Kinetic glass transition in granular gases and nonlinear molecular fluids.

In this paper, we investigate, both analytically and numerically, the emergence of a kinetic glass transition in two different model systems: a uniformly heated granular gas and a molecular fluid with nonlinear drag. Despite the profound differences between these two physical systems, their behavior in thermal cycles share strong similarities, which stem from the relaxation time diverging algebraically at low temperatures for both systems. When the driving intensity--for the granular gas-or the bath temperature-for the molecular fluid-is decreased to sufficiently low values, the kinetic temperature of both systems becomes "frozen" at a value that depends on the cooling rate through a power law with the same exponent. Interestingly, this frozen glassy state is universal in the following sense: for a suitable rescaling of the relevant variables, its velocity distribution function becomes independent of the cooling rate. Upon reheating, i.e., when either the driving intensity or the bath temperature is increased from this frozen state, hysteresis cycles arise and the apparent heat capacity displays a maximum. The numerical results obtained from the simulations are well described by a perturbative approach.

Strong nonexponential relaxation and memory effects in a fluid with nonlinear drag.

We analyze the dynamical evolution of a fluid with nonlinear drag, for which binary collisions are elastic, described at the kinetic level by the Enskog-Fokker-Planck equation. This model system, rooted in the theory of nonlinear Brownian motion, displays a really complex behavior when quenched to low temperatures. Its glassy response is controlled by a long-lived nonequilibrium state, independent of the degree of nonlinearity and also of the Brownian-Brownian collisions rate. The latter property entails that this behavior persists in the collisionless case, where the fluid is described by the nonlinear Fokker-Planck equation. The observed response, which includes nonexponential, algebraic, relaxation, and strong memory effects, presents scaling properties: the time evolution of the temperature-for both relaxation and memory effects-falls onto a master curve, regardless of the details of the experiment. To account for the observed behavior in simulations, it is necessary to develop an extended Sonine approximation for the kinetic equation-which considers not only the fourth cumulant but also the sixth one.

Optimal work in a harmonic trap with bounded stiffness.

We apply Pontryagin's principle to drive rapidly a trapped overdamped Brownian particle in contact with a thermal bath between two equilibrium states corresponding to different trap stiffness κ. We work out the optimal time dependence κ(t) by minimizing the work performed on the particle under the nonholonomic constraint 0≤κ≤κ_{max}, an experimentally relevant situation. Several important differences arise, as compared with the case of unbounded stiffness that has been analyzed in the literature. First, two arbitrary equilibrium states may not always be connected. Second, depending on the operating time t_{f} and the desired compression ratio κ_{f}/κ_{i}, different types of solutions emerge. Finally, the differences in the minimum value of the work brought about by the bounds may become quite large, which may have a relevant impact on the optimization of heat engines.

Induction of anti-VEGF therapy resistance by upregulated expression of microseminoprotein (MSMP).

Anti-vascular endothelial growth factor (VEGF) therapy has demonstrated efficacy in treating human metastatic cancers, but therapeutic resistance is a practical limitation and most tumors eventually become unresponsive. To identify microenvironmental factors underlying the resistance of cancer to antiangiogenesis therapy, we conducted genomic analyses of intraperitoneal ovarian tumors in which adaptive resistance to anti-VEGF therapy (B20 antibody) developed. We found that expression of the microseminoprotein, prostate-associated (MSMP) gene was substantially upregulated in resistant compared with control tumors. MSMP secretion from cancer cells was induced by hypoxia, triggering MAPK signaling in endothelial cells to promote tube formation in vitro. Recruitment of the transcriptional repressor CCCTC-binding factor (CTCF) to the MSMP enhancer region was decreased by histone acetylation under hypoxic conditions in cancer cells. MSMP siRNA, delivered in vivo using the DOPC nanoliposomes, restored tumor sensitivity to anti-VEGF therapy. In ovarian cancer patients treated with bevacizumab, serum MSMP concentration increased significantly only in non-responders. These findings imply that MSMP inhibition combined with the use of antiangiogenesis drugs may be a new strategy to overcome resistance to antiangiogenesis therapy.

Global stability and H theorem in lattice models with nonconservative interactions.

