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Author(s):  
Jesús Piqueras ◽  
Marianne Achiam ◽  
Susanna Edvall ◽  
Charlotte Ek

Abstract Scientific representations of human evolution often embrace stereotypes of ethnicity and gender that are more aligned with socio-cultural discourses and norms than empirical facts. The present study has two connected aims: to understand how ethnicity and gender are represented in an exhibition about human evolution, and to understand how that representation influences learners’ meaning making. First, we analysed an exhibition with realistic reconstructions of early hominids in a museum of natural history, to identify dualisms related to the representation of gender and ethnicity that have been recognised in research. Then, we studied the processes of meaning making in the exhibition during an out-of-school educational activity, in which groups of teenaged students explore and discuss the hominid reconstructions. Our results show that the exhibition displays human evolution in the form of a linear sequence from a primitive African prehistory to a more advanced European present. Behind this depiction of human evolution lies stereotypic notions of ethnicity and gender: notions that were incorporated into the students’ meaning making during the educational activity. When students noticed aspects of ethnicity, their meaning making did not dispute the messages represented in the exhibition; these were accepted as scientific facts. Conversely, when the students noticed aspects related to gender, they often adopted a more critical stance and challenged the representations from different perspectives. We discuss the implications of our findings for exhibit design and evolution education more generally. In doing so, we offer our perspectives on the design of learning environments to salvage inherently sexist, racist, imperial science.


2021 ◽  
Author(s):  
◽  
Hemi Cumming

<p>Pateamine A (14) is a natural product that was extracted from a marine sponge off the coast of the South Island of New Zealand. It exhibits potent biological activity, mediated by a number of protein targets. The most sensitive of these towards pateamine are the eIF4A isoforms, which have roles in translation of RNA into proteins and in nonsensemediated decay. The inhibition of these enzymes may be beneficial in the treatment of cancer or certain types of genetic diseases. Unfortunately, the naturally available supply of pateamine is very limited and its total synthesis is complex. This provides an imperative for the design of a synthetic strategy that would allow the preparation of simplified analogues of pateamine to gain further insight into the necessary features for activity and selectivity of the eIF4A isoforms. Based on the principles of pharmacophore modification, chemical synthesis and the structure-activity relationships (SARs) reported by Romo and co-workers, a simplified analogue of pateamine, 107, was targeted that lacked a number of pendant methyl groups and contained a triazole in place of the thiazole. Synthesis of the target analogue 107 was achieved through preparation of four fragments, followed by an investigation of suitable coupling reactions and the optimal order of connectivity. This included the preparation of two macrocycles that lacked the trienecontaining sidechain, and of simplified model substrates that allowed investigation of two olefination reactions (namely, the Wittig and Julia-Kocienski reactions) for the attachment of the sidechain fragment. After substantial optimisation of the fragment preparation and connectivity, the complete synthesis of the target pateamine analogue 107 was achieved. The synthesis features: 1) a Julia Kocienski olefination between a highly functionalised three-carbon sulfone and a conjugated aldehyde to attach the sidechain; 2) copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction to form the triazole; 3) ring opening of a δ-substituted α,β-unsaturated lactone to access the Z,E-dienoate moiety; and 4) Yamaguchi macrolactonisation. This synthesis represents a convergent strategy with 11 steps in the longest linear sequence, which utilises easily accessible starting materials (i.e. furan (or cis-butenediol), epichlorohydrin, ε-caprolactone and 1,3-propanediol) and reagents. The approach is also broadly applicable to the preparation of a range of analogue variants. The simplified analogue (107) was found to have significantly lower activity, in comparison to pateamine A (14), in a growth inhibitory assay. Presuming this loss of bioactivity is at least partially caused by the incorporation of the triazole (in place of the thiazole), this raises an interesting question as to the role of the thiazole moiety in the bioactivity of pateamine A. The adaptation of the synthetic strategy devised in this thesis to the preparation of future analogues will enable study of the mechanism of action of pateamine and related compounds, and probe the requirements for effective binding to the eIF4A isoforms.</p>


