bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and characterization of novel dual Fc antibody with enhanced avidity for Fc receptors
Authors: Goulet Dennis R. , Zwolak Adam , Williams James A. , Chiu Mark L. , Atkins William M.
Published: November 2019

Monoclonal antibodies (mAbs) have become an important class of therapeutics, particularly in the realm of anticancer immunotherapy. While the two antigen‐binding fragments (Fabs) of an mAb allow for high‐avidity binding to molecular targets, the crystallizable fragment (Fc) engages immune effector elements. mAbs of the IgG class are used for the treatment of autoimmune diseases and can elicit antitumor immune functions not only by several mechanisms including direct antigen engagement via their Fab arms but also by Fab binding to tumors combined with Fc engagement of complement component C1q and Fcγ receptors. Additionally, IgG binding to the neonatal Fc receptor (FcRn) allows for endosomal recycling and prolonged serum half‐life. To augment the effector functions or half‐life of an IgG1 mAb, we constructed a novel “2Fc” mAb containing two Fc domains in addition to the normal two Fab domains. Structural and functional characterization of this 2Fc mAb demonstrated that it exists in a tetrahedral‐like geometry and retains binding capacity via the Fab domains. Furthermore, duplication of the Fc region significantly enhanced avidity for Fc receptors FcγRI, FcγRIIIa, and FcRn, which manifested as a decrease in complex dissociation rate that was more pronounced at higher densities of receptor. At intermediate receptor density, the dissociation rate for Fc receptors was decreased 6‐ to 130‐fold, resulting in apparent affinity increases of 7‐ to 42‐fold. Stoichiometric analysis confirmed that each 2Fc mAb may simultaneously bind two molecules of FcγRI or four molecules of FcRn, which is double the stoichiometry of a wild‐type mAb. In summary, duplication of the IgG Fc region allows for increased avidity to Fc receptors that could translate into clinically relevant enhancement of effector functions or pharmacokinetics.
Herbal medicinal products for inflammatory bowel disease: A focus on those assessed in double‐blind randomised controlled trials
Authors: Holleran Grainne , Scaldaferri Franco , Gasbarrini Antonio , Currò Diego
Published: November 2019

Inflammatory bowel disease patients frequently use herbal products as complementary or alternative medicines to current pharmacotherapies and obtain information on them mainly from the internet, social media, or unlicensed practitioners. Clinicians should therefore take a more active role and become knowledgeable of the mechanisms of action and potential drug interactions of herbal medicines for which evidence of efficacy is available. The therapeutic efficacy and safety of several herbal medicines have been studied in double‐blind randomised controlled trials (RCTs). Evidence of efficacy is available for Andrographis paniculata extract; curcumin; a combination of myrrh, extract of chamomile flower, and coffee charcoal; and the Chinese herbal medicines Fufangkushen colon‐coated capsule and Xilei san in patients with ulcerative colitis; and Artemisia absinthium extract and Boswellia serrata resin extract in patients with Crohn's disease. However, most of this evidence comes from single small RCTs with short follow‐up, and the long‐term effects and safety of their use have not yet been established. Thus, our findings indicate that further appropriately sized RCTs are necessary prior to the recommended use of these herbal medicines in therapy. In the meantime, increasing awareness of their use, and potential drug interactions among physicians may help to reduce unwanted effects and adverse disease outcomes.
Grain Quality Engineering for Organic Metal Halide Perovskites Using Mixed Antisolvent Spraying Treatment
Authors: Lee Da Seul , Bing Jueming , Kim Jincheol , Green Martin A. , Huang Shujuan , Ho-Baillie Anita W. Y.
Published: November 2019

Herein, a mixed anti‐solvent treatment by spraying acetonitrile (ACN)‐added chlorobenzene (CBZ) for the fabrication of high‐quality perovskite films is proposed. While the lower‐boiling‐point ACN preserves the morphology of the perovskite film, it has a significant impact on perovskite crystallization dynamics. While CBZ is responsible for facilitating nucleation, ACN performs two functions. ACN as a weak polarity solvent allows the organic salt in the perovskite complex to be redissolved for perovskite formation and loosens the dimethyl sulfoxide (DMSO)–PbI2 bond for more rapid perovskite crystallization. For the mixed anti‐solvent treatment to be successful, an appropriate amount of ACN is the key and the use of spraying to dispense the mixed anti‐solvent is crucial. This is due to the more instant and rapid reaction caused by the ACN which is faster than spreading the ACN across the substrate by the spinning motion. The resultant film using an appropriate mixed anti‐solvent treatment is a pinhole‐free high‐quality perovskite film with larger grain and enhanced crystallinity compared with CBZ‐only treatment film. The best solar cell using this mixed anti‐solvent treatment with 20% of ACN and 80% of CBZ achieves a PCE of 20.1% due to the reduced recombination.
Integrated management of water resources: A novel approach for water‐stressed regions
Authors: Haroun Mohammed , Punjabi Soham , Suboyin Abhijith , Anastasiou Stavroula , de Bakker Joost
Published: November 2019

