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Game-based learning to improve understanding of point mutations at secondary school level
Get PDFUnderstanding mutations is central to molecular and evolutionary biology and aspects of biomedical sciences. However, via static graphics alone, it is difficult for school students to understand the terminology and the consequences of mutations on amino acids and protein sequences. To help secondary school (high school) students better understand these concepts, we developed a curriculum-linked, three-dimensional visualisation of the following point mutations in Minecraft: substitution, frameshift, and nonsense. This aims to clarify aspects used in bioinformatics workshops for schools, where the mouse GULO gene is aligned against the homologous pseudogene in the human genome, which contains frameshift mutations. Two focus groups were conducted in the first case-study, one consisting of secondary-level educators and the other consisting of masters students from both biological and non-biological degree programmes. These showed that non-specialist students feel they gain an understanding of frameshift mutations from the model and that teachers considered the model had potential for classroom use. These were followed up by a public engagement activity with school students, which suggested students found the visualisation helpful to understand mutations. Our model is available to download for free at https://4273pi.or
Masculinity and psychological adjustment in men living with prostate cancer:A systematic review and meta-analysis
Get PDFObjective. This pre-registered systematic review and meta-analysis aimed to examine the relationship between masculinity and psychological adjustment outcomes among men with prostate cancer by synthesising the current quantitative evidence.Methods. Embase, PsycINFO, MEDLINE, and CINAHL Plus were systematically searched. We performed primary meta-analyses, moderator analyses, quality assessment, and publication bias analyses. Results. 22 studies involving 6614 participants were included. More positive self-appraisal of masculine identity was strongly associated with greater positive adjustment outcomes (Z = .68, SE = .06, p < .001) and less negative outcomes (Z = -.62, SE = .15, p < .001). Conformity to masculine norms, on the other hand, showed no significant relationship with either positive adjustment (Z = -.07, SE = .09, p = .25) or psychological distress (Z = .04, SE = .05, p = .38). Narrative synthesis suggested that masculine threat or loss consistently associated with poorer adjustment.Conclusion. Masculinity plays a critical role in the psychological adjustment of men with prostate cancer. Tailored interventions should be developed and implemented to improve men’s sense of masculinity following prostate cancer; this may be achieved by facilitating men’s cognitive reappraisal of masculine beliefs and values in the context of prostate cancer. </div
Modelling ocean melt of ice mélange at Greenland's marine-terminating glaciers
Get PDFMany of Greenland's marine-terminating glaciers have retreated and accelerated in recent decades, contributing significantly to sea level rise. Increased submarine melting of calving fronts is often cited as the dominant driver of this retreat. However, the presence of ice mélange and its associated buttressing force on a glacier terminus is also thought to significantly impact glacier advance and retreat. The buttressing force depends on the mélange thickness, and thickness will be modulated by ocean melt rate, but our understanding of the melting of ice mélange by the ocean remains limited, and it is not yet known how these melt rates vary across a range of glacial and environmental conditions. Here, we perform high-resolution numerical simulations using MITgcm to model the circulation of ocean waters through an ice mélange close to marine-terminating glaciers and estimate the resultant melt. We explore the sensitivity of mélange melt rate to environmental conditions, finding that melt rates increase sublinearly with subglacial discharge and approximately linearly with ocean temperature. In this sense, mélange melt rate appears to respond to environmental forcing in a similar manner to submarine melting of the calving front, and can be parameterised as such. This work is a step towards both a better understanding of ice mélange dynamics and a better parameterisation of its effects on glaciers and the ocean
The Draco Dwarf Spheroidal Galaxy in the First Year of DESI Data
Get PDFWe investigate the spatial distribution, kinematics, and metallicity of stars in the Draco dwarf spheroidal galaxy using data from the Dark Energy Spectroscopic Instrument (DESI). We identify 155 high probability members of Draco using line of sight velocity and metallicity information derived from DESI spectroscopy along with Gaia DR3 proper motions. We find a mean line of sight velocity of −290.62±0.80 km s−1 with dispersion = 9.57+0.66−0.62 km s−1 and mean metallicity [Fe/H] = −2.10±0.04,consistent with previous results. We also find that Draco has a steep metallicity gradient within the half-light radius, and a metallicity gradient that flattens beyond the half-light radius. We identify eight high probability members outside the King tidal radius, four of which we identify for the first time. These extra-tidal stars are not preferentially aligned along the orbit of Draco. We compute an averagesurface brightness of 34.02 mag arcsec−2 within an elliptical annulus from the King tidal radius of 48.1 arcmin to 81 arcmin
Can protein expression be ‘solved’?
