Pedestrian flow in two dimensions: Optimal psychological stress leads to less evacuation time and decongestion.

Collective motion is an innate ability of all living systems, which depends on physiological and psychosocial factors in the case of humans. Such a collective organization is becoming of great interest in collective motion in human crowds. Using a cellular automaton (CA) simulation model, we demonstrate that emergency egress from a two-dimensional corridor with optimal stress leads to less evacuation time and efficient mass evacuations. We study how three types of stress (i.e., mild stress, optimal stress, and anxiety) described in the literature have a significant impact on the collective dynamics. We found that low-stress levels could decrease the evacuation time in an entire occupied room since agents choose alternative routes rather than the shortest path to the exit and display cooperative behavior. Therefore, the combination of mild and optimal stress can lead to efficient evacuations. Also CA simulations may be used to find safer and more efficient ways to conduct mass evacuation procedures.

Simulating the city traffic complexity induced by traffic light periods.

We revisited the global traffic light optimization problem through a cellular automata model, which allows us to address the relationship between the traffic lights and car routing. We conclude that both aspects are not separable. Our results show that a good routing strategy weakens the importance of the traffic light period for mid-densities, thus limiting the parameter space where such optimization is relevant. This is confirmed by analyzing the travel time normalized by the shortest path between the origin and destination. As an unforeseen result, we report what seems to be a power-law distribution for such quantities, indicating that the travel time distribution slowly decreases for long travel times. The power-law exponent depends on the density, traffic light period, and routing strategy, which in this case is parametrized by the tendency of agents to abandon a route if it becomes stagnant. These results could have relevant consequences on how to improve the overall traffic efficiency in a particular city, thus providing insight into useful measurements, which are often counter-intuitive, which may be valuable to traffic controllers that operate through traffic light periods and phases.

Does following optimized routes for single cars improve car routing?

We study the impact of deserting a pre-established path, determined by a navigation software, on the overall city traffic. To do so, we consider a cellular automaton model for vehicular traffic, where the cars travel between two randomly assigned points in the city following three different navigation strategies based on the minimization of the individual paths or travel times. We found, in general, that, above a critical car density, the transport improves in all strategies if we decrease the time that the vehicles persist in trying to follow a particular strategy when a route is blocked, namely, the mean flux increases, the individual travel times decrease, and the fluctuations of density in the streets decrease; consequently, deserting helps prevent traffic jams.

Growth of Ni nanoclusters on irradiated graphene: a molecular dynamics study.

We studied the soft landing of Ni atoms on a previously damaged graphene sheet by means of molecular dynamics simulations. We found a monotonic decrease of the cluster frequency as a function of its size, but few big clusters comprise an appreciable fraction of the total number of Ni atoms. The aggregation of Ni atoms is also modeled by means of a simple phenomenological model. The results are in clear contrast with the case of hard or energetic landing of metal atoms, where there is a tendency to form mono-disperse metal clusters. This behavior is attributed to the high diffusion of unattached Ni atoms, together with vacancies acting as capture centers. The findings of this work show that a simple study of the energetics of the system is not enough in the soft landing regime, where it is unavoidable to also consider the growth process of metal clusters.

Pharyngeal pouch surgery: a combined open and endoscopic approach.

Pharyngeal pouches are common, particularly in the elderly population, in whom they can cause significant morbidity. The advanced age of many patients and existing comorbidities mean that in some cases neither open nor endoscopic pouch stapling is possible. We present a technique of combined open and endoscopic pharyngeal pouch surgery, which may be used when other therapeutic options are limited.

Optimization of photoluminescence of Y(2)O(3):Eu and Gd(2)O(3):Eu phosphors synthesized by thermolysis of 2,4-pentanedione complexes.

