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G protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C. elegans. These two mutant libraries enable effective deorphanization of chemoreceptors, and characterization of receptors for neuropeptides in various cellular processes. Mutating a set of closely related GPCRs in a single strain permits the assignment of functions to GPCRs with functional redundancy. Our analyses identify a neuropeptide that interacts with three receptors in hypoxia-evoked locomotory responses, unveil a collection of regulators in pathogen-induced immune responses, and define receptors for the volatile food-related odorants. These results establish our GPCR and neuropeptide mutant libraries as valuable resources for the C. elegans community to expedite studies of GPCR signaling in multiple contexts. To overcome challenges posted by vast number of GPCR genes and redundancy, the authors disrupted nearly all GPCR-encoding genes in C. elegans, enabling effective examination of GPCR signaling and offering a valuable resource for the research community. [ABSTRACT FROM AUTHOR]

In this paper, we demonstrate the coupling of synchrotron small angle X-ray scattering (SAXS) to asymmetrical flow-field flow fractionation (AF4) for protein characterization. To the best of our knowledge, this is the first time AF4 is successfully coupled to a synchrotron for on-line measurements on proteins. This coupling has potentially high impact, as it opens the possibility to characterize individual constituents of sensitive and/or complex samples, not suited for separation using other techniques, and for low electron density samples where high X-ray flux is required, e.g., biomolecules and biologics. AF4 fractionates complex samples in native or close to native environment, with low shear forces and system surface area. Many orders of magnitude in size can be fractionated in one measurement, without having to reconfigure the experimental setup. We report AF4 fractionations with correlated UV and statistically adequate SAXS data of bovine serum albumin and a monoclonal antibody and evaluate SAXS data recorded for the two protein systems. [ABSTRACT FROM AUTHOR]

This paper departs from the Trump administration's main trade policy objective, i.e. to reduce the US trade deficit, which it considered to be harmful to the US economy. The main means for doing so has been to increase in import tariffs, despite most economists' view that a country's trade balance is driven by macroeconomic factors such as savings and investment rather than by trade policy. The paper reviews the various steps taken in the US trade dispute(s), primarily with China, including steps towards de-escalation in the final year of the Trump presidency. It then assesses the economic impact of the US trade dispute with China and the Phase One Deal, using computable general equilibrium (CGE) techniques. Importantly, it does so by updating the database to reflect the consequences of the shale gas revolution on US energy production and trade. Results are presented not only for the USA and China, but also on their trade with third countries by broad product category. [ABSTRACT FROM AUTHOR]

Physiochemical degradation of therapeutic proteins in vivo during plasma circulation after administration can have a detrimental effect on their efficacy and safety profile. During drug product development, in vivo animal studies are necessary to explore in vivo protein behaviour. However, these studies are very demanding and expensive, and the industry is working to decrease the number of in vivo studies. Consequently, there is considerable interest in the development of methods to pre-screen the behaviour of therapeutic proteins in vivo using in vitro analysis. In this work, asymmetrical flow field-flow fractionation (AF4) and liquid chromatography–mass spectrometry (LC-MS) were combined to develop a novel analytical methodology for predicting the behaviour of therapeutic proteins in vivo. The method was tested with two proteins, a monoclonal antibody and a serum albumin binding affibody. After incubation of the proteins in plasma, the method was successfully used to investigate and quantify serum albumin binding, analyse changes in monoclonal antibody size, and identify and quantify monoclonal antibody aggregates. [ABSTRACT FROM AUTHOR]

1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) is widely used as a crosslinker for fluorescence labeling of protein in the fields of biochemistry and food analysis. Many natural polysaccharides often contain some proteins or peptides that are very low in content but play a vital role in their biological function as well as technical applications. Determination of these low-content proteinaceous matters requires a highly sensitive and selective method. In this study, a methodological approach for investigations of the presence of proteinaceous material over the molar mass distribution (MD) of polysaccharides was developed using gum acacia (GA) as a model polysaccharide. EDC fluorescence-labeling method was modified by changing the pH (7, 9, and 11) of the solution for the analysis of low-content protein in food materials. Fluorescence spectroscopy and asymmetrical flow field-flow fractionation (AF4) were employed for characterizing the labeling efficiency and physiochemical properties of unlabeled and fluorescence-labeled GA. AF4 provided molar mass (M) and the radius of gyration (rG) of arabinogalactan (AG) and arabinogalactan protein complex (AGP) and determined the presence of proteinaceous matter over the MD. The labeling efficiencies of GA at pH 7, 9, and 11 determined by fluorescence spectroscopy were 56.5, 68.4, and 72.0%, respectively, with an increment of 15.5% when pH was increased from 7 to 11. The modified EDC fluorescence-labeling method allows highly sensitive and selective analysis of low-content proteinaceous matters and their distribution in natural polysaccharides. [ABSTRACT FROM AUTHOR]

5-Azacitidine (AZA) therapy is used in high-risk myelodysplastic syndrome (MDS) patients who often show abnormalities in their immunophenotype. We explored the potential impact of AZA on these immunophenotypic abnormalities in serial bone marrow studies performed in 81 patients from five centers. We compared the immunophenotypic features before and after therapy with AZA, established definitions consistent with flow cytometry immunophenotyping (FCI) improvement, and explored its clinical significance. After a median of 6 cycles of AZA, 41% of patients showed a FCI improvement and this finding associated with best possible clinical response (P < 0.001). FCI improvement also correlated with hematological improvement (HI) (53/78 patients; 68%), independently of their eligibility for stem cell transplantation. Among patients who achieved a HI after 6 cycles of AZA, the probability of maintaining this response at 12 cycles of AZA was twice as large (67%) for those patients who also achieved a FCI improvement after 6 cycles of AZA as compared to patients who did not (33%, P < 0.01). These findings support that monitoring of the immunophenotypic abnormalities during therapy with AZA may assist in redefining the quality of response in patients with MDS. [ABSTRACT FROM AUTHOR]