Get PDFRecombinant protein expression is central to biotechnology's application. However, not all proteins can be expressed in all organisms, and, given the vast experimental space, it can be challenging to identify the conditions that will yield successful protein expression. The field lacks a predictive model of soluble protein expression that could replace laborious experimental trial and error. Here, we discuss the state of the field and identify the lack of large, high-fidelity datasets as the primary bottleneck to progress. We outline a proposed path toward an extensible experimental platform for collecting soluble overexpression data across organisms.</p
In Silico identification and modelling of FDA-approved drugs targeting T-type calcium channels
Get PDFStudies have shown that inhibition of the Cav3.1 T-type calcium channel can prevent or suppress neurological diseases, such as epileptic seizures and diabetic neuropathy. In this study, we aimed to use in silico simulations to identify a U.S. Food and Drug Administration (FDA)-approved drug that can bind to the Cav3.1 T-type calcium channel. We used the automated docking suite GOLD v5.5 with the genetic algorithm to simulate molecular docking and predict the protein-ligand binding modes, and the ChemPLP empirical scoring function to estimate the binding affinities of 2,115 FDA-approved drugs to the human Cav3.1 channel. Drugs with high binding affinity and appropriate pharmacodynamic and pharmacokinetic properties were selected for molecular mechanics Poisson-Boltzmann surface area (MMPBSA) and molecular mechanics generalised Born surface area (MMGBSA) binding free energy calculations, GROMACS molecular dynamics (MD) simulations and Monte Carlo Cell (MCell) simulations. The docking results indicated that the FDA-approved drug montelukast has a high binding affinity to Cav3.1, and data from the literature suggested that montelukast has the appropriate drug-like properties to cross the human blood-brain barrier and reach synapses in the central nervous system. MMPBSA, MMGBSA, and MD simulations showed the high stability of the montelukast-Cav3.1 complex. MCell simulations indicated that the blockage of Cav3.1 by montelukast reduced the number of synaptic vesicles being released from the pre-synaptic region to the synaptic cleft, which may reduce the probability and amplitude of postsynaptic potentials.</p
Numerical simulation of a torque controlled horizontal-axis tidal turbine using CFD/LES, ALM and MPPT
Get PDFThis paper describes a holistic horizontal-axis tidal turbine model, which considers the interactions surrounding flow - rotor blades and rotor blades - electrical generator and controller. The flow is simulated using Large Eddy Simulation Computational Fluid Dynamics, and the rotor blades by the Actuator Line Method. The Maximum Power Point Tracking algorithm is implemented to balance the rotor and reacting electromagnetic torques. This work analyses the impact of the turbulent flow on the mechanical and electrical variables, as well as the impact of the control system response on the flow surrounding the rotor blades. The simulations start with the turbine at rest but subjected to turbulent flow. After an initial period of transience, the torque control system settles on and maintains the optimal turbine rotational speed. Thus, the coupled system reaches an electro-mechanical-hydro-control energy balance. The model is validated, regarding mean values of mechanical variables, using measurements from a tank test campaign. The validation showed good agreement. However, the highest errors and a particular behaviour of them are found for the thrust. Even once the energy balance is reached, the impact of the turbulent flow is notorious. This issue can compromise the quality of the supplied power to the grid.</p
More than a game:Seasonal handball in Scotland
