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Educational technologies in mathematics typically focus on fostering either procedural knowledge by means of structured tasks or, less often, conceptual knowledge by means of exploratory tasks. However, both types of knowledge are needed for complete domain knowledge that persists over time and supports subsequent learning. We investigated in two quasi-experimental studies whether a combination of an exploratory learning environment, providing exploratory tasks, and an intelligent tutoring system, providing structured tasks, fosters procedural and conceptual knowledge more than the intelligent tutoring system alone. Participants were 121 students from the UK (aged 8-10 years old) and 151 students from Germany (aged 10-12 years old) who were studying equivalent fractions. Results confirmed that students learning with a combination of exploratory and structured tasks gained more conceptual knowledge and equal procedural knowledge compared to students learning with structured tasks only. This supports the use of different but complementary educational technologies, interleaving exploratory and structured tasks, to achieve a "combination effect" that fosters robust fractions knowledge.

The monitoring by teachers of collaborative, cognitive, and meta-cognitive student activities in collaborative learning is crucial for fostering beneficial student interaction. In a quasi-experimental study, we trained pre-service teachers (N = 74) to notice behavioral indicators for these three dimensions of student activities. Video clips of student interactions in collaborative learning settings served as learning opportunities in the training and as test scenarios for measuring monitoring competency in an assessment tool. Participants completed the assessment tool before and immediately after the training program. A control group (N = 33) completed the assessment tool twice but did not receive training in between. Results show that monitoring competency increased significantly in the training group but not in the control group. This provides initial evidence that a video-based training program can effectively enhance pre-service teachers' noticing of behavioral indicators of collaborative, cognitive, and meta-cognitive student activities in a relatively short time. Our findings are of practical relevance as evaluating student interactions in a collaborative learning setting is challenging, yet also a skill much needed in teacher practice.

This article describes teacher competencies for implementing collaborative learning in the classroom. Research has shown that the effectiveness of collaborative learning largely depends on the quality of student interaction. We therefore focus on what a "teacher" can do to foster student interaction. First, we present a framework that draws a comprehensive picture of a teacher role we see as germane to fostering student interaction. The framework distinguishes between five teacher competencies that span across all implementation phases of collaborative learning: the ability to plan student interaction, monitor, support, and consolidate this interaction, and finally reflect upon it. Then, we review research on collaborative learning and structure this review along the five teacher competencies presented in the framework. The review targets relevant concepts and pivotal empirical research results about how to foster student interaction. For each competency, we first summarize relevant concepts and empirical results. We then apply the concepts and findings to a classroom situation. These teaching vignettes illustrate the functions of the five teacher competencies in fostering student interaction in collaborative learning. For each vignette, we discuss and highlight specific aspects of the presented teacher role and draw practical implications. Monitoring and supporting in the classroom should be trained in teacher education and facilitated by providing teachers with tools such as a checklist of beneficial student behaviors. These practical implications can inform educational practices and offer new directions for future research regarding promoting collaborative learning.

Despite steady progress in research in technology-enhanced learning (TEL), the translation of research findings and technology into educational practices falls short of expectations. We present five Areas of Tension which were identified and evaluated in an international Delphi study on TEL. These tensions might impede a more comprehensive inclusion of information and communication technologies (ICT) in educational settings. The Delphi study was embedded in the European Network of Excellence STELLAR (Sustaining Technology Enhanced Learning LArge-scale multidisciplinary Research). Five Delphi rounds were conducted to identify Areas of Tension and Core Research Areas in TEL. An Area of Tension opposes two conflicting views on a certain technological development regarding the future of TEL. In the present article we describe the design of the Delphi study and report the results regarding the Areas of Tension. These areas were identified by collecting visionary statements on the future of TEL (Round 1) and by having 230 international experts evaluate those statements (Round 2). The emerging tensions were integrated into five Areas of Tension (Round 3) and evaluated by 569 international experts on several dimensions for their significance for TEL and TEL research (Round 4). The identified areas concern a) data tracking for personalized learning versus data privacy, b) the spreading of technology reducing the digital divide versus even increasing it, c) ubiquitous learning opportunities versus critical and focused processing of information, d) continuous innovation in the classroom versus approved practices, and e) individualized versus standardized learning paths. (Contains 7 tables and 3 figures.)