Spherical shaped nanoparticles of series Y(2 - x)Eu(x)O(3) (x = 0.06, 0.10, 0.20, and 2) and Gd(2 - x)Eu(x)O(3) (x = 0.06, 0.10) were prepared by thermolysis of 2,4-pentanedione complexes of Y, Gd, and Eu. The bixbyite phase of Gd(2 - x)Eu(x)O(3) samples was formed at 500 degrees C, whereas the thermal decomposition of Y and Eu complexes' mixtures occurred at higher temperatures. Linearity in the concentration dependence on lattice parameter confirmed the formation of solid solutions. The distribution of Eu(3+) in Gd(2 - x)Eu(x)O(3) was changed with thermal annealing: in the as-prepared sample (x = 0.10) the distribution was preferential at C(3i) sites while in the annealed samples, Eu(3+) were distributed at both C(2) and C(3i) sites. Rietveld refinement of site occupancies as well as emission spectra showed a random distribution of cations in Y(2 - x)Eu(x)O(3). The photoluminescence (PL) measurements of the sample showed red emission with the main peak at 614 nm ((5)D(0)-(7)F(2)). The PL intensity increased with increasing concentration of Eu(3+) in both series. Infrared excitation was required to obtain good Raman spectra. The linear dependence of the main Raman peak wavenumber offers a non-destructive method for monitoring the substitution level and its homogeneity at the micron scale.

Characterization of the nontrivial and chaotic behavior that occurs in a simple city traffic model.

We explore in detail the nontrivial and chaotic behavior of the traffic model proposed by Toledo et al. [Phys. Rev. E 70, 016107 (2004)] due to the richness of behavior present in the model, in spite of the fact that it is a minimalistic representation of basic city traffic dynamics. The chaotic behavior, previously shown for a given lower bound in acceleration/brake ratio, is examined more carefully and the region in parameter space for which we observe this nontrivial behavior is found. This parameter region may be related to the high sensitivity of traffic flow that eventually leads to traffic jams. Approximate scaling laws are proposed.

Resonance, criticality, and emergence in city traffic investigated in cellular automaton models.

The complex behavior that occurs when traffic lights are synchronized is studied for a row of interacting cars. The system is modeled through a cellular automaton. Two strategies are considered: all lights in phase and a "green wave" with a propagating green signal. It is found that the mean velocity near the resonant condition follows a critical scaling law. For the green wave, it is shown that the mean velocity scaling law holds even for random separation between traffic lights and is not dependent on the density. This independence on car density is broken when random perturbations are considered in the car velocity. Random velocity perturbations also have the effect of leading the system to an emergent state, where cars move in clusters, but with an average velocity which is independent of traffic light switching for large injection rates.

Optimal control in a noisy system.

We describe a simple method to control a known unstable periodic orbit (UPO) in the presence of noise. The strategy is based on regarding the control method as an optimization problem, which allows us to calculate a control matrix A. We illustrate the idea with the Rossler system, the Lorenz system, and a hyperchaotic system that has two exponents with positive real parts. Initially, a UPO and the corresponding control matrix are found in the absence of noise in these systems. It is shown that the strategy is useful even if noise is added as control is applied. For low noise, it is enough to find a control matrix such that the maximum Lyapunov exponent lambda(max)<0, and with a single non-null entry. If noise is increased, however, this is not the case, and the full control matrix A may be required to keep the UPO under control. Besides the Lyapunov spectrum, a characterization of the control strategies is given in terms of the average distance to the UPO and the control effort required to keep the orbit under control. Finally, particular attention is given to the problem of handling noise, which can affect considerably the estimation of the UPO itself and its exponents, and a cleaning strategy based on singular value decomposition was developed. This strategy gives a consistent manner to approach noisy systems, and may be easily adapted as a parametric control strategy, and to experimental situations, where noise is unavoidable.

Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers.

Affymetrix U133plus2 GeneChips were used to profile 59 head and neck squamous cell cancers. A hypoxia metagene was obtained by analysis of genes whose in vivo expression clustered with the expression of 10 well-known hypoxia-regulated genes (e.g., CA9, GLUT1, and VEGF). To minimize random aggregation, strongly correlated up-regulated genes appearing in >50% of clusters defined a signature comprising 99 genes, of which 27% were previously known to be hypoxia associated. The median RNA expression of the 99 genes in the signature was an independent prognostic factor for recurrence-free survival in a publicly available head and neck cancer data set, outdoing the original intrinsic classifier. In a published breast cancer series, the hypoxia signature was a significant prognostic factor for overall survival independent of clinicopathologic risk factors and a trained profile. The work highlights the validity and potential of using data from analysis of in vitro stress pathways for deriving a biological metagene/gene signature in vivo.

Universal and nonuniversal features in a model of city traffic.