With the imminent global water crisis, it is imperative to revolutionize how water as a commodity is managed. Currently, there is a disconnect between how various sectors of the society withdraw and consume water especially in hydrocarbon‐rich, water scarce regions such as the Middle East. This study proposes a multi‐criteria, multidisciplinary decision analysis model for integrated technology development across private and public sectors in such regions. The increasing water stress provides the oil and gas industry an opportunity to play a pivotal role in harnessing its technologies to sustainably support the water demand. The proposed concept is supported with case studies highlighting challenges and innovative solutions applied across the globe. This study builds a case for a framework on the basis of a step‐change opportunity to manage water needs and effectively plan technology, investment, and regulatory requirements for sustainable access to future sustainable freshwater management.
The Hampering Effect of Precipitated Carbon on Hot Metal Desulfurization with Magnesium
Authors: Schrama Frank N. H. , Beunder Elisabeth M. , Visser Hessel-Jan , Sietsma Jilt , Boom Rob , Yang Yongxiang
Published: November 2019

Carbon may precipitate during the hot metal desulfurization (HMD) process as a result of carbon oversaturation because of temperature decrease. The precipitated carbon flakes form a layer between hot metal and slag. It is postulated that this carbon layer hampers desulfurization with magnesium by preventing MgS particles from reaching the slag phase. At Tata Steel in IJmuiden, the Netherlands, carbon in hot metal is measured in 657 heats after reagent injection. With this data, it can be determined whether the hampering effect of precipitated carbon on MgS flotation has a significant effect on the performance of the industrial HMD process. Plant data show a correlation between the precipitated carbon and the specific magnesium consumption for hot metal with a low initial sulfur concentration (below 225 ppm). This correlation cannot be found for hot metal with a higher initial sulfur concentration (above 275 ppm). Furthermore, a sulfur mass balance is made over the converter process, that shows no effect of carbon precipitation during HMD on resulfurization in the converter. The limited experimental accuracy of the plant data prevents a quantitative description of the hampering effect. The measurements do suggest that the effect is small.
Germinated Wheat Starch as a Substrate to Produce Cyclodextrins: Application in Inclusion Complex to Improve the Thermal Stability of Orange Essential Oil
Authors: Kringel Dianini Hüttner , Baranzelli Julia , Schöffer Jéssie Da Natividade , El Halal Shanise Lisie Mello , De Miranda Martha Zavariz , Dias Alvaro Renato Guerra , Zavareze Elessandra Da Rosa
Published: November 2019

Wheat pre‐harvest sprouting (PHS) is caused by high rainfall especially when the grain is in the filling stage. PHS decreases the grain yield, and is harmful to flour technological quality for baking, with a consequent decrease in economic value. However, the amylolytic activity promoted by germination can facilitate the production of cyclodextrin (CDs). The influence of germinated wheat starch concentration (1% and 10%) on the production of α, β, and γ‐CD is verified. In addition, the thermal stability of the inclusion complex between CDs produced from germinated wheat starch and orange essential oil (CDs/OEO) is also evaluated. The germination promotes the highest conversion yield (54.4%) at the lowest starch concentration (1%) used. The CDs/OEO increase the orange essential oil thermal stability, promoting their protection at high temperatures. Therefore, this study shows that germinated wheat starch is a promising substrate for the cyclodextrin production, adding value to this product that is, normally, not used by the food industry, but for animal nutrition or discarded.
The effect of local rebar geometry on global strain measurements in pull out tests
Authors: Leibovich Orit , Yankelevsky David Z. , Dancygier Avraham N.
Published: November 2019

Strain gauges are the common means to measure local strains in structural elements. It is well known that the strain at a given coordinate on the boundary of a structural element depends on the geometry, boundary conditions, loading system, and material properties. The precise location of the strain gauge along a line is not considered critical to obtaining a quality strain measurement at a specific location, wherever a continuous variation of strain along this line is expected, and a slight deviation of the gauge location will yield similar measurements. In a recent study, precise measurement of the circumferential strains on the outer face of cylindrical concrete specimens was carried out during pullout of a central rebar. Analyzing the measured data indicated that a slight shift in the strain gauge location on the order of millimeters only may considerably affect the measured strain. These controlled pullout tests highlighted the pronounced effect of the relative distance between the rebar rib and the strain gauge location on the strain magnitude and its variation with the increasing slip. This effect has not been reported before. It means that a slight difference in the strain gauge location yields different strain–slip relationships. This new finding may affect the interpretation of the measured strains. Attention should be given to the exact strain gauges' locations and detailed rebar ribs locations to properly interpret the measured data.
Unpacking students’ epistemic cognition in a physics problem‐solving environment
Authors: Lindfors Maria , Bodin Madelen , Simon Shirley
Published: November 2019

