This aricle discusses the similarity between the propagation of pathogens (viruses and worms) on computer networks and the proliferation of pathogens in cellular organisms (organisms with genetic material contained within a membrane-encased nucleus). It introduces several biological mechanisms which are used in these organisms to protect against such pathogens and presents security models for networked computers inspired by several biological paradigms, including genomics (RNA interference), proteomics (pathway mapping), and physiology (immune system). In addition, the study of epidemiological models for disease (...) control can inspire methods for controlling the spread of pathogens across multiple nodes of a network. It also presents results based on the authors’ research in immune system modeling. (shrink)

This paper addresses the growing problem of retractions in the scientific literature of publications that contain bad data, also called “false science.” While the problem is particularly acute in the biomedical literature because of the life-threatening implications when treatment recommendations and decisions are based on false science, it is relevant for any knowledge domain, including the social sciences, law, and education. Yet current practices for handling retractions are seen as inadequate. We use the metaphor of a virus to illustrate (...) how such studies can spread and contaminate the knowledge system, when they continue to be treated as valid. We suggest drawing from public health models designed to prevent the spread of biological viruses and compare the strengths and weaknesses of the current governance model of professional self-regulation with a proposed public health governance model. The paper concludes by considering the value of adding a triple-helix model that brings industry into the university-state governance mechanisms and incorporates bibliometric capabilities needed for a holistic treatment of the retraction process. (shrink)

The existing literature on the development of recombinant DNA technology and genetic engineering tends to focus on Stanley Cohen and Herbert Boyer's recombinant DNA cloning technology and its commercialization starting in the mid-1970s. Historians of science, however, have pointedly noted that experimental procedures for making recombinant DNA molecules were initially developed by Stanford biochemist Paul Berg and his colleagues, Peter Lobban and A. Dale Kaiser in the early 1970s. This paper, recognizing the uneasy disjuncture between scientific authorship and legal invention (...) in the history of recombinant DNA technology, investigates the development of recombinant DNA technology in its full scientific context. I do so by focusing on Stanford biochemist Berg's research on the genetic regulation of higher organisms. As I hope to demonstrate, Berg's new venture reflected a mass migration of biomedical researchers as they shifted from studying prokaryotic organisms like bacteria to studying eukaryotic organisms like mammalian and human cells. It was out of this boundary crossing from prokaryotic to eukaryotic systems through virus model systems that recombinant DNA technology and other significant new research techniques and agendas emerged. Indeed, in their attempt to reconstitute 'life' as a research technology, Stanford biochemists' recombinant DNA research recast genes as a sequence that could be rewritten thorough biochemical operations. The last part of this paper shifts focus from recombinant DNA technology's academic origins to its transformation into a genetic engineering technology by examining the wide range of experimental hybridizations which occurred as techniques and knowledge circulated between Stanford biochemists and the Bay Area's experimentalists. Situating their interchange in a dense research network based at Stanford's biochemistry department, this paper helps to revise the canonized history of genetic engineering's origins that emerged during the patenting of Cohen-Boyer's recombinant DNA cloning procedures. (shrink)

In 1937, a group of researchers in Nazi Germany began investigating tobacco mosaic virus with the hope of using the virus as a model system for understanding gene behavior in higher organisms. They soon developed a creative and interdisciplinary work style and were able to continue their research in the postwar era, when they made significant contributions to the history of molecular biology. This group is significant for two major reasons. First, it provides an example of how (...) researchers were able to produce excellent scientific research in the midst of dictatorship and war. Coupled with the group's ongoing success in postwar Germany, the German TMV investigators provide a dramatic example of how scientific communities deal with adversity as well as rapid political and social change. Second, since the researchers focused heavily on TMV, their story allows us to analyze how an experimental system other than phage contributed to the emergence of molecular biology. (shrink)

Thresholds for disease extinction provide essential information for the prevention and control of diseases. In this paper, a stochastic epidemic model, a continuous-time Markov chain, for the transmission dynamics of West Nile virus in birds is developed based on the assumptions of its analogous deterministic model. The branching process is applied to derive the extinction threshold for the stochastic model and conditions for disease extinction or persistence. The probability of disease extinction computed from the branching process (...) is shown to be in good agreement with the probability approximated from numerical simulations. The disease dynamics of both models are compared to ascertain the effect of demographic stochasticity on West Nile virus dynamics. Analytical and numerical results show differences in model predictions and asymptotic dynamics between stochastic and deterministic models that are crucial for the prevention of disease outbreaks. It is found that there is a high probability of disease extinction if the disease emerges from exposed mosquitoes unlike if it emerges from infectious mosquitoes and birds. Finite-time to disease extinction is estimated using sample paths and it is shown that the epidemic duration is shortest if the disease is introduced by exposed mosquitoes. (shrink)

