bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Origin of Cells
Authors: Lynch Michael R. 
Published: March 2024

Abstract
Laboratory experiments provide compelling support for life’s inevitable emergence out of inorganic materials on an Earth-like planet. Moreover, although many uncertainties remain, the fossil record makes clear that microbial life was established on Earth nearly four billion years ago. Potential geological settings for the origin of life include specialized environments, such as hydrothermal vents and geothermal fields, that may have provided the peculiar mix of metabolic building blocks and metal cofactors upon which all of life came to depend. However, the order in which the three major requirements for life (metabolism for resource acquisition, a mechanism for heritable genome transmission, and external membranes for individuality) were established remains unclear. A plausible scenario for the earliest steps in the emergence of life invokes a world in which RNA provided the basis for all aspects of information storage and biosynthesis, although the validity of this hypothesis remains unclear. The major challenge for genome expansion, essential for a breadth of metabolic functions, must have been the establishment of mechanisms for accurate replication and transcription.
The Cellular Environment
Authors: Lynch Michael R. 
Published: March 2024

Abstract
The biochemical and biophysical properties common to all of life ultimately constrain the ways in which cells evolve. The majority of cell mass consists of water molecules, whose highly unique properties govern almost every aspect of biology. About half of dry weight is composed of carbon atoms, mostly incorporated into proteins and lipids. Only about 20 additional elements are utilized in biology, most with intracellular concentrations many orders of magnitude higher than environmental levels. Amounts of DNA and numbers of protein and messenger RNA molecules per cell scale in predictable ways with cell volume across the Tree of Life. Stochasticity in molecular numbers is a significant constraint on the evolution of small cells, whereas molecular diffusion rates can limit the biological potential of large cells. Through its influence on molecular motion and stability, temperature plays a central role in all cellular processes, and mathematical summary statements can be made on the scaling of such effects. In today’s world, almost all of biology is dependent on organic compounds produced by photosynthetic organisms, which provide both carbon skeletons and energy for growth and other cellular functions. The heat of combustion of such compounds provides a reliable indicator of their available energy content. The upper limit to the efficiency of utilization of ingested carbon is about 80%, and general statements can be made as to the rate of biomass production per unit ATP utilization.
Cell Growth and Division
Authors: Lynch Michael R. 
Published: March 2024

Abstract
Numerous correlates of cell growth are thought to be general enough to be christened as growth laws, although few have been examined thoroughly in multiple organisms. One well-established relationship is the linear increase in ribosome number with the cell-division rate, which reflects the necessity of ribosomes for the construction of cellular material. Cell division rates have a hyperbolic relationship with concentrations of limiting nutrients. The growth of individual cells is generally exponential, with cytosolic compositions remaining constant throughout growth. Cells often determine their times of division by waiting for critical increments in growth, which naturally results in cell-size homeostasis. Although the detailed molecular mechanisms governing these kinds of behavior are generally unknown, modifications of a small number of genes have been implicated as potential routes to cell-size evolution. In all observed species, whereas cell size increases with nutrient availability, it decreases with increasing temperature, although the molecular mechanisms driving these universal responses remain unknown. Despite these general features of cell growth, stochastic sources of internal cellular variation translate into considerable phenotypic variation among genetically identical cells. Such variation can obscure the visibility of genetic differences to natural selection, while also leading to parent–offspring similarity associated with non-genetic effects. These aspects of phenotypic inheritance are inevitable consequences of the structure of cells, and there is no evidence that high levels of phenotypic variation are advanced by natural selection as means for coping with variable environments.
Cytoskeleton, Cell Shape, and Motility
Authors: Lynch Michael R. 
Published: March 2024

Abstract
Many prokaryotes and eukaryotes rely on cell walls for external support. However, the chemical compositions of cell walls vary substantially among phylogenetic lineages, especially among the major eukaryotic groups. The summed costs of cell envelope components are commonly on the order of one-third of a cell’s total energy budget, decreasing in larger cells with reduced ratios of surface area to cell volume. As both prokaryotes and eukaryotes also harbor internal polymeric filaments, such fibrils must have been present in the last universal ancestor of all life. Cytoskeletal functions are elaborated in eukaryotes, where they serve as both endoskeletons and as highways for vesicle trafficking. Unlike prokaryotes, which rely on intracellular diffusion for most molecular motion, eukaryotic cells invest heavily in molecular motors for vesicle transport and other functions. The families of such motors have expanded substantially within and among phylogenetic lineages by gene duplication and divergence. Nearly all swimming cells achieve motility by use of external flagella, which have evolved independently and operate by different mechanisms in archaea, bacteria, and eukaryotes. Swimming speeds, in units of cell length, are several times higher in prokaryotes than in eukaryotes. However, the conversion of chemical energy to swimming motion is universally inefficient. Owing to the energetic expense of constructing and running flagella, there is a strong selective premium for their elimination unless the advantages outweigh the costs.
Intracellular Errors
Authors: Lynch Michael R. 
Published: March 2024