Little is known about which factors actually motivate individuals with psychosis to seek help or how psychosis may complicate the help-seeking process. The aim of this article is to examine the steps of this process and how psychopathological experiences might affect and interfere with it. In this qualitative study we interviewed nine patients with a first episode of psychosis. The interviews were transcribed and analysed according to the principles of thematic analysis using inductive as well as deductive methods. The crucial step in help-seeking behaviour seemed to be for the patients to identify the kind of problem they were facing. None of them clearly recognized their psychotic or otherwise anomalous experiences as symptoms of a mental disorder, and most of them did not seriously question the reality status of these experiences. For most of the patients it was an untenable social situation that caused them to seek help. When they did seek help the majority did not initially contact the psychiatric services. It seems paradoxical to expect patients who experience symptoms of psychosis for the first time to be able to unambiguously identify them as being exactly that and accordingly seek out psychiatric help, as diminished insight into illness is an inherent feature of psychosis. However, the phenomenon of 'double bookkeeping' seemed to provide an opening for seeking help from psychiatry in spite of compromised insight. This observation should be included in everyday clinical work and in future information campaigns. [ABSTRACT FROM AUTHOR]

Coupling of surface plasmon resonance (SPR) detection to asymmetric flow field-flow fractionation (AF4) offers the possibility to study active fractions of bio-separations on real samples, such as serum and saliva, including the assessment of activity of possibly aggregated species. The coupling of SPR with AF4 requires the possibility to select fractions from a fractogram and redirect them to the SPR. The combination of SPR with chromatography-like methods also requires a mechanism for regeneration of the receptor immobilised onto the SPR sensor surface. In recent work, the combination of size exclusion chromatography (SEC) with SPR was pioneered as a successful methodology for identification, characterisation and quantification of active biocomponents in biological samples. In this study, the approach using AF4 is evaluated for the antibody trastuzumab in buffer and serum. The particular object of this study was to test the feasibility of using AF4 in combination with SPR to detect and quantify proteins and aggregates in complex samples such as blood serum. Also, in the investigation, three different immobilisation methods for the receptor HER-2 were compared, which involved (1) direct binding via EDC/NHS, the standard approach; (2) immobilisation via NTA-Ni-Histag complexation; and (3) biotin/avidin-linked chemistry using a regenerable form of avidin. The highest specific activity was obtained for the biotin-avidin method, while the lowest specific activity was observed for the NTA-Ni-Histag linkage. The data show that AF4 can separate trastuzumab monomers and aggregates in blood serum and that SPR has the ability to selectively monitor the elution. This is an encouraging result for automated analysis of complex biological samples using AF4-SPR. [ABSTRACT FROM AUTHOR]

The mechanisms of amyloid-β (Aβ)-degradation and clearance in Alzheimer's disease (AD) pathogenesis have been relatively little studied. Short Aβ-fragments form by enzymatic cleavage and alternate amyloid-beta precursor protein (APP)-processing. Here we characterized a novel polyclonal Aβ-antibody raised against an Aβ mid-domain and used it to investigate microglial Aβ-uptake in situ by microscopy at the light- and ultrastructural levels. The rabbit Aβ-mid-domain antibody (ab338), raised against the mid-domain amino acids 21–34 (Aβ21–34), was characterized with biochemical and histological techniques. To identify the epitope in Aβ recognized by ab338, solid phase and solution binding data were compared with peptide folding scores as calculated with the Tango software. The ab338 antibody displayed high average affinity (KD: 6.2 × 10−10 M) and showed preference for C-terminal truncated Aβ-peptides ending at amino acid 34 and Aβ-mid domain peptides with high scores of β-turn structure. In transgenic APP-mouse brain, ab338 labelled amyloid plaques and detected Aβ-fragments in microglia at the ultra- and light microscopic levels. This reinforces a role of microglia/macrophages in Aβ-clearance in vivo. The ab338 antibody might be a valuable tool to study Aβ-clearance by microglial uptake and Aβ-mid-domain peptides generated by enzymatic degradation and alternate production. [ABSTRACT FROM AUTHOR]

Tree mortality from insect infestations can significantly reduce carbon storage in forest soils. In subarctic birch forests (Betula pubescens), ecosystem C cycling is largely affected by recurrent outbreaks of defoliating geometrid moths (Epirrita autumnata, Operophtera brumata). Here, we show that soil C stocks in birch forests across Fennoscandia did not change up to 8 years after moth outbreaks. We found that a decrease in woody fine roots was accompanied by a lower soil CO2 efflux rate and a higher soil N availability following moth outbreaks. We suggest that a high N availability and less ectomycorrhiza likely contributed to lowered heterotrophic respiration and soil enzymatic activity. Based on proxies for decomposition (heterotrophic respiration, phenol oxidase potential activity), we conclude that a decrease in decomposition is a prime cause why soil C stocks of mountain birch forest ecosystems have not changed after moth outbreaks. Compared to disturbed temperate and boreal forests, a CO2-related positive feedback of forest disturbance on climate change might therefore be smaller in subarctic regions. [ABSTRACT FROM AUTHOR]

