidity measurements, and Particle Vision Microscope (PVM) measurements are found to be powerful tools for the monitoring of the temperature-dependent transition of such thermo-responsive polymers. These in-line technologies allow for monitoring of either the reduced scattering coefficient and the absorption coefficient, the chord length distribution, the reflected intensities, or the relative backscatter index via in-process imaging, respectively. Varying heating and cooling rates result in rate-dependent lower critical solution temperatures (LCST), with different impact of cooling and heating. Particularly, the data obtained by PDW spectroscopy can be used to estimate the thermodynamic transition temperature of PNIPAM for infinitesimal heating or cooling rates. In addition, an inverse hysteresis and a reversible building of micrometer-sized agglomerates are observed for the PNIPAM transition process.
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http://dx.doi.org/10.1007/s00216-016-0050-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233752PMC
January 2017

Feasibility and acceptance of simultaneous amyloid PET/MRI.

Eur J Nucl Med Mol Imaging 2016 Nov 19;43(12):2236-2243. Epub 2016 Jul 19.

Department of Nuclear Medicine, Leipzig University Hospital, Liebigstr. 18, 04103, Leipzig, Germany.

Purpose: Established Alzheimer's disease (AD) biomarker concepts classify into amyloid pathology and neuronal injury biomarkers, while recent alternative concepts classify into diagnostic and progression AD biomarkers. However, combined amyloid positron emission tomography/magnetic resonance imaging (PET/MRI) offers the chance to obtain both biomarker category read-outs within one imaging session, with increased patient as well as referrer convenience. The aim of this pilot study was to investigate this matter for the first time.

Methods: 100 subjects (age 70 ± 10 yrs, 46 female), n = 51 with clinically defined mild cognitive impairment (MCI), n = 44 with possible/probable AD dementia, and n = 5 with frontotemporal lobe degeneration, underwent simultaneous [F]florbetaben or [C]PIB PET/MRI (3 Tesla Siemens mMR). Brain amyloid load, mesial temporal lobe atrophy (MTLA) by means of the Scheltens scale, and other morphological brain pathologies were scored by respective experts. The patients/caregivers as well as the referrers were asked to assess on a five-point scale the convenience related to the one-stop-shop PET and MRI approach.

Results: In three subjects, MRI revealed temporal lobe abnormalities other than MTLA. According to the National Institute on Aging-Alzheimer's Association classification, the combined amyloid-beta PET/MRI evaluation resulted in 31 %, 45 %, and 24 % of the MCI subjects being categorized as "MCI-unlikely due to AD", "MCI due to AD-intermediate likelihood", and "MCI due to AD-high likelihood", respectively. 50 % of the probable AD dementia patients were categorized as "High level of evidence of AD pathophysiological process", and 56 % of the possible AD dementia patients as "Possible AD dementia - with evidence of AD pathophysiological process". With regard to the International Working Group 2 classification, 36 subjects had both positive diagnostic and progression biomarkers. The patient/caregiver survey revealed a gain of convenience in 88 % of responders as compared to a theoretically separate PET and MR imaging. In the referrer survey, an influence of the combined amyloid-beta PET/MRI on the final diagnosis was reported by 82 % of responders, with a referrer acceptance score of 3.7 ± 1.0 on a 5-point scale.

Conclusion: Simultaneous amyloid PET/MRI is feasible and provides imaging biomarkers of all categories which are able to supplement the clinical diagnosis of MCI due to AD and that of AD dementia. Further, patient and referrer convenience is improved by this one-stop-shop imaging approach.
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http://dx.doi.org/10.1007/s00259-016-3462-xDOI Listing
November 2016

Elucidation of the genetic basis of variation for stem strength characteristics in bread wheat by Associative Transcriptomics.

BMC Genomics 2016 07 16;17:500. Epub 2016 Jul 16.

John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK.

Background: The current approach to reducing the tendency for wheat grown under high fertilizer conditions to collapse (lodge) under the weight of its grain is based on reducing stem height via the introduction of Rht genes. However, these reduce the yield of straw (itself an important commodity) and introduce other undesirable characteristics. Identification of alternative height-control loci is therefore of key interest. In addition, the improvement of stem mechanical strength provides a further way through which lodging can be reduced.