Qualitative validation consists in showing that a model is able to mimic available observed data. In population level biological models, the available data frequently represent a group status, such as pool testing, rather than the individual statuses. They are aggregated. Our objective was to explore an approach for qualitative validation of a model with aggregated data and to apply it to validate a stochastic model simulating the bovine viral-diarrhoea virus (BVDV) spread within a dairy cattle herd. (...) Repeated measures of the level of BVDV-specific antibodies in the bulk-tank milk (total milk production of a herd) were used to summarise the BVDV herd status. First, a domain of validation was defined to ensure a comparison restricted to dynamics of pathogen spread well identified among observed aggregated data (new herd infection with a wide BVDV spread). For simulations, scenarios were defined and simulation outputs at the individual animal level were aggregated at the herd level using an aggregation function. Comparison was done only for observed data and simulated aggregated outputs that were in the domain of validation. The validity of our BVDV model was not rejected. Drawbacks and ways of improvement of the approach are discussed. (shrink)

The existing literature on the development of recombinant DNA technology and genetic engineering tends to focus on Stanley Cohen and Herbert Boyer's recombinant DNA cloning technology and its commercialization starting in the mid-1970s. Historians of science, however, have pointedly noted that experimental procedures for making recombinant DNA molecules were initially developed by Stanford biochemist Paul Berg and his colleagues, Peter Lobban and A. Dale Kaiser in the early 1970s. This paper, recognizing the uneasy disjuncture between scientific authorship and legal invention (...) in the history of recombinant DNA technology, investigates the development of recombinant DNA technology in its full scientific context. I do so by focusing on Stanford biochemist Berg's research on the genetic regulation of higher organisms. As I hope to demonstrate, Berg's new venture reflected a mass migration of biomedical researchers as they shifted from studying prokaryotic organisms like bacteria to studying eukaryotic organisms like mammalian and human cells. It was out of this boundary crossing from prokaryotic to eukaryotic systems through virus model systems that recombinant DNA technology and other significant new research techniques and agendas emerged. Indeed, in their attempt to reconstitute 'life' as a research technology, Stanford biochemists' recombinant DNA research recast genes as a sequence that could be rewritten thorough biochemical operations. The last part of this paper shifts focus from recombinant DNA technology's academic origins to its transformation into a genetic engineering technology by examining the wide range of experimental hybridizations which occurred as techniques and knowledge circulated between Stanford biochemists and the Bay Area's experimentalists. Situating their interchange in a dense research network based at Stanford's biochemistry department, this paper helps to revise the canonized history of genetic engineering's origins that emerged during the patenting of Cohen-Boyer's recombinant DNA cloning procedures. (shrink)

The primary impediment to formulating a general theory for adaptive evolution has been the unknown distribution of fitness effects for new beneficial mutations. By applying extreme value theory, Gillespie circumvented this issue in his mutational landscape model for the adaptation of DNA sequences, and Orr recently extended Gillespie's model, generating testable predictions regarding the course of adaptive evolution. Here we provide the first empirical examination of this model, using a single-stranded DNA bacteriophage related to phiX174, and find (...) that our data are consistent with Orr's predictions, provided that the model is adjusted to incorporate mutation bias. Orr's work suggests that there may be generalities in adaptive molecular evolution that transcend the biological details of a system, but we show that for the model to be useful as a predictive or inferential tool, some adjustments for the biology of the system will be necessary. (shrink)

Virus and information spreading dynamics widely exist in complex systems. However, systematic study still lacks for the interacting spreading dynamics between the two types of dynamics. This paper proposes a mathematical model on multiplex networks, which considers the heterogeneous susceptibility and infectivity in two subnetworks. By using a heterogeneous mean-field theory, we studied the dynamic process and outbreak threshold of the system. Through extensive numerical simulations on artificial networks, we find that the virus’s spreading dynamics can be (...) suppressed by increasing the information spreading probability, decreasing the protection power, or decreasing the susceptibility and infectivity. (shrink)

Currently, the concept of the cell as a society or an ecosystem of molecular elements is gaining increasing acceptance. The basic idea arose in the 19th century, from the surmise that there is not just a single unit underlying an individual’s appearance, but a plurality of entities with both collaborative and conflicting relationships. The following hypothesis is based around this model. The incompatible activities taking place between different original elements, which were subsumed into the first cell and could not (...) be eliminated, had to be controlled very closely. Similarly, a strong level of control had to be developed over many cellular elements after the cell changed its genome to DNA. We assume that at least some of those original RNA agents and other biomolecules which carry incompatibilities and risks, are retained within current cells, although they are now under strict control. A virus functions as a signal informing these repressed cellular RNAs and other elements of ancient origin how to restore suppressed degrees of molecular freedom, favoring pre-existing molecular affinities and activities, re-establishing ancient molecular webs of interactions, and giving fragments of ancient coded information the opportunity to be re-expressed. Collectively, these newly activated mechanisms lead to different possibilities for pathological cell states. All these processes are opposed by cell-control mechanisms. Thus, in this new scenario, the battle is considered intracellular rather than between the virus and the cell. And so the virus is treated as the signal that precipitates the cell’s change from a latent to an active pathological state. (shrink)