End-use efficiency, demand response and coupling of different energy vectors are important aspects of future renewable energy systems. Growth in the number of data centres is leading to an increase in electricity demand and the emergence of a new electricity-intensive industry. Studies on data centres and energy use have so far focused mainly on energy efficiency. This paper contributes with an assessment of the potential for energy system integration of data centres via demand response and waste heat utilization, and with a review of EU policies relevant to this. Waste heat utilization is mainly an option for data centres that are close to district heating systems. Flexible electricity demand can be achieved through temporal and spatial scheduling of data centre operations. This could provide more than 10 GW of demand response in the European electricity system in 2030. Most data centres also have auxiliary power systems employing batteries and stand-by diesel generators, which could potentially be used in power system balancing. These potentials have received little attention so far and have not yet been considered in policies concerning energy or data centres. Policies are needed to capture the potential societal benefits of energy system integration of data centres. In the EU, such policies are in their nascent phase and mainly focused on energy efficiency through the voluntary Code of Conduct and criteria under the EU Ecodesign Directive. Some research and development in the field of energy efficiency and integration is also supported through the EU Horizon 2020 programme. Our analysis shows that there is considerable potential for demand response and energy system integration. This motivates greater efforts in developing future policies, policy coordination, and changes in regulation, taxation and electricity market design. [ABSTRACT FROM AUTHOR]

Starch is one of the main carbohydrates in food; it is formed by two polysaccharides: amylose and amylopectin. The granule size of starch varies with different botanical origins and ranges from less than 1 μm to more than 100 μm. Some physicochemical and functional properties vary with the size of the granule, which makes it of great interest to find an efficient and accurate size-based separation method. In this study, the full-feed depletion mode of split-flow thin cell fractionation (FFD-SF) was employed for a size-based fractionation of two types of starch granules (corn and potato) on a large scale. The fractionation efficiency (FE) of fraction-a for corn and potato granules was 98.4 and 99.4%, respectively. The FFD-SF fractions were analyzed using optical microscopy (OM) and gravitational field-flow fractionation (GrFFF). The respective size distribution results were in close agreement for the corn starch fractions, while they were slightly different for the potato starch fractions. The thermal properties of FFD-SF fractions were analyzed, and the results for the potato starch showed that the peak temperature of gelatinization (Tp) slightly decreases as the size of the granules increases. Additionally, the enthalpy of gelatinization (ΔH) increases when the granule size increases and shows negative correlation with the gelatinization range (ΔT). [ABSTRACT FROM AUTHOR]

Self-disorders have been hypothesized to be an underlying and trait-like core feature of schizophrenia-spectrum disorders and a certain degree of temporal stability of self-disorders would therefore be expected. The aim of the study was to examine the persistence of self-disorders measured by the Examination of Anomalous Self Experiences over a time span of 5 years. 48 patients with schizophrenia-spectrum disorders were thoroughly assessed for psychopathology at baseline and 5 years later. Self-disorders were assessed by the Examination of Anomalous Self Experiences. The level of self-disorders was same at the two occasions for the full Examination of Anomalous Self Disorders and for four out of the five domains. For one domain, the level of self-disorders increased slightly from baseline to follow-up. The correlations between baseline and follow-up were moderate. 9 out of the 13 most-frequently rated items at baseline showed equal frequencies at follow-up. The baseline level of self-disorders predicted global symptomatic, but not functional outcome. Self-disorders measured by the Examination of Anomalous Self Experiences show a high level of temporal persistence over 5 years and predict symptomatic outcome. [ABSTRACT FROM AUTHOR]

The analysis of aggregates of therapeutic proteins is crucial in order to ensure efficacy and patient safety. Typically, the analysis is performed in the finished formulation to ensure that aggregates are not present. An important question is, however, what happens to therapeutic proteins, with regard to oligomerization and aggregation, after they have been administrated (i.e., in the blood). In this paper, the separation of whole blood, plasma, and serum is shown using asymmetric flow field-flow fractionation (AF4) with a minimum of sample pre-treatment. Furthermore, the analysis and size characterization of a fluorescent antibody in blood plasma using AF4 are demonstrated. The results show the suitability and strength of AF4 for blood analysis and open new important routes for the analysis and characterization of therapeutic proteins in the blood. [ABSTRACT FROM AUTHOR]

Purpose: The study examined the effects of short-term field-based military training with partial sleep deprivation on whole-body endurance performance in well-trained individuals.Methods: Before and after a 2-day sustained operations (SUSOPS), 14 cadets performed a 15-min constant-load cycling at 65% of peak power output (PPO; CLT65), followed by an exhaustive constant-load trial at 85% of PPO (CLT85). Physiological [oxygen uptake ([Formula: see text]O2), heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and regional oxygenation (TOI) in the frontal cerebral cortex and vastus lateralis muscle] and psychological [effort perception (RPE), affective valence (FS), and perceived activation (FAS)] variables were monitored during exercise.Results: SUSOPS reduced time to exhaustion in CLT85 by 29.1% (p = 0.01). During the CLT65 trial, SUSOPS potentiated the exercise-induced elevations in [Formula: see text]O2 and HR (p < 0.05), and blunted MAP (p = 0.001). CO did not differ between trials. Yet, towards the end of both CLT85 trials, CO tended to decline (p ≤ 0.08); a response that occurred at an earlier stage in the SUSOPS trial. During CLT65, SUSOPS altered neither cerebral nor muscle TOI. The SUSOPS CLT85 trial, however, was terminated at similar leg-muscle deoxygenation (p > 0.05) and lower prefrontal cortex deoxygenation (p < 0.01). SUSOPS increased RPE at submaximal intensities (p = 0.05), and suppressed FAS and FS throughout (p < 0.01).Conclusions: The present findings indicate, therefore, that a brief period of military sustained operations with partial sleep deprivation augment cardiorespiratory and psychological strain, limiting high-intensity endurance capacity. [ABSTRACT FROM AUTHOR]

