pwc-archive/papers-with-abstracts huggingface dataset:
Osteostatin potentiates the bioactivity of mesoporous glass scaffolds containing Zn2+ ions in human mesenchymal stem cell cultures
Authors: C. Heras, S. Sanchez-Salcedo, D. Lozano, J. Peña, P. Esbrit, M. Vallet-Regi, A. J. Salinas
Date: 2021-03-23 00:00:00
Tasks: Cultural Vocal Bursts Intensity Prediction

There is an urgent need of biosynthetic bone grafts with enhanced osteogenic capacity. In this study, we describe the design of hierarchical meso-macroporous 3D-scaffolds based on mesoporous bioactive glasses (MBGs), enriched with the peptide osteostatin and Zn2+ ions, and their osteogenic effect on human mesenchymal stem cells (hMSCs) as a preclinical strategy in bone regeneration. By using additive fabrication techniques, scaffolds exhibiting hierarchical porosity: mesopores , macropores and big channels, were prepared. These MBG scaffolds with or without osteostatin were evaluated in cell cultures of hMSCs. Zinc promoted hMSCs colonization (both the surface and inside) of MBG scaffolds. Moreover, Zn2+ ions and osteostatin together, but not independently, in the scaffolds were found to induce the osteoblast differentiation genes runt related transcription factor-2 (RUNX2) and alkaline phosphatase (ALP) in hMSCs after 7 d of culture in the absence of an osteogenic differentiation-promoting medium. These results add credence to the combined use of zinc and osteostatin as an effective strategy for bone regeneration applications.
Inferring simple but precise quantitative models of human oocyte and early embryo development
Authors: Brian D Leahy, Catherine Racowsky, Daniel Needleman
Date: 2021-03-22 00:00:00

Macroscopic, phenomenological models have proven useful as concise framings of our understandings in fields from statistical physics to economics to biology. Constructing a phenomenological model for development would provide a framework for understanding the complicated, regulatory nature of oogenesis and embryogenesis. Here, we use a data-driven approach to infer quantitative, precise models of human oocyte maturation and pre-implantation embryo development, by analyzing existing clinical In-Vitro Fertilization (IVF) data on 7,399 IVF cycles resulting in 57,827 embryos. Surprisingly, we find that both oocyte maturation and early embryo development are quantitatively described by simple models with minimal interactions. This simplicity suggests that oogenesis and embryogenesis are composed of modular processes that are relatively siloed from one another. In particular, our analysis provides strong evidence that (i) pre-antral follicles produce anti-M{\"u}llerian hormone independently of effects from other follicles, (ii) oocytes mature to metaphase-II independently of the woman's age, her BMI, and other factors, (iii) early embryo development is memoryless for the variables assessed here, in that the probability of an embryo transitioning from its current developmental stage to the next is independent of its previous stage. Our results both provide insight into the fundamentals of oogenesis and embryogenesis and have implications for the clinical practice of IVF.
Is there an infant mortality in bacteria?
Authors: Eduardo M. Garcia-Roger, Peter Richmond, Bertrand M. Roehner
Date: 2021-03-18 00:00:00

This manuscript proposes a significant step in our long-run investigation of infant mortality across species. Since 2016 (Berrut et al. 2016) a succession of studies (Bois et al. 2019) have traced infant mortality from organisms of high complexity (e.g. mammals) down to unicellular organisms. Infant mortality may be considered as a filtering process through which organisms with potentially lethal congenital defects are eliminated. Such defects may have many causes but here we focus particularly on mishaps resulting from non-optimal conditions in the production of proteins, enzymes and other crucial macromolecules. The statistical signature of infant mortality consists in a falling age-specific death rate. The question we address here is whether infant mortality episodes take place in bacteria in the minutes precededing or following cell division. It will be shown that while experiments carried out in the 20th century tried but failed to detect such an effect (mostly because of limited sample size), more recent observations provided consistent evidence of a sizeable mortality, with a rate of the order of 0.7 per 1,000 per hour, in the exponential growth phase of E. coli. A further crucial test will be to measure the age-specific, post-division death rate. An experiment is outlined for that purpose. It is based on the selection of stained cells through flow cytometry and the derivation of their ages at death from their sizes. If an infant mortality effect can be identified in E. coli it can be conjectured that a similar effect also exists in other unicellular organisms, both prokaryote and eukaryote.
Analytic model for feature maps in the primary visual cortex
Authors: Xiaochen Liu, Peter A. Robinson
Date: 2021-03-17 00:00:00

