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In this report, we illustrate the considerable impact of researcher degrees of freedom with respect to exclusion of participants in paradigms with a learning element. We illustrate this empirically through case examples from human fear conditioning research, in which the exclusion of ‘non-learners’ and ‘non-responders’ is common – despite a lack of consensus on how to define these groups. We illustrate the substantial heterogeneity in exclusion criteria identified in a systematic literature search and highlight the potential problems and pitfalls of different definitions through case examples based on re-analyses of existing data sets. On the basis of these studies, we propose a consensus on evidence-based rather than idiosyncratic criteria, including clear guidelines on reporting details. Taken together, we illustrate how flexibility in data collection and analysis can be avoided, which will benefit the robustness and replicability of research findings and can be expected to be applicable to other fields of research that involve a learning element.
Enzyme immobilization using nanomaterials offers new approaches to enhanced bioelectrochemical performance and is essential for the preparation of bioelectrodes with high reproducibility and low cost. In this report, we describe the development of new three-dimensional (3D) bioelectrodes by immobilizing a "bioink" of glucose oxidase (GOD) in a matrix of reduced graphene oxides (RGOs), polyethylenimine (PEI), and ferrocene carboxylic acid (FcCOOH) on carbon paper (CP). CP with 3D interwoven carbon fibers serves as a solid porous and electronically conducting skeleton, providing large surface areas and space for loading the bioink and diffusion of substrate molecules, respectively. RGO enhances contact between the GOD-matrix and CP, maintaining high conductivity. The composition of the bioink has been systematically optimized. The GOD bioelectrodes show linearly increasing electrocatalytic oxidation current toward glucose concentration up to 48 mM. A hybrid enzymatic biofuel cell equipped with the GOD bioelectrode as a bioanode and a platinum cathode furthermore registers a maximum power density of 5.1 mu W cm(-2) and an open circuit voltage of 0.40 V at 25 degrees C. The new method reported of preparing a bioelectrode by drop-casting the bioink onto the substrate electrode is facile and versatile, with the potential of application also for other enzymatic bioelectrodes.
The significance of phytoliths for the control of silicon (Si) fluxes from terrestrial to aquatic ecosystems has been recognized as a key factor. Humankind actively influences Si fluxes by intensified land use, i.e., agriculture and forestry, on a global scale. We hypothesized phytolith distribution and assemblages in soils of agricultural and forestry sites to be controlled by vegetation (which is directed by land use) with direct effects on extractable Si fractions driven mainly by phytolith characteristics, i.e., dissolution status (dissolution signs) and morphology (morphotype proportions). To test our hypothesis we combined different chemical extraction methods (calcium chloride, ammonium oxalate, Tiron) for the quantification of different Si fractions (plant available Si, Si adsorbed to/occluded in pedogenic oxides/hydroxides, amorphous Si) and microscopic techniques (light microscopy, confocal laser scanning microscopy, scanning electron microscopy) for detailed analyses of phytoliths extracted using gravimetric separation (physical extraction) from exemplary loess soils of agricultural (arable land and grassland/meadow) and forestry (beech and pine) sites in Poland. We found differences in dissolution signs, morphotype proportions, and vertical distribution of phytoliths in soil horizons per site. In general, dominant morphotypes of assignable phytoliths in the studied soil profiles were elongate phytoliths and short cells, both of which are typical for grass-dominated vegetation. However, the organic layers of forest soils were dominated by globular phytoliths, which are typical indicators for mosses. As expected soil horizons under different vegetation generally were characterized by differences in extractable Si fractions, especially in the upper soil horizons. However, phytogenic Si pools counter-intuitively showed no correlations with chemically extracted Si fractions and soil pH at all. Our findings indicate that it is necessary to combine microscopic analyses and Si extraction techniques for examinations of Si cycling in biogeosystems, because extractions of Si fractions alone do not allow drawing any conclusions about phytolith characteristics or interactions between phytolith pools and chemically extractable Si fractions and do not necessarily reflect phytogenic Si pool quantities in soils and vice versa.
Protein interaction and protein imaging strongly benefit from the advancements in time-resolved and superresolution fluorescence microscopic techniques. However, the techniques were typically applied separately and ex vivo because of technical challenges and the absence of suitable fluorescent protein pairs. Here, we show correlative in vivo fluorescence lifetime imaging microscopy Forster resonance energy transfer (FLIM-FRET) and stimulated emission depletion (STED) microscopy to unravel protein mechanics and structure in living cells. We use magnetotactic bacteria as a model system where two proteins, MamJ and MamK, are used to assemble magnetic particles called magnetosomes. The filament polymerizes out of MamK and the magnetosomes are connected via the linker MamJ. Our system reveals that bacterial filamentous structures are more fragile than the connection of biomineralized particles to this filament. More importantly, we anticipate the technique to find wide applicability for the study and quantification of biological processes in living cells and at high resolution.