Abstract
All cells are confronted with the recurrent production of errors at the genome, transcriptional, and translational levels. Transcript errors arise orders of magnitude more frequently than do replication errors, and translation error rates are inflated to even higher degrees. As a result, all cells contain populations of variant molecules. Although arguments have been made that high rates of production of erroneous mRNAs and proteins are promoted by natural selection, there is no direct evidence for this. Rather, the strength of selection for accuracy is naturally reduced by the transient nature of mRNA and protein molecules. Intracellular error surveillance is provided by processes of kinetic proofreading, which rely on repeated rounds of competitive binding of alternative substrate molecules to diminish the rates of acceptance of erroneous substrates. However, the energetic costs of such processes result in intrinsic trade-offs between speed, energetic expense, and accuracy. The existence of multiple layers of error-correcting mechanisms for various cellular processes encourages the view that cells have evolved mechanisms for enhancing robustness. However, such evolutionary layering does not appear to result in improved overall accuracy, but instead simply leads to more complex systems with the ultimate performance being similar to the ancestral state.
Environmental Sensing
Authors: Lynch Michael R. 
Published: March 2024

Abstract
Unicellular organisms use signal transduction (ST) systems to sense external environmental stimuli and relay information to internal regulators of intracellular responses, chemotaxis being one such example. Most ST systems operate via additions and removals of phosphoryl groups on the participating proteins. Substitutions of just a few amino-acid residues are often sufficient to alter the mode of intermolecular communication, providing a potential means for the origin of new systems as well as the neutral drift of pre-existing systems. Bacterial ST systems are typically quite simple and modular in nature, relying on pairs of sensor and regulator proteins whose crosstalk is insulated from other such pairs; in most species, dozens to hundreds of such systems are specialized to sensing different environmental stimuli. The maintenance of ST systems in states of readiness entails a considerable cost in terms of recurrent ATP expenditure. Although the underlying participants operate as conventional Michaelis–Menten enzymes, the pathways are structured in ways that can generate very steep responses to external signal concentrations, in some cases allowing for near switch-like behavior in downstream responses. With certain kinds of positive-feedback loops included, such systems can lead to semi-stable bimodal phenotype distributions among otherwise genetically uniform cells. This may be either advantageous or maladaptive depending on the environmental context. Eukaryotic ST systems tend to be much more complicated than those in bacteria, commonly involving cascades of multiple intermediate steps, and with considerable crosstalk among different partners. It remains unclear whether this added complexity has been driven by adaptive or nonadaptive forces peculiar to multicellular species.
Origins of Organismal Complexity
Authors: Lynch Michael R. 
Published: March 2024

Abstract
Rather than being an inexhaustible search for ways to construct more complex organisms, selection instead favours simplicity. Observations from the microbial world show that, despite their tendency not to gravitate to more complex forms, microbes are capable of doing so when the appropriate ecological opportunities are present. Although a substantial increase in genome size accompanied the emergence of eukaryotes from prokaryotes, most of it involves non-coding and non-functional DNA, particularly in multicellular lineages. This considerable bioenergetic and mutational burden was an inevitable outcome of the increased tendency of random genetic drift to overpower natural selection’s ability to oppose insertions of excess DNA. Further reorganization of the ancestral eukaryotic genome by gene-duplication events, followed by gene loss and subfunctionalization, led to new reproductively isolated lineages and encouraged transitions of homomeric molecular complexes to heteromeric forms. Ecological opportunity played a central role in the emergence of land plants and animals, but the evolution of complex multicellularity relied more on division of labor among cell types than on the emergence of new gene functions. Multicellular lineages experienced a further reduction in effective population sizes, imposing additional downstream costs including reduced growth-rate capacity, increased energetic cost and mutational vulnerability of genomes, gratuitous investment in overly complex cellular features, and the constant threat of mutant somatic cheater cells. The paths down which evolution proceeds are constrained by both the population-genetic environment and historical cellular contingencies, and this provides a mechanistic basis for understanding all aspects of biodiversity across the Tree of Life.
Introduction
Authors: Davies David 
Published: March 2024