The use of polymers for the delivery of drugs has increased dramatically in the last decade. To ensure the desired properties and functionality of such substances, adequate characterization in terms of the molar mass (M) and size is essential. The aim of this study was to evaluate the changes in the M and size of PVP-b-PAMPS when the amounts of the synthesis reactants in the two-step radical reaction were varied. The determination of the M and size distributions was performed by an asymmetric flow field-flow fractionation (AF4) system connected to multiangle light scattering (MALS) and differential refractive index (dRI) detectors. The results show that the M of the polymers varies depending on the relative amounts of the reactants and that AF4-MALS-dRI is a powerful characterization technique for analyzing polymers. Using AF4, it was possible to separate the product of the first radical reaction (PVP-CTA) into two populations. The first population had an elongated, rod-like or random coil conformation, and the second had a conformation corresponding to homogeneous spheres or a microgel structure. PVP-b-PAMPS had only one population, which had a rod-like conformation. The molar masses of PVP-CTA and PVP-b-PAMPS found in this study were higher than those reported in previous studies. [ABSTRACT FROM AUTHOR]

In this work, asymmetrical flow field-flow fractionation (AF4) coupled with UV/Vis, multi-angle light scattering (MALS), and differential refractive index (dRI) detectors (AF4-UV-MALS-dRI) was employed for analysis of glutamate decarboxylase ( LbGadB) from Lactobacillus brevis ( L. brevis). AF4 provided molecular weight ( MW) (or size)-based separation of dimer, hexamer, and aggregates of LbGadB. The effect of pH on oligomerization of LbGadB was investigated, and then AF4 results were compared to those from molecular modeling. The MWs measured by AF4-UV-MALS-dRI for dimeric and hexameric forms of LbGadB were 110 and 350 kDa, respectively, which are in good agreements with those theoretically calculated (110 and 330 kDa). The molecular sizes determined by AF4-UV-MALS-dRI were also in good agreement with those obtained from molecular modeling (6 and 10 nm, respectively, for dimeric and hexameric from AF4-UV-MALS-dRI and 6.4 × 7.6 and 7.6 × 13.1 nm from molecular modeling). The effects of temperature, salt type, and salt concentration on oligomerization of LbGadB were also investigated using dynamic light scattering (DLS). It was found that the hexameric form of LbGadB was most stable at pH 6 and in presence of NaCl or KCl. The results indicate that AF4, in combination of various online detectors mentioned above, provides an effective tool for monitoring of oligomerization of LbGadB under different conditions, such as temperature, pH, type of salts, and salt concentrations. [ABSTRACT FROM AUTHOR]

The macromolecular composition of beer is largely determined by the brewing and the mashing process. It is known that the physico-chemical properties of proteinaceous and polysaccharide molecules are closely related to the mechanism of foam stability. Three types of 'American pale ale' style beer were prepared using different mashing protocols. The foam stability of the beers was assessed using the Derek Rudin standard method. Asymmetric flow field-flow fractionation (AF4) in combination with ultraviolet (UV), multiangle light scattering (MALS) and differential refractive index (dRI) detectors was used to separate the macromolecules present in the beers and the molar mass ( M) and molar mass distributions ( MD) were determined. Macromolecular components were identified by enzymatic treatments with β-glucanase and proteinase K. The MD of β-glucan ranged from 10 to 10 g/mol. In addition, correlation between the beer's composition and foam stability was investigated (increased concentration of protein and β-glucan was associated with increased foam stability). [ABSTRACT FROM AUTHOR]

The objective of the present study was to examine relations between social network size and three cognitive abilities (episodic memory, semantic memory, visuospatial ability) in middle-aged adults. We analyzed cross-sectional data on social network size and cognitive functioning that were available for 804 participants aged 40-60 years. In addition, we examined 5- and 10-year follow-up measurements of cognitive functioning that were available for 604 and 255 participants, respectively. Cross-sectional analyses revealed a positive association between social network size and each of the three cognitive abilities. Baseline network size was positively related to 5-year changes in semantic memory, and to 10-year changes in semantic as well as episodic memory, but was unrelated to changes in visuospatial performance. A minor portion of the sample ( n = 131) had 10-year follow-up data on network size. Cross-lagged panel correlations revealed that baseline network size was associated with follow-up measurement in cognitive functioning (episodic memory, semantic memory), whereas baseline cognitive performance was unrelated to future network size. Together, the results demonstrate a small but positive relation between network size and declarative memory abilities, in line with models proposing a cognitive reserve built up by factors such as the increased cognitive stimulation associated with a more extensive social network. [ABSTRACT FROM AUTHOR]

Anticipatory trade effects of free trade agreements (FTAs) have been documented in various papers. One reason put forward trying to explain this phenomenon is reduced trade policy uncertainty. This paper is one of the first to explore the role of anticipation and trade policy uncertainty in the case of a recently concluded deep and comprehensive EU FTA, including significant behind the border measures. We use monthly data at a lower level of aggregation (8-digit level) compared to previous studies and we account for changes in the EU product classification over time. We also distinguish between the impact on products which are actually subject to liberalisation under the FTA as opposed to those which are already duty-free and we examine the effects on both the extensive margin and the intensive margin. We consider the impact of the FTA during three different periods of time (the start of negotiations, initialling of the agreement and entry into force), while comparing with the period before negotiations began. The results indicate that the FTA has had a positive impact on exports on both margins. The impact on the EU is somewhat higher indicating that EU exporters have more to gain in terms of increasing the predictability of the trade policy regime of the destination market and lowering its tariffs than vice versa. The results demonstrate that the impact of FTAs should not be assessed against the time period just prior to entry into force of the agreement, but much earlier to account for anticipation effects. [ABSTRACT FROM AUTHOR]

Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10). Suggestive associations (Meta P value <1 × 10) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10) and the multimodal analysis (Fisher P value = 1 × 10). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that neoliberal governance dismantles professionals’ will to critique, counteracting efforts to improve quality by preventing professionals in all sectors of the labour market from grounding work in their professional convictions. Managing attempts at governance has therefore become an important professional competence. This paper investigates how higher education prepares students for work under neoliberal forms of control. How are they trained to analyse and describe the effects of governance and prepared to work with the standards, manuals and documentation that influence quality in their lines of work? ‘Interruptive focus group conversations’ were performed with students from various professional programmes at a Swedish university. Student reasoning about governance is explored using theories of governance and subjectification. The results demonstrate that students are aware of the ways in which their professions are governed, the need to conduct discretionary work, but do not have skills to deal with governance critically. This latitude for pedagogical intervention is underutilized. [ABSTRACT FROM PUBLISHER]

In this paper, we investigate whether dissolution in water under autoclaving conditions (140 °C, 20 min) or in dimethyl sulfoxide, DMSO (100 °C, 1 h), is preferable for characterization of amylose. Two types of amylose, potato and maize, were dissolved either in water using an autoclave or in DMSO. On the aqueous solutions obtained, the extent of molecular dissolution of the sample (referred to as the dissolution yield) was determined by enzymatic analysis as well as the molecular properties, such as molar mass and root-mean-square radius, obtained with asymmetrical flow field-flow fractionation coupled to multi-angle light scattering and differential refractive index detection (AF4-MALS-dRI). The results showed that both dissolution methods are efficient at dissolving amylose. However, AF4-MALS-dRI analysis revealed substantial differences. Amylose aqueous solutions obtained by dissolution in DMSO were relatively stable over time, but the dissolution method in autoclave caused some degradation of the molecules, and their solutions display a high tendency to retrograde. [ABSTRACT FROM AUTHOR]

In many countries, practice-oriented programmes have been recast as university programmes, fuelling debate on the purpose of higher education. We highlight two ways of talking about the challenges for higher education we think are already familiar to readers. We label them ‘political-worry discourse’ and ‘academic-worry discourse’. We argue for a third position that gives due recognition to the turn in governance. Professional work today is performed in a new landscape where maintaining the conditions for autonomy and discretionary work is more important than ever. This has implications for the pedagogic focus of higher education institutions. The proposed ‘dual learning’ concept addresses this challenge through educating students about governance and allowing students to position themselves in relation to the governance of their professions. By discussing governance, we contribute to a previously neglected field and support the position that higher education may indeed be the best place to provide professional education. [ABSTRACT FROM PUBLISHER]

Purpose: Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits. Methods: Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [C]AZD2184. The binding potential BP was calculated using linear graphical analysis with the cerebellum as reference region. Results: The binding of [C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BP were ApoE ε4 allele carriers. Conclusions: We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits. [ABSTRACT FROM AUTHOR]

We have investigated methods of starch dissolution with the aim of finding an optimum method to completely dissolve starch granules to form a molecularly dissolved starch solution without degradation of the polymers. Glycogen was used as a model molecule for amylopectin, to identify the dissolution conditions under which the degradation of the polymers was limited or not present. Dissolution was performed in water with temperatures up to 200 °C, facilitated by the use of heating in an autoclave or a microwave oven, or in dimethyl sulfoxide (DMSO) at 100 °C. Waxy maize starch was chosen due to its high content of amylopectin and very low content of amylose. The degree of starch dissolution under different conditions was determined enzymatically. The effect of different dissolution conditions on the molar mass and root-mean-square radius of the polymers was determined with asymmetrical flow field-flow fractionation coupled to multi-angle light scattering and differential refractive index (AF4-MALS-dRI) detectors under aqueous conditions. The results suggest that reliable and accurate size separation and characterization of amylopectin can be obtained by dissolution of starch granules in an aqueous environment at 140 °C by autoclaving or in DMSO at 100 °C. The results also clearly show an upper limit for heat treatment of starch, above which degradation cannot be avoided. [ABSTRACT FROM AUTHOR]