Schwartz and Martin ("Cogn Instr" 22:129-184, 2004) as well as Kapur ("Instr Sci", this issue, 2012) have found that students can be better prepared to learn about mathematical formulas when they try to invent them in small groups before receiving the canonical formula from a lesson. The purpose of the present research was to investigate how the effectiveness of invention activities may be mediated by composition of the small groups in terms of their mathematical skills. In two studies, small groups of undergraduates engaged in an "inventing standard deviation" task. Results suggested that groups may need at least one member with high math ability to take advantage of "learning by invention". Groups consisting of both high and low math ability members generated a broader range of solution attempts during the invention task, and this seemed to be related to better uptake of the standard deviation formula from a later lesson.

Host cell proteins (HCPs) are inevitable process‐related impurities in biotherapeutics commonly monitored by enzyme‐linked immunosorbent assays (ELISAs). Of particular importance for their reliable detection are the anti‐HCP polyclonal antibodies (pAbs), supposed to detect a broad range of HCPs. The present study focuses on the identification of suitable host animal species for the development of high‐performance CHO‐HCP ELISAs, assuming the generation of pAbs with adequate coverage and specificity. Hence, antibodies derived from immunization of sheep, goats, donkeys, rabbits, and chickens were compared concerning their amount of HCP‐specific antibodies, coverage, and performance in a sandwich ELISA. Immunization of sheep, goats, donkeys, and rabbits met all test criteria, whereas the antibodies from chickens cannot be recommended based on the results of this study. Additionally, a mixture of antibodies from the five host species was prepared to assess if coverage and ELISA performance can be improved by a multispecies approach. Comparable results were obtained for the single‐ and multispecies ELISAs in different in‐process samples, indicating no substantial improvement for the latter in ELISA performance while raising ethical and financial concerns. [ABSTRACT FROM AUTHOR]

In the control strategy for process related impurities in biopharmaceuticals, the enzyme linked immunosorbent assay (ELISA) is the method of choice for the quantification of host cell proteins (HCPs). Besides two dimensional‐western blots (2D‐WB), the coverage of ELISA antibodies is increasingly evaluated by affinity purification‐based liquid chromatography–tandem mass spectrometry (AP‐MS) methods. However, all these methods face the problem of unspecific binding issues between antibodies and the matrix, involving the application of arbitrarily defined thresholds during data evaluation. To solve this, a new approach (optimized AP‐MS) was developed in this study, for which a cleavable linker was conjugated to the ELISA antibodies enabling the subsequent isolation of specifically interacting HCPs. By comparing both approaches in terms of method variability and the number of false positive or negative hits, we could demonstrate that the optimized AP‐MS method is very reproducible and superior in the identification of antibody detection gaps, while previously described strategies suffered from over‐ or underestimating the coverage. As only antibody associated HCPs were identified, we demonstrated that the method is beneficial for hitchhiker analysis. Overall, the method described herein has proven as a powerful tool for reliable coverage determination of ELISA antibodies, without the need to arbitrarily exclude HCPs during the coverage evaluation. [ABSTRACT FROM AUTHOR]

The perpendicular magnetic behavior of molecular beam epitaxy grown X/Co/Y sandwich structures are determined by in situ polar Kerr ellipticity, where X and Y are combinations of Au, Pd, Ag or Cu. The perpendicular anisotropy reaches a peak at approximately 1 of the Y overlayer coverage.