Get PDFTraditional football and handball are found in various locations across the UK. Particularly associated with the period around Shrove Tuesday and Christmas, they have their origins in centuries-old, rough-and-ready street games. The article reflects on the degree of disorder and violence which are commonly assumed to characterise the games and reflects on the prospects for their survival in an increasingly litigious society. The focus is on the handball tradition in the Scottish Borders and Orkney, with additional comparative material from two examples of English street football. These games do not take place in a designated play-space, but rather the town centre and surrounding streets, where shops are boarded up in advance, but yet are still open for business. The events are only lightly regulated, police presence is minimal and there are no barriers to protect onlookers. The game has few rules and is highly physical. It can appear to the outsider not as a form of sport, but rather as something which resembles violent disorder. Indeed, it is frequently presented in this way in the form of video packages on YouTube. But what is violence in the context of this tradition? Can a traditional form maintain its unregulated character while presenting a risk to players, onlookers and property
A More-than-Moore Optical Multi-Sensing Platform
Get PDFThis work demonstrates the integration of a photoluminescent sensing film on a complementary metal– oxide–semiconductor (CMOS) sensor application-specific integrated circuit (ASIC) for time-resolved optical oxygen sensing. A phosphorescent dye, platinum octaethylporphyrin (PtOEP), embedded in a polydimethylsiloxane (PDMS) matrix, was deposited on the ASIC using spin coating and photolithographic patterning. The custom ASIC includes an array of closely spaced silicon LED (SiLED) emitters and single photon avalanche diode (SPAD) detectors with the capability of multimodal sensing. The platform benefits from the dye’s long emission lifetime, resistance to photobleaching, and the intrinsic nature of the lifetime measurement concerning the analyte and dye. A custom printed circuit board (PCB) incorporating a time-correlated single photon counting (TCSPC) module based on an ARM Cortex-M7 microcontroller was developed to drive the sensor and acquire nanosecond-resolution photon timing data. The integrated sensor system was rigorously characterized in a controlled gas chamber, showing reliable oxygen detection via luminescence quenching and strong Stern–Volmer linearity ( R 2 = 0.9771 ). It exhibited excellent repeatability (<5% variation across cycles) and fast, real-time response. In order to demonstrate the multimodal sensing, we integrated multiple oxygen-sensitive dyes—PtOEP, palladium octaethylporphine (PdOEP), and zinc octaethylporphyrin (ZnOEP)—over different CMOS regions. The system was adapted for multianalyte sensing without cross sensitivity, highlighting its potential for biomedical applications in hypoxic environments.</p
The LAW Theorem:Local Reads and Linearizable Asynchronous Replication
Get PDFDistributed datastores underpin highly concurrent, read-intensive applications, ensuring consistency, availability, and performance. They use crash-tolerant protocols to replicate data and endure replica server crashes. To ensure safety and meet the performance demands, replication must support high-throughput, strongly consistent (i.e., linearizable) reads without assuming any synchrony. However, existing protocols either 1 relax consistency, or provide linearizable reads that are 2 fully asynchronous but remote (involving multiple replicas), or 3 local but require synchrony.This work explores the tradeoffs between consistency, asynchrony, and performance in crash-tolerant protocols, and proves that in linearizable asynchronous read/write registers tolerating a single crash, no reads can be local. Building on this, we introduce almost-local reads (ALRs), a new abstraction that ensures crash tolerance and linearizability under asynchrony. While ALRs have slightly higher latency than local reads, they remain lightweight, with computation and network costs close to single-node reads.We present two simple yet effective ALR schemes that enhance protocols across all three categories. For protocols with local reads, ALRs address consistency or synchrony issues with minimal throughput loss. In asynchronous linearizable protocols, they improve performance without compromises. Our evaluation shows that ALR-enhanced ZAB and Hermes achieve within 2% and 5% of their original throughput in 95% reads while ensuring linearizability under asynchrony. On Raft, ALRs deliver over 2.5x higher throughput without compromising consistency or asynchrony
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