COVID-19 spreading under containment actions.

We propose an epidemiological model that explores the effect of human mobility on the spatio-temporal dynamics of the COVID-19 outbreak, in the spirit to those considered in Refs. Barmak et al. (2011, 2016) and Medus and Dorso (2011) [1].

Beyond the faster-is-slower effect.

The "faster-is-slower" effect arises when crowded people push each other to escape through an exit during an emergency situation. As individuals push harder, a statistical slowing down in the evacuation time can be achieved. The slowing down is caused by the presence of small groups of pedestrians (say, a small human cluster) that temporarily block the way out when trying to leave the room.

Modelling interventions during a dengue outbreak.

We present a stochastic dynamical model for the transmission of dengue that considers the co-evolution of the spatial dynamics of the vectors (Aedes aegypti) and hosts (human population), allowing the simulation of control strategies adapted to the actual evolution of an epidemic outbreak. We observed that imposing restrictions on the movement of infected humans is not a highly effective strategy. In contrast, isolating infected individuals with high levels of compliance by the human population is efficient even when implemented with delays during an ongoing outbreak.

Potency, selectivity and prolonged binding of saxagliptin to DPP4: maintenance of DPP4 inhibition by saxagliptin in vitro and ex vivo when compared to a rapidly-dissociating DPP4 inhibitor.

Background: Dipeptidylpeptidase 4 (DPP4) inhibitors have clinical benefit in patients with type 2 diabetes mellitus by increasing levels of glucose-lowering incretin hormones, such as glucagon-like peptide -1 (GLP-1), a peptide with a short half life that is secreted for approximately 1 hour following a meal. Since drugs with prolonged binding to their target have been shown to maximize pharmacodynamic effects while minimizing drug levels, we developed a time-dependent inhibitor that has a half-life for dissociation from DPP4 close to the duration of the first phase of GLP-1 release.

Results: Saxagliptin and its active metabolite (5-hydroxysaxagliptin) are potent inhibitors of human DPP4 with prolonged dissociation from its active site (Ki = 1.

Dengue epidemics and human mobility.

In this work we explore the effects of human mobility on the dispersion of a vector borne disease. We combine an already presented stochastic model for dengue with a simple representation of the daily motion of humans on a schematic city of 20 × 20 blocks with 100 inhabitants in each block. The pattern of motion of the individuals is described in terms of complex networks in which links connect different blocks and the link length distribution is in accordance with recent findings on human mobility.

Modeling dengue outbreaks.

We introduce a dengue model (SEIR) where the human individuals are treated on an individual basis (IBM) while the mosquito population, produced by an independent model, is treated by compartments (SEI). We study the spread of epidemics by the sole action of the mosquito. Exponential, deterministic and experimental distributions for the (human) exposed period are considered in two weather scenarios, one corresponding to temperate climate and the other to tropical climate.

Alternative approach to community detection in networks.

The problem of community detection is relevant in many disciplines of science and modularity optimization is the widely accepted method for this purpose. It has recently been shown that this approach presents a resolution limit by which it is not possible to detect communities with sizes smaller than a threshold, which depends on the network size. Moreover, it might happen that the communities resulting from such an approach do not satisfy the usual qualitative definition of commune; i.

ReaxFF reactive force field for the Y-doped BaZrO3 proton conductor with applications to diffusion rates for multigranular systems.

Proton-conducting perovskites such as Y-doped BaZrO 3 (BYZ) are promising candidates as electrolytes for a proton ceramic fuel cell (PCFC) that might permit much lower temperatures (from 400 to 600 degrees C). However, these materials lead to relatively poor total conductivity ( approximately 10 (-4) S/cm) because of extremely high grain boundary resistance. In order to provide the basis for improving these materials, we developed the ReaxFF reactive force field to enable molecular dynamics (MD) simulations of proton diffusion in the bulk phase and across grain boundaries of BYZ.

Expansion dynamics of Lennard-Jones systems.

The dynamics of the expansion of a Lennard-Jones system, initially confined at high density and subsequently expanding freely in a vacuum, is compared with an expanding statistical ensemble derived in the diluted quasi-ideal Boltzmann approximation. The description proves to be fairly accurate at predicting average one-body global observables, but important deviations are observed in the configuration-space structure of the events. Possible implications for finite expanding physical systems are outlined.

