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Solution processed semiconductors are in demand for present and next-generation optoelectronic technologies ranging from displays to quantum light sources because of their scalability and ease of integration into devices with diverse form factors. One of the central requirements for semiconductors used in these applications is a narrow photoluminescence (PL) linewidth. Narrow emission linewidths are needed to ensure both color and single-photon purity, raising the question of what design rules are needed to obtain narrow emission from semiconductors made in solution. In this review we first examine the requirements for colloidal emitters for a variety of applications including light-emitting diodes, photodetectors, lasers, and quantum information science. Next, we will delve into the sources of spectral broadening, including “homogeneous” broadening from dynamical broadening mechanisms in single-particle spectra, heterogeneous broadening from static structural differences in ensemble spectra, and spectral diffusion. Then, we compare the current state of the art in terms of emission linewidth for a variety of colloidal materials including II-VI quantum dots (QDs) and nanoplatelets, III-V QDs, alloyed QDs, metal-halide perovskites including nanocrystals and 2D structures, doped nanocrystals, and, finally, as a point of comparison, organic molecules. We end with some conclusions and connections, including an outline of promising paths forward.

Macrophages are able to differentiate into classically polarized (M1) or alternatively polarized (M2) states upon encountering pro-inflammatory cytokines such as interferon (IFN) γ or anti-inflammatory cytokines such as interleukin (IL) -4/IL-13, respectively. Moreover, macrophages are known to regulate lipid metabolism via multiple members of the nuclear hormone receptor family, including the retinoid X receptors (RXR). It has been also documented that cytokines are able to modulate macrophage responses to lipid signals but the nature of these interactions and the underlying mechanisms of these processes especially at the level of the chromatinized genome are not well understood. Previous work from our laboratory suggested that STAT6 is a facilitator of nuclear receptor mediated transcriptional activity acting at the genome level. This prompted us to investigate genome-wide DNA binding events and the development of cistromes in human CD14+ monocyte-derived macrophages upon exposure to IL-4. We determined the impact of IL-4 on the PU.1, RXR and STAT6 cistromes within the active enhancer regions marked by H3K27-acetylation using chromatin immunoprecipitation followed by deep sequencing and integrated bioinformatics analyses. We found that about 2/3rd of the IL-4 induced STAT6 peaks co-localized with RXR peaks. These STAT6/RXR co-peaks differed at least in part from the non-overlapping RXR peaks regarding the most enriched de novo transcription factor binding motifs. Interestingly, RXR-binding was not regulated at the STAT6/RXR co-bound enhancers following IL-4 stimulation, but differential enhancer interactions were observed between the IL-4/STAT6 and RXR signaling pathways acting in a gene selective manner. Our results suggest that there is a novel, so far uncharacterized cistromic crosstalk between RXR and STAT6 that is likely to contribute to the formation of the active enhancer repertoire, transcriptome and differential signal-specific gene regulation of polarized macrophages.

The construction and use of haploblocks [adjacent single nucleotide polymorphisms (SNP) in strong linkage disequilibrium] for genomic evaluation is advantageous, because the number of effects to be estimated can be reduced without discarding relevant genomic information. Furthermore, haplotypes (the combination of 2 or more SNP) can increase the probability of capturing the quantitative trait loci effect compared with individual SNP markers. With regards to haplotypes, the allele frequency parameter is also of interest, because as a selection criterion, it allows the number of rare alleles to be reduced, and the effects of those alleles are usually difficult to estimate. We have proposed a simple pipeline that simultaneously incorporates linkage disequilibrium and allele frequency information in genomic evaluation, and here we present the first results obtained with this procedure. We used a population of 2,235 progeny-tested bulls from the Montbeliarde breed for the tests. Phenotype data were available in the form of daughter yield deviations on 5 production traits, and genotype data were available from the 50K SNP chip. We conducted a classical validation study by splitting the population into training (80% oldest animals) and validation (20% youngest animals) sets to emulate a real-life scenario in which the selection candidates had no available phenotype data. We measured all reported parameters for the validation set. Our results proved that the proposed method was indeed advantageous, and that the accuracy of genomic evaluation could be improved. Compared with results from a genomic BLUP analysis, correlations between daughter yield deviations (a proxy for true) and genomic estimated breeding values increased by an average of 2.7 percentage points for the 5 traits. Inflation of the genomic evaluation of the selection candidates was also significantly reduced. The proposed method outperformed the other SNP and haplotype-based tests we had evaluated in a previous study. The combination of linkage disequilibrium–based haploblocks and allele frequency–based haplotype selection methods is a promising way to improve the efficiency of genomic evaluation. Further work is needed to optimize each step in the proposed analysis pipeline.