Results: To investigate the prospects for genetic alternatives to Rht, we assessed variation for plant height and stem strength properties in a training genetic diversity panel of 100 wheat accessions fixed for Rht. Using mRNAseq data derived from RNA purified from leaves, functional genotypes were developed for the panel comprising 42,066 Single Nucleotide Polymorphism (SNP) markers and 94,060 Gene Expression Markers (GEMs). In the first application in wheat of the recently-developed method of Associative Transcriptomics, we identified associations between trait variation and both SNPs and GEMs. Analysis of marker-trait associations revealed candidates for the causative genes underlying the trait variation, implicating xylan acetylation and the COP9 signalosome as contributing to stem strength and auxin in the control of the observed variation for plant height. Predictive capabilities of key markers for stem strength were validated using a test genetic diversity panel of 30 further wheat accessions.

Conclusions: This work illustrates the power of Associative Transcriptomics for the exploration of complex traits of high agronomic importance in wheat. The careful selection of genotypes included in the analysis, allowed for high resolution mapping of novel trait-controlling loci in this staple crop. The use of Gene Expression markers coupled with the more traditional sequence-based markers, provides the power required to understand the biological context of the marker-trait associations observed. This not only adds to the wealth of knowledge that we strive to accumulate regarding gene function and plant adaptation, but also provides breeders with the information required to make more informed decisions regarding the potential consequences of incorporating the use of particular markers into future breeding programmes.
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http://dx.doi.org/10.1186/s12864-016-2775-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947262PMC
July 2016

The wheat Phs-A1 pre-harvest sprouting resistance locus delays the rate of seed dormancy loss and maps 0.3 cM distal to the PM19 genes in UK germplasm.

J Exp Bot 2016 07 23;67(14):4169-78. Epub 2016 May 23.

John Innes Centre, Norwich Research Park, NR4 7UH, UK

The precocious germination of cereal grains before harvest, also known as pre-harvest sprouting, is an important source of yield and quality loss in cereal production. Pre-harvest sprouting is a complex grain defect and is becoming an increasing challenge due to changing climate patterns. Resistance to sprouting is multi-genic, although a significant proportion of the sprouting variation in modern wheat cultivars is controlled by a few major quantitative trait loci, including Phs-A1 in chromosome arm 4AL. Despite its importance, little is known about the physiological basis and the gene(s) underlying this important locus. In this study, we characterized Phs-A1 and show that it confers resistance to sprouting damage by affecting the rate of dormancy loss during dry seed after-ripening. We show Phs-A1 to be effective even when seeds develop at low temperature (13 °C). Comparative analysis of syntenic Phs-A1 intervals in wheat and Brachypodium uncovered ten orthologous genes, including the Plasma Membrane 19 genes (PM19-A1 and PM19-A2) previously proposed as the main candidates for this locus. However, high-resolution fine-mapping in two bi-parental UK mapping populations delimited Phs-A1 to an interval 0.3 cM distal to the PM19 genes. This study suggests the possibility that more than one causal gene underlies this major pre-harvest sprouting locus. The information and resources reported in this study will help test this hypothesis across a wider set of germplasm and will be of importance for breeding more sprouting resilient wheat varieties.
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http://dx.doi.org/10.1093/jxb/erw194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301926PMC
July 2016

Combined PET/MRI: Multimodality insights into acute stroke hemodynamics.

Neurology 2016 05;86(20):1926-7

From the University Hospital Leipzig (P.W., D.S., J.C., O.S., K.-T.H., H.B.) and Max Planck Institute for Human Cognitive and Brain Sciences (T.M., H.M.), Leipzig, Germany.

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http://dx.doi.org/10.1212/WNL.0000000000002682DOI Listing
May 2016

Superconductivity in Weyl semimetal candidate MoTe2.

Nat Commun 2016 Mar 14;7:11038. Epub 2016 Mar 14.

Max Planck Institute for Chemical Physics of Solids, Nöthnitzer Straße 40, 01187 Dresden, Germany.