The complex behavior that occurs when traffic lights are synchronized is studied. Two strategies are considered: all lights in phase, and a "green wave" with a propagating green signal. It is found that traffic variables such as traveling time, velocity, and fuel consumption, near resonance, follow critical scaling laws. For the green wave, it is shown that time and velocity scaling laws hold even for random separation between traffic lights. These results suggest the concept of transient resonances, which can be induced by adaptively changing the phase of traffic lights. This may be important to consider when designing strategies for traffic control in cities, where short trajectories, and thus transient solutions, are likely to be relevant.

The relation between hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha expression with anemia and outcome in surgically treated head and neck cancer.

BACKGROUND: Hypoxia promotes tumorigenesis through the hypoxia-inducible factor (HIF) pathway. There are 2 main homologues of the regulatory proteins, HIF-1alpha and HIF-2alpha, which have different effects in genetic knock-out experiments. Anemia may contribute to hypoxia by reducing oxygen delivery, but it is not known whether this influences HIF-alpha expression in tumors. METHODS: The expression of HIF-1alpha, HIF-2alpha, carbonic anhydrase-9 (CA-9), and peripheral hemoglobin (Hb) levels in 151 patients who underwent surgery for head and neck squamous cell carcinoma (HNSCC) were analyzed and related to outcome. RESULTS: High HIF-1alpha was expressed in 45 of 140 tumors (30%), HIF-2alpha was expressed in 21 of 139 tumors (14%), and CA-9 was expressed in 56 of 149 tumors (62%). There was a positive correlation between HIF-1alpha expression and HIF-2alpha expression (P =.0001). HIF-1alpha alone was associated with a worse disease-specific survival (DSS) (P =.05) and disease-free survival (DFS) (P = .03) in multivariate analyses. Nine percent of tumors expressed both high HIF-1alpha and high HIF-2alpha. High HIF-1alpha/high HIF-2alpha expression was an independent prognostic factors in DSS (P = .04) and DFS (P =.005) in multivariate analyses. There was no correlation noted between Hb and HIF-1alpha, HIF-2alpha, or CA-9. CONCLUSIONS: HIF-1alpha alone was correlated with DSS and DFS. The additive effect of HIF-2alpha on poor prognosis suggested that different pathways may be regulated by HIF-2alph. Anemia that was not related to HIF-alpha expression suggests that tumor intrinsic factors regulate HIF-alpha therefore, anemia may be a surrogate marker for other factors that affect outcome.

Relation of erythropoietin and erythropoietin receptor expression to hypoxia and anemia in head and neck squamous cell carcinoma.

PURPOSE: The use of erythropoietin in head and neck squamous cell carcinoma (HNSCC) has been associated with poor survival. This study examines the protein and mRNA expression of erythropoietin and erythropoietin receptor in HNSCC and their relation to hypoxia, hemoglobin (Hb), and clinical outcome. EXPERIMENTAL DESIGN: The immunohistochemical expression of erythropoietin and erythropoietin receptor was assessed in 151 cases of HNSCC. Expression was compared with the hypoxia-dependent proteins hypoxia-inducible factor-1alpha (HIF-1alpha) and carbonic anhydrase-9 (CA-9) and correlated with clinical outcome. The mRNA expression of erythropoietin and erythropoietin receptor was measured in paired samples of HNSCC. RESULTS: Erythropoietin and erythropoietin receptor were expressed in 95% and 99% of tumors, respectively. Using a weighed expression score, there was a positive correlation between erythropoietin and erythropoietin receptor expression (r = 0.18, P = 0.03). HIF-1alpha (r = 0.38, P < 0.01) and CA-9 (r = 0.26, P = 0.002) correlated with erythropoietin expression, but there was no correlation with erythropoietin receptor. No correlation was found between Hb and erythropoietin (r = 0.07, P = 0.36) or erythropoietin receptor (r = -0.02, P = 0.8), and no survival difference between high and low erythropoietin or erythropoietin receptor expression (P = 0.59 and P = 0.98, respectively). The mRNA expression of erythropoietin (P = 0.03) but not erythropoietin receptor (P = 0.62) was significantly increased in 11 paired samples of HNSCC. CONCLUSION: In vivo, the HIF pathway regulates erythropoietin at the mRNA level but not erythropoietin receptor expression in HNSCC. Anemia does not seem to influence the hypoxic microenvironment of tumors sufficiently to alter the expression of erythropoietin. The effects of exogenous erythropoietin may be acting via receptors expressed on tumor cells in vivo, or on vascular cells, which also express the pathway.