A compact analytic model is proposed to describe the combined orientation preference (OP) and ocular dominance (OD) features of simple cells and their layout in the primary visual cortex (V1). This model consists of three parts: (i) an anisotropic Laplacian (AL) operator that represents the local neural sensitivity to the orientation of visual inputs; (ii) a receptive field (RF) operator that models the anisotropic spatial RF that projects to a given V1 cell over scales of a few tenths of a millimeter and combines with the AL operator to give an overall OP operator; and (iii) a map that describes how the parameters of these operators vary approximately periodically across V1. The parameters of the proposed model maximize the neural response at a given OP with an OP tuning curve fitted to experimental results. It is found that the anisotropy of the AL operator does not significantly affect OP selectivity, which is dominated by the RF anisotropy, consistent with Hubel and Wiesel's original conclusions that orientation tuning width of V1 simple cell is inversely related to the elongation of its RF. A simplified OP-OD map is then constructed to describe the approximately periodic OP-OD structure of V1 in a compact form. Specifically, the map is approximated by retaining its dominant spatial Fourier coefficients, which are shown to suffice to reconstruct the overall structure of the OP-OD map. This representation is a suitable form to analyze observed maps compactly and to be used in neural field theory of V1. Application to independently simulated V1 structures shows that observed irregularities in the map correspond to a spread of dominant coefficients in a circle in Fourier space.
Fabrication of a nanoparticle-containing 3D porous bone scaffold with proangiogenic and antibacterial properties
Authors: Juan L. Paris, Nuria Lafuente-Gomez, M. Victoria Cabanas, Jesus Roman, Juan Pena, Maria Vallet-Regi
Date: 2021-03-17 00:00:00

3D porous scaffolds based on agarose and nanocrystalline apatite, two structural components that act as a temporary mineralized extracellular matrix, were prepared by the GELPOR3D method. This shaping technology allows the introduction of thermally-labile molecules within the scaffolds during the fabrication procedure. An angiogenic protein, Vascular Endothelial Growth Factor, and an antibiotic, cephalexin, loaded in mesoporous silica nanoparticles, were included to design multifunctional scaffolds for bone reconstruction. The dual release of both molecules showed a pro-angiogenic behaviour in chicken embryos grown ex ovo, while, at the same time providing an antibiotic local concentration capable of inhibiting Staphylococcus aureus bacterial growth. In this sense, different release patterns, monitored by UV-spectroscopy, could be tailored as a function of the cephalexin loading strategy. The scaffold surface was characterized by a high hydrophilicity, as determined by contact angle measurements, that facilitated the adhesion and proliferation of preosteoblastic cells.
Structural underpinnings of control in multiplex networks
Authors: Pragya Srivastava, Peter J. Mucha, Emily Falk, Fabio Pasqualetti, Danielle S. Bassett
Date: 2021-03-15 00:00:00

To design control strategies that predictably manipulate a system's behavior, it is first necessary to understand how the system's structure relates to its response. Many complex systems can be represented as multilayer networks whose response and control can be studied in the framework of network control theory. It remains unknown how a system's layered architecture dictates its control properties, particularly when control signals can only access the system through a single input layer. Here, we use the framework of linear control theory to probe the control properties of a duplex network with directed interlayer links. We determine the manner in which the structural properties of layers and relative interlayer arrangement together dictate the system's response. For this purpose, we calculate the exact expression of optimal control energy in terms of layer spectra and the relative alignment between the eigenmodes of the input layer and the deeper target layer. For a range of numerically constructed duplex networks, we then calculate the control properties of the two layers as a function of target-layer densities and layer topology. The alignment of layer eigenmodes emerges as an important parameter that sets the cost and routing of the optimal energy for control. We understand these results in a simplified limit of a single-mode approximation, and we build metrics to characterize the routing of optimal control energy through the eigenmodes of each layer. Our analytical and numerical results together provide insights into the relationships between structure and control in duplex networks. More generally, they serve as a platform for future work designing optimal \emph{interlayer} control strategies.
Concanavalin A-targeted mesoporous silica nanoparticles for infection treatment
Authors: Marina Martinez-Carmona, Isabel Izquierdo-Barba, Montserrat Colilla, Maria Vallet-Regi
Date: 2021-03-12 00:00:00

