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Supplemental Digital Content is Available in the Text.PRIVENT study report No. 3—Prescreening data—Objective tyndallometry (laser flare photometry) is independently influenced by age, sex, lens status, and the presence and the extent of rhegmatogenous retinal detachment.

Numerical solutions of a nonlinear Schrödinger equation may suffer from the spurious four-wave mixing processes. We study how these nonphysical resonances appear in solutions of a much more stiff generalized nonlinear Schrödinger equation with an arbitrary dispersion operator and determine the necessary restrictions on temporal and spatial resolution of a numerical scheme. The restrictions are especially important to meet when an envelope equation has to be applied in a wide spectral window, e.g., because of the spectral broadening.

Bei einer Verbrennung oder Verätzung der Augenoberfläche kann der Verlust von Limbusepithelstammzellen zu einer kompromittierten Selbsterneuerung des Hornhautepithels führen. Hierdurch kommt es zu einem dauerhaften Sehverlust. In diesen Situationen kann die Transplantation von kultivierten Limbusepithelzellen auf einer Amnionmembran oder einem Fibringel als Träger (Holoclar®, Holostem Terapie Avanzate s.r.l., Modena, Italien) zu einer Regeneration der Hornhautoberfläche beitragen. Die erforderlichen Zellen werden dem gesunden Partnerauge entnommen – sofern vorhanden. Alternative Zellquellen sind adulte Stammzellen aus anderen Körperregionen (Haarfollikel, Mundschleimhaut, mesenchymale Stromazellen) oder induzierte pluripotente Stammzellen (ursprünglich z. B. Hautfibroblasten). Das Umprogrammieren solcher Zellen kann unter Zuhilfenahme von Transkriptionsfaktoren erfolgen. Zusätzlich wird an biosynthetischen oder synthetischen Matrices gearbeitet, die nicht nur als Trägermaterial für die Transplantation dienen, sondern auch die Funktionen der Zellen (Selbsterneuerung, hornhautepitheltypischer Phänotyp) unterstützen sollen.

How specificity is conferred within gene regulatory networks is an important problem in biology. The basic helix–loop–helix PHYTOCHROME-INTERACTING FACTORs (PIFs) and single zinc-finger CYCLING DOF FACTORs (CDFs) mediate growth responses of Arabidopsis to light and temperature. We show that these two classes of transcription factor (TF) act cooperatively. CDF2 and PIF4 are temporally and spatially co-expressed, they interact to form a protein complex and act in the same genetic pathway to promote hypocotyl cell elongation. Furthermore, PIF4 substantially strengthens genome-wide occupancy of CDF2 at a subset of its target genes. One of these, YUCCA8, encodes an auxin biosynthesis enzyme whose transcription is increased by PIF4 and CDF2 to contribute to hypocotyl elongation. The binding sites of PIF4 and CDF2 in YUCCA8are closely spaced, and in vitro PIF4 enhances binding of CDF2. We propose that this occurs by direct protein interaction and because PIF4 binding alters DNA conformation. Thus, we define mechanisms by which PIF and CDF TFs cooperate to achieve regulatory specificity and promote cell elongation in response to light.