In kinetic theory, a system is usually described by its one-particle distribution function f(r,v,t), such that f(r,v,t)drdv is the fraction of particles with positions and velocities in the intervals (r,r+dr) and (v,v+dv), respectively. Therein, global stability and the possible existence of an associated Lyapunov function or H theorem are open problems when nonconservative interactions are present, as in granular fluids. Here, we address this issue in the framework of a lattice model for granularlike velocity fields. For a quite general driving mechanism, including both boundary and bulk driving, we show that the steady state reached by the system in the long-time limit is globally stable. This is done by proving analytically that a certain H functional is nonincreasing in the long-time limit. Moreover, for a quite general energy injection mechanism, we are able to demonstrate that the proposed H functional is nonincreasing for all times. Also, we put forward a proof that clearly illustrates why the "classical" Boltzmann functional H_{B}[f]=∫drdvf(r,v,t)lnf(r,v,t) is inadequate for systems with nonconservative interactions. This is done not only for the simplified kinetic description that holds in the lattice models analyzed here but also for a general kinetic equation, like Boltzmann's or Enskog's.

Multiple high-risk HPV genotypes are grouped by type and are associated with viral load and risk factors.

Investigating whether high-risk human papillomavirus (HR-HPV) types tend to become grouped in a particular way and whether factors are associated with such grouping is important for measuring the real impact of vaccination. In total, 219 women proving positive for HPV as detected by real-time PCR were included in the study. Each sample was analysed for detecting and quantifying six viral types and the hydroxymethylbilane synthase gene. Multiple correspondence analysis led to determining grouping patterns for six HR-HPV types and simultaneous association with multiple variables and whether viral load was related to the coexistence of other viral types. Two grouping profiles were identified: the first included HPV-16 and HPV-45 and the second profile was represented by HPV-31, HPV-33 and HPV-58. Variables such as origin, contraceptive method, births and pregnancies, educational level, healthcare affiliation regime, atypical squamous cells of undetermined significance and viral load were associated with these grouping profiles. Different socio-demographic characteristics were found when coinfection occurred by phylogenetically related HPV types and when coinfection was due to non-related types. Biological characteristics, the number of viral copies, temporality regarding acquiring infection and competition between viral types could influence the configuration of grouping patterns. Characteristics related to women and HPV, influence such interactions between coexisting HPV types reflecting the importance of their evaluation.

Bifurcation analysis and phase diagram of a spin-string model with buckled states.

We analyze a one-dimensional spin-string model, in which string oscillators are linearly coupled to their two nearest neighbors and to Ising spins representing internal degrees of freedom. String-spin coupling induces a long-range ferromagnetic interaction among spins that competes with a spin-spin antiferromagnetic coupling. As a consequence, the complex phase diagram of the system exhibits different flat rippled and buckled states, with first or second order transition lines between states. This complexity translates to the two-dimensional version of the model, whose numerical solution has been recently used to explain qualitatively the rippled to buckled transition observed in scanning tunneling microscopy experiments with suspended graphene sheets. Here we describe in detail the phase diagram of the simpler one-dimensional model and phase stability using bifurcation theory. This gives additional insight into the physical mechanisms underlying the different phases and the behavior observed in experiments.

Statistics of the dissipated energy in driven diffusive systems.

Understanding the physics of non-equilibrium systems remains one of the major open questions in statistical physics. This problem can be partially handled by investigating macroscopic fluctuations of key magnitudes that characterise the non-equilibrium behaviour of the system of interest; their statistics, associated structures and microscopic origin. During the last years, some new general and powerful methods have appeared to delve into fluctuating behaviour that have drastically changed the way to address this problem in the realm of diffusive systems: macroscopic fluctuation theory (MFT) and a set of advanced computational techniques that make it possible to measure the probability of rare events. Notwithstanding, a satisfactory theory is still lacking in a particular case of intrinsically non-equilibrium systems, namely those in which energy is not conserved but dissipated continuously in the bulk of the system (e.g. granular media). In this work, we put forward the dissipated energy as a relevant quantity in this case and analyse in a pedagogical way its fluctuations, by making use of a suitable generalisation of macroscopic fluctuation theory to driven dissipative media.

Theory of force-extension curves for modular proteins and DNA hairpins.