2021 ◽  
Author(s):  
◽  
Hemi Cumming

<p>Pateamine A (14) is a natural product that was extracted from a marine sponge off the coast of the South Island of New Zealand. It exhibits potent biological activity, mediated by a number of protein targets. The most sensitive of these towards pateamine are the eIF4A isoforms, which have roles in translation of RNA into proteins and in nonsensemediated decay. The inhibition of these enzymes may be beneficial in the treatment of cancer or certain types of genetic diseases. Unfortunately, the naturally available supply of pateamine is very limited and its total synthesis is complex. This provides an imperative for the design of a synthetic strategy that would allow the preparation of simplified analogues of pateamine to gain further insight into the necessary features for activity and selectivity of the eIF4A isoforms. Based on the principles of pharmacophore modification, chemical synthesis and the structure-activity relationships (SARs) reported by Romo and co-workers, a simplified analogue of pateamine, 107, was targeted that lacked a number of pendant methyl groups and contained a triazole in place of the thiazole. Synthesis of the target analogue 107 was achieved through preparation of four fragments, followed by an investigation of suitable coupling reactions and the optimal order of connectivity. This included the preparation of two macrocycles that lacked the trienecontaining sidechain, and of simplified model substrates that allowed investigation of two olefination reactions (namely, the Wittig and Julia-Kocienski reactions) for the attachment of the sidechain fragment. After substantial optimisation of the fragment preparation and connectivity, the complete synthesis of the target pateamine analogue 107 was achieved. The synthesis features: 1) a Julia Kocienski olefination between a highly functionalised three-carbon sulfone and a conjugated aldehyde to attach the sidechain; 2) copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction to form the triazole; 3) ring opening of a δ-substituted α,β-unsaturated lactone to access the Z,E-dienoate moiety; and 4) Yamaguchi macrolactonisation. This synthesis represents a convergent strategy with 11 steps in the longest linear sequence, which utilises easily accessible starting materials (i.e. furan (or cis-butenediol), epichlorohydrin, ε-caprolactone and 1,3-propanediol) and reagents. The approach is also broadly applicable to the preparation of a range of analogue variants. The simplified analogue (107) was found to have significantly lower activity, in comparison to pateamine A (14), in a growth inhibitory assay. Presuming this loss of bioactivity is at least partially caused by the incorporation of the triazole (in place of the thiazole), this raises an interesting question as to the role of the thiazole moiety in the bioactivity of pateamine A. The adaptation of the synthetic strategy devised in this thesis to the preparation of future analogues will enable study of the mechanism of action of pateamine and related compounds, and probe the requirements for effective binding to the eIF4A isoforms.</p>


2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Ahmad Al Cheikha ◽  
Diana Mokayes

In the current time there is an important problem that is for a received linear or nonlinear binary sequence {zn} how we can find the nonlinear feedback shift register and its linear equivalent which generate this sequence. The linear orthogonal sequences, special M-Sequences, play a big role in these methods for solving this problem. In the current research trying give illuminations about the methods which are very useful for solving this problem under short sequences, and study these methods for finding the nonlinear feedback shift register of a multiplication sequence and its linear equivalent feedback shift register of a received multiplication binary sequence{zn} where the multiplication on h degrees of a binary linear sequence {an}, or finding the equivalent linear feedback shift register of {zn}, where the sequence {zn}of the form M-sequence, and these methods are very effectively. We can extend these methods for the large sequences using programming and modern computers with large memory.