Transition metal dichalcogenides have attracted research interest over the last few decades due to their interesting structural chemistry, unusual electronic properties, rich intercalation chemistry and wide spectrum of potential applications. Despite the fact that the majority of related research focuses on semiconducting transition-metal dichalcogenides (for example, MoS2), recently discovered unexpected properties of WTe2 are provoking strong interest in semimetallic transition metal dichalcogenides featuring large magnetoresistance, pressure-driven superconductivity and Weyl semimetal states. We investigate the sister compound of WTe2, MoTe2, predicted to be a Weyl semimetal and a quantum spin Hall insulator in bulk and monolayer form, respectively. We find that bulk MoTe2 exhibits superconductivity with a transition temperature of 0.10 K. Application of external pressure dramatically enhances the transition temperature up to maximum value of 8.2 K at 11.7 GPa. The observed dome-shaped superconductivity phase diagram provides insights into the interplay between superconductivity and topological physics.
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http://dx.doi.org/10.1038/ncomms11038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793082PMC
March 2016

Fully automated calculation of image-derived input function in simultaneous PET/MRI in a sheep model.

EJNMMI Phys 2016 Dec 13;3(1). Epub 2016 Feb 13.

Department of Nuclear Medicine, Leipzig University Hospital, Liebigstr. 18, Leipzig, Germany.

Background: Obtaining the arterial input function (AIF) from image data in dynamic positron emission tomography (PET) examinations is a non-invasive alternative to arterial blood sampling. In simultaneous PET/magnetic resonance imaging (PET/MRI), high-resolution MRI angiographies can be used to define major arteries for correction of partial-volume effects (PVE) and point spread function (PSF) response in the PET data. The present study describes a fully automated method to obtain the image-derived input function (IDIF) in PET/MRI. Results are compared to those obtained by arterial blood sampling.

Methods: To segment the trunk of the major arteries in the neck, a high-resolution time-of-flight MRI angiography was postprocessed by a vessel-enhancement filter based on the inertia tensor. Together with the measured PSF of the PET subsystem, the arterial mask was used for geometrical deconvolution, yielding the time-resolved activity concentration averaged over a major artery. The method was compared to manual arterial blood sampling at the hind leg of 21 sheep (animal stroke model) during measurement of blood flow with O15-water. Absolute quantification of activity concentration was compared after bolus passage during steady state, i.e., between 2.5- and 5-min post injection. Cerebral blood flow (CBF) values from blood sampling and IDIF were also compared.

Results: The cross-calibration factor obtained by comparing activity concentrations in blood samples and IDIF during steady state is 0.98 ± 0.10. In all examinations, the IDIF provided a much earlier and sharper bolus peak than in the time course of activity concentration obtained by arterial blood sampling. CBF using the IDIF was 22 % higher than CBF obtained by using the AIF yielded by blood sampling.

Conclusions: The small deviation between arterial blood sampling and IDIF during steady state indicates that correction of PVE and PSF is possible with the method presented. The differences in bolus dynamics and, hence, CBF values can be explained by the different sampling locations (hind leg vs. major neck arteries) with differences in delay/dispersion. It will be the topic of further work to test the method on humans with the perspective of replacing invasive blood sampling by an IDIF using simultaneous PET/MRI.
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http://dx.doi.org/10.1186/s40658-016-0139-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752572PMC
December 2016

Valence band offset at the Si/SiSn interface by applying deep level transient spectroscopy.

Nanotechnology 2016 Feb 18;27(7):075705. Epub 2016 Jan 18.

Institute of Semiconductor- and Solid State Physics, Johannes Kepler Universität, A-4040 Linz, Austria.

A set of Si1-x Sn x /Si(001) quantum wells (QWs) is grown by applying molecular beam epitaxy. The activation energies of holes in these QWs are studied by deep-level transient spectroscopy. It is observed that the holes activation energies increase monotonically with the Sn fraction (x). The valence band offset between pseudomorphic Si1-x Sn x and Si obeys the dependence ΔE(v) = 1.69x eV, while the offset between the average valence bands of unstrained Si1-x Sn x /Si heterojunction was deduced and obeys the dependence ΔE(v(av)) = 1.27x eV.
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http://dx.doi.org/10.1088/0957-4484/27/7/075705DOI Listing
February 2016

Eshelby Twist as a Possible Source of Lattice Rotation in a Perfectly Ordered Protein/Silica Structure Grown by a Simple Organism.