Modeling traffic through a sequence of traffic lights.

We introduce a microscopic traffic model, based on kinematic behavior, which consists of a single vehicle traveling through a sequence of traffic lights that turn on and off with a specific frequency. The reconstructed function that maps the state of the vehicle from light to light displays complex behavior for certain conditions. This chaotic behavior, which arises by the discontinuous nature of the map, displays an essential ingredient in traffic patterns and could be of relevance in studying traffic situations.

A randomized prospective crossover trial of amlodipine in pediatric hypertension.

Amlodipine has potential advantages in children since it can be dissolved into a liquid preparation and has a long elimination half-life, allowing for once-daily administration. The objective of this study was to compare the efficacy and compliance of amlodipine with that of standard long-acting calcium channel blockers (felodipine or nifedipine) in hypertensive children. A randomized, prospective, crossover study of 11 hypertensive children (9-17 years of age, 10 renal transplant patients) was performed with electronic monitoring of compliance. Each treatment arm was 30 days. No significant differences were observed in mean systolic (SBP) and diastolic blood pressures (DBP) between amlodipine and the other calcium channel blockers. Using 24-h blood pressure monitoring there were no significant differences over each drug treatment period in both mean day-time and night-time SBP and DBP. Patient compliance was similar in both the amlodipine and the nifedipine/felodipine treatment periods. These data suggest that amlodipine is as effective in pediatric nephrology patients as nifedipine and felodipine. Amlodipine may be optimally suited for treatment of young children because at present it is the only calcium channel blocker which can be administered once daily as a liquid preparation.

Efficacy of amlodipine in pediatric bone marrow transplant patients.

The calcium antagonist amlodipine may have the potential for expanded use in children owing to its physiochemistry and pharmacokinetic profile that facilitates once-daily dosing in a liquid formulation. Its safety and efficacy have not been previously evaluated in children. A retrospective analysis of 15 pediatric bone marrow transplant patients who had amlodipine incorporated into their antihypertensive drug regimen reveals significantly lower blood pressure as compared with baseline therapy (123.5+/-2.1 mmHg and 117.2+/-2.2 mmHg, systolic blood pressure before and during amlodipine, P<0.05; 81.5+/-1.8 mmHg and 75.5+/-2.6 mmHg, diastolic blood pressure before and during amlodipine, P<0.05). Amlodipine provided improved blood pressure control in this cohort and may provide a valuable pharmacologic alternative for treatment of pediatric hypertension.

EVA: a new theoretically based molecular descriptor for use in QSAR/QSPR analysis.

A new descriptor of molecular structure, EVA, for use in the derivation of robustly predictive QSAR relationships is described. It is based on theoretically derived normal coordinate frequencies, and has been used extensively and successfully in proprietary chemical discovery programmes within Shell Research. As a result of informal dissemination of the methodology, it is now being used successfully in related areas such as pharmaceutical drug discovery. Much of the experimental data used in development remain proprietary, and are not available for publication. This paper describes the method and illustrates its application to the calculation of nonproprietary data, log P(ow), in both explanatory and predictive modes. It will be followed by other publications illustrating its application to a range of data derived from biological systems.

Indobufen in secondary prevention of transient ischaemic attack. Multicentre Ischaemic Attack Study Group.

The secondary prevention of transient ischaemic attacks was assessed in 270 patients treated orally with 100 mg indobufen given twice daily for 12 months. After 1 month's treatment, the average number and average incidence of transient ischaemic attacks were reduced significantly (P less than 0.001) and remained suppressed throughout the treatment period. Treatment was interrupted in 17 patients: in two because of side-effects (gastric disturbances); in 10 because of fatal events (six completed strokes, two myocardial infarcts and two unrelated deaths); and in five due to poor protocol compliance. Progression to reversible ischaemic neurological deficit occurred in five patients. Most side-effects were mild and transient, mainly occurring in the first month of treatment. Overall, indobufen was judged to have good efficacy and safety by both patients and physicians.