Epigenetic mechanisms largely influence how genetic information on DNA level is translated into different phenotypes. DNA methylations and histone post-translational modifications make up what is referred to as "epigenetic landscape", an interconnected pattern that regulates access to genes and serves as platform for specific binding partners. The epigenetic landscape is maintained by "writers", which add the modifications, "erasers", which delete the modifications and "readers" which specifically bind modifications and mediate their location to other proteins connected to transcription. In the context of acetylations, which are the focus of this thesis, the writers are called histone acetyl transferases (HATs), the erasers are called histone deacetylases (HDACs) and the readers comprise Bromodomains (BRDs) as well as Yaf9, ENL, AF9, Taf14, Sas5 (YEATS) domains. An aberrant epigenetic landscape and mutated forms of epigenetic readers can lead to diseases including cancer and inflammatory diseases, making epigenetic reader domains attractive drug targets. The focus of this thesis were YEATS domains and the development of inhibitors for this new class of epigenetic readers. Eleven-nineteen-leukemia protein (ENL) and ALL1-fused gene from chromosome 9 protein (AF9) are also part of the super elongation complex and are common fusion partners of mixed lineage leukemia protein (MLL) in acute myeloid leukemia (AML) (Wan et al., 2017, Erb et al., 2017). In this thesis, the first ligand-free crystal structure of ENL YEATS revealed an inherent flexibility of the Y78 side chain in the aromatic triad and two conserved water molecules. Soaking experiments led to the first co-crystal structures between a YEATS domain and small molecule inhibitors and defined prerequisites for ENL YEATS inhibitor scaffolds. The discovered inhibitory fragments had a central amide bond in common, which replaced one of the two conserved water molecules to form beta-sheet-like hydrogen bonds between the loop 6 backbone and the S58 side chain. The amide bond was flanked by two aromatic moieties, of which one stacks with H56 in the front pocket and the other interacts with the aromatic triad in the rear pocket. The development of the first chemical probe for ENL/AF9, SGC-iMLLT, show that the affinity is increased to low nanomolar levels if the rear flanking aromatic moiety forms additional hydrogen bonds with loop 6 and the side chain of E75 (Moustakim et al., 2018). In case of the probe, this is achieved with a 2-methyl-pyrrolidine-benzimidazole moiety. The probe binds with high affinity to ENL (129 nM) and AF9 (77 nM) and shows no significant affinity towards other human YEATS domains or BRDs. Target engagement was shown by fluorescence recovery after photobleaching (FRAP), cellular thermal shift assay (CETSA) and in case of AF9 also with NanoBRET. The probe changed the expression of three AML-related genes (MYC, dendrin and CD86) in MV4;11 cells, encouraging application of this probe in more AML cell lines.

Multiple hydrokinetic turbines in three array configurations were characterized computationally by employing Reynolds Averaged Navier-Stokes equations. The simulations were conducted for pre-existing turbines operating at their optimum power coefficient of 0.43 which was obtained by design and optimization process. Mechanical power for two adjacent units was predicted for various lateral separation distances. An additional two-by-two turbine array was studied, mimicking a hydro-farm. Numerical simulations were performed using actual physical turbines in the field rather than using low fidelity models such as actuator disk theory. Steady state simulations were conducted using both Coupled and SIMPLE pressure-velocity solvers. Steady three dimensional flow structures were calculated using the k-ω Shear Stress Transport (SST) turbulence model. At a lateral separation distance of 0.5Dt, the turbines produced an average 86% of the peak power a single turbine producing. Interaction effects at lateral separation distances greater than 2.5Dt were negligible. The wake interaction behind the upstream turbines causes a significant performance reduction for downstream turbines within 6Dt longitudinal spacing. Downstream turbines employed for the present study performed around 20% or less of a single unit turbine performance for the same operating conditions. Downstream turbines yielded comparable reductions in power to that of experimental results.