We study a model describing the force-extension curves of modular proteins, nucleic acids, and other biomolecules made out of several single units or modules. At a mesoscopic level of description, the configuration of the system is given by the elongations of each of the units. The system free energy includes a double-well potential for each unit and an elastic nearest-neighbor interaction between them. Minimizing the free energy yields the system equilibrium properties whereas its dynamics is given by (overdamped) Langevin equations for the elongations, in which friction and noise amplitude are related by the fluctuation-dissipation theorem. Our results, both for the equilibrium and the dynamical situations, include analytical and numerical descriptions of the system force-extension curves under force or length control and agree very well with actual experiments in biomolecules. Our conclusions also apply to other physical systems comprising a number of metastable units, such as storage systems or semiconductor superlattices.

Memory effect in uniformly heated granular gases.

We evidence a Kovacs-like memory effect in a uniformly driven granular gas. A system of inelastic hard particles, in the low density limit, can reach a nonequilibrium steady state when properly forced. By following a certain protocol for the drive time dependence, we prepare the gas in a state where the granular temperature coincides with its long time value. The temperature subsequently does not remain constant but exhibits a nonmonotonic evolution with either a maximum or a minimum, depending on the dissipation and on the protocol. We present a theoretical analysis of this memory effect at Boltzmann-Fokker-Planck equation level and show that when dissipation exceeds a threshold, the response can be called anomalous. We find excellent agreement between the analytical predictions and direct Monte Carlo simulations.

Kovacs-like memory effect in driven granular gases.

While memory effects have been reported for dense enough disordered systems such as glasses, we show here by a combination of analytical and simulation techniques that they are also intrinsic to the dynamics of dilute granular gases. By means of a certain driving protocol, we prepare the gas in a state where the granular temperature T coincides with its long time limit. However, T does not subsequently remain constant but exhibits a nonmonotonic evolution before reaching its nonequilibrium steady value. The corresponding so-called Kovacs hump displays a normal behavior for weak dissipation (as observed in molecular systems) but is reversed under strong dissipation, where it, thus, becomes anomalous.

Kovacs effect in the one-dimensional Ising model: a linear response analysis.

We analyze the so-called Kovacs effect in the one-dimensional Ising model with Glauber dynamics. We consider small enough temperature jumps, for which a linear response theory has been recently derived. Within this theory, the Kovacs hump is directly related to the monotonic relaxation function of the energy. The analytical results are compared with extensive Monte Carlo simulations, and an excellent agreement is found. Remarkably, the position of the maximum in the Kovacs hump depends on the fact that the true asymptotic behavior of the relaxation function is different from the stretched exponential describing the relevant part of the relaxation at low temperatures.

Typical and rare fluctuations in nonlinear driven diffusive systems with dissipation.

We consider fluctuations of the dissipated energy in nonlinear driven diffusive systems subject to bulk dissipation and boundary driving. With this aim, we extend the recently introduced macroscopic fluctuation theory to nonlinear driven dissipative media, starting from the fluctuating hydrodynamic equations describing the system mesoscopic evolution. Interestingly, the action associated with a path in mesoscopic phase space, from which large-deviation functions for macroscopic observables can be derived, has the same simple form as in nondissipative systems. This is a consequence of the quasielasticity of microscopic dynamics, required in order to have a nontrivial competition between diffusion and dissipation at the mesoscale. Euler-Lagrange equations for the optimal density and current fields that sustain an arbitrary dissipation fluctuation are also derived. A perturbative solution thereof shows that the probability distribution of small fluctuations is always Gaussian, as expected from the central limit theorem. On the other hand, strong separation from the Gaussian behavior is observed for large fluctuations, with a distribution which shows no negative branch, thus violating the Gallavotti-Cohen fluctuation theorem, as expected from the irreversibility of the dynamics. The dissipation large-deviation function exhibits simple and general scaling forms for weakly and strongly dissipative systems, with large fluctuations favored in the former case but heavily suppressed in the latter. We apply our results to a general class of diffusive lattice models for which dissipation, nonlinear diffusion, and driving are the key ingredients. The theoretical predictions are compared to extensive numerical simulations of the microscopic models, and excellent agreement is found. Interestingly, the large-deviation function is in some cases nonconvex beyond some dissipation. These results show that a suitable generalization of macroscopic fluctuation theory is capable of describing in detail the fluctuating behavior of nonlinear driven dissipative media.

Sawtooth patterns in force-extension curves of biomolecules: an equilibrium-statistical-mechanics theory.