We investigate and analyze the dynamics of hepatitis B with various infection phases and multiple routes of transmission. We formulate the model and then fractionalize it using the concept of fractional calculus. For the purpose of fractionalizing, we use the Caputo–Fabrizio operator. Once we develop the model under consideration, existence and uniqueness analysis will be discussed. We use fixed point theory for the existence and uniqueness analysis. We also prove that the model under consideration possesses a bounded (...) and positive solution. We then find the basic reproductive number to perform the steady-state analysis and to show that the fractional-order epidemiological model is locally and globally asymptotically stable under certain conditions. For the local and global analysis, we use linearization, mean value theorem, and fractional Barbalat’s lemma, respectively. Finally, we perform some numerical findings to support the analytical work with the help of graphical representations. (shrink)

Ecology is usually described as the study of organisms interacting with one another and their environments. From this view of ecology, viruses – not usually considered to be organisms – would merely be part of the environment. Since the late 1980s, however, a growing stream of micrographic, experimental, molecular, and model-based (theoretical) research has been investigating how and why viruses should be understood as ecological actors of the most important sort. Viruses, especially phage, have been revealed as participants in (...) the planet's most crucial food webs, even though viruses technically consume nothing (they do not metabolize by themselves). Even more impressively, viruses have been identified as regulators of planetary biogeochemistry, in which they control cycles such as carbon, nitrogen and phosphorus – cycles on which all life depends. Although much biogeochemical research black-boxes the entities filling functional roles, it is useful to focus a little more closely to understand how viruses can be held responsible for the global processes of life. This paper will give a brief overview of the history of virus ecology and tease out the implications of large-scale ecological modelling with viruses. This analysis suggests that viruses should be conceptualized as ecological actors that are at least comparable and possibly equal to organismal actors. Ecological agency can therefore be distinguished from standard interpretations of biological agency. (shrink)

In addition to their function in transport of water, ions, small metabolites, and growth factors in normal plant tissue, the plasmodesmata presumably serve as routes for cell‐to‐cell movement of plant viruses in infected tissue. Virus cell‐to‐cell spread through plasmodesmata is an active process mediated by specialized virus encoded movement proteins; however, the mechanism by which these proteins operate is not clear. We incorporate recent information on the biochemical properties of plant virus movement proteins and their interaction with (...) plasmodesmata in a model for transport of nucleic acids through plasmodesmatal channels. We propose that only single stranded (ss) nucleic acids can be transported efficiently through plasmodesmata, and that movement proteins function as molecular chaperones for ss nucleic acids to form unfolded movement protein‐ss nucleic acid complexes. These complexes are targeted to plasmodesmata. Plasmodesmatal permeability is then increased following interaction with movement protein and the entire movement complex or its nucleic acid component is translocated across the plasmodesmatal channel. (shrink)

The evolution of research on the biochemistry of virus multiplication cannot be understood without knowing something of the structure of biochemistry and of virology before, during and immediately after World War II. My own research on virus multiplication began after studies on plant viruses and wartime research on the rickettsial components of the typhus vaccine, all of which involved work on the nucleic acids. Interest in the chemotherapy of virus disease led to a search for a (...) class='Hi'>model system. A simple methodology for handling phage systems enabled biochemists to examine infected cells. The fortuitous use of an extremely virulent phage group (the T‐even phages) which evoke marked changes in polymeric products without affecting the production of energy and small building blocks facilitated these studies. An exaggerated synthesis of viral DNA by these phages concentrated our attention on the origins of this substance, which proved to contain a new pyrimidine deoxyribonucleotide, synthesized by a novel virus‐determined enzyme. The generality of the existence of virus‐induced enzymes and other proteins may be the key to a chemotherapy of virus infection. (shrink)

The interplay between the virus, infected cells and immune responses to SARS-CoV-2 is still under debate. By extending the basic model of viral dynamics, we propose here a formal approach to describe neutralisation versus weak (or non-)neutralisation scenarios and compare them with the possible effects of antibody-dependent enhancement (ADE). The theoretical model is consistent with the data available in the literature; we show that both weakly neutralising antibodies and ADE can result in final viral clearance or disease (...) progression, but that the immunodynamics are different in each case. As a significant proportion of the world’s population is already naturally immune or vaccinated, we also discuss the implications for secondary infections after vaccination or in the presence of immune system dysfunctions. (shrink)