Background: The development of cardiac arrhythmias resulting in cardiac arrest represents a severe complication in patients with acute myocardial infarction. While the worsening of the prognosis in this vulnerable patient collective is well known, less attention has been paid to its age-specific relevance from a long-term perspective. Methods: Based on a clinical acute myocardial infarction registry we analysed 832 patients with acute myocardial infarction within the current analysis. Patients were stratified into equal groups ( n=208 per group) according to age in less than 45 years, 45–64 years, 65–84 years and 85 years and older via propensity score matching. Multivariate Cox regression analysis was used to assess the age-dependent influence of cardiac arrest on mortality. Results: The total number of cardiac arrests differed significantly between age groups, demonstrating the highest incidence in the youngest population with 18.8% ( n=39), and a significantly lower incidence by increasing age (−11.6%; P=0.01). After a mean follow-up time of 8 years, a total of 264 patients (31.7%) died due to cardiovascular causes. While cardiac arrest was a strong and independent predictor for mortality within the total study population with an adjusted hazard ratio of 3.21 (95% confidence interval 2.23–4.61; PConclusion: We found that arrhythmias resulting in cardiac arrest are more common in very young acute myocardial infarction patients (

NERC’s TPL 7 (see Glossary, Page 14) ground conductivity (β) scaling factors rely on Earth conductivity estimates assembled quickly for EPRI in 20 1D models by Dr. Peter Fernberg (“an independent researcher from Ottawa”) and published in 2012. These default scaling factors and their underlying 1D models suffer from omissions, ambiguities, misinterpretations — identified here and tabulated in Appendix A — which merit attention because TPL 7 allows planners for regulated entities to use different “specific earth model(s) with documented justification.” This paper does not address pros and cons of 1D, 2D, 3D models and their assumptions. This paper may support improvement of Earth conductivity models, a high priority for NERC.

Based on 25-page NOAA 2017 Space Weather inventory Report to Congress (second file, provided by U.S. Senate), author prepared 1-pagetable summarizing space weather assets of NOAA and partners, civilian and military, US and non-US (first file).

The North American Electric Reliability Corporation (NERC) submitted a revised GMD research work plan in response to the Federal Energy RegulatoryCommission's Order No. 830 on April 19, 2018. These Comments, filed pursuant to the Secretary’s Notice of April 20, 2018, support the plan and raise strengthening questions as to Electromagnetic pulse, EMP Commission reports and Earth conductivity issues. &nbsp

International audience; Information relative to haploblocks, i.e., haplotypes constructed based on linkage disequilibrium, can be used to potentially increase the accuracy of genomic evaluations. Jónás et al. (2016) developed an approach to optimally select SNP in order to reduce the frequency of under- or over- represented haplotype alleles. When applied to haploblocks in the Montbéliarde breed, this strategy led to substantially better validation results. In this study, we applied this strategy to 36 traits in the French Holstein breed, with a large reference population. Several scenarios for constructing haploblocks were compared with GBLUP and BayesCpi In contrast with previous results with smaller reference populations, the overall average correlations between predictions and phenotypes were within ±0.5 percentage point of the one obtained with GBLUP, whatever the scenarios (including the BayesC case), with very little variation across traits. Among the various haploblock construction strategies, the one in which haploblocks endpoints were defined based on a linkage disequilibrium measure on the HD chip gave the best results. Our implementation of a genomic evaluation based on haploblocks was too simplistic: it assumed that all haploblocks contributed to each trait and were all explaining the same fraction of the total genetic variance. Despite these naïve assumptions, it led to results comparable to the current most popular approaches. Any approach giving a higher variance to haploblocks actually carrying QTL should hopefully give better results. The idea of haploblocks remains appealing because it fits better the concepts of chromosome segment transmission and of maintenance of LD between SNP haplotypes and QTL. Keywords: genomic evaluation, dairy cattle, methods, haplotype, haploblock