Hintergrund: Die Ansprüche an ein Bindehautersatzgewebe sind hoch: Es muss elastisch, klinisch verträglich sowie chirurgisch handhabbar sein und das Becherzellwachstum unterstützen. Fragestellung: Diese Arbeit gibt einen Überblick über aktuell verwendete und in der Forschung untersuchte Bindehautersatzgewebe. Methode: Es erfolgen eine Darstellung und Diskussion aktueller Publikationen zum klinischen Bindehautersatz und zu Geweben, die sich in der wissenschaftlichen Erforschung befinden und bereits im Tiermodell getestet wurden. Ergebnisse: Ersatzgewebe in der klinischen Anwendung sind autologe oder allogene Bindehaut, Nasen- oder Mundschleimhaut, Amnionmembran und dezellularisierte Gewebe. Hierbei zeigt autologe Bindehaut sehr gute Ergebnisse, ist aber aufgrund der limitierten Verfügbarkeit nicht für große Defekte geeignet. Hier kann autologe Nasen- und Mundschleimhaut angewendet werden. Allerdings sind die Erfolgsraten bei Autoimmunerkrankungen reduziert. Amnionmembran wird klinisch vielfach eingesetzt, hat aber den Nachteil, dass keine vitalen Zellen transplantiert werden und dass das Becherzellwachstum eingeschränkt ist. Des Weiteren werden dezellularisierte Gewebe klinisch angewendet, und in vivo war Becherzellwachstum nachweisbar. Aussagekräftige vergleichende Studien für den Bindehautersatz fehlen allerdings. Biologische Matrices wie Fibrin, Kollagen, Elastin, Gelatine oder Hyaluronat und synthetische Gewebe aus der Gruppe der Polyester werden im Labor und im Tiermodell untersucht. Studien zeigen eine gute Epithelialisierung und Becherzellbesiedlung in vivo. Schlussfolgerung: Die Bindehaut‑, Nasen‑/Mundschleimhaut- und Amnionmembrantransplantation zeigen klinisch befriedigende Ergebnisse, haben aber individuelle Nachteile. Es bedarf weiterer Untersuchungen im Tiermodell und in der Klinik, um andere Matrices wie zellfreie Gewebe oder weitere biologische und synthetische Matrices genauer zu evaluieren.

Assessment of the impact of variation in chloroplast and mitochondrial DNA (collectively termed the plasmotype) on plant phenotypes is challenging due to the difficulty in separating their effect from nuclear-derived variation (the nucleotype). Haploid-inducer lines can be used as efficient plasmotype donors to generate new plasmotype–nucleotype combinations (cybrids)1. We generated a panel comprising all possible cybrids of seven Arabidopsis thalianaaccessions and extensively phenotyped these lines for 1,859 phenotypes under both stable and fluctuating conditions. We show that natural variation in the plasmotype results in both additive and epistatic effects across all phenotypic categories. Plasmotypes that induce more additive phenotypic changes also cause more epistatic effects, suggesting a possible common basis for both additive and epistatic effects. On average, epistatic interactions explained twice as much of the variance in phenotypes as additive plasmotype effects. The impact of plasmotypic variation was also more pronounced under fluctuating and stressful environmental conditions. Thus, the phenotypic impact of variation in plasmotypes is the outcome of multi-level nucleotype–plasmotype–environment interactions and, as such, the plasmotype is likely to serve as a reservoir of variation that is predominantly exposed under certain conditions. The production of cybrids using haploid inducers is a rapid and precise method for assessment of the phenotypic effects of natural variation in organellar genomes. It will facilitate efficient screening of unique nucleotype–plasmotype combinations to both improve our understanding of natural variation in these combinations and identify favourable combinations to enhance plant performance.

The electronic states of quantum materials based on transition-metal, rare-earth and actinide elements are dominated by electrons in the dand forbitals intertwined with the strong band formation of the solid. Until now, to estimate which specific orbitals contribute to the ground state and thereby determine their physical properties we have had to rely on theoretical calculations combined with spectroscopy. Here, we show that s-core-level non-resonant inelastic X-ray scattering can directly image the active orbital in real space, without the necessity for any modelling. The power and accuracy of this new technique is shown using the textbook example, x2− y2/3z2− r2orbital of the Ni2+ion in NiO single crystal.