It is a widely held view that students’ epistemic beliefs influence the way they think and learn in a given context, however, in the science learning context, the relationship between sophisticated epistemic beliefs and success in scientific practice is sometimes ambiguous. Taking this inconsistency as a point of departure, we examined the relationship between students’ scientific epistemic beliefs (SEB), their epistemic practices, and their epistemic cognition in a computer simulation in classical mechanics. Tenth grade students’ manipulations of the simulation, spoken comments, and behavior were screen and video‐recorded and subsequently transcribed and coded. In addition, a stimulated recall interview was undertaken to access students’ thinking and reflections on their practice, in order to understand their practice and make inferences about their process of epistemic cognition. The paper reports on the detailed analysis of the data sets for three students of widely different SEB and performance levels. Comparing the SEB, problem solutions and epistemic practices of the three students has enabled us to examine the interplay between SEB, problem‐solving strategies (PS), conceptual understanding (CU), and metacognitive reflection (MCR), to see how these operate together to facilitate problem solutions. From the analysis, we can better understand how different students’ epistemic cognition is adaptive to the context. The findings have implications for teaching science and further research into epistemic cognition.
Positioning participation in the NGSS era: What counts as success?
Authors: Zangori Laura , Pinnow Rachel J.
Published: November 2019

The Next Generation Science Standards (NGSS) strives to shift science learning from the teacher as a single cognitive agent, to a classroom community in which participants are working together in directing the classroom's communal knowledge to figure out questions about how phenomena occur, and building, testing, and refining their ideas to address those questions. To achieve this type of classroom environment, teachers should attend to students' knowledge and ideas and pay attention to how students are located within teacher‐led interactions, such as being positioned as active discussants or designated listeners. In this study, we explore if and how this is occurring in the NGSS era. We used a naturalistic inquiry to explore how an experienced first‐grade teacher used a new NGSS‐aligned unit that called for students to use the science and engineering practices (SEP) to build content knowledge. We used a macro‐analytic lens to answer the research question “how are class discussions shaped to address the SEP”? We used a micro‐analytic lens to answer the research question “how are students positioned during these science discussions in this classroom?” Evidence suggests that the teachers' whole class discussions incorporated and involved the SEP which were specified in the unit lessons for content learning. However, on a micro‐analytic level, we found that few students were positioned as active discussants. The teacher heavily relied on those students who could provide succinct and clearly relevant answers while positioning the remainder of the students as silent spectators. Implications from this research suggest that not only new NGSS curriculum materials need to focus on what students should know and do but they also need to address heuristics for teachers that show them how to position all of their students as active doers of science so all students have opportunities to build deeper, core science knowledge.
mRNA 3′ end formation in plants: Novel connections to growth, development and environmental responses
Authors: Hunt Arthur G.
Published: November 2019

3′ end processing and mRNA polyadenylation is a vital aspect of gene expression in eukaryotes, and also a step at which expression may be regulated. A spate of recent research in plants links different subunits of the polyadenylation complex with growth and development. These reports provide insight into mechanisms by which APA may be regulated, and perhaps into mechanisms by which pre‐mRNAs are processed and polyadenylated. In this review, several of these recent reports are discussed, with the purpose of highlighting novel features of mRNA 3′ end formation in plants and also developing broad themes that connect APA with plant growth, development, and responses to the environment.

This article is categorized under:

RNA Processing > 3′ End Processing

RNA in Disease and Development > RNA in Development
Highly charged ions in a new era of high resolution X‐ray astrophysics
Authors: Hell Natalie , Beiersdorfer Peter , Brown Gregory V. , Eckart Megan E. , Kelley Richard L. , Kilbourne Caroline A. , Leutenegger Maurice A. , Lockard Thomas E. , Porter F. Scott , Wilms Jörn
Published: November 2019

X‐ray astronomy and ground‐based atomic physics have a long history of fruitful collaboration: Sound understanding of the underlying atomic physics is the key to reliable interpretation of the spectra from celestial sources; conversely, astronomical spectra have been used to benchmark and advance atomic physics. This interplay is about to become even more important as we enter a new era of high‐resolution X‐ray astrophysics with large effective collection area. Although high‐resolution observations with the gratings on the Chandra and XMM‐Newton observatories continue to drive new science, upcoming planned and proposed missions will open up new discovery space in the near future that is currently challenging to access: high‐resolution spectroscopy on extended sources, in the Fe K band, and on short time scales. This review summarizes open questions in these areas and the design parameters for the Hitomi, XRISM, Athena, and Arcus observatories. The expected high quality of spectra taken with these observatories puts new constraints on the accuracy of atomic reference data required to take full advantage of the diagnostic potential of these spectra.
A New Three‐dimensional Metal‐organic Framework based on Dinuclear Rare Earth Cluster and Olsalazine
Authors: Zhang Xin , Zhong Fangyuan , Liu Jun , Xu Hui , Gao Junkuo , Xu Shiqing
Published: November 2019

A new microporous metal organic frameworks Eu2(olz)3·7(DMF), based on olsalazine, has been successfully designed and synthesized. Eu‐olz has three‐dimensional structure with dinuclear rare earth cluster and drug molecule olsalazine as ligand, and features as low toxic MOF materials. The Eu‐olz exhibits weak fluorescent emission which can be ascribed to the luminescence of the organic ligand.
Thermodynamic instabilities of generalized exotic BTZ black holes
Authors: Cong Wan , Mann Robert B.
Published: November 2019