The great auk was once abundant and distributed across the North Atlantic. It is now extinct, having been heavily exploited for its eggs, meat, and feathers. We investigated the impact of human hunting on its demise by integrating genetic data, GPS-based ocean current data, and analyses of population viability. We sequenced complete mitochondrial genomes of 41 individuals from across the species' geographic range and reconstructed population structure and population dynamics throughout the Holocene. Taken together, our data do not provide any evidence that great auks were at risk of extinction prior to the onset of intensive human hunting in the early 16th century. In addition, our population viability analyses reveal that even if the great auk had not been under threat by environmental change, human hunting alone could have been sufficient to cause its extinction. Our results emphasise the vulnerability of even abundant and widespread species to intense and localised exploitation.
Lateral movements of alluvial river channels control the extent and reworking rates of alluvial fans, floodplains, deltas, and alluvial sections of bedrock rivers. These lateral movements can occur by gradual channel migration or by sudden changes in channel position (avulsions). Whereas models exist for rates of river avulsion, we lack a detailed understanding of the rates of lateral channel migration on the scale of a channel belt. In a two-step process, we develop here an expression for the lateral migration rate of braided channel systems in coarse, non-cohesive sediment. On the basis of photographic and topographic data from laboratory experiments of braided channels performed under constant external boundary conditions, we first explore the impact of autogenic variations of the channel-system geometry (i.e. channel-bank heights, water depths, channel-system width, and channel slope) on channel-migration rates. In agreement with theoretical expectations, we find that, under such constant boundary conditions, the laterally reworked volume of sediment is constant and lateral channel-migration rates scale inversely with the channel-bank height. Furthermore, when channel-bank heights are accounted for, lateral migration rates are independent of the remaining channel geometry parameters. These constraints allow us, in a second step, to derive two alternative expressions for lateral channel-migration rates under different boundary conditions using dimensional analysis. Fits of a compilation of laboratory experiments to these expressions suggest that, for a given channel bank-height, migration rates are strongly sensitive to water discharges and more weakly sensitive to sediment discharges. In addition, external perturbations, such as changes in sediment and water discharges or base level fall, can indirectly affect lateral channel-migration rates by modulating channel-bank heights.
NK cells have emerged as promising candidates for cancer immunotherapy, especially due to their ability to fight circulating tumor cells thereby preventing metastases formation. Hence several studies have been performed to generate and expand highly cytotoxic NK cells ex vivo, e.g., by using specific cytokines to upregulate both their proliferation and surface expression of distinct activating receptors. Apart from an enhanced activity, application of NK cells as immunotherapeutic agent further requires sufficient cell numbers and a high purity. All these parameters depend on a variety of different factors including the starting material, additives like cytokines as well as the culture system. Here we analyzed PBMC-derived NK cells of five anonymized healthy donors expanded under specific conditions in an innovative perfusion bioreactor system with respect to their phenotype, IFN gamma production, and cytotoxicity in vitro. Important features of the meander type bioreactors used here are a directed laminar flow of medium and control of relevant process parameters. Cells are cultivated under "steady state" conditions in perfusion mode. Our data demonstrate that expansion of CD3(+) T cell depleted PBMCs in our standardized system generates massive amounts of highly pure (>85%) and potent anticancer active NK cells. These cells express a variety of important receptors driving NK cell recruitment, adhesion as well as activation. More specifically, they express the chemokine receptors CXCR3, CXCR4, and CCR7, the adhesion molecules L-selectin, LFA-1, and VLA-4, the activating receptors NKp30, NKp44, NKp46, NKG2D, DNAM1, and CD16 as well as the death ligands TRAIL and Fas-L. Moreover, the generated NK cells show a strong IFN gamma expression upon cultivation with K562 tumor cells and demonstrate a high cytotoxicity toward leukemic as well as solid tumor cell lines in vitro. Altogether, these characteristics promise a high clinical potency of thus produced NK cells awaiting further evaluation.
On May 17, 2012, the social networking company Facebook Inc. fixes its initial public offering (IPO) price at $38.00 a share. Over the next couple of months, contrary to expectations raised by previous IPOs, the stock price crashes more than 50 per cent. Immediately, the question arises whether the issuer’s or the stock market’s pricing of the share are in line with the firm’s fundamentals. Thus, the purpose of this paper is to determine the company value in close proximity to the date of IPO.