Extended Gibbs ensembles with flow.

A recently proposed [Ph. Chomaz, F. Gulminelli, and O.

Fisher equation for anisotropic diffusion: simulating South American human dispersals.

The Fisher equation is commonly used to model population dynamics. This equation allows describing reaction-diffusion processes, considering both population growth and diffusion mechanism. Some results have been reported about modeling human dispersion, always assuming isotropic diffusion.

Synthesis and biological activity of 5-aryl-4-(4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl)pyrimidine analogs as potent, highly selective, and orally bioavailable NHE-1 inhibitors.

A series of potent inhibitors of the sodium hydrogen exchanger-1 (NHE-1) is described. Structure-activity relationships identified the 3-methyl-4-fluoro analog 9t as a highly potent (IC50 = 0.0065 microM) and selective (NHE-2/NHE-1=1400) non-acylguanidine NHE-1 inhibitor.

Aminoimidazoles as bioisosteres of acylguanidines: novel, potent, selective and orally bioavailable inhibitors of the sodium hydrogen exchanger isoform-1.

Inhibition of the sodium hydrogen exchanger isoform-1 (NHE-1) has been shown to limit damage to the myocardium under ischemic conditions in animals. While most known NHE-1 inhibitors are acylguanidines, this report describes the design and synthesis of a series of heterocyclic inhibitors of NHE-1 including aminoimidazoles with undiminished in vitro activity and oral bioavailability.

Arylcyclopropanecarboxyl guanidines as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1.

A novel series of arylcyclopropanecarboxyl guanidines was synthesized and evaluated for activity against the sodium hydrogen exchanger isoform-1 (NHE-1). In biological assays conducted in an AP1 cell line expressing the human NHE-1 isoform, the starting cyclopropane 3a (IC(50) = 3.5 microM) shows inhibitory activity comparable to cariporide (IC(50) = 3.

Local (in time) maximal lyapunov exponents of fragmenting drops.

We analyze the dynamics of fragment formation in simulations of exploding three-dimensional Lennard-Jones hot drops, using the maximum local (in time) Lyapunov exponent (MLLE). The dependence of this exponent on the excitation energy of the system displays two different behaviors according to the stage of the dynamical evolution: one related to the highly collisional stage of the evolution, at early times, and the other related to the asymptotic state. We show that in the early, highly collisional, stage of the evolution the MLLE is an increasing function of the energy, as in an infinite-size system.

Proarrhythmic effects of pinacidil are partially mediated through enhancement of catecholamine release in isolated perfused guinea-pig hearts.

The contribution of adrenergic stimulation to the proarrhythmic effects of pinacidil (30 microM), an opener of ATP-sensitive potassium channels (K+ATP), was tested in an isolated guinea-pig heart model of global ischemia (10 min) and reperfusion (10 min). None (0%) of the control hearts (n=10) elicited arrhythmias during ischemia or reperfusion. In the pinacidil-treated group, one heart (5%) experienced episodes of ventricular tachycardia (VT)/fibrillation (VF) during normoxia.

In vivo pharmacology of dual neutral endopeptidase/angiotensin-converting enzyme inhibitors.

The natriuretic and depressor responses to novel dual inhibitors of neutral endopeptidase (NEP) EC 3.4.24.

Renal and depressor activities of inhibitors of neutral endopeptidase and angiotensin converting enzyme in monkeys infused with angiotensin II.

In a previous study, the depressor activity of combined selective inhibitors of neutral endopeptidase EC 3.4.24.

Determinants of in vivo activity of neutral endopeptidase 3.4.24.11 and angiotensin converting enzyme inhibitors.

Simultaneous inhibition of neutral endopeptidase EC 3.4.24.

A role for endothelin ETA receptors in regulation of renal function in spontaneously hypertensive rats.

While there is evidence to suggest that endothelin-1 is involved in regulation of kidney function and blood pressure, the importance of endothelin ETA receptors in this area has not been clearly defined. The novel, non-peptide endothelin ETA receptor antagonist, BMS-182874, (5-(dimethylamino)-N-(3,4- dimethyl-5-isoxazolyl)-1-naphthalene sulfonamide) was used to examine effects of endothelin ETA receptor blockade on renal function in spontaneously hypertensive rats. Preliminary studies were conducted to determine an effective dose of BMS-182874.