The performance of immunoassays for the detection and quantification of host‐cell proteins (HCPs) in biopharmaceuticals depends on the quality of the critical assay reagents. Not only their preparation, but also a stringent life‐cycle management, including reagent qualification, requalification, and replacement, plays a crucial role in ensuring consistent and reliable results. To provide a cross‐industry perspective on HCP reagent management, we conducted a survey on common practices among several pharmaceutical and biotech companies. Based on its outcome, as well as informed by a corresponding roundtable session ("Managing critical reagents over time") at the BioPharmaceutical Emerging Best Practices Association HCP conference in 2019, this study presents specific recommendations and proven concepts to support immunoassay reagent management for monitoring HCPs. [ABSTRACT FROM AUTHOR]

Host cell proteins (HCPs) constitute a major class of process‐related impurities, whose substantial clearance must be demonstrated by suitable analytical methods to warrant product quality and reduce potential safety risks for patients. In this regard, enzyme linked immunosorbent assays (ELISAs), which primarily rely on the quality of the HCP reference standard (immunogen) and HCP‐specific polyclonal antibodies, are considered the gold standard for HCP monitoring. For the qualification of the employed antibodies, two‐dimensional (2D) western blots (2D‐WBs) are the preferred technique to determine the coverage, though a number of practical constraints are well recognized. By using several orthogonal approaches, such as affinity‐based mass spectrometry and indirect ELISA, the present study revealed potential detection gaps (i.e., noncovered HCPs) of conventional 2D‐WBs, which can be primarily attributed to two different root causes: (i) low amounts of proteins or antibodies being unable to overcome the detection limit and (ii) western blot artifacts due to the loss of conformational epitopes through protein denaturation hindering HCP‐antibody recognition. In contrast, the lack of specific antibodies against certain (particularly, low molecular weight) HCPs, as proposed in previous studies, seems to play only a minor role. Together, these findings imply that CHO‐HCP ELISA antibodies are better than qualification studies by 2D‐WBs indicate. [ABSTRACT FROM AUTHOR]

Low- and high-energy electron diffraction analyses of the structure and magnetic properties of metal/Co/insulator and metal/Co/metal sandwiches reveal the absence of any abrupt alterations in the out-of-plane lattice and surface spacings. The absence of changes suggests that the magnetic anisotropy peak is not characteristic of the lattice structure. Analysis of the influence of an insulating layer on magnetic anisotropy reveals a decrease in the anisotropy in the perpendicular direction.

The influence of transition-metal overlayers on the magnetic properties of ultra-thin Co films grown by molecular beam epitaxy was investigated using in situ polar Kerr ellipticity measurements. The results showed that the deposition of transition-metal overlayers on the Co film caused nonmonotonic behavior in the hysteresis curve at a coverage level of approximately 1.5 angstroms.

Presents a study which used molecular-beam epitaxy to grow cobalt/palladium superlattices along the three high-symmetry crystal axes. Process used in clarifying the roles of magnetocrystalline, magnetoelastic and interface anisotropies in multilayers; Factor that provided the oriented growth of the superlattices; Details on the estimates of the magnetocrystalline and magnetoelastic contributions for the samples.

The degradation of proteins by asparagine deamidation and aspartate isomerization is one of several chemical degradation pathways for recombinant antibodies. In this study, we have identified two solvent accessible degradation sites (light chain aspartate-56 and heavy chain aspartate-99/101) in the complementary-determining regions of a recombinant IgG1 antibody susceptible to isomerization under elevated temperature conditions. For both hot-spots, the degree of isomerization was found to be significantly higher than the deamidation of asparagine-(387, 392, 393) in the conserved CH3 region, which has been identified as being solvent accessible and sensitive to chemical degradation in previous studies. In order to reduce the time for simultaneous identification and functional evaluation of potential asparagine deamidation and aspartate isomerization sites, a test system employing accelerated temperature conditions and proteolytic peptide mapping combined with quantitative UPLC-MS was developed. This method occupies the formulation buffer system histidine/HCl (20 mM; pH 6.0) for denaturation/reduction/digestion and eliminates the alkylation step. The achieved degree of asparagine deamidation and aspartate isomerization was adequate to identify the functional consequence by binding studies. In summary, the here presented approach greatly facilitates the evaluation of fermentation, purification, formulation, and storage conditions on antibody asparagine deamidation and aspartate isomerization by monitoring susceptible marker peptides located in the complementary-determining regions of recombinant antibodies. [ABSTRACT FROM AUTHOR]