The ability of bacteria to form biofilms hinders any conventional treatment against chronic infections and has serious socio-economic implications. In this sense, a nanocarrier capable of overcoming the barrier of the mucopolysaccharide matrix of the biofilm and releasing its loaded-antibiotic within would be desirable. Herein, a new nanosystem based on levofloxacin (LEVO)-loaded mesoporous silica nanoparticles (MSNs) decorated with lectin Concanavalin A (ConA) has been developed. The presence of ConA promotes its internalization into the biofilm matrix, which increases the antimicrobial efficacy of the antibiotic hosted within the mesopores. This nanodevice is envisioned as a promising alternative to conventional infection treatments by improving the antimicrobial efficacy and reducing side effects.
Effect of receptor clustering on chemotactic performance of Escherichia coli: sensing versus adaptation
Authors: Shobhan Dev Mandal, Sakuntala Chatterjee
Date: 2020-09-06 00:00:00
Tasks: Clustering

We show how the competition between sensing and adaptation can result in a performance peak in E.coli chemotaxis using extensive numerical simulations in a detailed theoretical model. Receptor clustering amplifies the input signal coming from ligand binding which enhances chemotactic efficiency. But large clusters also induce large fluctuations in total activity since the number of clusters go down. The activity and hence the run-tumble motility now gets controlled by methylation levels which are part of adaptation module, rather than ligand binding. This reduces chemotactic efficiency.
Dimensional Reduction in Complex Living Systems: Where, Why, and How
Authors: Jean-Pierre Eckmann, Tsvi Tlusty
Date: 2021-03-02 00:00:00

The unprecedented prowess of measurement techniques provides a detailed, multi-scale look into the depths of living systems. Understanding these avalanches of high-dimensional data -- by distilling underlying principles and mechanisms -- necessitates dimensional reduction. We propose that living systems achieve exquisite dimensional reduction, originating from their capacity to learn, through evolution and phenotypic plasticity, the relevant aspects of a non-random, smooth physical reality. We explain how geometric insights by mathematicians allow one to identify these genuine hallmarks of life and distinguish them from universal properties of generic data sets. We illustrate these principles in a concrete example of protein evolution, suggesting a simple general recipe that can be applied to understand other biological systems.
Evaluation of Peppermint Leaf Flavonoids as SARS-CoV-2 Spike Receptor-Binding Domain Attachment Inhibitors to the Human ACE2 Receptor: A Molecular Docking Study
Authors: M. L. Pereira Júnior, R. T. de Sousa Junior, G. D. Amvame Nze, W. F. Giozza, L. A. Ribeiro Júnior
Date: 2021-02-25 00:00:00
Tasks: Molecular Docking

Virtual screening is a computational technique widely used for identifying small molecules which are most likely to bind to a protein target. Here, we performed a molecular docking study to propose potential candidates to prevent the RBD/ACE2 attachment. These candidates are sixteen different flavonoids present in the peppermint leaf. Results showed that Luteolin 7-O-neohesperidoside is the peppermint flavonoid with a higher binding affinity regarding the RBD/ACE2 complex (about -9.18 Kcal/mol). On the other hand, Sakuranetin presented the lowest affinity (about -6.38 Kcal/mol). Binding affinities of the other peppermint flavonoids ranged from -6.44 Kcal/mol up to -9.05 Kcal/mol. The binding site surface analysis showed pocket-like regions on the RBD/ACE2 complex that yield several interactions (mostly hydrogen bonds) between the flavonoid and the amino acid residues of the proteins. This study can open channels for the understanding of the roles of flavonoids against COVID-19 infection.
Estimating the effective reproduction number for heterogeneous models using incidence data
Authors: D. C. P. Jorge, J. F. Oliveira, J. G. V. Miranda, R. F. S. Andrade, S. T. R. Pinho
Date: 2021-02-25 00:00:00

