This paper describes some numerical experiments with variable-storage quasi-Newton methods for the optimization of some large-scale models (coming from fluid mechanics and molecular biology). In addition to assessing these kinds of methods in real-life situations, we compare an algorithm of A. Buckley with a proposal by J. Nocedal. The latter seems generally superior, provided that careful attention is given to some nontrivial implementation aspects, which concern the general question of properly initializing a quasi-Newton matrix. In this context, we find it appropriate to use a diagonal matrix, generated by an update of the identity matrix, so as to fit the Rayleigh ellipsoid of the local Hessian in the direction of the change in the gradient.Also, a variational derivation of some rank one and rank two updates in Hilbert spaces is given.
Andrei Preoteasa, Andreas Grigorjew, Alexandru I. Tomescu
et al.
Life over the past four billion years has been shaped by proteins and their capacity to assemble into three dimensional conformations. Protein sequence alignments have been the enabling technology for exploring the evolution and functional adaptation of proteins across the tree of life. Recent advancements in scaling the prediction of three dimensional protein structures from primary sequence alone, revealed that different modes of conservation and function operate on the sequence and structure level. This difference in protein conservation patterns and their underlying functional change that could emerge in suboptimal alignment configurations is often ignored in optimal protein alignment approaches. We introduce EMERALD-UI, an open-source interactive web application which is designed to reveal unexplored biology by visualising stable structural conformations or protein regions hidden in the suboptimal alignment space. Availability: EMERALD-UI is available at https://algbio.github.io/emerald-ui/. Contact: hdrost001@dundee.ac.uk or alexandru.tomescu@helsinki.fi.
Celina Love, Jan Steinkühler, David T. Gonzales
et al.
Abstract In situ, reversible coacervate formation within lipid vesicles represents a key step in the development of responsive synthetic cellular models. Herein, we exploit the pH responsiveness of a polycation above and below its pKa, to drive liquid–liquid phase separation, to form single coacervate droplets within lipid vesicles. The process is completely reversible as coacervate droplets can be disassembled by increasing the pH above the pKa. We further show that pH‐triggered coacervation in the presence of low concentrations of enzymes activates dormant enzyme reactions by increasing the local concentration within the coacervate droplets and changing the local environment around the enzyme. In conclusion, this work establishes a tunable, pH responsive, enzymatically active multi‐compartment synthetic cell. The system is readily transferred into microfluidics, making it a robust model for addressing general questions in biology, such as the role of phase separation and its effect on enzymatic reactions using a bottom‐up synthetic biology approach.
Part 1 Bone biology - general. Part 2 Bioceramics - present and future. Part 3 Bioceramics - preparation and properties: alumina zirconia calcium phosphates bioglass composites coatings cements. Part 4 Cells and bioceramics interactions in vitro. Part 5 Tissue response to bioceramics. Part 6 Biomimetics, tissue engineering, growth factors, drug delivery: biomimetics tissue engineering and growth factors drug delivery. Part 7 Clinical applications: dental applications medical applications. Part 8 Methods - special preparation and analysis: surface modifications of implant special preparations and analytical techniques.
Deepti Negi, Penelope M. Tsimbouri, Matthew J. Dalby
et al.
Bone is a dynamic tissue with ecological and evolutionary importance, as it can grow and remodel itself in response to mechanical stimuli. In mammals, osteocytes are widely recognised as the central regulators of bone formation and mechanotransduction. However, many advanced teleosts lack these cells yet still exhibit evidence of bone formation and remodelling. This challenges the prevailing view that osteocytes are indispensable for these processes. Notably, these anosteocytic teleosts exhibit clear responses to mechanical loading, suggesting alternative mechanisms at play. African cichlids, known for their remarkable ecological diversification, which occurs in craniofacial bone morphology. However, these differences are based on very few genetic changes, while including interspecific variation in bone remodeling capacities. Thus, cichlid, being anosteocytic, and variable in remodeling abilities based on very few genetic changes, represents an ideal model system for understanding the mechanisms underlying remodeling. This protocol outlines the development of primary cell cultures from cichlid jaw bones that can be applied across species, establishing a foundation for future research aimed at elucidating the cellular and molecular mechanisms underlying bone formation and remodelling in anosteocytic systems.
Large language models (LLMs) are powerful artificial intelligence (AI) tools transforming how research is conducted. However, their use in research has been met with skepticism, due to concerns about hallucinations, biases and potential harms to research. These emphasize the importance of clearly understanding the strengths and weaknesses of LLMs to ensure their effective and responsible use. Here, we present a roadmap for integrating LLMs into cross-disciplinary research, where effective communication, knowledge transfer and collaboration across diverse fields are essential but often challenging. We examine the capabilities and limitations of LLMs and provide a detailed computational biology case study (on modeling HIV rebound dynamics) demonstrating how iterative interactions with an LLM (ChatGPT) can facilitate interdisciplinary collaboration and research. We argue that LLMs are best used as augmentative tools within a human-in-the-loop framework. Looking forward, we envisage that the responsible use of LLMs will enhance innovative cross-disciplinary research and substantially accelerate scientific discoveries.