2021 ◽  
Author(s):  
◽  
Liang Chen

<p>The aim of the research is to develop a new model of bicycling supporting infrastructure that is cost-efficient, easily fabricated and installed, energy-efficient, globally transportable and adaptable to site. Cycling has entered into a new era, with a large population of active cyclists competing with unsustainable fossil fuel transport systems. The increase in cycling is a result of rising fossil fuel costs and a more environmentally aware public. The thesis seeks an architectural way of provoking greater incentives for cycling by increasing its appeal and ease of engagement, while decreasing related infrastructure costs.  The design proposes ‘Bike Shop’, an architecturally integrated cycling support facility that can be positioned at regular intervals along a cycling route. The design research challenge is to conceive a facility that is self-sustaining, adaptable, economically produced, environmentally sensitive, portable and able to be applied globally. As a vehicle for design, the Great Harbour Way/Te Aranui o Pōneke will be used. The Great Harbour Way includes plans for a parallel cycling route that stretches over 50 kilometres along the shoreline in the Greater Wellington region from Eastbourne to Owhiro Bay. The Greater Wellington Regional Council has proposed their second highest funding of large projects over $5 million for walking and cycling development in the region. The funding of $17.05 million goes towards the development for a walkway/cycleway between Ngaraunga and Petone. This thesis will test how prefabricated methods such as kit-of-parts and mass customisation techniques can reduce costs yet encourage adaptability to address the wide range of conditions that the Great Harbour Way offers. The challenge of the design experiment for this facility will be to become a new model of cycling infrastructure around the world.  The thesis proposes to reinterpret the Bike Shop as a linear sequence of cycling facilities that inhabit the Great Harbour Way. The Bike Shop is to be placed on this stretch of shoreline at fixed intervals. At these locations with the wide range of site conditions the design challenge is for the facility to arrive as a kit-of-parts, be assembled quickly and adapted to unique site conditions.  The thesis proposes a program where each architecturally integrated facility along the linear sequence will function as new cycling infrastructure, where simultaneously a bike can be repaired or a tire can be inflated or a bicyclist can rest and rehydrate with other cyclists off the road. In this way, each facility will promote safe cycling, thereby providing safety, environmentally sustainable energy, and public health benefits to more cyclists. In this way, the thesis argues that the facilities will be recognized as signifiers of the city as well as markers of location and orientation. Overall this thesis invites prefabricated elements to be adaptable in ways that make them responsive and beautifully reflect the site rather than just repetitive.</p>


2021 ◽  
Author(s):  
◽  
Liang Chen

<p>The aim of the research is to develop a new model of bicycling supporting infrastructure that is cost-efficient, easily fabricated and installed, energy-efficient, globally transportable and adaptable to site. Cycling has entered into a new era, with a large population of active cyclists competing with unsustainable fossil fuel transport systems. The increase in cycling is a result of rising fossil fuel costs and a more environmentally aware public. The thesis seeks an architectural way of provoking greater incentives for cycling by increasing its appeal and ease of engagement, while decreasing related infrastructure costs.  The design proposes ‘Bike Shop’, an architecturally integrated cycling support facility that can be positioned at regular intervals along a cycling route. The design research challenge is to conceive a facility that is self-sustaining, adaptable, economically produced, environmentally sensitive, portable and able to be applied globally. As a vehicle for design, the Great Harbour Way/Te Aranui o Pōneke will be used. The Great Harbour Way includes plans for a parallel cycling route that stretches over 50 kilometres along the shoreline in the Greater Wellington region from Eastbourne to Owhiro Bay. The Greater Wellington Regional Council has proposed their second highest funding of large projects over $5 million for walking and cycling development in the region. The funding of $17.05 million goes towards the development for a walkway/cycleway between Ngaraunga and Petone. This thesis will test how prefabricated methods such as kit-of-parts and mass customisation techniques can reduce costs yet encourage adaptability to address the wide range of conditions that the Great Harbour Way offers. The challenge of the design experiment for this facility will be to become a new model of cycling infrastructure around the world.  The thesis proposes to reinterpret the Bike Shop as a linear sequence of cycling facilities that inhabit the Great Harbour Way. The Bike Shop is to be placed on this stretch of shoreline at fixed intervals. At these locations with the wide range of site conditions the design challenge is for the facility to arrive as a kit-of-parts, be assembled quickly and adapted to unique site conditions.  The thesis proposes a program where each architecturally integrated facility along the linear sequence will function as new cycling infrastructure, where simultaneously a bike can be repaired or a tire can be inflated or a bicyclist can rest and rehydrate with other cyclists off the road. In this way, each facility will promote safe cycling, thereby providing safety, environmentally sustainable energy, and public health benefits to more cyclists. In this way, the thesis argues that the facilities will be recognized as signifiers of the city as well as markers of location and orientation. Overall this thesis invites prefabricated elements to be adaptable in ways that make them responsive and beautifully reflect the site rather than just repetitive.</p>