International audience; Spp1 is the H3K4me3 reader subunit of the Set1 complex (COMPASS/Set1C) that contributes to the mechanism by which meiotic DNA break sites are mechanistically selected. We previously proposed a model in which Spp1 interacts with H3K4me3 and the chromosome axis protein Mer2 that leads to DSB formation. Here we show that spatial interactions of Spp1 and Mer2 occur independently of Set1C. Spp1 exhibits dynamic chromatin binding features during meiosis, with many de novo appearing and disappearing binding sites. Spp1 chromatin binding dynamics depends on its PHD finger and Mer2-interacting domain and on modifiable histone residues (H3R2/K4). Remarkably, association of Spp1 with Mer2 axial sites reduces the effective turnover rate and diffusion coefficient of Spp1 upon chromatin binding, compared with other Set1C subunits. Our results indicate that ``chromosomal turnover rate'' is a major molecular determinant of Spp1 function in the framework of meiotic chromatin structure that prepares recombination initiation sites for break formation.

BACKGROUND Weighing the benefit of revascularization procedures against the risk of adverse events is particularly challenging in elderly patients suffering acute myocardial infarction (AMI). Based on a general gender gap in coronary interventions, the restraint in invasive procedures may be particularly high in elderly women. We therefore investigated gender-related differences in the frequency of coronary interventions as well as gender- and age-specific outcomes after coronary interventions in patients with AMI. DESIGN We included 906 AMI patients in the final analysis. Among patients ≥ 80 years (n = 453), the intention to intervention (lysis and/or coronary angiography) for women was significantly lower compared to men (65·7% vs. 80·8%; P < 0·001), whereas in patients < 80 years (n = 453), the rate was similar between both genders (94·8% vs. 95·1%, P = 0·89). However, the assessment of potential risk factors for adverse events did not explain the gender gap. When assessing the benefit of any coronary intervention (stenting and/or lysis and/or coronary artery bypass graft), elderly women benefited at least as much with a hazard ratio (HR) for cardiovascular mortality of 0·56 (95% confidence interval [CI] 0·37-0·84, P = 0·005) compared to a HR of 0·96 (95% CI 0·76-1·23, P = 0·766) in elderly men. CONCLUSION We observed a lower intention to coronary intervention in elderly women compared with men. However, the distribution of risk factors in elderly women and men who did not undergo coronary intervention was similar and therefore seemed not to be causal for the gender gap although the benefit of any coronary interventions was even higher in elderly women.

SummaryWe aimed to assess whether the CRUSADE risk score represents a robust instrument for stratification of bleeding risk in elderly myocardial infarction (MI) patients (≥80 years) and further aimed to identify age-specific predictors of major bleeding events. Binary logistic regression models were applied to assess the effect of variables on the occurrence of bleeding events during hospital stay. Receiver operating characteristic (ROC) analysis was used to evaluate the discriminatory power. Out of 387 patients in the final study cohort, 74 patients (19.1 %) experienced a major bleeding event according to the definition of the International Society on Thrombosis and Haemostasis. The CRUSADE risk score demonstrated only a weak discriminatory power to predict bleeding in this group of patients (area under the ROC curve: 0.57 [0.51–0.65]; p=0.05). In the multivariate regression analysis, history of bleeding with an adjusted hazard ratio (HR) of 3.21(95 % confidence interval: 1.29–8.03, p=0.01) and C-reactive protein with an adjusted HR per increase of 10 mg/l of 1.05 (1.01–1.10) were independent predictors of major bleeding. Integration of both variables into the CRUSADE score demonstrated a significantly improved performance for bleeding as indicated by a significant increase in the ROC analysis (area under the curve: 0.64 vs 0.57; for comparison p