We analyze the force-extension curve for a general class of systems, which are described at the mesoscopic level by a free energy depending on the extension of its components. Similarly to what is done in real experiments, the total length of the system is the controlled parameter. This imposes a global constraint in the minimization procedure leading to the equilibrium values of the extensions. As a consequence, the force-extension curve has multiple branches in a certain range of forces. The stability of these branches is governed by the free energy: there are a series of first-order phase transitions at certain values of the total length, in which the free energy itself is continuous but its first derivative, the force, has a finite jump. This behavior is completely similar to that observed in real experiments with biomolecules like proteins and with other complex systems.

Nonlinear driven diffusive systems with dissipation: fluctuating hydrodynamics.

We consider a general class of nonlinear diffusive models with bulk dissipation and boundary driving and derive its hydrodynamic description in the large size limit. Both the average macroscopic behavior and the fluctuating properties of the hydrodynamic fields are obtained from the microscopic dynamics. This analysis yields a fluctuating balance equation for the local energy density at the mesoscopic level, characterized by two terms: (i) a diffusive term, with a current that fluctuates around its average behavior given by nonlinear Fourier's law, and (ii) a dissipation term which is a general function of the local energy density. The quasielasticity of microscopic dynamics, required in order to have a nontrivial competition between diffusion and dissipation in the macroscopic limit, implies a noiseless dissipation term in the balance equation, so dissipation fluctuations are enslaved to those of the density field. The microscopic complexity is thus condensed in just three transport coefficients-the diffusivity, the mobility, and a new dissipation coefficient-which are explicitly calculated within a local equilibrium approximation. Interestingly, the diffusivity and mobility coefficients obey an Einstein relation despite the fully nonequilibrium character of the problem. The general theory here presented is applied to a particular albeit broad family of systems, the simplest nonlinear dissipative variant of the so-called KMP model for heat transport. The theoretical predictions are compared to extensive numerical simulations, and an excellent agreement is found.

Spin-oscillator model for the unzipping of biomolecules by mechanical force.

A spin-oscillator system models unzipping of biomolecules (such as DNA, RNA, or proteins) subject to an external force. The system comprises a macroscopic degree of freedom, represented by a one-dimensional oscillator, and internal degrees of freedom, represented by Glauber spins with nearest-neighbor interaction and a coupling constant proportional to the oscillator position. At a critical value F(c) of an applied external force F, the oscillator rest position (order parameter) changes abruptly and the system undergoes a first-order phase transition. When the external force is cycled at different rates, the extension given by the oscillator position exhibits a hysteresis cycle at high loading rates, whereas it moves reversibly over the equilibrium force-extension curve at very low loading rates. Under constant force, the logarithm of the residence time at the stable and metastable oscillator rest position is proportional to F-F(c) as in an Arrhenius law.

Human decidual stromal cells secrete C-X-C motif chemokine 13, express B cell-activating factor and rescue B lymphocytes from apoptosis: distinctive characteristics of follicular dendritic cells.

BACKGROUND: Decidual stromal cells (DSCs) have classically been considered fibroblastic cells, although their function, cell lineage and origin are not fully understood. We previously demonstrated that human DSCs showed similarities with follicular dendritic cells (FDCs): DSCs expressed FDC-associated antigens, both types of cells are contractile and both are related to mesenchymal stem cells (MSCs). To further characterize DSCs, we investigated whether DSCs and FDCs share any distinctive phenotypical and functional characteristics. METHODS: Human FDC lines were obtained from tonsillectomy samples, human DSC lines from elective termination of pregnancy samples and human MSC lines from bone marrow aspirates. We isolated DSC, FDC and MSC lines and compared their characteristics with flow cytometry and enzyme-linked immunosorbent assay. Cell lines were cultured with tumour necrosis factor (TNF) and lymphotoxin (LT)α(1)ß(2), cytokines involved in FDC differentiation. Cell lines were also differentiated in culture after exposure to progesterone and cAMP, factors involved in the differentiation (decidualization) of DSC. RESULTS: Like MSCs, DSCs and FDCs expressed MSC-associated antigens (CD10, CD29, CD54, CD73, CD106, α-smooth muscle actin and STRO-1) and lacked CD45 expression, and all three types of cell line showed increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) when cultured TNF and LTα(1)ß(2). DSCs and FDCs, however, exhibited characteristics not observed in MSCs: DSCs expressed FDC-associated antigens CD14, CD21 and CD23, B cell-activating factor and secreted C-X-C motif chemokine 13. Moreover, DSC lines but not MSC lines inhibited the spontaneous apoptosis of B lymphocytes, a typical functional attribute of FDC. During culture with progesterone and cAMP, FDCs, like DSCs but in contrast to MSCs, changed their morphology from a fibroblastic to a rounder shape, and cells secreted prolactin. CONCLUSIONS: Our results suggest that DSCs and FDCs share a common precursor in MSCs but this precursor acquires new capacities when it homes to peripheral tissues. We discuss these shared properties in the context of immune-endocrine regulation during pregnancy.