Research in infection biology aims to understand the complex nature of host–pathogen interactions. While this knowledge facilitates strategies for preventing and treating diseases, it can also be intentionally misused to cause harm. Such dual-use risk is potentially high for highly pathogenic microbes such as Risk Group-3 (RG3) bacteria and RG4 viruses, which could be used in bioterrorism attacks. However, other pathogens such as influenza virus (IV) and enterohemorrhagic Escherichia coli (EHEC), usually classified as RG2 pathogens, also demonstrate high dual-use (...) risk. As the currently approved therapeutics against these pathogens are not satisfactorily effective, previous outbreaks of these pathogens caused enormous public fear, media attention and economic burden. In this interdisciplinary review, we summarize the current perspectives of dual-use research on IV and EHEC, and further highlight the dual-use risk associated with evolutionary experiments with these infectious pathogens. We support the need to carry out experiments pertaining to pathogen evolution, including to gain predictive insights on their evolutionary trajectories, which cannot be otherwise achieved with stand-alone theoretical models and epidemiological data. However, we also advocate for increased awareness and assessment strategies to better quantify the risks-versus-benefits associated with such evolutionary experiments. In addition to building public trust in dual-use research, we propose that these approaches can be extended to other pathogens currently classified as low risk, but bearing high dual-use potential, given the particular pressing nature of their rapid evolutionary potential. (shrink)

Theiler's virus is a picornavirus of mouse which causes an acute encephalomyelitis followed by a persistent infection of the white matter resulting in chronic inflammation and demyelination. This disease has been studied as a model for multiple sclerosis. Inbred strains of mice are either resistant--they clear the infection after the acute encephalomyelitis--or susceptible to persistent infection and demyelination. Susceptibility is a polygenic trait which has been analyzed using methods of association with “candidate” genes, and linkage analysis after a (...) complete genome scan. The H-2Db gene is responsible for an efficient CTL response which makes some strains resistant. Non H-2 genes responsible for the susceptibility of other strains have been mapped by linkage analysis to the Ifng and, possibly, the Mbp loci. The analysis of a set of congenic mice ruled out the possiblity that the relevant gene codes for interferon gamma, and showed that the region around Ifngprobably contains two susceptibility genes. The analysis of mutant mice showed further that the Mbp gene, which codes for the myelin basic protein, has a major effect on viral persistence. BioEssays 20:627–633, 1998. © 1998 John Wiley & Sons Inc. (shrink)

Health care workers with needlestick exposures to patients' blood often request a test of the patient for evidence of infection with human immunodeficiency virus. If the patient refuses the test, a conflict develops between the interests of the health care worker and those of the patient. Traditional approaches to this dilemma attempt to balance the rights or utilities of abstract patients and health care workers. While these approaches have the advantage of offering clear guidelines in advance of conflict, the (...) interests of the actual participants may differ from those used to create the guidelines. In nonmedical settings, conflicts are often resolved efficiently through negotiation and monetary exchanges. Although negotiated monetary settlements between health care workers and patients may be an impractical way to resolve medical conflicts, models developed from these perspectives provide insights into the individual interests of physicians and patients. Changing existing rules about medical record documentation, or increasing the penalties for the misuse of medical information, may satisfy the interests on both sides of the conflict and so represent integrative bargaining solutions. Even so, as the relationship between health care workers and their patients evolves, more explicit strategies for negotiation may become a reasonable solution to the problem of conflict. (shrink)

Tobacco mosaic virus has served as a model organism for pathbreaking work in plant pathology, virology, biochemistry and applied genetics for more than a century. We were intrigued by a photograph published in Phytopathology in 1934 showing that Tabasco pepper plants responded to TMV infection with localized necrotic lesions, followed by abscission of the inoculated leaves. This dramatic outcome of a biological response to infection observed by Francis O. Holmes, a virologist at the Rockefeller Institute for Medical Research, (...) was used to score plants for resistance to TMV infection. Our objective was to gain a better understanding of early to mid-twentieth century ideas of genetic resistance to viruses in crop plants. We investigated Holmes’ observation as a practical exercise in reworking an experiment, having been inspired by Pamela Smith’s innovative Making and Knowing Project. We had a great deal of difficulty replicating Holmes’ experiment, finding that biological materials and experimental customs change over time, in ways that ideas do not. Using complementary tools plus careful study and interpretation of the original text and figures, we were able to rework, yet only partially replicate, this experiment. Reading peer-reviewed manuscripts that cited Holmes’ 1934 report provided an additional level of insight into the interpretation and replication of this work in the decades that followed. From this, we touch on how experimental reworking can inform our strategies to address the reproducibility “crisis” in twenty-first century science. (shrink)