Abstract

We examine the conjecture that black holes violating the reverse isoperimetric inequality have negative specific heat at constant volume CV [1]. We test this conjecture on the family of generalized exotic Bañados, Teitelboim and Zanelli (BTZ) black holes and find that CV can be positive even when the reverse isoperimetric inequality is violated, providing a counter example to the conjecture. However in all cases where CV is positive, the specific heat at constant pressure CP is negative, indicating that generalized exotic black holes are thermodynamically unstable, suggesting that a broader version of the conjecture might hold.
Double Higgs boson production at NLO: combining the exact numerical result and high-energy expansion
Authors: Davies Joshua , Heinrich Gudrun , Jones Stephen P. , Kerner Matthias , Mishima Go , Steinhauser Matthias , Wellmann David
Published: November 2019

Abstract

We consider the next-to-leading order QCD corrections to Higgs boson pair production, using our recent calculation of the form factors in the high-energy limit. We compute the virtual corrections to the partonic cross section, applying Padé approximations to extend the range of validity of the high-energy expansion. This enables us to compare to the exact numerical calculation in a significant part of the phase space and allows us to extend the virtual matrix element grid, based on the exact numerical calculation, to larger values of the (partonic) transverse momentum of the Higgs boson, which is important for boosted Higgs studies. Improved predictions for hadron colliders with centre-of-mass energies of 14 TeV and 100 TeV are presented. The updated grid is made publicly available.
The Burgers’ equation with stochastic transport: shock formation, local and global existence of smooth solutions
Authors: Alonso-Orán Diego , Bethencourt de León Aythami , Takao So
Published: November 2019

In this work, we examine the solution properties of the Burgers’ equation with stochastic transport. First, we prove results on the formation of shocks in the stochastic equation and then obtain a stochastic Rankine–Hugoniot condition that the shocks satisfy. Next, we establish the local existence and uniqueness of smooth solutions in the inviscid case and construct a blow-up criterion. Finally, in the viscous case, we prove global existence and uniqueness of smooth solutions.
Modulation of radiation-induced oral mucositis (mouse) by dermatan sulfate: effects on differentiation processes
Authors: Cini Nilsu , Gruber Sylvia , Arican Alicikus Zumre , Dörr Wolfgang
Published: November 2019

Purpose

During head and neck cancer radiotherapy, oral mucositis is the most frequent early side effect. Systemic dermatan sulfate (DS) administration has been shown to significantly decrease oral mucosal radiation reactions during daily fractionated irradiation (IR) in an established mouse model. The aim of this study was to investigate the mechanism of the oral epithelial differentiation process, during IR alone and in combination with DS treatment in the same mouse model.

Methods

Fractionated IR 5 × 3 Gy/week was given to the snouts of mice over two weeks, either alone (IR) or in combination with daily DS treatment of 4 mg/kg (IR + DS). Groups of mice (n = 3) were sacrificed every second day over the course of 14 days in both experimental arms. Their tongue was excised and subjected to immunohistochemical processing.

Results

In the p16 analysis as a proliferation marker, the difference between IR alone and IR + DS in the germinal (proliferation) layer was not significant, not stimulating the proliferation process. For the p21 analysis as a differentiation marker on the functional (differentiation) layer, the difference between IR alone and IR + DS arms was significant, indicating that DS inhibited the differentiation process. In the cytokeratin (CK) analysis as the indicator of cellular skeletal integrity, the percentage of antibody-positive cells was above the normal level in both experimental arms and significantly superior in the IR + DS arm.

Conclusion

The mucosal protective activity of DS, instead of stimulating proliferation, is based on prevention of cell loss by a combination of effects leading to the inhibition of cellular differentiation and an increase in the expression of epithelial mechanical strength between intercellular mechanical junctions.
Derivation of the Time Dependent Gross–Pitaevskii Equation in Two Dimensions
Authors: Jeblick Maximilian , Leopold Nikolai , Pickl Peter
Published: November 2019

We present microscopic derivations of the defocusing two-dimensional cubic nonlinear Schrödinger equation and the Gross–Pitaevskii equation starting from an interacting N-particle system of bosons. We consider the interaction potential to be given either by $$W_\beta (x)=N^{-1+2 \beta }W(N^\beta x)$$Wβ(x)=N-1+2βW(Nβx), for any $$\beta >0$$β>0, or to be given by $$V_N(x)=e^{2N} V(e^N x)$$VN(x)=e2NV(eNx), for some spherical symmetric, nonnegative and compactly supported $$W,V \in L^\infty ({\mathbb {R}}^2,{\mathbb {R}})$$W,V∈L∞(R2,R). In both cases we prove the convergence of the reduced density corresponding to the exact time evolution to the projector onto the solution of the corresponding nonlinear Schrödinger equation in trace norm. For the latter potential $$V_N$$VN we show that it is crucial to take the microscopic structure of the condensate into account in order to obtain the correct dynamics.
Atherosclerotic ICA stenosis coinciding with ICA asymmetry associated with Circle of Willis variations can mimic near-occlusion
Authors: Johansson Elias , Aviv Richard I. , Fox Allan J.
Published: November 2019