Purpose: The concepts of creativity and intuition have been well studied in isolation, but less is known about their distinctive contributions to option generation in decision making. Method: We examined the relation between creative and intuitive decision making in two studies-one involving coaches and one involving soccer players-using video footage of real soccer matches. Additionally, we analyzed whether this relation is culture generic or culture specific by conducting matched cross-cultural studies in a European and a South American country. Results: In Study 1, results indicate a conceptual overlap of creativity and intuition for Brazilian and German soccer coaches. Furthermore, coaches did not differ in their evaluation of creative and intuitive actions of players of both cultures. In Study 2, we found that for both subsamples the total number of generated options was positively correlated with the quality of the first and the final option and that the quality of players' first (intuitive) option was higher than that of options generated later. Moreover, results indicate a positive correlation between a player's creativity score and the quality of the first generated option for the whole sample. Conclusion: Overall, our findings provide meaningful information regarding athletes' and coaches' option-generation processes in decision making in complex team sports.
Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER (TM) technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.
Ecological communities are undeniably diverse, both in terms of the species that compose them as well as the type of interactions that link species to each other. Despite this long recognition of the coexistence of multiple interaction types in nature, little is known about the consequences of this diversity for community functioning. In the ongoing context of global change and increasing species extinction rates, it seems crucial to improve our understanding of the drivers of the relationship between species diversity and ecosystem functioning. Here, using a multispecies dynamical model of ecological communities including various interaction types (e.g. competition for space, predator interference, recruitment facilitation in addition to feeding), we studied the role of the presence and the intensity of these interactions for species diversity, community functioning (biomass and production) and the relationship between diversity and functioning. Taken jointly, the diverse interactions have significant effects on species diversity, whose amplitude and sign depend on the type of interactions involved and their relative abundance. They however consistently increase the slope of the relationship between diversity and functioning, suggesting that species losses might have stronger effects on community functioning than expected when ignoring the diversity of interaction types and focusing on feeding interactions only.
We present a survey for metal absorption systems traced by neutral oxygen over 3.2 < z < 6.5. Our survey uses Keck/ESI and VLT/X-Shooter spectra of 199 QSOs with redshifts up to 6.6. In total, we detect 74 OI absorbers, of which 57 are separated from the background QSO by more than 5000 km s(-1). We use a maximum likelihood approach to fit the distribution of OI lambda 1302 equivalent widths in bins of redshift and from this determine the evolution in number density of absorbers with W-1302 > 0.05 angstrom, of which there are 49 nonproximate systems in our sample. We find that the number density does not monotonically increase with decreasing redshift, as would naively be expected from the buildup of metal-enriched circumgalactic gas with time. The number density over 4.9 < z < 5.7 is a factor of 1.7-4.1 lower (68% confidence) than that over 5.7 < z < 6.5, with a lower value at z < 5.7 favored with 99% confidence. This decrease suggests that the fraction of metals in a low-ionization phase is larger at z similar to 6 than at lower redshifts. Absorption from highly ionized metals traced by CIV is also weaker in higher-redshift OI systems, supporting this picture. The evolution of OI absorbers implies that metal-enriched circumgalactic gas at z similar to 6 is undergoing an ionization transition driven by a strengthening ultraviolet background. This in turn suggests that the reionization of the diffuse intergalactic medium may still be ongoing at or only recently ended by this epoch.
Zinc is an essential trace element, making it crucial to have a reliable biomarker for evaluating an individual’s zinc status. The total serum zinc concentration, which is presently the most commonly used biomarker, is not ideal for this purpose, but a superior alternative is still missing. The free zinc concentration, which describes the fraction of zinc that is only loosely bound and easily exchangeable, has been proposed for this purpose, as it reflects the highly bioavailable part of serum zinc. This report presents a fluorescence-based method for determining the free zinc concentration in human serum samples, using the fluorescent probe Zinpyr-1. The assay has been applied on 154 commercially obtained human serum samples. Measured free zinc concentrations ranged from 0.09 to 0.42 nM with a mean of 0.22 ± 0.05 nM. It did not correlate with age or the total serum concentrations of zinc, manganese, iron or selenium. A negative correlation between the concentration of free zinc and total copper has been seen for sera from females. In addition, the free zinc concentration in sera from females (0.21 ± 0.05 nM) was significantly lower than in males (0.23 ± 0.06 nM). The assay uses a sample volume of less than 10 µL, is rapid and cost-effective and allows us to address questions regarding factors influencing the free serum zinc concentration, its connection with the body’s zinc status, and its suitability as a future biomarker for an individual’s zinc status.