Global warming severely affects flowering time and reproductive success of plants. Alternative splicing of pre-messenger RNA (mRNA) is an important mechanism underlying ambient temperature-controlled responses in plants, yet its regulation is poorly understood. An increase in temperature promotes changes in plant morphology as well as the transition from the vegetative to the reproductive phase in Arabidopsis thalianavia changes in splicing of key regulatory genes. Here we investigate whether a particular histone modification affects ambient temperature-induced alternative splicing and flowering time. We use a genome-wide approach and perform RNA-sequencing (RNA-seq) analyses and histone H3 lysine 36 tri-methylation (H3K36me3) chromatin immunoprecipitation sequencing (ChIP-seq) in plants exposed to different ambient temperatures. Analysis and comparison of these datasets reveal that temperature-induced differentially spliced genes are enriched in H3K36me3. Moreover, we find that reduction of H3K36me3 deposition causes alteration in temperature-induced alternative splicing. We also show that plants with mutations in H3K36me3 writers, eraser, or readers have altered high ambient temperature-induced flowering. Our results show a key role for the histone mark H3K36me3 in splicing regulation and plant plasticity to fluctuating ambient temperature. Our findings open new perspectives for the breeding of crops that can better cope with environmental changes due to climate change.

AimTo determine whether clinical performance is negatively affected by prestripping Descemet membrane endothelial keratoplasty (DMEK) grafts from organ-cultured corneas.MethodsWe reviewed clinical records of all patients who underwent DMEK surgery for Fuchs endothelial dystrophy between 28 October 2014 and 11 August 2015. Grafts had been prepared from organ-cultured corneoscleral buttons 24 hours prior to surgery or during surgery. We included only patients for which at least one follow-up examination was available at a minimum of 2 months postoperatively. Main outcome measures: best-corrected visual acuity (BCVA), central corneal thickness, endothelial cell count and rebubbling rates.ResultsData given are mean±SD. No statistically significant differences were recorded at baseline between the partially stripped group (n=65) and the control group (n=72) with regard to donor age (70±9 vs 69±8 years; p=0.49), donor cornea endothelial cell density (2586±604 vs 2522±186 cells/mm2; p=0.6), BCVA (before DMEK: 0.77±0.5 vs 0.63±0.3 logMAR; p=0.27; before triple-DMEK: 0.56±0.2 vs 0.52±0.2 logMAR; p=0.33) or central corneal thickness (621±72 vs 607±53 μm; p=0.49). Mean follow-up was 149±83 versus 148±77 days; p=0.79. No statistically significant differences were observed between the two groups postoperatively with regard to BCVA (after DMEK: 0.25±0.2 vs 0.21±0.2 logMAR; p=0.59; after triple-DMEK: 0.22±0.2 vs 0.2±0.1 logMAR; p=0.98), central corneal thickness (502±42 vs 508±41 μm; p=0.47), endothelial cell count (1537±245 vs 1551±287 cells/mm2; p=0.65) and number of graft detachments requiring rebubbling (4.6% vs 9.7%; p=0.33).ConclusionsWe found no evidence that the use of prestripped DMEK grafts is inferior to same-day preparation in organ-cultured corneas within the given follow-up.

Long-read sequencing can overcome the weaknesses of short reads in the assembly of eukaryotic genomes; however, at present additional scaffolding is needed to achieve chromosome-level assemblies. We generated Pacific Biosciences (PacBio) long-read data of the genomes of three relatives of the model plant Arabidopsis thalianaand assembled all three genomes into only a few hundred contigs. To improve the contiguities of these assemblies, we generated BioNano Genomics optical mapping and Dovetail Genomics chromosome conformation capture data for genome scaffolding. Despite their technical differences, optical mapping and chromosome conformation capture performed similarly and doubled N50 values. After improving both integration methods, assembly contiguity reached chromosome-arm-levels. We rigorously assessed the quality of contigs and scaffolds using Illumina mate-pair libraries and genetic map information. This showed that PacBio assemblies have high sequence accuracy but can contain several misassemblies, which join unlinked regions of the genome. Most, but not all, of these misjoints were removed during the integration of the optical mapping and chromosome conformation capture data. Even though none of the centromeres were fully assembled, the scaffolds revealed large parts of some centromeric regions, even including some of the heterochromatic regions, which are not present in gold standard reference sequences.

