Finite element graft stress for anteromedial portal, transtibial, and hybrid transtibial femoral drillings under anterior translation and medial rotation: an exploratory study.

Stress concentration on the Anterior Cruciate Ligament Reconstruction (ACLr) for femoral drillings is crucial to understanding failures. Therefore, we described the graft stress for transtibial (TT), the anteromedial portal (AM), and hybrid transtibial (HTT) techniques during the anterior tibial translation and medial knee rotation in a finite element model. A healthy participant with a non-medical record of Anterior Cruciate Ligament rupture with regular sports practice underwent finite element analysis. We modeled TT, HTT, AM drillings, and the ACLr as hyperelastic isotropic material. The maximum Von Mises principal stresses and distributions were obtained from anterior tibial translation and medial rotation. During the anterior tibia translation, the HTT, TT, and AM drilling were 31.5 MPa, 34.6 Mpa, and 35.0 MPa, respectively. During the medial knee rotation, the AM, TT, and HTT drilling were 17.3 MPa, 20.3 Mpa, and 21.6 MPa, respectively. The stress was concentrated at the lateral aspect of ACLr,near the femoral tunnel for all techniques independent of the knee movement. Meanwhile, the AM tunnel concentrates the stress at the medial aspect of the ACLr body under medial rotation. The HTT better constrains the anterior tibia translation than AM and TT drillings, while AM does for medial knee rotation.

On the effectiveness of communication strategies as non-pharmaceutical interventions to tackle epidemics.

When pharmaceutical interventions are unavailable to deal with an epidemic outbreak, adequate management of communication strategies can be key to reduce the contagion risks. On the one hand, accessibility to trustworthy and timely information, whilst on the other, the adoption of preventive behaviors may be both crucial. However, despite the abundance of communication strategies, their effectiveness has been scarcely evaluated or merely circumscribed to the scrutiny of public affairs. To study the influence of communication strategies on the spreading dynamics of an infectious disease, we implemented a susceptible-exposed-infected-removed-dead (SEIRD) epidemiological model, using an agent-based approach. Agents in our systems can obtain information modulating their behavior from two sources: (i) through the local interaction with other neighboring agents and, (ii) from a central entity delivering information with a certain periodicity. In doing so, we highlight how global information delivered from a central entity can reduce the impact of an infectious disease and how informing even a small fraction of the population has a remarkable impact, when compared to not informing the population at all. Moreover, having a scheme of delivering daily messages makes a stark difference on the reduction of cases, compared to the other evaluated strategies, denoting that daily delivery of information produces the largest decrease in the number of cases. Furthermore, when the information spreading relies only on local interactions between agents, and no central entity takes actions along the dynamics, then the epidemic spreading is virtually independent of the initial amount of informed agents. On top of that, we found that local communication plays an important role in an intermediate regime where information coming from a central entity is scarce. As a whole, our results highlight the importance of proper communication strategies, both accurate and daily, to tackle epidemic outbreaks.

Orientational and Folding Thermodynamics via Electric Dipole Moment Restraining.

The projection of molecular processes onto a small set of relevant descriptors, the so-called reaction coordinates or collective variables (CVs), is a technique nowadays routinely employed by the biomolecular simulation community. In this work, we implemented two CVs to manipulate the orientation (i.e., angle) (µâƒ—a) and magnitude (|µâƒ—|) of the electric dipole moment. In doing so, we studied the thermodynamics of water orientation under the application of external voltages and the folding of two polypeptides at zero-field conditions. The projection of the free-energy [potential of mean force (PMF)] along water orientation defined an upper limit of around 0.3 V for irrelevant thermodynamic effects. On the other hand, sufficiently strong µâƒ—a restraints applied on 12-alanine (Ala12) triggered structural effects because of the alignment of local dipoles; for lower restraints, a full-body rotation is achieved. The manipulation of |µâƒ—| produced strong perturbations on the secondary structure of Ala12, promoting an enhanced sampling to its configurational space. Rigorous free-energy calculations in the form of 2-D PMFs for deca-alanine showed the utility of |µâƒ—| as a reaction coordinate to study folding in small α helices. As a whole, we propose that the manipulation of both components of the dipole moment, µâƒ—a and |µâƒ—|, provides thermodynamics insights into the structural conformation and stability of biomolecules. These new CVs are implemented in the Colvars module, available for NAMD and LAMMPS.

Stochastic simulation of multiscale complex systems with PISKaS: A rule-based approach.

Computational simulation is a widely employed methodology to study the dynamic behavior of complex systems. Although common approaches are based either on ordinary differential equations or stochastic differential equations, these techniques make several assumptions which, when it comes to biological processes, could often lead to unrealistic models. Among others, model approaches based on differential equations entangle kinetics and causality, failing when complexity increases, separating knowledge from models, and assuming that the average behavior of the population encompasses any individual deviation. To overcome these limitations, simulations based on the Stochastic Simulation Algorithm (SSA) appear as a suitable approach to model complex biological systems. In this work, we review three different models executed in PISKaS: a rule-based framework to produce multiscale stochastic simulations of complex systems. These models span multiple time and spatial scales ranging from gene regulation up to Game Theory. In the first example, we describe a model of the core regulatory network of gene expression in Escherichia coli highlighting the continuous model improvement capacities of PISKaS. The second example describes a hypothetical outbreak of the Ebola virus occurring in a compartmentalized environment resembling cities and highways. Finally, in the last example, we illustrate a stochastic model for the prisoner's dilemma; a common approach from social sciences describing complex interactions involving trust within human populations. As whole, these models demonstrate the capabilities of PISKaS providing fertile scenarios where to explore the dynamics of complex systems.

Characterization of a novel water pocket inside the human Cx26 hemichannel structure.

Connexins (Cxs) are a family of vertebrate proteins constituents of gap junction channels (GJCs) that connect the cytoplasm of adjacent cells by the end-to-end docking of two Cx hemichannels. The intercellular transfer through GJCs occurs by passive diffusion allowing the exchange of water, ions, and small molecules. Despite the broad interest to understand, at the molecular level, the functional state of Cx-based channels, there are still many unanswered questions regarding structure-function relationships, perm-selectivity, and gating mechanisms. In particular, the ordering, structure, and dynamics of water inside Cx GJCs and hemichannels remains largely unexplored. In this work, we describe the identification and characterization of a believed novel water pocket-termed the IC pocket-located in-between the four transmembrane helices of each human Cx26 (hCx26) monomer at the intracellular (IC) side. Using molecular dynamics (MD) simulations to characterize hCx26 internal water structure and dynamics, six IC pockets were identified per hemichannel. A detailed characterization of the dynamics and ordering of water including conformational variability of residues forming the IC pockets, together with multiple sequence alignments, allowed us to propose a functional role for this cavity. An in vitro assessment of tracer uptake suggests that the IC pocket residue Arg-143 plays an essential role on the modulation of the hCx26 hemichannel permeability.

A new isomer of C20 and a way to a new C240.

Here we show that the dynamic simulation of a molecular collision can give insight into new molecular species. In this way, a new stable isomer of C(20) (IV) has been found. It is planar with pentagonal form. This isomer is high in energy compared to the three most stable previously known isomers of C(20): cage (I), bowl (II) and ring (III). Most interestingly, we show that using this new isomer it is possible to construct a macrobucky C(240) (V) that is also stable. The electronic structure of this new isomer of C(240) is very different from properties of the C(240) fullerene. Contrary to the C(240) fullerene, in the new isomer the π electrons are localized.