Notice à Reprendre car pas de Clé UT au 6 Mars 2017; An important prerequisite for high prediction accuracy in genomic prediction is the availability of a large training population, which allows accurate marker effect estimation. This requirement is not fulfilled in case of regional breeds with a limited number of breeding animals. We assessed the efficiency of the current French routine genomic evaluation procedure in four regional breeds (Abondance, Tarentaise, French Simmental and Vosgienne) as well as the potential benefits when the training populations consisting of males and females of these breeds are merged to form a multibreed training population. Genomic evaluation was 5–11% more accurate than a pedigree-based BLUP in three of the four breeds, while the numerically smallest breed showed a < 1% increase in accuracy. Multibreed genomic evaluation was beneficial for two breeds (Abondance and French Simmental) with maximum gains of 5 and 8% in correlation coefficients between yield deviations and genomic estimated breeding values, when compared to the single-breed genomic evaluation results. Inflation of genomic evaluation of young candidates was also reduced. Our results indicate that genomic selection can be effective in regional breeds as well. Here, we provide empirical evidence proving that genetic distance between breeds is only one of the factors affecting the efficiency of multibreed genomic evaluation.

Retinoid X receptor (RXR) is a promiscuous nuclear receptor forming heterodimers with several other receptors, which activate different sets of genes. Upon agonist treatment, the occupancy of its genomic binding regions increased, but only a modest change in the number of sites was revealed by chromatin immunoprecipitation followed by sequencing, suggesting a rather static behavior. However, such genome-wide and biochemical approaches do not take into account the dynamic behavior of a transcription factor. Therefore, we characterized the nuclear dynamics of RXR during activation in single cells on the subsecond scale using live-cell imaging. By applying fluorescence recovery after photobleaching and fluorescence correlation spectroscopy (FCS), techniques with different temporal and spatial resolutions, a highly dynamic behavior could be uncovered which is best described by a two-state model (slow and fast) of receptor mobility. In the unliganded state, most RXRs belonged to the fast population, leaving ∼ 15% for the slow, chromatin-bound fraction. Upon agonist treatment, this ratio increased to ∼ 43% as a result of an immediate and reversible redistribution. Coactivator binding appears to be indispensable for redistribution and has a major contribution to chromatin association. A nuclear mobility map recorded by light sheet microscopy-FCS shows that the ligand-induced transition from the fast to the slow population occurs throughout the nucleus. Our results support a model in which RXR has a distinct, highly dynamic nuclear behavior and follows hit-and-run kinetics upon activation.

Genomic evaluation methods today use single nucleotide polymorphism (SNP) as genomic markers to trace quantitative trait loci (QTL). Today most genomic prediction procedures use biallelic SNP markers. However, SNP can be combined into short, multiallelic haplotypes that can improve genomic prediction due to higher linkage disequilibrium between the haplotypes and the linked QTL. The aim of this study was to develop a method to identify the haplotypes, which can be expected to be superior in genomic evaluation, as compared with either SNP or other haplotypes of the same size. We first identified the SNP (termed as QTL-SNP) from the bovine 50K SNP chip that had the largest effect on the analyzed trait. It was assumed that these SNP were not the causative mutations and they merely indicated the approximate location of the QTL. Haplotypes of 3, 4, or 5 SNP were selected from short genomic windows surrounding these markers to capture the effect of the QTL. Two methods described in this paper aim at selecting the most optimal haplotype for genomic evaluation. They assumed that if an allele has a high frequency, its allele effect can be accurately predicted. These methods were tested in a classical validation study using a dairy cattle population of 2,235 bulls with genotypes from the bovine 50K SNP chip and daughter yield deviations (DYD) on 5 dairy cattle production traits. Combining the SNP into haplotypes was beneficial with all tested haplotypes, leading to an average increase of 2% in terms of correlations between DYD and genomic breeding value estimates compared with the analysis when the same SNP were used individually. Compared with haplotypes built by merging the QTL-SNP with its flanking SNP, the haplotypes selected with the proposed criteria carried less under- and over-represented alleles: the proportion of alleles with frequencies 40% decreased, on average, by 17.4 and 43.4%, respectively. The correlations between DYD and genomic breeding value estimates increased by 0.7 to 0.9 percentage points when the haplotypes were selected using any of the proposed methods compared with using the haplotypes built from the QTL-SNP and its flanking markers. We showed that the efficiency of genomic prediction could be improved at no extra costs, only by selecting the proper markers or combinations of markers for genomic prediction. One of the presented approaches was implemented in the new genomic evaluation procedure applied in dairy cattle in France in April 2015.