This study describes a method to obtain a certain humidity level by a certain drying treatment. This treatment was applied on cement based materials in order to identify the critical moisture level above which ion transport can occur. The drying is performed in two steps, first in one direction to reach a certain moisture level and then in the opposite direction to identify if ions can move at this lower level. This treatment gives an opportunity to determine ion transport at a well defined humidity, both in terms of moisture content and relative humidity. Ion transport was indicated by analyzing the potassium distribution on slices of mortar by SEM-EDS. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the stability of the polyfructan levan under different pH solution conditions by monitoring changes in the levan physicochemical properties, such as molar mass ( M), root mean square radius ( r), hydrodynamic radius ( r), structure factor ( r /r), and aggregation state with respect to solution pH and hydrolysis time. A commercial levan produced from Z. Mobilis was characterized using asymmetric flow field-flow fractionation (AF4) in combination with online multiangle light scattering (MALS) and differential refractive index (dRI) detection. Under neutral pH solution conditions the levan was found to have a M ranging from 10 to 5 × 10 g/mol, a r ranging from ~25 to 100 nm and a r from ~3 to 151 nm. Two populations were observed in the sample. One population with a M less than 10 g/mol which represented ~60 % of the sample and a second population with an ultrahigh M up to 5 × 10 g/mol, which comprised ~40 % of the sample. The measured r /r structure factor decreased from 1.8 to 0.65 across the AF4 fractogram indicating that early eluting low M levan species had a random coil configuration and late eluting high M species had more homogeneous spherical structures. The measured apparent density values decreased from 80 to 10 kg/m across the elution profile and suggest that the observed second population also contains aggregates. The stability of levan in different pH conditions ranging from 1.3 to 8.5 was assessed by tracking changes in the average M and r, and monitoring the formation of fructose over 1 week. The onset of levan acid hydrolysis was observed to occur sooner at lower pH conditions and no hydrolysis was observed for pH 5.5 and higher. [ABSTRACT FROM AUTHOR]

The soluble proteins and protein aggregates in Belinda oats were characterized using asymmetric flow field-flow fractionation (AF4) coupled with online UV-vis spectroscopy and multiangle light-scattering detection (MALS). Fractions from the AF4 separation were collected and further characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The AF4 fractogram of the oat extracts revealed three peaks which were determined to be monomeric forms of soluble proteins, globulin aggregates, and β-glucan, respectively. The early eluting monomeric proteins ranged in molar mass (MM) between 5 and 90 kg/mol and in hydrodynamic diameter ( D) from 1.6 to 13 nm. The MM at peak maximum of the globulin aggregate peak was found to be ∼300 kg/mol and the D was measured to be ∼20 nm. SDS-PAGE of the collected fraction across this peak revealed two bands with MM of 37 and 27 kg/mol which correspond to the α and β subunits of globulin indicating the elution of globulin aggregates. A third peak at long retention time was determined to be β-glucan through treatment of the oat extract with β-glucanase and by injection of β-glucan standards. The amount of soluble protein was measured to be 83.1 ± 2.3 wt.%, and the amount of albumin proteins was measured to be 17.6 ± 5.7 wt.% of the total protein in the oats. The results for Belinda oat extracts show that the AF4-MALS/UV platform is capable of characterizing the physicochemical properties such as MM and hydrodynamic size distribution of proteins and protein aggregates within a complicated food matrix environment and without the need to generate protein isolates. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Aims: We investigated the influence of tree species on the natural N abundance in forest stands under elevated ambient N deposition. Methods: We analysed δN in litter, the forest floor and three mineral soil horizons along with ecosystem N status variables at six sites planted three decades ago with five European broadleaved tree species and Norway spruce. Results: Litter δN and N enrichment factor (δN-δN) were positively correlated with N status based on soil and litter N pools, nitrification, subsoil nitrate concentration and forest growth. Tree species differences were also significant for these N variables and for the litter δN and enrichment factor. Litter from ash and sycamore maple with high N status and low fungal mycelia activity was enriched in N (+0.9 delta units) relative to other tree species (European beech, pedunculate oak, lime and Norway spruce) even though the latter species leached more nitrate. Conclusions: The δN pattern reflected tree species related traits affecting the N cycling as well as site fertility and former land use, and possibly differences in N leaching. The tree species δN patterns reflected fractionation caused by uptake of N through mycorrhiza rather than due to nitrate leaching or other N transformation processes. [ABSTRACT FROM AUTHOR]

Purpose: To develop a systems pharmacology model based on hormone physiology and pharmacokinetic-pharmacodynamic concepts describing the impact of thyroperoxidase (TPO) inhibition on thyroid hormone homeostasis in the dog and to predict drug-induced changes in thyroid hormones in humans. Methods: A population model was developed based on a simultaneous analysis of concentration-time data of T, T and TSH in dogs following once daily oral dosing for up to 6-months of a myeloperoxidase inhibitor (MPO-IN1) with TPO inhibiting properties. The model consisted of linked turnover compartments for T, T and TSH including a negative feedback from T on TSH concentrations. Results: The model could well describe the concentration-time profiles of thyroid hormones in dog. Successful model validation was performed by predicting the hormone concentrations during 1-month administration of MPO-IN2 based on its in vitro dog TPO inhibition potency. Using human thyroid hormone turnover rates and TPO inhibitory potency, the human T and TSH concentrations upon MPO-IN1 treatment were predicted well Conclusions: The model provides a scientific framework for the prediction of drug induced effects on plasma thyroid hormones concentrations in humans via TPO inhibition based on results obtained in in vitro and animal studies. [ABSTRACT FROM AUTHOR]