A simplified model using kinetic logic is proposed to approach the problem after Hepatitis B viral (HBV) infection. It accounts for several stable regimes or attractors corresponding to the essential dynamic behaviour of the replication of the Hepatitis B virus. Infection with the virus can result in viral clearance, fulminant hepatic failure and death, or chronic transmissible infection, that is multistationarity corresponding to the existence of the positive feedback circuit in our modelling. Another implication of this (...) class='Hi'>model is the existence of oscillations or homeostatic mechanisms, sometimes observed in the viral cycle, consistent with the existence of the negative feedback circuit. Thus, this report shows how a simple model of kinetic logic may be used to account for the variety of manifestations of HBV infection. This model implies the presence of the Hepatitis B e antigen, whose conservation suggests that it plays an important role in the life cycle of hepadnaviruses. Its function in the viral cycle is still unknown, but our model suggests that this antigen could explain the passage from one state of the viral infection (acute or latent) to another, as well as the oscillatory behavior which may account for the intermittent symptoms of hepatitis observed in some patients. Furthermore, this model shows a virgin state. This state is also reached after recovery. The model proposed demonstrates that starting from a viral acute infection, the host's immune response, depending on the immunological status of the patient, can lead to viral clearance, or to periodic spontaneous reactivation. (shrink)

We review mathematical models of HIV dynamics, disease progression, and therapy. We start by introducing a basic model of virus infection and demonstrate how it was used to study HIV dynamics and to measure crucial parameters that lead to a new understanding of the disease process. We discuss the diversity threshold model as an example of the general principle that virus evolution can drive disease progression and the destruction of the immune system. Finally, we show how (...) mathematical models can be used to understand correlates of long‐term immunological control of HIV, and to design therapy regimes that convert a progressing patient into a state of long‐term non‐progression. BioEssays 24:1178–1187, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

Biomedical science has been remarkably successful in explaining illness by categorizing diseases and then by identifying localizable lesions such as a virus and neoplasm in the body that cause those diseases. Not surprisingly, researchers have aspired to apply this powerful paradigm to addiction. So, for example, in a review of the neuroscience of addiction literature, Hyman and Malenka (2001, p. 695) acknowledge a general consensus among addiction researchers that “[a]ddiction can appropriately be considered as a chronic medical illness.” Like (...) other diseases, “Once addiction has taken hold, it tends to follow a chronic course.” (Koob and La Moal 2006, p. ?). Working from this perspective, much effort has gone into characterizing the symptomology of addiction and the brain changes that underlie them. Evidence for involvement of dopamine transmission changes in the ventral tegmental area (VTA) and nucleus accumbens (NAc) have received the greatest attention. Kauer and Malenka (2007, p. 844) put it well: “drugs of abuse can co-opt synaptic plasticity mechanisms in brain circuits involved in reinforcement and reward processing”. Our goal in this chapter to provide an explicit description of the assumptions of medical models, the different forms they may take, and the challenges they face in providing explanations with solid evidence of addiction. <br>. (shrink)

Phylogenetic trees based on gene sequence data contain information about the evolutionary processes responsible for their genesis. Methods have now been developed which help to reveal those processes. The methods are based on simple models of evolutionary change but, when applied across individuals in a population, rather than across species in a higher‐level taxon, they can reveal the past history of population change. Examples from salamanders and viruses are used to illustrate how the past history of changes in speciation rate (...) and the origin of epidemics can be inferred in the absence of fossil material or historical documentation. (shrink)

Toxic speech inflicts damage to mental and physical health. This process can be chronic or acute, temporary or permanent. Understanding how toxic speech inflicts these harms requires both an account of linguistic practices and, because language is inherently social, tools from epidemiology. This paper explores what we can learn from two epidemiological models: a common source model that emphasizes poisons, and a propagated transmission model that better fits contagions like viruses.