Differentiating carotid near-occlusion (tight atherosclerotic stenosis causing distal artery size reduction) from conventional stenosis is the first step when grading carotid stenoses with NASCET method. The internal carotid artery (ICA) can be asymmetrically associated with Circle of Willis variations. When such ICA asymmetry coincides with stenosis, it may mimic near-occlusion. We studied ICA anatomical variant prevalence in 4042 consecutive CTA exams from all indications, 53 excluded due to carotid occlusion, 814 with any ≥ 50% steno-occlusive disease intra- or extracranially, 3228 without. Of the 3989 included cases, 568 (14%) had ICA asymmetry, of which 335 (59%) were from associated with Circle of Willis variations. Of 3228 patients without ≥ 50% stenosis or other steno-occlusive disease intra- and extracranially; 257 (8.0%) demonstrated ICA asymmetry associated with Circle of Willis variations, equally common among sexes and age unrelated and most frequently attributed to an ipsilateral A1 hypoplasia/aplasia, less often attributed to large contralateral posterior communicating artery. As ICA asymmetry associated with Circle of Willis variations are common, caution should be exercised diagnosing near-occlusion on asymmetry alone.
Variation in the Concentration of Metals in Road Dust Size Fractions Between 2 µm and 2 mm: Results from Three Metallurgical Centres in Poland
Authors: Logiewa Agata , Miazgowicz Agnieszka , Krennhuber Klaus , Lanzerstorfer Christof
Published: November 2019

The composition of road dust is influenced by emissions from local industry as well as by traffic emissions. Thus, the composition of urban road dust can be used as an indicator for environmental pollution. Pollutants contained in road dust also are transferred into the atmosphere by resuspension and into the aquatic system by wash-off. In this transfer, the particle size of the road dust particles is of extreme importance. Therefore, information about the composition of road dust in dependence of the particle size is crucial. In this study, road dust samples were separated by air classification into size fractions down to 2 µm. The chemical analysis of the size fractions also revealed a significant size dependence of the metal concentrations in the finest size fractions. The least polluted size fraction was generally the fraction 200–500 µm, whereas the highest concentrations were measured in the finest size fraction < 2 µm. These results are important for the assessment of the mass fraction of the various pollutants in the mobile size fractions in re-entrainment as well as in run-off during rainfall.
In vivo three-dimensional evaluation of tumour hypoxia in nasopharyngeal carcinomas using FMT-CT and MSOT
Authors: Huang Wenhui , Wang Kun , An Yu , Meng Hui , Gao Yuan , Xiong Zhiyuan , Yan Hao , Wang Qian , Cai Xuekang , Yang Xin , Zhang Bin , Chen Qiuying , Yang Xing , Tian Jie , Zhang Shuixing
Published: November 2019

Purpose

Accurate evaluation of hypoxia is particularly important in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. The aim of this study was to propose a novel imaging strategy for quantitative three-dimensional (3D) evaluation of hypoxia in a small animal model of NPC.

Methods

A carbonic anhydrase IX (CAIX)-specific molecular probe (CAIX-800) was developed for imaging of hypoxia. Mouse models of subcutaneous, orthotopic, and spontaneous lymph node metastasis from NPC (5 mice per group) were established to assess the imaging strategy. A multi-modality imaging method that consisted of a hybrid combination of fluorescence molecular tomography-computed tomography (FMT-CT) and multispectral optoacoustic tomography (MSOT) was used for 3D quantitative evaluation of tumour hypoxia. Magnetic resonance imaging, histological examination, and immunohistochemical analysis were used as references for comparison and validation.

Results

In the early stage of NPC (2 weeks after implantation), FMT-CT enabled precise 3D localisation of the hypoxia biomarker with high sensitivity. At the advanced stage (6 weeks after implantation), MSOT allowed multispectral analysis of the biomarker and haemoglobin molecules with high resolution. The combination of high sensitivity and high resolution from FMT-CT and MSOT could not only detect hypoxia in small-sized NPCs but also visualise the heterogeneity of hypoxia in 3D.

Conclusions

Integration of FMT-CT and MSOT could allow comprehensive and quantifiable evaluation of hypoxia in NPC. These findings may potentially benefit patients with NPC undergoing radiotherapy in the future.
The P2X7 receptor tracer [11C]SMW139 as an in vivo marker of neuroinflammation in multiple sclerosis: a first-in man study
Authors: Hagens Marloes H. J. , Golla Sandeep S. V. , Janssen Bieneke , Vugts Danielle J. , Beaino Wissam , Windhorst Albert D. , O’Brien-Brown James , Kassiou Michael , Schuit Robert C. , Schwarte Lothar A. , de Vries Helga E. , Killestein Joep , Barkhof Frederik , van Berckel Bart N. M. , Lammertsma Adriaan A.
Published: November 2019

Purpose

The novel PET tracer [11C]SMW139 binds with high affinity to the P2X7 receptor, which is expressed on pro-inflammatory microglia. The purposes of this first in-man study were to characterise pharmacokinetics of [11C]SMW139 in patients with active relapsing remitting multiple sclerosis (RRMS) and healthy controls (HC) and to evaluate its potential to identify in vivo neuroinflammation in RRMS.

Methods

Five RRMS patients and 5 age-matched HC underwent 90-min dynamic [11C]SMW139 PET scans, with online continuous and manual arterial sampling to generate a metabolite-corrected arterial plasma input function. Tissue time activity curves were fitted to single- and two-tissue compartment models, and the model that provided the best fits was determined using the Akaike information criterion.