Small 2015 Nov 14;11(42):5636-41. Epub 2015 Sep 14.

Department of Materials Science and Engineering, Technion, Haifa, 32000, Israel.

The formation mechanism of a perfectly ordered protein/silica structure in the axial filament of the anchor spicule of the silica sponge Monorhaphis chuni is suggested. Experimental evidence shows that the growth of this architecture is realized by a thermodynamically driven dislocation-mediated spiral growth mechanism, resulting in a specific rotation of the mesoscopic crystal lattice (Eshelby twist).
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http://dx.doi.org/10.1002/smll.201502244DOI Listing
November 2015

Simultaneous PET/MRI in stroke: a case series.

J Cereb Blood Flow Metab 2015 Sep 15;35(9):1421-5. Epub 2015 Jul 15.

Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany.

Prospective studies on magnetic resonance imaging (MRI)-guided systemic thrombolysis >4.5 hours after stroke onset did not reach their primary end points. It was discussed and observed in post hoc data re-assessment that this was partly because of limited MRI accuracy to measure critical hypoperfusion. We report the first cases of simultaneous [(15)O]H2O-positron emission tomography (PET)/MRI in stroke patients and an ovine model. Discrepancies between simultaneously obtained PET and MRI readouts were observed that might explain the above current limitations of stroke MRI. By offering highly complementary information, [(15)O]H2O-PET/MRI might help to identify critically hypoperfused tissue resulting in an improved patient stratification in thrombolysis trials.
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http://dx.doi.org/10.1038/jcbfm.2015.158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640332PMC
September 2015

Electron microscope analyses of the bio-silica basal spicule from the Monorhaphis chuni sponge.

J Struct Biol 2015 Aug 19;191(2):165-74. Epub 2015 Jun 19.

MPI of Colloids and Interfaces, Am Mühlenberg 1, D-14476 Potsdam, Germany.

We report on a structural analysis of several basal spicules of the deep-sea silica sponge Monorhaphis chuni by electron microscope techniques supported by a precise focused ion beam (FIB) target preparation. To get a deeper understanding of the spicules length growth, we concentrated our investigation onto the apical segments of two selected spicules with apparently different growth states and studied in detail permanent and temporary growth structures in the central compact silica axial cylinder (AC) as well as the structure of the organic axial filament (AF) in its center. The new findings concern the following morphology features: (i) at the tip we could identify thin silica layers, which overgrow as a tongue-like feature the front face of the AC and completely fuse during the subsequent growth state. This basically differs from the radial growth of the surrounding lamellar zone of the spicules made of alternating silica lamellae and organic interlayers. (ii) A newly detected disturbed cylindrical zone in the central region of the AC (diameter about 30 μm) contains vertical and horizontal cavities, channels and agglomerates, which can be interpreted as permanent leftover of a formerly open axial channel, later filled by silica. (iii) The AF consists of a three-dimensional crystal-like arrangement of organic molecules and amorphous silica surrounding these molecules. Similar to an inorganic crystal, this encased protein crystal is typified by crystallographic directions, lattice planes and surface steps. The 〈001〉 growth direction is especially favored, thereby scaffolding the axial cylinders growth and consequently the spicules' morphology.
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http://dx.doi.org/10.1016/j.jsb.2015.06.018DOI Listing
August 2015

Lean body mass correction of standardized uptake value in simultaneous whole-body positron emission tomography and magnetic resonance imaging.

Phys Med Biol 2015 Jun 28;60(12):4651-64. Epub 2015 May 28.

Department of Nuclear Medicine, Leipzig University Hospital Liebigstr. 18, D-04103 Leipzig, Germany.