The Covid-19 global pandemic had a profound effect on scientific practice. During this time, officials crucially relied on the work done by modellers. This raises novel questions for the philosophy of science. Here, I investigate the possibility of ‘natural models’ in predicting the virus’ trajectory for epidemiological purposes. I argue that to the extent that these can be consideredscientific models, they support the possibility of a continuum from scientific models to natural models differing in artifactual commitment. In making my (...) case, I draw from work on model organisms and natural experiments as well as recent work in epidemiology. (shrink)

Classification in statistics is usually used to solve the problems of identifying to which set of categories, such as subpopulations, new observation belongs, based on a training set of data containing information whose category membership is known. The article aims to use the Gaussian Mixture Model to model the daily closing price index over the period of 1/1/2013 to 16/8/2020 in the Kingdom of Saudi Arabia. The daily closing price index over the period declined, which might be the (...) effect of corona virus, and the mean of the study period is about 7866.965. The closing price is the last regular deal that took place during the continuous trading period. If there are no transactions on the stock during the day, the closing price is the previous day’s closing price. The closing auction period comes after the continuous trading period, during which investors can enter by buying and selling the stocks at this period. The experimental results show that the best mixture model is E with three components according to the BIC criterion. The expectation-maximization algorithm converged in 2 repetitions. The data source is from Tadawul KSA. (shrink)

Death of motor neurones following invasion of the central nervous system by poliovirus may result in paralysis of specific muscles. Virulence may be tested by injection into monkeys by routes which bypass natural infection. Transmissibility is also very important, but cannot be measured, only inferred. An infection may lead to immunity or paralysis. In epidemics, the highest incidence among children 0-2 years was 2% and among those over 10 years was 25%: these figures fit a model of genetic susceptibility (...) of homozygotes and heterozygotes with phenotypic susceptibility increasing with age. Hypogamma-globulinemics, some neonates and pregnant women are more susceptible than others. Intra-muscular injections may increase the risk of paralysis. Strenuous exercise and IM injections given when poliovirus has already reached the spinal cord can increase the severity of paralysis or convert a non-paralytic attack to paralysis. Although vaccines reduced polio in temperate countries, polio was thought to be no problem in the tropics. Since 1977 polio has been recognised as a massive problem in the third world: because it affects babies and very young children, it is properly infantile paralysis. (shrink)

Marginal structural models can be used to estimate the causal effect of a potentially time-varying treatment in the presence of time-dependent confounding via weighted regression. The standard approach of using inverse probability of treatment weighting can be sensitive to model misspecification and lead to high-variance estimates due to extreme weights. Various methods have been proposed to partially address this, including covariate balancing propensity score to mitigate treatment model misspecification, and truncation and stabilized-IPTW to temper extreme weights. In this (...) article, we present kernel optimal weighting, a convex-optimization-based approach that finds weights for fitting the MSMs that flexibly balance time-dependent confounders while simultaneously penalizing extreme weights, directly addressing the above limitations. We further extend KOW to control for informative censoring. We evaluate the performance of KOW in a simulation study, comparing it with IPTW, sIPTW, and CBPS. We demonstrate the use of KOW in studying the effect of treatment initiation on time-to-death among people living with human immunodeficiency virus and the effect of negative advertising on elections in the United States. (shrink)

In contrast to bilaterian animals, non‐bilaterian mitochondrial genomes contain atypical genes, often attributed to horizontal gene transfer (HGT) as an ad hoc explanation. Although prevalent in plants, HGT into animal mitochondrial genomes is rare, lacking suitable explanatory models for their occurrence. HGT of the mismatch DNA repair gene (mtMutS) from giant viruses to octocoral (soft corals and their kin) mitochondrial genomes provides a model for how barriers to HGT to animal mitochondria may be overcome. A review of the available (...) literature suggests that this HGT was mediated by an alveolate endosymbiont infected with a lysogenic phycodnavirus that enabled insertion of the homing endonuclease containing mtMutS into octocoral mitochondrial genomes. We posit that homing endonuclease domains and similar selfish elements play a crucial role in such inter‐domain gene transfers. Understanding the role of selfish genetic elements in HGT has the potential to aid development of tools for manipulating animal mitochondrial DNA. (shrink)

Amid the COVID-19 pandemic, fear has run rampant across the globe. To curb the spread of the virus, several governments have taken measures to drastically transition businesses, work, and schooling to virtual settings. While such transitions are warranted and well-intended, these measures may come with unforeseen consequences. Namely, one’s fear of COVID-19 may more readily manifest as aggressive behaviors in an otherwise incognito virtual social ecology. In the current research, a moderated mediation model examined the mechanisms underlying the (...) relation between fear of COVID-19 and overt and relational aggressive online behavior among Chinese college students. Utilizing a large sample of Chinese college students, results indicated that moral disengagement mediated the effect of fear of COVID-19 on college students’ overt and relational online aggressive behavior. A positive family cohesion buffered the effect of moral disengagement on relational aggressive behavior, but only for females. The findings, theoretical contributions, and practical implications of the present paper are also discussed. (shrink)