The effective reproduction number, R(t), is a central point in the study of infectious diseases. It establishes in an explicit way the extent of an epidemic spread process in a population. The current estimation methods for the time evolution of R(t), using incidence data, rely on the generation interval distribution, g(\tau), which is usually obtained from empirical data or already known distributions from the literature. However, there are systems, especially highly heterogeneous ones, in which there is a lack of data and an adequate methodology to obtain g(\tau). In this work, we use mathematical models to bridge this gap. We present a general methodology for obtaining an explicit expression of the reproduction numbers and the generation interval distributions provided by an arbitrary compartmental model. Additionally, we present the appropriate expressions to evaluate those reproduction numbers using incidence data. To highlight the relevance of such methodology, we apply it to the spread of Covid-19 in municipalities of the state of Rio de janeiro, Brazil. Using two meta-population models, we estimate the reproduction numbers and the contributions of each municipality in the generation of cases in all others. Our results point out the importance of mathematical modelling to provide epidemiological meaning of the available data.
Replicator equations induced by microscopic processes in nonoverlapping population playing bimatrix games
Authors: Archan Mukhopadhyay, Sagar Chakraborty
Date: 2021-02-17 00:00:00

This paper is concerned with exploring the microscopic basis for the discrete versions of the standard replicator equation and the adjusted replicator equation. To this end, we introduce frequency-dependent selection -- as a result of competition fashioned by game-theoretic consideration -- into the Wright--Fisher process, a stochastic birth-death process. The process is further considered to be active in a generation-wise nonoverlapping finite population where individuals play a two-strategy bimatrix population game. Subsequently, connections among the corresponding master equation, the Fokker--Planck equation, and the Langevin equation are exploited to arrive at the deterministic discrete replicator maps in the limit of infinite population size.
Deciphering chaos in evolutionary games
Authors: Archan Mukhopadhyay, Sagar Chakraborty
Date: 2021-02-17 00:00:00

Discrete-time replicator map is a prototype of evolutionary selection game dynamical models that have been very successful across disciplines in rendering insights into the attainment of the equilibrium outcomes, like the Nash equilibrium and the evolutionarily stable strategy. By construction, only the fixed point solutions of the dynamics can possibly be interpreted as the aforementioned game-theoretic solution concepts. Although more complex outcomes like chaos are omnipresent in the nature, it is not known to which game-theoretic solutions they correspond. Here we construct a game-theoretic solution that is realized as the chaotic outcomes in the selection monotone game dynamic. To this end, we invoke the idea that in a population game having two-player--two-strategy one-shot interactions, it is the product of the fitness and the heterogeneity (the probability of finding two individuals playing different strategies in the infinitely large population) that is optimized over the generations of the evolutionary process.
Periodic Orbit can be Evolutionarily Stable: Case Study of Discrete Replicator Dynamics
Authors: Archan Mukhopadhyay, Sagar Chakraborty
Date: 2021-02-17 00:00:00

In evolutionary game theory, it is customary to be partial to the dynamical models possessing fixed points so that they may be understood as the attainment of evolutionary stability, and hence, Nash equilibrium. Any show of periodic or chaotic solution is many a time perceived as a shortcoming of the corresponding game dynamic because (Nash) equilibrium play is supposed to be robust and persistent behaviour, and any other behaviour in nature is deemed transient. Consequently, there is a lack of attempt to connect the non-fixed point solutions with the game theoretic concepts. Here we provide a way to render game theoretic meaning to periodic solutions. To this end, we consider a replicator map that models Darwinian selection mechanism in unstructured infinite-sized population whose individuals reproduce asexually forming non-overlapping generations. This is one of the simplest evolutionary game dynamic that exhibits periodic solutions giving way to chaotic solutions (as parameters related to reproductive fitness change) and also obeys the folk theorems connecting fixed point solutions with Nash equilibrium. Interestingly, we find that a modified Darwinian fitness -- termed heterogeneity payoff -- in the corresponding population game must be put forward as (conventional) fitness times the probability that two arbitrarily chosen individuals of the population adopt two different strategies. The evolutionary dynamics proceeds as if the individuals optimize the heterogeneity payoff to reach an evolutionarily stable orbit, should it exist. We rigorously prove that a locally asymptotically stable period orbit must be heterogeneity stable orbit -- a generalization of evolutionarily stable state.
Cooperators overcome migration dilemma through synchronization
Authors: Shubhadeep Sadhukhan, Rohitashwa Chattopadhyay, Sagar Chakraborty
Date: 2021-02-17 00:00:00