Results

The optimal model for describing [11C]SMW139 kinetics in both RRMS and HC was a reversible two-tissue compartment model with blood volume parameter and with the dissociation rate k4 fixed to the whole-brain value. Exploratory group level comparisons demonstrated an increased volume of distribution (VT) and binding potential (BPND) in RRMS compared with HC in normal appearing brain regions. BPND in MS lesions was decreased compared with non-lesional white matter, and a further decrease was observed in gadolinium-enhancing lesions. In contrast, increased VT was observed in enhancing lesions, possibly resulting from disruption of the blood-brain barrier in active MS lesions. In addition, there was a high correlation between parameters obtained from 60- to 90-min datasets, although analyses using 60-min data led to a slight underestimation in regional VT and BPND values.

Conclusions

This first in-man study demonstrated that uptake of [11C]SMW139 can be quantified with PET using BPND as a measure for specific binding in healthy controls and RRMS patients. Additional studies are warranted for further clinical evaluation of this novel neuroinflammation tracer.
Assessment of Socio-Economic and Climate Change Impacts on Water Resources in Four European Lagoon Catchments
Authors: Stefanova Anastassi , Hesse Cornelia , Krysanova Valentina , Volk Martin
Published: November 2019

This study demonstrates the importance of considering potential land use and management changes in climate impact research. By taking into account possible trends of economic development and environmental awareness, we assess effects of global warming on water availability and quality in the catchments of four European lagoons: Ria de Aveiro (Portugal), Mar Menor (Spain), Vistula Lagoon (Poland and Russia), and Tyligulskyi Liman (Ukraine). Different setups of the process-based soil and water integrated model (SWIM), representing one reference and four socio-economic scenarios for each study area: the “business as usual”, “crisis”, “managed horizons”, and “set-aside” scenarios are driven by sets of 15 climate scenarios for a reference (1971–2000) and near future (2011–2040) scenario period. Modeling results suggest a large spatial variability of potential impacts across the study areas, due to differences in the projected precipitation trends and the current environmental and socio-economic conditions. While climate change may reduce water and nutrients input to the Ria de Aveiro and Tyligulsyi Liman and increase water inflow to the Vistula Lagoon the socio-economic scenarios and their implications may balance out or reverse these trends. In the intensely managed Mar Menor catchment, climate change has no notable direct impact on water resources, but changes in land use and water management may certainly aggravate the current environmental problems. The great heterogeneity among results does not allow formulating adaptation or mitigation measures at pan-European level, as initially intended by this study. It rather implies the need of a regional approach in coastal zone management.
Patients’ views on the implementation of artificial intelligence in radiology: development and validation of a standardized questionnaire
Authors: Ongena Yfke P. , Haan Marieke , Yakar Derya , Kwee Thomas C.
Published: November 2019

Objectives

The patients’ view on the implementation of artificial intelligence (AI) in radiology is still mainly unexplored territory. The aim of this article is to develop and validate a standardized patient questionnaire on the implementation of AI in radiology.

Methods

Six domains derived from a previous qualitative study were used to develop a questionnaire, and cognitive interviews were used as pretest method. One hundred fifty-five patients scheduled for CT, MRI, and/or conventional radiography filled out the questionnaire. To find underlying latent variables, we used exploratory factor analysis with principal axis factoring and oblique promax rotation. Internal consistency of the factors was measured with Cronbach’s alpha and composite reliability.

Results

The exploratory factor analysis revealed five factors on AI in radiology: (1) distrust and accountability (overall, patients were moderately negative on this subject), (2) procedural knowledge (patients generally indicated the need for their active engagement), (3) personal interaction (overall, patients preferred personal interaction), (4) efficiency (overall, patients were ambiguous on this subject), and (5) being informed (overall, scores on these items were not outspoken within this factor). Internal consistency was good for three factors (1, 2, and 3), and acceptable for two (4 and 5).

Conclusions

This study yielded a viable questionnaire to measure acceptance among patients of the implementation of AI in radiology. Additional data collection with confirmatory factor analysis may provide further refinement of the scale.

Key Points

• Although AI systems are increasingly developed, not much is known about patients’ views on AI in radiology.

• Since it is important that newly developed questionnaires are adequately tested and validated, we did so for a questionnaire measuring patients’ views on AI in radiology, revealing five factors.

• Successful implementation of AI in radiology requires assessment of social factors such as subjective norms towards the technology.
A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study
Authors: Papadimitriou Nikos , Muller David , van den Brandt Piet A. , Geybels Milan , Patel Chirag J. , Gunter Marc J. , Lopez David S. , Key Timothy J. , Perez-Cornago Aurora , Ferrari Pietro , Vineis Paolo , Weiderpass Elisabete , Boeing Heiner , Agudo Antonio , Sánchez María-José , Overvad Kim , Kühn Tilman , Fortner Renee T. , Palli Domenico , Drake Isabel , Bjartell Anders , Santiuste Carmen , Bueno-de-Mesquita Bas H. , Krogh Vittorio , Tjønneland Anne , Lauritzen Dorthe Furstrand , Gurrea Aurelio Barricarte , Quirós José Ramón , Stattin Pär , Trichopoulou Antonia , Martimianaki Georgia , Karakatsani Anna , Thysell Elin , Johansson Ingegerd , Ricceri Fulvio , Tumino Rosario , Larrañaga Nerea , Khaw Kay Tee , Riboli Elio , Tzoulaki Ioanna , Tsilidis Konstantinos K.
Published: November 2019

Purpose

The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive.