Aphids display an abundance of adaptations that are not easily studied in existing model systems. Here we review the biology of a new genomic model system, the pea aphid, Acyrthosiphon pisum. We then discuss several phenomena that are particularly accessible to study in the pea aphid: the developmental genetic basis of polyphenisms, aphid–bacterial symbioses, the genetics of adaptation and mechanisms of virus transmission. The pea aphid can be maintained in the laboratory and natural populations can be studied (...) in the field. These properties allow controlled experiments to be performed on problems of direct relevance to natural aphid populations. Combined with new genomic approaches, the pea aphid is poised to become an important model system for understanding the molecular and developmental basis of many ecologically and evolutionarily relevant problems. BioEssays 28: 747–755, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Objective: The COVID-19 pandemic is negatively impacting the mental health of COVID-19 patients and family members. Given the restrictions limiting in person contact to reduce the spread of the virus, a digital approach is needed to tackle the psychological aftermath of the pandemic. We present the development of a brief remote psychotherapy program for COVID-19 patients and/or their relatives.Methods: We first reviewed the literature on psychotherapeutic interventions for COVID-19 related symptoms. Based on this evidence, we leveraged ongoing clinical experiences (...) with COVID-19 survivors and family members to design an intervention model that could be disseminated and integrated into the workflow of the mental health system.Results: This 8-session model –inspired by constructivist and hermeneutic-phenomenological therapies– serves COVID-19 patients during hospitalization, remission and recovery. This model can also be delivered to people dealing with the COVID-19 hospitalization/discharge of a family member, or the loss of a family member due to COVID-19.Conclusion: We described a remote psychotherapeutic approach to tackle the COVID-19 pandemic psychological aftermath. To date, the approach seems feasible and highly customizable to patients’ needs. Studies are underway to test its preliminary efficacy. Once proven efficacious, this treatment model could provide a blueprint for future tele-psychology wide-scale interventions. (shrink)

Ever since the outbreak of the coronavirus disease, people have been flooded with vast amounts of information related to the virus and its social consequences. This paper draws on social amplification theory and the extended parallel process model and assesses the following: how two amplification stations—news media and peoples’ personal networks—influence the risk-related perceptions of people and how these risk-related perceptions impact people’s health-protective behaviors. This study surveyed 1,946 participants. The results indicate that peoples’ exposure to news media (...) significantly and positively predicted both perceived efficacy and perceived threat. It also shows that peoples’ exposure to risk-related information through their personal networks negatively predicted their perceived efficacy, but it positively predicted their perceived threat. The mediating effect of fear was examined, and the result was contradictory to the EPPM. In short, this study reveals the underlying mechanism of individuals’ exposure to risk information, processing, and precautionary measures. (shrink)

Exact solutions of epidemic models are critical for identifying the severity and mitigation possibility for epidemics. However, solving complex models can be difficult when interfering conditions from the real-world are incorporated into the models. In this paper, we focus on the generally unsolvable adaptive susceptible-infected-susceptible epidemic model, a typical example of a class of epidemic models that characterize the complex interplays between the virus spread and network structural evolution. We propose two methods based on mean-field approximation, i.e., the (...) first-order mean-field approximation and higher-order mean-field approximation, to derive the exact solutions to ASIS models. Both methods demonstrate the capability of accurately approximating the metastable-state statistics of the model, such as the infection fraction and network density, with low computational cost. These methods are potentially powerful tools in understanding, mitigating, and controlling disease outbreaks and infodemics. (shrink)

So-called ‘gain-of-function’ (GOF) research is virological research that results in a virus substantially more virulent or transmissible than its wild antecedent. GOF research has been subject to ethical analysis in the past, but the methods of GOF research have to date been underexamined by philosophers in these analyses. Here, we examine the typical animal used in influenza GOF experiments, the ferret, and show how despite its longstanding use, it does not easily satisfy the desirable criteria for an _animal model_. (...) We then discuss the limitations of the ferret model, and how those epistemic limitations bear on ethical and policy questions around the risks and benefits of GOF research. We conclude with a reflection on how philosophy of science can contribute to ethical and policy debates around the risks, benefits and relative priority of life sciences research. (shrink)

During the COVID-19 epidemic, personal safety has received increasing attention, leading to behavioral changes. Mobile-wallet makes it easier for people to keep social distance, which helps stop the spread of the COVID-19 virus. Evolving Internet technology has brought about changes in consumer lifestyle. The current situation of COVID-19 has created a business environment to shift from traditional ways and adopt e-commerce solutions worldwide. Grounded in technology acceptance model theory, this study’s objective is two-fold: First, this study intends to (...) examine perceived susceptibility to COVID-19, perceived severity of COVID-19, insecurity and discomfort as the predictors of perceived usefulness and perceived ease of use. Second, the current research intends to test the moderating effect of electronic words-of-mouth on the relationship between attitude and usage intention. Using survey methods, 226 usable responses were collected through a mall intercept survey in Pakistan. Data were analyzed using partial least square. The results revealed that PEOU and PU positively influence attitude toward M-wallet. This study has found that attitude positively influences the usage intention in adopting M-wallet. The results also support the moderating role of eWOM. These findings contribute to the marketing literature in several ways, particularly in Pakistan. This is the first study to use eWOM as a moderating variable in the TAM theory. In addition, this study adds to the current body of knowledge by considering eWOM as a multi-dimensional construct novel in m-wallet literature. (shrink)