Abstract
The Introduction briefly summarizes certain considerations that have been proposed as explananda for an ontology of ‘multiple artworks’. These proposed explananda structure the overall argument of this book, on the assumption that the ontology of multiple artworks is in the business of explaining such things. But this might be disputed. On Amie Thomasson’s ‘easy’ view of ontology, the task of the art ontologist is to analyse the concepts of those responsible for grounding our art-referential terms in the world. According to my ‘pragmatic constraint’ and Julian Dodd’s ‘discovery view’, on the other hand, ontology of art is a genuinely explanatory project that aims to better understand the nature of the things that are central to our artistic practices. Thomasson’s position is sketched and it is argued that the methodological approach in this book is something Thomasson should recognize as a legitimate alternative to the conceptual analysis required by ‘easy’ ontology. Nine purported features of multiple artworks that have been proposed by ontologists, as things their accounts purport to explain, are then sketched. A first pass is made at characterizing these explananda, and at grounding them in aspects of our artistic practices. It is made clear how they have played a central role in contemporary debates about the ontology of multiple artworks.
A counterfactual cycle
Authors: Patard Adeline 
Published: March 2024

Abstract
The chapter investigates the existence of a linguistic cycle for counterfactual imperfect constructions based on data from Latin and French. It further aims at explaining why (imperfective) aspect is ‘fake’ in counterfactuals (Iatridou 2000). After arguing for a strict definition of counterfactuality, the chapter expands on the idea that imperfects may trigger counterfactual implicatures. Then it explores the pragmatic origin and conventionalization of the counterfactual imperfect in Latin data and French corpora. Data unveil the repetition of a cycle: (i) the imperfect first develops in counterfactual contexts to refer to the past; (ii) it then extends to non-past counterfactual contexts and becomes part of the construction; (iii) finally the cycle ends when the imperfect construction is reanalysed as a marker of unreality. In the proposed analysis, aspect is ‘fake’ in counterfactuals because it has bleached as a consequence of the constructionalization of the imperfect counterfactual construction.
Variation and stability
Authors: Bruyn Bert Le , van der Klis Martijn , de Swart Henriëtte 
Published: March 2024

Abstract
In recent work, we showcased Translation Mining as a novel translation corpus-based approach to cross-linguistic research. This chapter works out how Translation Mining compares to other translation corpus-based approaches, and in particular how its analyses compare to those of Primary Data Typology and Corpus-Based Contrastive Linguistics. Study 1 shows how Translation Mining allows one to compare multiple constructions across multiple languages in parallel. Study 2 checks the foundational assumption of translation corpus-based approaches according to which the meanings of contexts across translations are constant. The two studies focus on the have-perfect as their empirical domain, consolidate and extend the findings of our earlier work, and contribute to translation corpus-based research methodology.
Empirical contributions to the study of aspect from the field of cognitive science
Authors: Madden-Lombardi Carol , Flecken Monique 
Published: March 2024

Abstract
The present chapter offers an overview of empirical contributions to the study of the linguistic category of aspect in cognitive science. While a great deal of linguistic research focuses on the study of the language system itself, cognitive researchers are interested in how the human mind processes and represents language. The field of linguistics has provided many interesting perspectives on the temporal nature of language, which should have consequences for the mental representations that we form when understanding language input, called ‘situation models’. Cognitive research has indeed provided empirical tests to explore the extent to which, and how, aspect constrains the mental processes and representations underlying language in use. The present chapter presents an overview of experimental research on aspect, reviewing the questions and specific experimental methodologies used by cognitive researchers to tap into the mental processes and representations associated with the use of grammatical aspect.
Final Conclusions and Recommendations
Authors: dos Santos Fernando 
Published: March 2024

Abstract
The chapter concludes that Africa possesses the ability to reclaim its space in global innovation if philosophical, policy, legal, and institutional interventions are effected. It summarizes the findings of the book and emphasizes the important role that intellectual property (IP) plays in promoting technology transfer and fostering innovation. The chapter asserts that while IP is generally seen as the main culprit for Africa’s exclusion on technological progress, the corollary is that, within the same system, remedies can be found. The chapter reiterates that Article 66.2 of the TRIPS Agreement offers the strongest legal basis to support Africa’s claims regarding innovation and technology transfer. The chapter highlights two alternatives to address the obstacles that have prevented the effective transfer of technology to LDCs: either improving the implementation of Article 66.2 or adopting an all-encompassing international legal instrument on technology transfer: the Agreement on Trade-Related Issues of Technology Transfer and Innovation (TRITTI).
Physiological mechanisms of heat tolerance in insects
Authors: González-Tokman Daniel , Villada-Bedoya Sebastián 
Published: March 2024