Many systems involve numerous interacting parts and the whole system can have properties that the individual parts do not. I take this novelty as the defining characteristic of an emergent property. Other characteristics associated with emergence discussed include universality, order, complexity, unpredictability, irreducibility, diversity, self-organisation, discontinuities, and singularities. Emergent phenomena are widespread across physics, biology, social sciences, and computing, and are central to major scientific and societal challenges. Understanding emergence involves considering the stratification of reality across different scales (energy, time, length, complexity), each with its distinct ontology and epistemology, leading to semi-autonomous scientific disciplines. A central challenge is bridging the gap between macroscopic emergent properties and microscopic component interactions. Identifying an intermediate mesoscopic scale where new, weakly interacting entities or modular structures emerge is key. Theoretical approaches, such as effective theories (describing phenomena at a specific scale) and toy models (simplified systems for analysis), are vital. The Ising model exemplifies how toy models can elucidate emergence characteristics. Emergence is central to condensed matter physics, chaotic systems, fluid dynamics, nuclear physics, quantum gravity, neural networks, protein folding, and social segregation. An emergent perspective should influence scientific strategy by shaping research questions, methodologies, priorities, and resource allocation. An elusive goal is the design and control of emergent properties.
Significant progress has been made in the 21st century towards a comprehensive understanding of the mechanisms of action of general anesthetics, coincident with progress in structural biology and molecular, cellular, and systems neuroscience. This review summarizes important new findings that include target identification through structural determination of anesthetic binding sites, details of receptors and ion channels involved in neurotransmission, and the critical roles of neuronal networks in anesthetic effects on memory and consciousness. These recent developments provide a comprehensive basis for conceptualizing pharmacological control of amnesia, unconsciousness, and immobility.
Life sciences faculty agree that developing scientific literacy is an integral part of undergraduate education and report that they teach these skills. However, few measures of scientific literacy are available to assess students’ proficiency in using scientific literacy skills to solve scenarios in and beyond the undergraduate biology classroom. In this paper, we describe the development, validation, and testing of the Test of Scientific Literacy Skills (TOSLS) in five general education biology classes at three undergraduate institutions. The test measures skills related to major aspects of scientific literacy: recognizing and analyzing the use of methods of inquiry that lead to scientific knowledge and the ability to organize, analyze, and interpret quantitative data and scientific information. Measures of validity included correspondence between items and scientific literacy goals of the National Research Council and Project 2061, findings from a survey of biology faculty, expert biology educator reviews, student interviews, and statistical analyses. Classroom testing contexts varied both in terms of student demographics and pedagogical approaches. We propose that biology instructors can use the TOSLS to evaluate their students’ proficiencies in using scientific literacy skills and to document the impacts of curricular reform on students’ scientific literacy.
Given the incredible scope of substance use disorders, this chapter will primarily focus on alcohol and opioid use disorders, while also discussing substance use broadly. Furthermore, this chapter does not provide detailed guidelines for managing patients with a substance use disorder. Instead, this review aims to provide the reader with conceptual background of the biology of addiction as well as a general framework for its diagnosis and management. While this chapter primarily focuses on physicians in the role of caregiver, it is important to note that physicians also struggle with SUDs, at a rate near that of the general population.25 This review contains 3 tables and 25 references.
Insight into the non-random distribution patterns of species in different regions is a foundational aim of research in community ecology and biogeography. The nestedness pattern, which investigates changes in species composition and abundance, has been widely used in numerous studies. However, studies on the nestedness of benthic diatoms are extremely rare, and consequently little has been mentioned of their assemblage mechanisms. To fill this gap, based on 168 benthic diatom species from 147 sampling sites in the Thousand Island Lake (TIL) catchment, we calculated their nestedness and niche width with the aim of i) analyzing the nestedness of benthic diatoms communities with different attachment abilities in TIL; ii) calculating niche width differences between nested and idiosyncratic species with different attachment abilities; iii) investigating the differences in alpha and beta diversity between nested and idiosyncratic sites; iv) examining whether environmental variables influencing the nestedness of benthic diatom communities are dependent on attachment ability. The results demonstrated a significant nestedness pattern in the benthic diatom metacommunity, and the sampling sites of low attachment species not only exhibited a nestedness pattern, but also with a lower nestedness value compared to the sampling sites of all species. Nested and idiosyncratic species differed in niche width, whereas differences between nested and idiosyncratic species of low attachment species were smaller. Additionally, significant differences in alpha and beta diversity were observed between nested and idiosyncratic sites. Furthermore, it was revealed that the nestedness of benthic diatom metacommunity in our study area were mostly influenced by local environmental variables. Our study contributes to the understanding of the significant nestedness observed in benthic diatom metacommunity in TIL, highlighting its relevance to biodiversity conservation efforts.
Nonlocality is important in realistic mathematical models of physical and biological systems when local models fail to capture the essential dynamics and interactions that occur over a range of distances. This review illustrates different nonlocal mathematical models applied to biology and life sciences. The major focus has been given to sources, developments, and applications of such models. Among other things, a systematic discussion has been provided for the conditions of pattern formations in biological systems of population dynamics. Special attention has also been given to nonlocal interactions on networks, network coupling and integration, including brain dynamics models that provide an important tool to understand neurodegenerative diseases better. In addition, we have discussed nonlocal modelling approaches for cancer stem cells and tumor cells that are widely applied in the cell migration processes, growth, and avascular tumors in any organ. Furthermore, the discussed nonlocal continuum models can go sufficiently smaller scales, including nanotechnology, where classical local models often fail to capture the complexities of nanoscale interactions, applied to build biosensors to sense biomaterial and its concentration. Piezoelectric and other smart materials are among them, and these devices are becoming increasingly important in the digital and physical world that is intrinsically interconnected with biological systems. Additionally, we have reviewed a nonlocal theory of peridynamics, which deals with continuous and discrete media and applies to model the relationship between fracture and healing in cortical bone, tissue growth and shrinkage, and other areas increasingly important in biomedical and bioengineering applications. Finally, we provided a comprehensive summary of emerging trends and highlighted future directions in this rapidly expanding field.