The past three years have seen a dramatic increase in our understanding of the structural organization and expression strategies of the dispersed, repetitive yeast transposon, Ty. These studies have led to a logical comparison of Ty with retroviral proviruses and other mobile, repetitive elements. Such comparisons have culminated in the hypotheses that transposition occurs via the formation of Ty‐encoded virus‐like particles and that these particles represent a basic unit of all ‘retro‐systems’.

In this paper, we propose two HIV infection models with specific nonlinear incidence rate by including a class of infected cells in the eclipse phase. The first model is described by ordinary differential equations and generalizes a set of previously existing models and their results. The second model extends our ODE model by taking into account the diffusion of virus. Furthermore, the global stability of both models is investigated by constructing suitable Lyapunov functionals. Finally, we check (...) our theoretical results with numerical simulations. (shrink)

To date, our knowledge of Rift Valley fever disease spread and maintenance is still limited, as flooding, humid weather and presence of biting insects such as mosquitoes, have not completely explained RVF outbreaks. We propose a model that includes livestock, mosquitoes and ticks compartments structured according to their questing and feeding behaviour in order to study the possible role of ticks on the dynamics of RVF. To quantify disease transmission at the initial stage of the epidemic, we derive an (...) explicit formula of the basic reproductive number, $$R_0$$ R 0. Using the concept of Metzler matrix, we state necessary conditions for global asymptotic stability of the disease-free equilibrium. Results suggest that although host-ticks interactions may serve as disease reservoirs or disease amplifiers, the Aedes reproductive number should be kept under unity if disease post-epizootics activities are to be controlled. Results of both local and global sensitivity analysis of selected model parameters indicate that $$R_0$$ R 0 is more sensitive to the ticks attachment and detachment rates, probability of transmission from ticks to host and from host to ticks, length of infection in livestock and ticks death rate. Furthermore, when comparing the mean value of $$R_0$$ R 0 with that from previous studies which did not include ticks we found that our $$R_0$$ R 0 is very much larger resulting in an increase in the exponential phase of an outbreak. These findings suggest that if ticks are capable of transmitting the virus, they may be contributing to disease outbreaks and endemicity. (shrink)

COVID-19 is a disease that affects the quality of life in all aspects. However, the government policy applied in 2020 impacted the lifestyle of the whole world. In this sense, the study of sentiments of people in different countries is a very important task to face future challenges related to lockdown caused by a virus. To contribute to this objective, we have proposed a natural language processing model with the aim to detect positive and negative feelings in open-text (...) answers obtained from a survey in pandemic times. We have proposed a distilBERT transformer model to carry out this task. We have used three approaches to perform a comparison, obtaining for our best model the following average metrics: Accuracy: 0.823, Precision: 0.826, Recall: 0.793 and F1 Score: 0.803. (shrink)

We use a cultural psychology approach to examine the relevance of the Health Belief Model for predicting a variety of behaviors that had been recommended by health officials during the initial stages of the COVID-19 lockdown for containing the spread of the virus and not overburdening the health system in Europe. Our study is grounded in the assumption that health behavior is activated based on locally relevant perceptions of threats, susceptibility and benefits in engaging in protective behavior, which (...) requires careful attention to how these perceptions might be structured and activated. We assess the validity of the HBM in two European countries that have been relatively understudied, using simultaneous measurements during acute periods of infection in Romania and Italy. An online questionnaire provided a total of valid answers from both countries. First, to understand individual difference patterns within and across populations, we fit a General Linear Model in which endorsement was predicted by behavior, country, their interaction, and a random effect for participants. Second, we assess the effect of demographics and health beliefs on prevention behaviors by fitting a multi-group path model across countries, in which each behavior was predicted by the observed health belief variables and demographics. Health beliefs showed stronger relationships with the recommended behaviors than demographics. Confirming previously reported relationships, self-efficacy, perceived severity, and perceived benefits were consistently related to the greater adoption of individual behaviors, whereas greater perceived barriers were related to lower adoption of health behaviors. However, we also point to important location specific effects that suggest that local norms shape protective behavior in highly contextualized ways. (shrink)