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Many peptide hormones form an α-helix on binding their receptors1-4, and sensitive methods for their detection could contribute to better clinical management of disease5. De novo protein design can now generate binders with high affinity and specificity to structured proteins6,7. However, the design of interactions between proteins and short peptides with helical propensity is an unmet challenge. Here we describe parametric generation and deep learning-based methods for designing proteins to address this challenge. We show that by extending RFdiffusion8 to enable binder design to flexible targets, and to refining input structure models by successive noising and denoising (partial diffusion), picomolar-affinity binders can be generated to helical peptide targets by either refining designs generated with other methods, or completely de novo starting from random noise distributions without any subsequent experimental optimization. The RFdiffusion designs enable the enrichment and subsequent detection of parathyroid hormone and glucagon by mass spectrometry, and the construction of bioluminescence-based protein biosensors. The ability to design binders to conformationally variable targets, and to optimize by partial diffusion both natural and designed proteins, should be broadly useful.

De novo enzyme design has sought to introduce active sites and substrate-binding pockets that are predicted to catalyse a reaction of interest into geometrically compatible native scaffolds1,2, but has been limited by a lack of suitable protein structures and the complexity of native protein sequence-structure relationships. Here we describe a deep-learning-based 'family-wide hallucination' approach that generates large numbers of idealized protein structures containing diverse pocket shapes and designed sequences that encode them. We use these scaffolds to design artificial luciferases that selectively catalyse the oxidative chemiluminescence of the synthetic luciferin substrates diphenylterazine3 and 2-deoxycoelenterazine. The designed active sites position an arginine guanidinium group adjacent to an anion that develops during the reaction in a binding pocket with high shape complementarity. For both luciferin substrates, we obtain designed luciferases with high selectivity; the most active of these is a small (13.9 kDa) and thermostable (with a melting temperature higher than 95 °C) enzyme that has a catalytic efficiency on diphenylterazine (kcat/Km = 106 M-1 s-1) comparable to that of native luciferases, but a much higher substrate specificity. The creation of highly active and specific biocatalysts from scratch with broad applications in biomedicine is a key milestone for computational enzyme design, and our approach should enable generation of a wide range of luciferases and other enzymes.

Field trips are steadily declining due to limited funding, time constraints, safety concerns, and other logistical issues. Many schools are resorting to a virtual field trip (VFT), especially when education is disrupted due to public health concerns, natural disasters, or other unforeseen significant events. Virtual reality as a common form of VFT is likely not an option for many schools due to cost and other barriers. The purpose of our study was to explore the potential of going in a VFT using 360-degree (360°) videos as an alternative to a physical field trip in primary education. We recruited third-grade pupils (aged 8-9) from two private elementary schools to experience VFTs using 360° videos (360V) and regular videos (REGV). Using a switching-replications experimental design, we compared their content recall (assessment tests) and VFT experience (attitude, perceived usefulness, involvement, inquiry, video engagement, and virtual guide) across four-time points. Our results show that the increase in content recall scores of 360V groups after VFTs was consistently higher compared to REGV groups at all time points, although it was only significant in one quarter. We also found pupils' video engagement, involvement, and attitude as significant factors in their VFT experience. These results call attention to a possible implementation of VFTs and continue the long-standing tradition that has been acknowledged as a student-centered, interactive instructional method.

An important element of STEAM education that teachers struggle with is the adoption and application of digital technologies. Digital technologies have the potential to enhance social inclusion and student-centred learning, and for this reason it is important for teachers across all levels of schooling to develop skills and confidence in this area (Digital Education Advisory Group, 2013). The aim of this article is to illustrate innovative teaching practices through an integrated STEAM project using Kitsi Blocks (Kitsunei, 2019) as the core digital technology. Kitsi Blocks may be described as a fabrication technology, enabling students to collect digital data for analytical purposes and/or to send data to instruct physical things to move, light up or make sounds. The technology is comprised of physical Kitsi Blocks, which house different electronic components in a small plastic casing, and virtual blocks that build the computational logic in a visual programming system called the Kitsunei Creator. The authors demonstrate a thematic STEAM approach to the ideas of 'beat' and 'rhythm' by describing the integration of science, mathematics, digital technologies and music that is aligned with the Australian Curriculum (ACARA, 2020).

The authors start from the premise that mathematical understanding and skills are fundamentally important in STEM education as they underpin the three other discplines of STEM. They describe how contextualised integrated STEM projects can bring mathematics into the foreground with digital technologies--such as Kitsi blocks. They outine a project in which the theme of 'rhythm and beat' was explored in the creation of a heart rate monitor.