This study explores the possibility of using simultaneous positron emission tomography--magnetic resonance imaging (PET-MRI) to estimate the lean body mass (LBM) in order to obtain a standardized uptake value (SUV) which is less dependent on the patients' adiposity. This approach is compared to (1) the commonly-used method based on a predictive equation for LBM, and (2) to using an LBM derived from PET-CT data. It is hypothesized that an MRI-based correction of SUV provides a robust method due to the high soft-tissue contrast of MRI. A straightforward approach to calculate an MRI-derived LBM is presented. It is based on the fat and water images computed from the two-point Dixon MRI primarily used for attenuation correction in PET-MRI. From these images, a water fraction was obtained for each voxel. Averaging over the whole body yielded the weight-normalized LBM. Performance of the new approach in terms of reducing variations of (18)F-Fludeoxyglucose SUVs in brain and liver across 19 subjects was compared with results using predictive methods and PET-CT data to estimate the LBM. The MRI-based method reduced the coefficient of variation of SUVs in the brain by 41 ± 10% which is comparable to the reduction by the PET-CT method (35 ± 10%). The reduction of the predictive LBM method was 29 ± 8%. In the liver, the reduction was less clear, presumably due to other sources of variation. In conclusion, employing the Dixon data in simultaneous PET-MRI for calculation of lean body mass provides a brain SUV which is less dependent on patient adiposity. The reduced dependency is comparable to that obtained by CT and predictive equations. Therefore, it is more comparable across patients. The technique does not impose an overhead in measurement time and is straightforward to implement.
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http://dx.doi.org/10.1088/0031-9155/60/12/4651DOI Listing
June 2015

Influence of the doping level on the porosity of silicon nanowires prepared by metal-assisted chemical etching.

Nanotechnology 2015 Jun 26;26(24):245301. Epub 2015 May 26.

Max Planck Institute of Microstructure Physics, Weinberg 2, D-06120 Halle, Germany.

A systematic method to control the porosity of silicon nanowires is presented. This method is based on metal-assisted chemical etching (MACE) and takes advantage of an HF/H2O2 etching solution and a silver catalyst in the form of a thin patterned film deposited on a doped silicon wafer. It is found that the porosity of the etched nanowires can be controlled by the doping level of the wafer. For low doping concentrations, the wires are primarily crystalline and surrounded by only a very thin layer of porous silicon (pSi) layer, while for highly doped silicon, they are porous in their entire volume. We performed a series of controlled experiments to conclude that there exists a well-defined critical doping concentration separating the crystalline and porous regimes. Furthermore, transmission electron microscopy investigations showed that the pSi has also a crystalline morphology on a length scale smaller than the pore size, determined from positron annihilation lifetime spectroscopy to be mesoscopic. Based on the experimental evidence, we devise a theoretical model of the pSi formation during MACE and apply it for better control of the nanowire morphology.
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http://dx.doi.org/10.1088/0957-4484/26/24/245301DOI Listing
June 2015

Ultra-long zinc oxide nanowires and boron doping based on ionic liquid assisted thermal chemical vapor deposition growth.

Nanoscale 2015 Jan;7(1):92-7

Laboratory for Nanotechnology, Department of Microsystems Engineering - IMTEK, University of Freiburg, Freiburg 79110, Germany.

Ionic liquid assisted growth of ultra-long ZnO nanowires from thermal chemical vapor deposition and the incorporation of dopants into the ZnO lattice have been investigated. We find that decomposed components of the ionic liquid at higher temperatures facilitate ultra-long vapor-liquid-solid ZnO nanowires that exhibit an unusual a-axis orientation. In particular, the ionic liquid BMImBF4 has been studied and the mechanism of the nanowire growth model in response to the use of the ionic liquid has been explained. We show that boron which is part of the investigated ionic liquid incorporates into the ZnO lattice and serves as a donor source. Electrical measurements were conducted and have shown an enhanced electrical conductivity (ρ = 0.09 Ω cm) when using the ionic liquid assisted growth approach. This work represents a step towards the controlled doping for designing future nanowire devices.
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http://dx.doi.org/10.1039/c4nr05426aDOI Listing
January 2015