Interactions between stem cells and their microenvironment are critical for regulation and maintenance of stem cell function. To elucidate the molecular interactions within the human limbal epithelial stem/progenitor cell (LEPC) niche, which is essential for maintaining corneal transparency and vision, we performed a comprehensive expression analysis of cell adhesion molecules (CAMs) using custom‐made quantitative real‐time polymerase chain reaction (qRT‐PCR) arrays and laser capture‐microdissected LEPC clusters, comprising LEPCs, melanocytes, mesenchymal cells, and transmigrating immune cells. We show that LEPCs are anchored to their supporting basement membrane by the laminin receptors α3β1 and α6β4 integrin and the dystroglycan complex, while intercellular contacts between LEPCs and melanocytes are mediated by N‐, P‐, and E‐cadherin together with L1‐CAM, a member of the immunoglobulin superfamily (Ig)CAMs. In addition to the LEPC‐associated heparan sulfate proteoglycans syndecan‐2, glypican‐3, and glypican‐4, the IgCAM members ICAM‐1 and VCAM‐1 were found to be variably expressed on LEPCs and associated niche cells and to be dynamically regulated in response to chemokines such as interferon‐γ to enhance interactions with immune cells. Moreover, junctional adhesion molecule JAM‐C accumulating in the subepithelial limbal matrix, appeared to be involved in recruitment of immune cells, while mesenchymal stromal cells appeared to use the nephronectin receptor integrin α8 for approaching the limbal basement membrane. In summary, we identified a novel combination of cell surface receptors that may regulate both stable and dynamic cell‐matrix and cell–cell interactions within the limbal niche. The findings provide a solid foundation for further functional studies and for advancement of our current therapeutic strategies for ocular surface reconstruction. StemCells2016;34:203–219 Laser confocal image of limbal epithelial progenitor cell cluster comprising cytokeratin 15 (CK15)‐positive epithelial progenitor cells (turquoise) and associated niche cells, i.e. Melan‐A‐positive melanocytes (yellow‐green) and vimentin‐positive subepithelial stromal cells (red) and intraepithelial immune cells (red); nuclei are counterstained with DAPI (blue).

We report on a 170Yb Mössabauer spectroscopy investigation of the low temperature magnetic properties of the cubic heavy electron material YbAuCu4. In the antiferromagnetically ordered phase (TN=1 K), we measure a 20 % reduction of the Yb+3saturated spontaneous moment with respect to that of the crystal field Γ7ground state and we evidence a sizeable anisotropy of the interionic magnetic interaction. We interpret these features in terms of 4f electron - conduction electron hybridisation, which accounts for the heavy electron properties. The energy scale kBT0of hybridisation is estimated to be 0.3 K. The Mössbauer spectra in the ordered and paramagnetic phases show inhomogeneous line broadenings which are interpreted as arising from a distribution of local strains along the 〈111〉 crystal axes, of mean magneto-elastic energy 0.2 – 0.4 K.

Background:Several case reports have documented acute kidney injury (AKI) attributable to antibiotic-impregnated cement (AIC) spacers. Objectives:To identify AKI risk factors among patients who underwent AIC placement and determine whether vancomycin-AIC placement affects systemic vancomycin dosing. Methods:Phase 1 was a case-control study to identify AKI risk factors among patients who underwent AIC placement. Cases experienced AKI; controls had unchanged renal function. Phase 2 was a retrospective cohort study. Patients who received ≥72 hours of intravenous (IV) vancomycin were divided into 2 groups according to whether they underwent vancomycin-AIC placement. Primary outcome was number of vancomycin dosing changes. Results:Phase 1: Among 26 cases and 74 controls AKI risk factors on univariate and multivariable analysis included exposure to angiotensin-converting-enzyme (ACE) inhibitor exposure within 7 days of AIC placement (42% vs 20%, P= 0.03) and piperacillin-tazobactam within 7 days following AIC placement (31% vs 12%, P= 0.03). Phase 2: Among 53 patients who underwent vancomycin-AIC placement and 104 who underwent another surgery type, vancomycin was adjusted more frequently in patients who underwent vancomycin-AIC placement (28% vs 15%, P= 0.06). Conclusions:Among patients who undergo AIC placement with vancomycin and/or tobramycin, exposure to ACE inhibitors and piperacillin-tazobactam are associated with increased risk of AKI in the immediate postoperative period. No empirical adjustments to IV vancomycin dosing are necessary in patients undergoing vancomycin-AIC placement.