Abstract
Insects use a wide variety of physiological mechanisms to survive high temperatures. After appropriately sensing temperature, a stress response mediated by heat shock proteins is triggered and protects insect tissues together with changes in metabolic rates, antioxidant defenses, biogenic amines and neuroendocrine factors, as well as physiological and behavioral mechanisms of thermoregulation. Bacterial endosymbionts also contribute to heat tolerance but their role remains largely unexplored. These mechanisms of heat tolerance are the basis for heat acclimation and adaptation, but are limited by life-history trade-offs and the presence of additional environmental stressors, which will define insect survival in a warming world.
Globalization and Medical Education in a Post-Pandemic World
Authors: Rao Nyapati R. 
Published: March 2024

Abstract
The chapter opens with a general definition of globalization, its characteristics, and its consequences on medical education. Globalization is a complex phenomenon with positive and negative impacts on the world: Central to globalization is the movement of people and ideas across borders in search of better opportunities. However, this rapid movement of people also enables the transmission of pathogens causing pandemics such as COVID-19 and Ebola. The COVID-19 pandemic has resulted in unprecedented devastation in all walks of life, but it hastened the adoption of innovative models of educating medical students and residents. To appreciate the profound changes in medical education caused by the pandemic, one needs to understand the pre-pandemic reforms in medical education. In this context, the author will discuss the pivotal points in a historical review of modern medicine’s global origins and development. He will highlight the contributions made by Flexner and his influence on the further development of American medical education. Simultaneously, the author will explore the critically important role of the World Health Organization in the worldwide expansion of medical education. A brief discussion of the quality of medical education and the controversies surrounding the proposed institutional accreditation as a tool to monitor will follow. Finally, a consideration of the significant impact of differences in colonial and current socio-economic realities between LMICs and HICs on the evolution of medical education will conclude the chapter.
Canada
Authors: Brager Nancy , Paget Mike , Holm Johanna , Wilkes T. Christopher R. 
Published: March 2024

Abstract
This chapter critically reviews the findings of two surveys, 2019 and 2021, on medical student wellbeing completed at the Cummings School of Medicine completed at the University of Calgary, Canada. Medical student endorsed a significant level of exhaustion at 74% with 20% of students reporting a diagnosis of a mental health disorder. Most common was attention deficit hyperactivity disorder (ADHD), anxiety, and a depressive disorder. 13% tested Cut, Annoyed, Guilty, and Eye (CAGE) positive and 18% endorsed using non-prescription drugs for mood enhancement. 9% reported using medication for cognitive enhancement. 39% reported previous use of cannabis. The role of mitigating factors in the personal, organizational, and cultural domains are explicated. The authors endorse a paradigm shift from pathogenesis to salutogenesis to enhance wellbeing and better coping strategies and avoid pathologizing which may inadvertently blame, and shame stressed students. Innovations in curriculum and student wellness (SAW) hub supports are outlined. In particular, SAW encourages confidential and timely access to mental health supports through a variety of student resources including workshops on the CaRMS matching process, mentoring, and FOF (Forum on Failure). The promotion of a university culture of liberal science, viewpoint diversity, and truth-seeking is emphasized as essential for the development of critical thinking skills, agency, and student resilience.
Wales
Authors: Dave Umakant , Grant Andrew , Forty Liz , Horn Chris , Hunt Sara 
Published: March 2024

Abstract
This chapter describes support for medical students’ mental health and wellbeing at Cardiff and Swansea medical schools. We present data from a 2019 study of medical students in Wales in which they were asked to describe their experience of mental ill-health and substance misuse. We describe a tailored, multidisciplinary approach to providing support. We look at ways in which issues relating to student support and wellbeing have been included in the curriculum. We present ways in which students prepare for the challenges in clinical practice, including the value placed on hearing the experiences of near-peers. We also examine how professionalism dilemmas are used as a basis for learning. A near-peer mentoring scheme is presented with evaluation data comparing those who come forward as mentors and mentees. There is similar provision of support for students where there is particular concern regarding their health and wellbeing.
Georgia
Authors: Berdzenishvili Ekaterine , Machavariani Eteri , Chkonia Eka 
Published: March 2024

Abstract
A number of potentially stressful factors have been reported among medical undergraduates. These include a highly stressful environment, competitiveness, excessive workload, sleep deprivation. A substantial number of studies have established that medical education does not provide a favourable environment for the mental health and wellbeing of medical students. The stressful factors accompanying the stringent educational process prevent medical doctors from acquiring the necessary personal and professional qualities to provide high-quality patient care. Our study, described as part of this chapter, aimed to investigate the main stress factors and mental health problems among medical students in Georgia. Interventions aiming to improve the wellbeing of medical students have been suggested.