We extract dynamic conditional factor premiums from the Fama-French factor model and find that most anomalies disappear after one accounts for time variation in these premiums. Vector autoregression evidence shows that mutual causation between dynamic conditional alphas and macroeconomic surprises serves as a core qualifying condition for fundamental factor selection. This economic insight is an incremental step toward drawing a distinction between rational risk and behavioral mispricing models. To the extent that dynamic conditional alphas can reveal the marginal investor's fundamental news and expectations about the cross-section of average asset returns, our economic insight helps enrich macroeconomic asset return prediction. [ABSTRACT FROM AUTHOR]

This paper reports a study of students' and teachers' perceptions of their classroom learning environment in Bhutanese eighth-grade mathematics classes. Research suggests that positive perceptions of the learning environment can have a positive influence on students' learning outcomes, interest and engagement in classroom activities. The study was conducted in 2013, using the survey samples of 608 students and 98 teachers from 22 lower- and middle-secondary schools in western Bhutan. Students' and teachers' perceptions of the classroom environment were measured using the Mathematics Classroom Learning Environment Survey (MCLES). Students and teachers mostly perceived their classroom environments favourably on the MCLES scales irrespective of gender, school level and school location. The study is significant for understanding and evaluating the implementation of new mathematics curriculum in Bhutanese schools because it could guide the development of strategies for more-productive mathematics classroom learning. It is also significant from the perspective of Bhutan's national goal of Gross National Happiness because perceptions and happiness always go hand-in-hand.

This paper reports on the initial phase of a Professional Learning Program (PLP) undertaken by 100 primary school teachers in China that aimed to facilitate the development of adaptive expertise in using technology to facilitate innovative science teaching and learning such as that envisaged by the Chinese Ministry of Education's (2010-2020) education reforms. Key principles derived from literature about professional learning and scaffolding of learning informed the design of the PLP. The analysis of data revealed that the participants had made substantial progress towards the development of adaptive expertise. This was manifested not only by advances in the participants' repertoires of Subject Matter Knowledge and Pedagogical Content Knowledge but also in changes to their levels of confidence and identities as teachers. By the end of the initial phase of the PLP, the participants had coalesced into a professional learning community that readily engaged in the sharing, peer review, reuse and adaption, and collaborative design of innovative science learning and assessment activities. The findings from the study indicate that those engaged in the development of PLPs for teachers in China need to take cognizance of certain cultural factors and traditions idiosyncratic to the Chinese educational system. A set of revised principles is then presented to inform the future design and implementation of PLPs for teachers in China.

This paper reports on a Professional Learning Programme undertaken by primary school teachers in China that aimed to facilitate the development of "adaptive expertise" in using technology to facilitate innovative science teaching and learning such as that envisaged by the Chinese Ministry of Education's (2010--2020) education reforms. The study found that the participants made substantial progress towards the development of adaptive expertise manifested not only by advances in the participants' repertoires of pedagogical content knowledge but also in changes to their levels of confidence and identities as teachers. By the end of the programme, the participants had coalesced into a professional learning community that readily engaged in the sharing, peer review, reuse and adaption, and collaborative design of innovative science learning and assessment activities. The findings from the study indicate that those engaged in the development of Professional Learning Programmes in Asia-Pacific nations need to take cognizance of certain cultural factors and traditions idiosyncratic to the educational systems. This is reflected in the amended set of principles to inform the design and implementation of professional learning programmes presented in the concluding sections of the paper.

This paper reports on a study that focused on growth of understanding about teaching geometry by a group of prospective teachers engaged in lesson plan study within a computer-supported collaborative learning (CSCL) environment. Participation in the activity was found to facilitate considerable growth in the participants' pedagogical-content knowledge (PCK). Factors that influenced growth in PCK included the nature of the lesson planning task, the cognitive scaffolds inserted into the CSCL virtual space, the meta-language scaffolds provided to the participants, and the provision of both private and public discourse spaces. The paper concludes with recommendations for enhancing effective knowledge-building discourse about mathematics PCK within prospective teacher education CSCL environments.

This paper reports on the initial phase of a Professional Learning Program (PLP) undertaken by 100 primary school teachers in China that aimed to facilitate the development of adaptive expertise in using technology to facilitate inno-vative science teaching and learning such as that envisaged by the Chinese Ministry of Education's (2010-2020) educa-tion reforms. Key principles derived from literature about professional learning and scaffolding of learning informed the design of the PLP. The analysis of data revealed that the participants had made substantial progress towards the devel-opment of adaptive expertise. This was manifested not only by advances in the participants' repertoires of Subject Matter Knowledge and Pedagogical Content Knowledge but also in changes to their levels of confidence and identities as teach-ers. By the end of the initial phase of the PLP, the participants had coalesced into a professional learning community that readily engaged in the sharing, peer review, reuse and adap-tion, and collaborative design of innovative science learning and assessment activities. The findings from the study indi-cate that those engaged in the development of PLPs for teach-ers in China need to take cognizance of certain cultural fac-tors and traditions idiosyncratic to the Chinese educational [ABSTRACT FROM AUTHOR]

We offer a model that sheds light on the debate over whether corporate ownership concentration converges to the Berle-Means image. Our model takes into account the importance of both legal rules and firm-specific arrangements. Our analytical result is that share ownership concentration either persists or falls depending on the relative importance of these protective arrangements. In particular, our model predicts: (a) diffuse corporate ownership in nations that impose legal limits on blockholders' clout to expropriate minority shareholder rights, and (b) concentrated corporate ownership in nations that rely on asset specificity as a form of investor protection. Our empirical work suggests partial convergence toward Berle-Means diffuse share ownership. It is thereby reasonable to infer the existence of path dependent forces on ownership concentration. But this result does not preclude the possibility of functional convergence or convergence to the diffuse form of share ownership via cross-listings on the major U.S. stock exchanges that impose stringent disclosure and listing requirements. In essence, these results suggest a case for the co existence of the preexisting path-dependency and functional-convergence stories. [ABSTRACT FROM AUTHOR]