This paper presents a method of separating cells that are connected to each other forming clusters. The difference to many other publications covering similar topics is that the cell types we are dealing with form clusters of highly varying morphology. An advantage of our method is that it can be universally used for different cell types. The segmentation method is based on a growth simulation starting from the nuclei areas. To start the evaluation, the cells need to be made visible with a histological stain, in our case with the May-Grünwald solution. After the staining process has been completed, the nuclei areas can be distinguished from the other cell areas by a histogram backprojection algorithm. The presented method can, in addition to histological stained cells, also be applied to fluorescent-stained cells.

A quasielastic neutron scattering study has been performed on UCu4+xAl8-x, a system which reveals an alloying-induced transition from magnetic order to heavy-fermion behavior. The magnetic response can be described by a broad quasielastic Lorentzian for all concentrations. No crystal field excitations could be detected. Remarkably, the linewidth decreases with increasing hybridization strength and seems to be no measure of the Kondo lattice temperature T*. In addition, electron spin resonance (ESR) experiments were performed which revealed that, even in the heavy-fermion regime, spin fluctuations play an important role. Both experimental findings are in distinct contrast to cerium-based heavy fermion systems.

• The driving performance of 20 subjects with central vision impairment due to either Stargardt disease or cone-rod dystrophy (visual acuity, 20/40 to 20/70) was compared with that of 29 control subjects with normal vision who had similar driving histories. Driving performance was defined by accident involvement based on self-report and state records and by an evaluation of performance on an interactive driving simulator. The proportion of individuals involved in accidents in the central vision loss group was comparable to that of the control group. For 13 of the 20 subjects with central vision loss who did not restrict their driving to daylight hours, there was a greater likelihood of involvement in nighttime accidents than in the control group. Visual function measures and simulator indexes did not predict accident involvement for the central visual loss group, although these subjects showed longer braking response times and a greater number of lane boundary crossings than the control group. These findings are in contrast to our previously published report of subjects with retinitis pigmentosa, who were more likely to have been involved in both daytime and nighttime accidents than a control group and for whom visual field extent was significantly related to accident involvement.

• The driving performance of 21 subjects with retinitis pigmentosa (RP) and varying degrees of peripheral field loss was compared with the performance of 31 normally sighted control subjects who did not differ statistically from the subjects with RP in age, gender, years of driving experience, or miles driven per year. Driving performance was assessed by selfreported accident frequency and by an evaluation of performance on an interactive driving simulator. A significantly greater proportion of individuals had selfreported accidents in the RP group than in the normal group. Likewise, a significantly greater proportion of subjects with RP than normal subjects had accidents on the driving simulator. Logistic regression analyses indicated that binocular horizontal field extent and binocular field area significantly differentiated between those having no self-reported accidents and those subjects with RP having one or more self-reported accidents. Because the simulator indexes were correlated with visual field measures for the subjects with RP, no additional information was incorporated into the regression model by adding the simulator measures. Therefore, our results indicate that visual field loss is a primary correlate of automotive accidents in individuals with RP.