Neuroinflammation is typically observed in neurodegenerative diseases such as Alzheimer's disease, as well as after traumatic injury and pathogen infection. Resident immune cells, microglia and astrocytes, are activated and joined by blood-borne monocytes that traverse the blood-brain barrier and convert into activated macrophages. The activated cells express various cytokines, chemokines and proteolytic enzymes. To study the role of heparan sulfate proteoglycans in neuroinflammation, we employed a transgenic mouse overexpressing heparanase, an endoglucuronidase that specifically degrades heparan sulfate side chains. Neuroinflammation was induced by systemic challenge with lipopolysaccharide, or by localized cerebral microinjection of aggregated amyloid-β peptide, implicated in Alzheimer's disease. Lipopolysaccharide-treated control mice showed massive activation of resident microglia as well as recruitment of monocyte-derived macrophages into the brain parenchyma. Microinjection of aggregated amyloid-β elicited a similar inflammatory response, albeit restricted to the injection site, which led to dispersion and clearance of the amyloid. In the heparanase-overexpressing mice, all aspects of immune cell recruitment and activation were significantly attenuated in both inflammation models, as was amyloid dispersion. Accordingly, an in vitro blood-brain barrier model constructed from heparanase-overexpressing cerebral vascular cells showed impaired transmigration of monocytes compared to a corresponding assembly of control cells. Our data indicate that intact heparan sulfate chains are required at multiple sites to mediate neuroinflammatory responses, and further point to heparanase as a modulator of this process, with potential implications for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background and aims: Under chronically elevated N deposition, N retention mainly occur at high soil C-to-N ratio. This may be mediated through soil microbes, such as ectomycorrhizal (EM) fungi, saprotrophic fungi and bacteria, and the aim of this study was to evaluate the relationship between soil microbes and forest floor C-to-N ratios. Methods: Soil samples from 33 Norway spruce ( Picea abies (L.) H. Karst) forests in Denmark and southern Sweden in a forest floor C-to-N ratio gradient (ranging from 14 to 35) were analysed regarding the content of phospholipid fatty acids (PLFAs) to estimate their soil microbial community composition and the relative biomasses of different microbial groups. The relation of EM biomass to total fungal biomass was estimated as the loss of the fungal PLFA 18:2ω6,9 during incubation of soils and the production of EM mycelia was estimated using fungal in-growth mesh bags. The soil microbial variables were correlated to forest floor C-to-N ratio, NO leaching, soil pH and stand age. Results: Fungal proportions of microbial biomass, EM to total fungi and EM mycelial production were all positively related to C-to-N ratio, while NO leaching was negatively related to C-to-N ratio. Conclusions: Both EM and saprotrophic fungi change with forest floor C-to-N ratios and appear to play a central role in N retention in forest soil. A better understanding of the mechanisms behind this process may be revealed if the role of recalcitrant fungal metabolites for N retention (and soil C sequestration) can be identified. Research along this line deserves further studies. [ABSTRACT FROM AUTHOR]

In this paper, we evaluate the Swedish Programme for improving energy efficiency in energy-intensive industries (PFE). Since 2005, some 100 energy-intensive companies have entered this 5-year voluntary agreement (VA) and been exempted from the EU minimum tax on electricity. In return, each company is required to: conduct an energy audit and analysis; identify and invest in profitable electricity saving measures; implement and certify an energy management system; introduce routines for energy efficient procurement and project planning. For most participants the first programme period was completed in 2009 and available data enables this PFE ex-post evaluation. An impact evaluation compiles and analyse data that the companies have reported to the administrating agency, the Swedish Energy Agency (SEA). This assessment of quantifiable results is complemented by a process-oriented approach that combines studies of policy documents, previous evaluations and personal communication with administrators as well as companies. The bottom-up calculation method distinguishes between gross and net impact. While the SEA estimates a gross impact of 1,450 GW h/year, the net impact consists of an interval between 689 and 1,015 GW h of net annual electricity savings. PFE has effectively and, to a low cost, exceeded the estimated impact of a minimum tax and can thus be judged as successful. A comprehensive evaluation plan could facilitate relevant data gathering in PFE and similar VAs and could, in doing so, improve accuracy and possibly reduce evaluation cost. Such a plan should give weight also to the organisational changes, with potential long-lasting effects, that these programmes are capable of promoting. [ABSTRACT FROM AUTHOR]

In this study, a coupled multi-species transport and chemical equilibrium model has been established. The model is capable of predicting time dependent variation of pore solution and solid-phase composition in concrete. Multi-species transport approaches, based on the Poisson-Nernst-Planck (PNP) theory alone, not involving chemical processes, have no real practical interest since the chemical action is very dominant for cement based materials. Coupled mass transport and chemical equilibrium models can be used to calculate the variation in pore solution and solid-phase composition when using different types of cements. For example, the physicochemical evaluation of steel corrosion initiation can be studied by calculating the molar ratio of chloride ion to hydroxide ion in the pore solution. The model can, further, for example, calculate changes of solid-phase composition caused by the penetration of seawater into the concrete cover. The mass transport part of the model is solved using a non-linear finite element approach adopting a modified Newton-Raphson technique for minimizing the residual error at each time step of the calculation. The chemical equilibrium part of the problem is solved by using the PHREEQC program. The coupling between the transport part and chemical part of the problem is tackled by using a sequential operator splitting technique and the calculation results are verified by comparing the elemental spacial distribution in concrete measured by the electron probe microanalysis (EPMA). [ABSTRACT FROM AUTHOR]

Energy service companies (ESCOs) are often portrayed as important change agents in capturing the opportunity to curb energy demand and mitigate climate change through increased efficiency. Yet, the literature in this area is limited. While many studies analyze economic and environmental savings from energy efficiency programs, far less attention has been devoted to evaluating managerial and other challenges for ESCOs to transform the “efficiency gap” into a viable business. Sweden presents an interesting case study given its early experience in energy market reform as well as the rapid growth in recent years of its ESCO market. By conducting in-depth interviews with ESCOs operating in Sweden, this research addresses the following: (1) current market opportunity analysis, including how Swedish market conditions shape firms' business strategies, (2) business characteristics and service functions, with attention to perceptions regarding which market segments are considered compelling, and (3) how policy might expand the size and attractiveness of additional sectors/market segments. This analysis is informed by additional discussions with policymaker, agencies, authorities, and customers. The insights garnered are important as Member States prepare to implement the Directive on Energy End-use Efficiency and Energy Services. Despite rapid growth, ongoing challenges remain for ESCOs. Government still has a role in education, policy, and residential sector solutions. Greater details and data on the energy savings produced by ESCO projects are needed. Future research could address best practices for reporting data from ESCO projects. Moreover, with additional data on ESCO projects, studies could benchmark these results with other international programs to promote energy efficiency. [ABSTRACT FROM AUTHOR]