Ripples in a string coupled to Glauber spins.

Each oscillator in a linear chain (a string) interacts with a local Ising spin in contact with a thermal bath. These spins evolve according to Glauber dynamics. Below a critical temperature, there appears an equilibrium, time-independent, rippled state in the string that is accompanied by a nonzero spin polarization. On the other hand, the system is shown to form "metastable," nonequilibrium long-lived ripples in the string for slow spin relaxation. The system vibrates rapidly about these quasistationary states, which can be described as snapshots of a coarse-grained stroboscopic map. For moderate observation times, ripples are observed irrespective of the final thermodynamically stable state (rippled or not). Interestingly, the system can be considered as a "minimal" model to understand rippling in clamped graphene sheets.

Apoptotic DC-SIGN+ cells in normal human decidua.

BACKGROUND: Normal pregnancy and spontaneous abortion in humans and mice are associated with immune responses. The decidua harbors dendritic cells identifiable in humans by their expression of DC-SIGN. Because dendritic cells are essential for immune response regulation, decidual DC-SIGN+ cells may play a role in normal or pathological pregnancy outcomes. Previous reports suggested that DC interact with NK cells in decidua, although the functional significance of this phenomenon remains unknown. OBJECTIVE: We studied the presence of conjugates of DC-SIGN+ cells with CD56+ NK cells in normal human decidua. METHODS: Conjugates of DC-SIGN+ cells with CD56+ NK cells were studied in leukocyte suspensions of normal human decidua (6-11 weeks) by flow cytometry and confocal microscopy. The presence of apoptotic cells was determined by the TUNEL assay, incubation with annexin V and confocal microscopy in decidual leukocyte suspensions and by the TUNEL assay in decidual sections. RESULTS: We observed conjugates of decidual DC-SIGN+ cells with CD56+ NK cells (40.2±26.1% of all the DC-SIGN+ cells by flow cytometry and 52.3±10.2% by confocal microscopy). We also found that a proportion of DC-SIGN+ cells were in apoptosis, since they were TUNEL+ (40.2±7.2% of all DC-SIGN+ cells in decidual sections) and annexin V+ (34.4±15.2% in leukocyte suspensions). And sorted DC-SIGN+ cells had multilobulated nuclei. CONCLUSIONS: The conjugates of decidual DC-SIGN+ cells with CD56+ NK cells strongly suggest that these latter cells induce apoptosis in DC-SIGN+ cells during normal pregnancy. We discuss this possibility in the context of maternal-fetal tolerance.

Use of Poultry Manure Combined with Soil Solarization as a Control Method for Meloidogyne incognita in Carnation.

The effectiveness of a combination of soil solarization and poultry manure (raw or pelletized) amendments for the control of root-knot nematode (Meloidogyne incognita) was tested in carnation (Dianthus caryophyllus) crops grown in in-ground beds under plastic-covered greenhouse conditions in southern Spain. Our trials demonstrated that soil solarization alone did not provide sufficient control of root-knot nematode, because the carnation growing season in this region only partly coincides with the most effective period for solarization, resulting in an insufficient duration of treatment during a key period for effectiveness. Chemical fumigation with 1,3-dichloropropene + chloropicrin prior to planting was effective in reducing nematode population densities in soil. Its effects spanned 9 months after planting, resulting in acceptable crop yields. In comparison, the combination of soil solarization and raw or pelletized poultry manure was slightly less effective than chemical fumigation for control of this pathogen but crop yields after 9 months were similar. However, the higher root gall indices observed after 9 months, in comparison with chemically fumigated plots, indicated the need for a reapplication of the organic manure treatment at the start of each successive growing season.