The specific heat of CeCu6−xAux withx=0,0.3, and 0.9, and of the corresponding La homologues has been measured between 1.5 K and 150 K. With increasingx we find progressively better-defined Schottky anomalies arising from the crystal-field splitting, which is attributed to the decrease of the Kondo temperature. Both observations are in line with the results of inelastic neutron-scattering data performed on samples withx=0.5. Overall, the crystal-field splitting does not change very much upon alloying with Au. A detailed analysis shows that forx=0.5 the quasielastic line width is smaller and the inelastic crystal-field transitions are better resolved compared to CeCu6.

It is well known that phonon anomalies will occur, if the charge relaxation rate is of the same order of magnitude as the phonon frequencies. Such an effect was observed by a strong softening of the LA-mode in <1,1,1>-direction in several intermediate valent systems with NaCl-structure. Here we will report on such an effect, which is found for the first time in a diluted intermediate valent system. We have performed an inelastic neutron scattering experiment on polycrystalline Tm0.05Y0.95Se using a time-of-flight spectrometer with a very good energy resolution. As a result of a |Q|-dependent analysis of the measured density of phonon states we found that the LA-mode in <1,1,1>-direction is also strongly softened in this dilute case.

The antiferromagnetic ordering temperatures of the rare earth (RE) moments in RE Ba2Cu3O7-gd, obtained from specific heat measurements, are roughly in agreement with the de Gennes factors, i.e., the ordering mechanism can be mainly seen as an indirect spin-spin exchange. However, the oxygen dependence of TNis found to be reversed for the light rare earths compared to the heavy rare earths. As origin for this systematic observation an indirect interaction between the 3d-moments of copper and the 4f-moments of rare earths is discussed as a second order effect. Such an interaction is supported by measurements of the 4f relaxation behavior on the Nd 1: 2: 3 cuprates by inelastic magnetic neutron scattering. Here, the usual thermally driven increase of the magnetic relaxation rate is suppressed up to about 80 K. This correlates with the appearance of a spin gap found by Rossat- Mignod in YBa2Cu3O7and therefore the 3d-4f coupling can be understood as an interaction of the 4f moments with a spin-fluctuation exchange in the CuO2planes. Furthermore, the quasielastic magnetic response has a Gaussian contribution at temperatures below 100 K, i.e., much above the long ranged ordering temperatures TN. Magnon-like excitations appear already at slightly larger temperatures than TN. In addition the paramagnetic inelastic spectra show only little dependence of the crystal field scheme on the oxygen concentration.

Flowering of many plant species depends on interactions between basic leucine zipper (bZIP) transcription factors and systemically transported florigen proteins. Members of the genus Arabidopsiscontain two of these bZIPs, FD and FDP, which we show have largely complementary expression patterns in shoot apices before and during flowering. CRISPR-Cas9-induced null mutants for FDPflower slightly earlier than wild-type, whereas fdmutants are late flowering. Identical G-box sequences are enriched at FD and FDP binding sites, but only FD binds to genes involved in flowering and only fdalters their transcription. However, both proteins bind to genes involved in responses to the phytohormone abscisic acid (ABA), which controls developmental and stress responses. Many of these genes are differentially expressed in both fdand fdpmutant seedlings, which also show reduced ABA sensitivity. Thus, florigen-interacting bZIPs have distinct functions in flowering dependent on their expression patterns and, at earlier stages in development, play common roles in phytohormone signaling.

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The low-energy part (h̷ω ≤ 2 meV) of the magnetic excitations of polycrystalline samples of Nd2−xCexCuO4with x= 0, 0.16 and 0.20 has been measured with inelastic magnetic neutron scattering between 1.8 and 300 K. All observed magnetic scattering originates from transitions within the ground-state doublet of Nd3+. For Nd2CuO4the response is inelastic at T= 1.8 K with Q-dependent positions and intensities of two strong and one weak mode. For x= 0.16 and 0.20 the magnetic response is mainly quasi-elastic with some residual inelastic intensity at low-Qvalues. For the higher temperatures all spectra become quasi-elastic. The shape of the response changes between 40 and 100 K from Gaussian to Lorentzian.