Haplotype construction methods to enhance genomic evaluation. 66. Annual Meeting of the European Federation of Animal Science (EAAP)

In this paper we discuss the development of TimeTravel, a mobile application for tracking personal time dilation. Time dilation is the relativistic warping effect on time that velocity and gravity produces. Predicted by Einstein's Special theory of relativity (1905) and verified by practical experiment, (Hafele and Keating 1972) time dilation affects all things in motion, anywhere in the Universe (Reinhardt 2007). Our project was to develop a simple application aimed at smart watches that could communicate the imperceptible effects of time dilation on a user's everyday activities in an easy to understand, meaningful way. We describe the development and consider what happens when we attempt to visualise the imperceptible

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Warmer spring temperatures, as caused by climate warming, led to an earlier bud burst in spring and an extended growing season in many temperate and boreal tree species. But to which extent will the phenology of these species keep tracking rising temperatures in future? Temperature, photoperiod and degree of winter chilling are the main environmental factors controlling tree spring phenology. Contrary to the high inter-annual variation of spring temperatures, photoperiod is an astronomical, weather independent environmental cue for the progression of the season. Photoperiodic control of spring development prevents trees from flushing too early under mild winter and early spring temperatures, before the period of potentially fatal freezing damage is over. Photoperiod sensitive species are therefore likely to stop tracking climate warming the closer the temperature modulated bud break is shifted toward the genetically fixed photoperiod threshold. I assessed the photoperiod sensitivity of spring bud swelling and bud burst in several common temperate tree species using growth chamber experiments with variable photoperiod × temperature interaction and evaluated commonly used phenological models to represent these interactions. Short photoperiods delayed bud burst in late successional species to various degrees, whereas no distinct photoperiod sensitivity of bud burst was observed in early successional and exotic (ornamental) species, which are thus mostly temperature controlled. Climate warming will thus not necessarily lead to progressively longer growing seasons in late successional species, as is often assumed.

Syftet med denna studie var att undersöka och kartlägga den komplexa språksituationen och - användningen hos en flerspråkig person. Den undersökta personen kallas för Frida. Hon hade redan i ung ålder lärt sig mer än två språk och har sedermera varit i kontakt med sju språk på en signifikant kunskapsnivå. Denna studie ville knyta an till de teorier och modeller som har presenterats i den modernare forskningen kring andra- och tredjespråksinlärning. Undersökningen baserades enbart på Fridas självredogörelser enligt tre kriterier; hennes språkbiografiska bakgrund, språkfärdigheten och hennes attityder gentemot sin egen språksituation och språk i allmänhet. Dessa kriterier undersöktes med hjälp av kvalitativa intervjuer och självbedömningsmallar. Resultaten bekräftade antaganden om att Fridas språkanvändning och –situation idag påverkas av ett komplext samspel mellan ett flertal multifaktorella komponenter som uppstår i en flerspråkig kontext. Kartläggningen av Fridas språkbiografiska bakgrund, hennes språkanvändning och hennes attityder gentemot språken samt medvetenhet har gett inblick i hur de underliggande mekanismerna inom flerspråkighet verkar. The aim of this study was to explore and analyse the complex language situation and use of a multilingual person. The examined person is called Frida. Already at a young age she had acquired more than two languages and today she has been in relevant contact with around seven languages. This study wanted to connect to the theories and models, which are presented in today’s research on Second and Third Language Acquisition. The study was entirely based on Frida’s self reports according to the following criteria: her background of language acquisition, her proficiency levels and her attitudes and perception towards her own language situation and languages in general. These criteria had been worked out with the help of guided qualitative interviews and a self-assessment grid for the language skills. The results approved that Frida’s language use and situation is affected by the interaction of an amount of multifactorial components, which occur in a multilingual context. This analysis of Frida’s language background, her language use, attitudes and awareness gave an insight into how the underlying mechanisms of multilingualism work.