The development of European power markets is highly influenced by integrated electricity and heat systems. Therefore, decarbonization policies for the electricity and heat sectors, as well as numerical models that are used to guide such policies, should consider cross-sectoral interdependencies and need evaluation. Many model-based policy assessments evaluate potential benefits of combined heat and power. However, the extent of benefits, such as emissions reductions, found in existing studies is subject to considerable variations. While scenarios and model inputs may partly explain such variations, differences in results may also be related to the model formulation itself. Against this background, this study is the first to compare electricity market models in the context of potential benefits of integrated electricity and heat systems in decarbonization. Five large-scale market models covering electricity and heat supply were utilized to study the interactions between a rather simple coal replacement scenario and a more ambitious policy that supports decarbonization through power-to-heat. With a focus on flexibility provision, emissions reduction, and economic efficiency, although the models agree on the qualitative effects, there are considerable quantitative differences. For example, the estimated reductions in overall CO 2 emissions range between 0.2 and 9.0 MtCO 2 /a for a coal replacement scenario and between 0.2 and 25.0 MtCO 2 /a for a power-to-heat scenario. Model differences can be attributed mainly to the level of detail of combined heat and power modeling and the endogeneity of generation investments. Based on a detailed comparison of the modeling results, implications for modeling choices and political decisions are discussed. • Assessment of benefits of combined heat and power in a model comparison experiment. • Case study analyzing a coal phase-out scenario and a power-to-heat scenario. • Focus on flexibility provision, emissions reduction, and economic efficiency. • Differences are driven by granularity of CHP modeling and endogeneity of investment. [ABSTRACT FROM AUTHOR]

Biotherapeutics are often produced in non-human host cells like Escherichia coli, yeast, and various mammalian cell lines. A major focus of any therapeutic protein purification process is to reduce host cell proteins to an acceptable low level. In this study, various E. coli host cell proteins were identified at different purifications steps by HPLC fractionation, SDS-PAGE analysis, and tryptic peptide mapping combined with online liquid chromatography mass spectrometry (LC-MS). However, no host cell proteins could be verified by direct LC-MS analysis of final drug substance material. In contrast, the application of affinity enrichment chromatography prior to comprehensive LC-MS was adequate to identify several low abundant host cell proteins at the final drug substance level. Bacterial alkaline phosphatase (BAP) was identified as being the most abundant host cell protein at several purification steps. Thus, we firstly established two different assays for enzymatic and immunological BAP monitoring using the cobas® technology. By using this strategy we were able to demonstrate an almost complete removal of BAP enzymatic activity by the established therapeutic protein purification process. In summary, the impact of fermentation, purification, and formulation conditions on host cell protein removal and biological activity can be conducted by monitoring process-specific host cell proteins in a GMP-compatible and high-throughput (> 1000 samples/day) manner. [ABSTRACT FROM AUTHOR]

Molecular diagnostic tests based on the PCR or alternative nucleic acid amplification technologies are commonly used for pathogen screening at blood drawing centers. Contrived process surveillance using test-specific external and internal controls is critical for the efficient leverage of PCR power. We describe here novel control constructs for use in nucleic acid amplification assays for pathogens with a single-stranded DNA genome, e.g., parvovirus B19. These controls are derived from a deletion mutant of the filamentous phage fd-tet, fKN16, and consist of single-stranded DNA packaged in a protein coat. They are essentially noninfectious to Escherichia coli and highly resistant to nuclease degradation. fKN16 based controls can be readily manufactured and highly purified. Despite their confirmed filamentous morphology, they can be precisely and accurately diluted over a wide range. Stability studies reveal that the novel control constructs are highly resistant to temperature stress, regardless of whether they are tested as concentrated stocks in storage buffer or diluted in buffer or human plasma. Real-time amplification curves derived from recombinant control constructs containing a parvovirus B19 specific sequence fragment match those derived from native virus. In summary, our data demonstrate the feasibility of novel nuclease-resistant single-stranded DNA controls as surrogates for parvovirus B19 and their applicability in routine molecular diagnostics.