Methods

A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR < 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS).

Results

A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-correctedP, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS.

Conclusions

Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature.
Cognitive and affective Theory of Mind in adolescence: developmental aspects and associated neuropsychological variables
Authors: Gabriel Edith Theresa , Oberger Raphaela , Schmoeger Michaela , Deckert Matthias , Vockh Stefanie , Auff Eduard , Willinger Ulrike
Published: November 2019

Theory of Mind (ToM) is the ability to represent and attribute mental states to oneself and others. So far, research regarding ToM processing across adolescence is scarce. Existing studies either yield inconsistent results or did not or not thoroughly investigate aspects like higher order ToM and associated neuropsychological variables which the current study tried to address. 643 typically developing early, middle, and late adolescents (age groups 13–14; 15–16; 17–18) performed cognitive and affective ToM tasks as well as neuropsychological tasks tapping the cognitive or affective domain. Regarding both ToM types, 15- to 16-year-olds and 17- to 18-year-olds outperformed 13- to 14-year-olds, whereas females were superior regarding cognitive ToM. Across adolescence, cognitive and affective ToM correlated with attention and affective intelligence, whereas working memory, language comprehension, and figural intelligence additionally correlated with cognitive ToM. In early adolescence, attention correlated with both ToM types, whereas cognitive ToM further correlated with language comprehension and affective ToM with verbal intelligence, verbal fluency, and verbal flexibility. In middle and late adolescence, affective intelligence correlated with both ToM types, whereas cognitive ToM additionally correlated with working memory, language comprehension, and figural intelligence. The current study shows a developmental step regarding cognitive and affective ToM in middle adolescence as well as gender differences in cognitive ToM processing. Associations between neuropsychological variables and ToM processing were shown across adolescence and within age groups. Results give new insights into social cognition in adolescence and are well supported by neuroscientific and neurobiological studies regarding ToM and the integration of cognitive and affective processes.

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Bestimmung und Abtrennung des Fremdstoffgehaltes von Bioabfällen mittels Siebung und Windsichtung
Authors: Ferreux Julie , do Carmo Precci Lopes Alice , Müller Wolfgang , Robra Sabine , Bockreis Anke
Published: November 2019

Kunststofffolien im Bioabfall führen zu Herausforderungen für Bioabfallbehandlungsanlagen, da sie trotz Aufbereitung in den fertigen Kompost gelangen. Anlässlich der neuen Grenzwerte des RAL-Gütezeichens wurde die Anwendung eines Stern- und Trommelsiebs sowie eines Querstrom-Windsichters in der Voraufbereitung von zwei Bioabfallbehandlungsanlagen in Deutschland untersucht.

Untersucht wurde die Effizienz der Kunststofffolienabtrennung und die Transferraten der Biogaserträge in die entstehenden Fraktionen. Dafür wurden Proben aus großtechnischen Versuchen gezogen, händisch sortiert und alle Fremdstoffe gewaschen und getrocknet. Anschließend wurde das Biogaspotenzial mit einem automatisierten Batch-Gärtest gemessen.

Die Ergebnisse weisen einen Verlust von ca. 30 % an Biogas aus, der durch die Abtrennung der anhaftenden organischen Substanz während der Aufbereitung bedingt ist. Dem gegenüber steht eine Abtrennung von ca. 90 % der Kunststofffolien, was ein Erreichen der Grenzwerte des RAL-Gütezeichens potenziell ermöglicht.
Coding-complete genome sequencing suggests that Newcastle disease virus challenge strain Herts’33 (IVMP) may represent a distinct genotype
Authors: Fehér Enikő , Bálint Ádám , Marton Szilvia , Bali Krisztina , Belák Sándor , Bányai Krisztián
Published: November 2019

We determined the genomic sequence of a Newcastle disease virus (NDV) line obtained directly from the first NDV isolate, named Herts’33. This strain shared ≤ 90% nucleotide sequence identity with the NDV sequences available in the GenBank database, and formed a distinct branch in a phylogenetic tree. This branch may be considered to represent a separate NDV genotype. Our study indicates that investigation of the genomic sequences of old NDV strains that originated from the early outbreaks of Newcastle disease may alter the phylogenetic grouping of the NDV strains and provide data on the evolution of viral genomes over time.
Toddlers’ diurnal cortisol levels affected by out-of-home, center-based childcare and at-home, guardian-supervised childcare: comparison between different caregiving contexts
Authors: Tervahartiala Katja , Karlsson Linnea , Pelto Juho , Kortesluoma Susanna , Hyttinen Sirpa , Ahtola Annarilla , Junttila Niina , Karlsson Hasse
Published: November 2019