We have investigated the structural dynamics in photoexcited 1,2-diiodotetrafluoroethane molecules (C2F4I2) in the gas phase experimentally using ultrafast electron diffraction and theoretically using FOMO-CASCI excited-state dynamics simulations. The molecules are excited by an ultraviolet femtosecond laser pulse to a state characterized by a transition from the iodine 5p perpendicular to orbital to a mixed 5p parallel to sigma hole and CF2 center dot antibonding orbital, which results in the cleavage of one of the carbon-iodine bonds. We have observed, with sub-Angstrom resolution, the motion of the nuclear wave packet of the dissociating iodine atom followed by coherent vibrations in the electronic ground state of the C2F4I radical. The radical reaches a stable classical (nonbridged) structure in less than 200 fs.
Value-added (VA) modeling can be used to quantify teacher and school effectiveness by estimating the effect of pedagogical actions on students’ achievement. It is gaining increasing importance in educational evaluation, teacher accountability, and high-stakes decisions. We analyzed 370 empirical studies on VA modeling, focusing on modeling and methodological issues to identify key factors for improvement. The studies stemmed from 26 countries (68% from the USA). Most studies applied linear regression or multilevel models. Most studies (i.e., 85%) included prior achievement as a covariate, but only 2% included noncognitive predictors of achievement (e.g., personality or affective student variables). Fifty-five percent of the studies did not apply statistical adjustments (e.g., shrinkage) to increase precision in effectiveness estimates, and 88% included no model diagnostics. We conclude that research on VA modeling can be significantly enhanced regarding the inclusion of covariates, model adjustment and diagnostics, and the clarity and transparency of reporting.
What is the added value from attending a certain school or being taught by a certain teacher? To answer this question, the value-added (VA) model was developed. In this model, the actual achievement attained by students attending a certain school or being taught by a certain teacher is juxtaposed with the achievement that is expected for students with the same background characteristics (e.g., pretest scores). To this end, the VA model can be used to compute a VA score for each school or teacher, respectively. If actual achievement is better than expected achievement, there is a positive effect (i.e., a positive VA score) of attending a certain school or being taught by a certain teacher. In other words, VA models have been developed to “make fair comparisons of the academic progress of pupils in different settings” (Tymms 1999, p. 27). Their aim is to operationalize teacher or school effectiveness objectively. Specifically, VA models are often used for accountability purposes and high-stakes decisions (e.g., to allocate financial or personal resources to schools or even to decide which teachers should be promoted or discharged). Consequently, VA modeling is a highly political topic, especially in the USA, where many states have implemented VA or VA-based models for teacher evaluation (Amrein-Beardsley and Holloway 2017; Kurtz 2018). However, this use for high-stakes decisions is highly controversial and researchers seem to disagree concerning the question if VA scores should be used for decision-making (Goldhaber 2015). For a more exhaustive discussion of the use of VA models for accountability reasons, see, for example, Scherrer (2011).
Given the far-reaching impact of VA scores, it is surprising that there is scarcity of systematic reviews of how VA scores are computed, evaluated, and how this research is reported. To this end, we review 370 empirical studies from 26 countries to rigorously examine several key issues in VA modeling, involving (a) the statistical model (e.g., linear regression, multilevel model) that is used, (b) model diagnostics and reported statistical parameters that are used to evaluate the quality of the VA model, (c) the statistical adjustments that are made to overcome methodological challenges (e.g., measurement error of the outcome variables), and (d) the covariates (e.g., pretest scores, students’ sociodemographic background) that are used when estimating expected achievement.
All this information is critical for meeting the transparency standards defined by the American Educational Research Association (AERA 2006). Transparency is vital for educational research in general and especially for highly consequential research, such as VA modeling. First, transparency is highly relevant for researchers. The clearer the description of the model, the easier it is to build upon the knowledge of previous research and to safeguard the potential for replicating previous results. Second, because decisions that are based on VA scores affect teachers’ lives and schools’ futures, not only educational agents but also the general public should be able to comprehend how these scores are calculated to allow for public scrutiny. Specifically, given that VA scores can have devastating consequences on teachers’ lives and on the students they teach, transparency is particularly important to evaluate the chosen methodology to compute VA models for a certain purpose. Such evaluations are essential to answer the question to what extent the quality of VA scores allows to base far-reaching decisions on these scores for accountability purposes.