Synchronization, cooperation, and chaos are ubiquitous phenomena in nature. In a population composed of many distinct groups of individuals playing the prisoner's dilemma game, there exists a migration dilemma: No cooperator would migrate to a group playing the prisoner's dilemma game lest it should be exploited by a defector; but unless the migration takes place, there is no chance of the entire population's cooperator-fraction to increase. Employing a randomly rewired coupled map lattice of chaotic replicator maps, modelling replication-selection evolutionary game dynamics, we demonstrate that the cooperators -- evolving in synchrony -- overcome the migration dilemma to proliferate across the population when altruism is mildly incentivized making few of the demes play the leader game.
Fluid-solid interaction in the rate-dependent failure of brain tissue and biomimicking gels
Authors: Michele Terzano, Andrea Spagnoli, Daniele Dini, Antonio Elia Forte
Date: 2021-02-15 00:00:00

Brain tissue is a heterogeneous material, constituted by a soft matrix filled with cerebrospinal fluid. The interactions between, and the complexity of each of these components are responsible for the non-linear rate-dependent behaviour that characterizes what is one of the most complex tissue in nature. Here, we investigate the influence of the cutting rate on the fracture properties of brain, through wire cutting experiments. We also present a model for the rate-dependent behaviour of fracture propagation in soft materials, which comprises the effects of fluid interaction through a poro-hyperelastic formulation. The method is developed in the framework of finite strain continuum mechanics, implemented in a commercial finite element code, and applied to the case of an edge-crack remotely loaded by a controlled displacement. Experimental and numerical results both show a toughening effect with increasing rates, which is linked to the energy dissipated by the fluid-solid interactions in the process zone ahead of the crack.
Schrödinger's "What is Life?" at 75
Authors: Rob Phillips
Date: 2021-02-07 00:00:00

2019 marked the 75th anniversary of the publication of Erwin Schr\"{o}dinger's "What is Life?", a short book described by Roger Penrose in his preface to a reprint of this classic as "among the most influential scientific writings of the 20th century." In this article, I review the long argument made by Schr\"{o}dinger as he mused on how the laws of physics could help us understand "the events in space and time which take place within the spatial boundary of a living organism." Though Schr\"{o}dinger's book is often hailed for its influence on some of the titans who founded molecular biology, this article takes a different tack. Instead of exploring the way the book touched biologists such as James Watson and Francis Crick, as well as its critical reception by others such as Linus Pauling and Max Perutz, I argue that Schr\"{o}dinger's classic is a timeless manifesto, rather than a dated historical curiosity. "What is Life?" is full of timely outlooks and approaches to understanding the mysterious living world that includes and surrounds us and can instead be viewed as a call to arms to tackle the great unanswered challenges in the study of living matter that remain for 21$^{st}$ century science.
Does Non-Genetic Heterogeneity Facilitate the Development of Genetic Drug Resistance?
Authors: Kevin S. Farquhar, Samira Rasouli Koohi, Daniel A. Charlebois
Date: 2021-02-05 00:00:00

Non-genetic forms of antimicrobial drug resistance can result from cell-to-cell variability that is not encoded in the genetic material. Data from recent studies also suggest that non-genetic mechanisms can facilitate the development of genetic drug resistance. In this Perspective article, we speculate on how the interplay between non-genetic and genetic mechanisms may affect microbial adaptation and evolution during drug treatment. We argue that cellular heterogeneity arising from fluctuations in gene expression, epigenetic modifications, as well as genetic changes contributes to drug resistance at different timescales, and that the interplay between these mechanisms may influence the evolutionary dynamics of pathogen resistance. Accordingly, developing a better understanding of non-genetic mechanisms in drug resistance and how they interact with genetic mechanisms will enhance our ability to combat antimicrobial resistance.