Previous research suggests that attending non-parental out-of-home childcare is associated with elevated cortisol levels for some children. We aimed to compare diurnal saliva cortisol levels between children having out-of-home, center-based childcare or those having at-home, guardian-supervised childcare in Finland. A total of 213 children, aged 2.1 years (SD = 0.6), were drawn from the ongoing Finnish birth cohort study. Saliva samples were collected over 2 consecutive days (Sunday and Monday), with four samples drawn during each day: 30 min after waking up in the morning, at 10 am, between 2 and 3 pm, and in the evening before sleep. These results suggest that the shapes of the diurnal cortisol profiles were similar in both childcare groups following a typical circadian rhythm. However, the overall cortisol levels were on average 30% higher (95% CI: [9%, 54%], p = .004) with the at-home childcare in comparison with the out-of-home childcare group. Furthermore, a slight increase in the diurnal cortisol pattern was noticed in both groups and in both measurement days during the afternoon. This increase was 27% higher ([2%, 57%], p = .031) in the out-of-home childcare group during the out-of-home childcare day in comparison with the at-home childcare day. The elevated afternoon cortisol levels were partly explained by the afternoon naps, but there were probably other factors as well producing the cortisol rise during the afternoon hours. Further research is needed to define how a child’s individual characteristic as well as their environmental factors associate with cortisol secretion patterns in different caregiving contexts.
Construction of a new integrating vector from actinophage ϕOZJ and its use in multiplex Streptomyces transformation
Authors: Ko Bryan , D’Alessandro John , Douangkeomany Lee , Stumpf Spencer , deButts Ashby , Blodgett Joshua
Published: November 2019

Streptomyces and other closely-related actinobacteria are important sources of bioactive molecules. Streptomyces synthetic biology and genetics empower therapeutic and agrichemical development through strain improvement and biosynthetic understanding. Such efforts rely on the availability of developed molecular toolsets. Among these tools, vectors that enable combinatorial chromosomal manipulations are particularly desirable. Towards developing tools for facile multiplex engineering, we herein describe the development of new integrating vectors derived from BD1 subgroup actinophage OzzyJ (ϕOZJ). By demonstrating the transformation of several Streptomyces spp. using ϕOZJ-derived vectors, we reveal their potential for strain engineering. We further report the development of new ϕC31 and ϕBT1-based vectors having orthogonal resistance, replication and integration features for concomitant transformation with our ϕOZJ-derived vectors. Importantly, the resulting compatible vector panel enabled us to demonstrate the transfer of up to three plasmids each into Streptomyces venezuelae, Streptomyces roseosporus and Streptomyces pristinaespiralis during a single conjugation experiment. To our knowledge this is the first documentation of conjugation-mediated multiplex plasmid transformation, a useful approach for rapid combinatorial strain development.
A new bi-objective model of the urban public transportation hub network design under uncertainty
Authors: Kaveh Firoozeh , Tavakkoli-Moghaddam Reza , Triki Chefi , Rahimi Yaser , Jamili Amin
Published: November 2019

This paper presents a new bi-objective multi-modal hub location problem with multiple assignment and capacity considerations for the design of an urban public transportation network under uncertainty. Because of the high construction costs of hub links in an urban public transportation network, it is not economic to create a complete hub network. Moreover, the demand is assumed to be dependent on the utility proposed by each hub. Thus, the elasticity of the demand is considered in this paper. The presented model also has the ability to compute the number of each type of transportation vehicles between every two hubs. The objectives of this model are to maximize the benefits of transportation by establishing hub facilities and to minimize the total transportation time. Since exact values of some parameters are not known in advance, a fuzzy multi-objective programming based approach is proposed to optimally solve small-sized problems. For medium and large-sized problems, a meta-heuristic algorithm, namely multi-objective particle swarm optimization is applied and its performance is compared with results from the non-dominated sorting genetic algorithm. Our experimental results demonstrated the validity of our developed model and approaches. Moreover, an intensive sensitivity analyze study is carried out on a real-case application related to the monorail project of the holy city of Qom.
Electrochemical recovery of tellurium from metallurgical industrial waste
Authors: Halli Petteri , Wilson Benjamin P. , Hailemariam Taye , Latostenmaa Petri , Yliniemi Kirsi , Lundström Mari
Published: November 2019

The current study outlines the electrochemical recovery of tellurium from a metallurgical plant waste fraction, namely Doré slag. In the precious metals plant, tellurium is enriched to the TROF (Tilting, Rotating Oxy Fuel) furnace slag and is therefore considered to be a lost resource—although the slag itself still contains a recoverable amount of tellurium. To recover Te, the slag is first leached in aqua regia, to produce multimetal pregnant leach solution (PLS) with 421 ppm of Te and dominating dissolved elements Na, Ba, Bi, Cu, As, B, Fe and Pb (in the range of 1.4–6.4 g dm−3), as well as trace elements at the ppb to ppm scale. The exposure of slag to chloride-rich solution enables the formation of cuprous chloride complex and consequently, a decrease in the reduction potential of elemental copper. This allows improved selectivity in electrochemical recovery of Te. The results suggest that electrowinning (EW) is a preferred Te recovery method at concentrations above 300 ppm, whereas at lower concentrations EDRR is favoured. The purity of recovered tellurium is investigated with SEM–EDS (scanning electron microscope–energy dispersion spectroscopy). Based on the study, a new, combined two-stage electrochemical recovery process of tellurium from Doré slag PLS is proposed: EW followed by EDRR.

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