Ortho-allyloxy alkinyl benzenes undergo, upon microwave irradiation in dimethylformamide, a tandem sequence of Claisen-rearrangement and 5-endo-dig cyclization to furnish 7-allyl-substituted benzofurans. With terminal alkynes, chroman-4-ones and enaminoketones become the main products. A mechanistic proposal for this observation relies on a reaction of the starting material with the solvent dimethylformamide under the microwave conditions.
We studied the photoinduced ultrafast relaxation dynamics of the nucleobase thymine using gas-phase time-resolved photoelectron spectroscopy. By employing extreme ultraviolet pulses from high harmonic generation for photoionization, we substantially extend our spectral observation window with respect to previous studies. This enables us to follow relaxation of the excited state population all the way to low-lying electronic states including the ground state. In thymine, we observe relaxation from the optically bright (1)pi pi* state of thymine to a dark (1)n pi* state within 80 +/- 30 fs. The (1)n pi* state relaxes further within 3.5 +/- 0.3 ps to a low-lying electronic state. By comparison with quantum chemical simulations, we can unambiguously assign its spectroscopic signature to the (3)pi pi* state. Hence, our study draws a comprehensive picture of the relaxation mechanism of thymine including ultrafast intersystem crossing to the triplet manifold.
During the last decades, increasing exports of both dissolved organic carbon (DOC) and iron were observed from peat catchments in North America and Europe with potential consequences for water quality of streamwater and carbon storages of soils. As mobilisation and transport processes of DOC and iron in peat catchments are only partly understood, the purpose of this study was to elucidate these processes in an intensively monitored and studied system. Specifically, it was hypothesised that dissimilatory iron reduction in riparian peatland soils mobilises DOC initially adsorbed to iron minerals. During stormflow conditions, both DOC and iron will be transported into the stream network. Ferrous iron may be reoxidised at redox interfaces on its way to the stream, and subsequently, ferric iron could be transported together with DOC as complexes. To test these hypotheses, generalised additive models (GAMs) were applied to 14 years of weekly time series of discharge and concentrations of selected solutes measured in a German headwater stream called Lehstenbach. This stream drains a 4.19-km(2) forested mountain catchment; one third of which is covered by riparian peatland soils. We interpreted results of different types of GAM in the way that (a) iron reduction drove the mobilisation of DOC from peatland soils and that (b) both iron and DOC were transported as complexes after their joint mobilisation to and within the steam. It was speculated that low nitrate availability in the uppermost wetland soil layer, particularly during the growing season, promoted iron reduction and thus the mobilisation of DOC. However, the influence of nitrate on the DOC mobilisation remains relatively uncertain. This influence could be further investigated using methods similar to the GAM analysis conducted here for other catchments with long-term data as well as detailed measurements of the relevant species in riparian wetland soils and the adjacent stream network.
On 2015 July 18, near perihelion at a heliocentric distance of 1.28 au, the Visible InfraRed Thermal Imaging Spectrometer (VIRTIS-M) on board the Rosetta spacecraft had the opportunity of observing dust activity in the inner coma with a view of the night side (shadowed side) of comet 67P/Churyumov-Gerasimenko. At the time of the measurements we present here, we observe a dust plume that originates on the far side of the nucleus. We are able to identify the approximate location of its source at the boundary between the Hapi and Anuket regions, and we find that it has been in darkness for some hours before the observation. Assuming that this time span is equal to the conductive time scale, we obtain a thermal inertia in the range 25-36 W K-1 m(-2) s(-1/2). These thermal inertia values can be used to verify with a 3D finite-element method (REM) numerical code whether the surface and subsurface temperatures agree with the values found in the literature. We explored three different configurations: (1) a layer of water ice mixed with dust beneath a dust mantle of 5 mm with thermal inertia of 36 J m(-2) K-1 S-0.5 ; (2) the same structure, but with thermal inertia of 100 J m(-2) K-1 S-0.5; (3) an ice-dust mixture that is directly exposed. Of these three configurations, the first seems to be the most reasonable, both for the low thermal inertia and for the agreement with the surface and subsurface temperatures that have been found for the comet 67P/Churyumov-Gerasimenko. The spectral properties of the plume show that the visible dust color ranged from 16 +/- 4.8%/100 nm to 13 +/- 2.6%/100 nm, indicating that this plume has no detectable color gradient. The morphology of the plume can be classified as a narrow jet that has an estimated total ejected mass of between 6 and 19 tons when we assume size distribution indices between -2.5 and -3.