2021 ◽  
Author(s):  
◽  
Carlton Downey

<p>Linear Genetic Programming (LGP) is a powerful problem-solving technique, but one with several significant weaknesses. LGP programs consist of a linear sequence of instructions, where each instruction may reuse previously computed results. This structure makes LGP programs compact and powerful, however it also introduces the problem of instruction dependencies. The notion of instruction dependencies expresses the concept that certain instructions rely on other instructions. Instruction dependencies are often disrupted during crossover or mutation when one or more instructions undergo modification. This disruption can cause disproportionately large changes in program output resulting in non-viable offspring and poor algorithm performance. Motivated by biological inspiration and the issue of code disruption, we develop a new form of LGP called Parallel LGP (PLGP). PLGP programs consist of n lists of instructions. These lists are executed in parallel, and the resulting vectors are summed to produce the overall program output. PLGP limits the disruptive effects of crossover and mutation, which allows PLGP to significantly outperform regular LGP. We examine the PLGP architecture and determine that large PLGP programs can be slow to converge. To improve the convergence time of large PLGP programs we develop a new form of PLGP called Cooperative Coevolution PLGP (CC PLGP). CC PLGP adapts the concept of cooperative coevolution to the PLGP architecture. CC PLGP optimizes all program components in parallel, allowing CC PLGP to converge significantly faster than conventional PLGP. We examine the CC PLGP architecture and determine that performance</p>


2021 ◽  
Author(s):  
◽  
Carlton Downey

<p>Linear Genetic Programming (LGP) is a powerful problem-solving technique, but one with several significant weaknesses. LGP programs consist of a linear sequence of instructions, where each instruction may reuse previously computed results. This structure makes LGP programs compact and powerful, however it also introduces the problem of instruction dependencies. The notion of instruction dependencies expresses the concept that certain instructions rely on other instructions. Instruction dependencies are often disrupted during crossover or mutation when one or more instructions undergo modification. This disruption can cause disproportionately large changes in program output resulting in non-viable offspring and poor algorithm performance. Motivated by biological inspiration and the issue of code disruption, we develop a new form of LGP called Parallel LGP (PLGP). PLGP programs consist of n lists of instructions. These lists are executed in parallel, and the resulting vectors are summed to produce the overall program output. PLGP limits the disruptive effects of crossover and mutation, which allows PLGP to significantly outperform regular LGP. We examine the PLGP architecture and determine that large PLGP programs can be slow to converge. To improve the convergence time of large PLGP programs we develop a new form of PLGP called Cooperative Coevolution PLGP (CC PLGP). CC PLGP adapts the concept of cooperative coevolution to the PLGP architecture. CC PLGP optimizes all program components in parallel, allowing CC PLGP to converge significantly faster than conventional PLGP. We examine the CC PLGP architecture and determine that performance</p>


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Manoj Kumar ◽  
Prasanth Padala ◽  
Jamal Fahoum ◽  
Fouad Hassouna ◽  
Tomer Tsaban ◽  
...  

AbstractUfmylation is a post-translational modification essential for regulating key cellular processes. A three-enzyme cascade involving E1, E2 and E3 is required for UFM1 attachment to target proteins. How UBA5 (E1) and UFC1 (E2) cooperatively activate and transfer UFM1 is still unclear. Here, we present the crystal structure of UFC1 bound to the C-terminus of UBA5, revealing how UBA5 interacts with UFC1 via a short linear sequence, not observed in other E1-E2 complexes. We find that UBA5 has a region outside the adenylation domain that is dispensable for UFC1 binding but critical for UFM1 transfer. This region moves next to UFC1’s active site Cys and compensates for a missing loop in UFC1, which exists in other E2s and is needed for the transfer. Overall, our findings advance the understanding of UFM1’s conjugation machinery and may serve as a basis for the development of ufmylation inhibitors.


2021 ◽  
Author(s):  
Matthew Crowther ◽  
Anil Wipat ◽  
Angel Goñi-Moreno

Visualising the complex information captured by synthetic biology designs is still a major challenge. The popular glyph approach where each genetic part is displayed on a linear sequence allows researchers to generate diagrams and visualise abstract designs, but only represents a single, static representation that results in visualisation that is not specific to the requirements of a user resulting in a one-size-fits-all visualisation. We developed a network visualisation technique that automatically turns all design information into a graph, displaying otherwise hidden data. The structure of the resulting graphs can be dynamically adjusted according to specific visualisation requirements, such as highlighting proteins, interactions or hierarchy. Since biological systems have an inherent affinity with network visualisation, we advocate for adopting this approach to standardise and automate the representation of complex information.


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