Olfactory impairments are present in common neurodegenerative disorders and predict conversion to dementia in non-demented individuals with cognitive impairment. In cognitively intact elderly, evidence is sparse regarding the role of olfactory deficits in predicting cognitive impairment. The present study investigated predictors of 5-year prospective decline in the Mini-Mental State Examination (MMSE) in a large ( n = 501), population-based sample of elderly (65–90 years) individuals. All participants were genotyped for the ApoE gene, assessed for health factors, and were non-demented at the baseline assessment. After partialling out the influences of demographic and health-factors at baseline and dementia at follow-up, poor odor identification ability in combination with older age and the ApoE-ε4 allele predicted larger prospective global cognitive decline. This effect could not be produced by a vocabulary test. In sum, the findings suggest that an olfactory deficit can dissociate between benign and malign global cognitive development in non-demented, very old ε4-carriers, who are at high risk of developing dementia. [ABSTRACT FROM AUTHOR]

B Correction to: Analytical and Bioanalytical Chemistry b https://doi.org/10.1007/s00216-020-03011-x Unfortunately, in Table 2 of this article, the data in the column headed CMD-NTA for the parameter K SB D sb were mistakenly listed too low by a factor 10; please find the correct information below: For the Parameter K SB D sb of the immobilization method CMD-NTA, the value should be 4.9e-10. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. [Extracted from the article]

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Allopregnanolone is an endogenous neuroactive steroid that, through its binding to the γ-aminobutyric acid (GABA) A receptor, has GABA-active properties. Animal studies indicate that allopregnanolone administration results in diminished learning and memory impairment. The aim of the current study was to investigate the effect of intravenously administered allopregnanolone on episodic memory, semantic memory, and working memory in healthy women. Twenty-eight healthy women were included in the study. The participants were scheduled for the memory tests twice in the follicular phase. During the test sessions, an intravenous allopregnanolone and placebo infusion were administered in a double-blinded, randomized order at intervals of 48 h. Before and 10 min after the allopregnanolone/placebo injections, memory tasks were performed. The study demonstrated that allopregnanolone impaired episodic memory in healthy women. There was a significant difference between pre- and postallopregnanolone injection episodic memory scores ( p < 0.05), whereas there was no change in episodic memory performance following the placebo injections. There was also a significant difference between allopregnanolone and placebo postinjection episodic memory scores ( p < 0.05). There were no effects of allopregnanolone on the semantic memory task or working memory task. Intravenous allopregnanolone impairs episodic memory in healthy women, but there is a high degree of individual variability. [ABSTRACT FROM AUTHOR]

The paper presents a mathematical model for calculating the nonisothermal moisture transfer in porous building materials. The simultaneous heat and moisture transfer problem was modeled. Vapor content and temperature were chosen as principal driving potentials. The coupled equations were solved by a numerical method. An experimental methodology for determining the temperature gradient coefficient for building materials was also proposed. Both the moisture diffusion coefficient and the temperature gradient coefficient for building material were experimentally evaluated. Using the measured moisture transport coefficients, the temperature and vapor content distribution inside building materials were predicted by the new model. The results were compared with experimental data. A good agreement was obtained. [ABSTRACT FROM AUTHOR]

Realizing a 20% energy efficiency improvement in Europe by 2020 requires the introduction of good new energy efficiency policies as well as strengthening and enforcing the existing policies. This raises the question: what characterizes good and effective energy efficiency policies and their implementation? Systematic ex post evaluation of energy efficiency policies can reveal factors determining not only what works and what does not but also explain why. Ex post evaluation of 20 energy efficiency policy instruments applied across different sectors and countries in Europe among others showed that ex post evaluation does not yet have a high priority among policy makers: Often, quantitative targets and clear timeframes are lacking, and monitoring information is not collected on a regular basis. Our analysis, however, did reveal some general factors in the process of design and implementation of policy instruments that appear as important including (1) existence of clear goals and a mandate for the implementing organization, (2) the ability to balance and combine flexibility and continuity, (3) the involvement of stakeholders, and (4) the ability to adapt to and integrate adjacent policies or develop consistent policy packages. The analysis was performed using a uniform methodology called “theory-based policy evaluation”. The general principle behind this approach is that a likely theory is drawn up on the program’s various steps of logic of intervention to achieve its targeted impact in terms of energy efficiency improvement. The approach has several benefits over other ex post evaluation methods because (1) the whole policy implementation process is evaluated and the focus is not just on the final impacts, (2) through the development of indicators for each step in the implementation process, the “successes and failures” can be determined to the greatest extent possible, and (3) by applying this approach, we not only learn whether policies are successful or not but also why they succeeded or failed and how they can be improved. [ABSTRACT FROM AUTHOR]

In this paper, we present an international network of researchers from projects examining the human aging process and its consequences. It is both vital and urgent to include aging and a life course perspective on the public health agenda, particularly in low-income countries. By announcing the network in a publication, we wish not just to position the network but, more importantly, to attract the attention of other potential collaborators either at the project, institutional, decision making, or applied level. [ABSTRACT FROM AUTHOR]