Entropic transport in confined media: a challenge for computational studies in biological and soft-matter systems

Transport in small-scale biological and soft-matter systems typically occurs under confinement conditions in which particles proceed through obstacles and irregularities of the boundaries that may significantly alter their trajectories. A transport model that assimilates the confinement to the presence of entropic barriers provides an efficient approach to quantify its effect on the particle current and the diffusion coefficient. We review the main peculiarities of entropic transport and treat two cases in which confinement effects play a crucial role, with the appearance of emergent properties. The presence of entropic barriers modifies the mean first-passage time distribution and therefore plays a very important role in ion transport through micro- and nano-channels. The functionality of molecular motors, modeled as Brownian ratchets, is strongly affected when the motor proceeds in a confined medium that may constitute another source of rectification. The interplay between ratchet and entropic rectification gives rise to a wide variety of dynamical behaviors, not observed when the Brownian motor proceeds in an unbounded medium. Entropic transport offers new venues of transport control and particle manipulation and new ways to engineer more efficient devices for transport at the nanoscale.

Sulfur isotope variations from orebody to hand-specimen scale at the Mezica lead-zinc deposit, Slovenia: a predominantly biogenic pattern

The Mississippi Valley-type (MVT) Pb-Zn ore district at Mezica is hosted by Middle to Upper Triassic platform carbonate rocks in the Northern Karavanke/Drau Range geotectonic units of the Eastern Alps, northeastern Slovenia. The mineralization at Mezica covers an area of 64 km(2) with more than 350 orebodies and numerous galena and sphalerite occurrences, which formed epigenetically, both conformable and discordant to bedding. While knowledge on the style of mineralization has grown considerably, the origin of discordant mineralization is still debated. Sulfur stable isotope analyses of 149 sulfide samples from the different types of orebodies provide new insights on the genesis of these mineralizations and their relationship. Over the whole mining district, sphalerite and galena have delta(34)S values in the range of -24.7 to -1.5% VCDT (-13.5 +/- 5.0%) and -24.7 to -1.4% (-10.7 +/- 5.9%), respectively. These values are in the range of the main MVT deposits of the Drau Range. All sulfide delta(34)S values are negative within a broad range, with delta(34)S(pyrite) < delta(34)S(sphalerite) < delta(34)S(galena) for both conformable and discordant orebodies, indicating isotopically heterogeneous H(2)S in the ore-forming fluids and precipitation of the sulfides at thermodynamic disequilibrium. This clearly supports that the main sulfide sulfur originates from bacterially mediated reduction (BSR) of Middle to Upper Triassic seawater sulfate or evaporite sulfate. Thermochemical sulfate reduction (TSR) by organic compounds contributed a minor amount of (34)S-enriched H(2)S to the ore fluid. The variations of delta(34)S values of galena and coarse-grained sphalerite at orefield scale are generally larger than the differences observed in single hand specimens. The progressively more negative delta(34)S values with time along the different sphalerite generations are consistent with mixing of different H(2)S sources, with a decreasing contribution of H(2)S from regional TSR, and an increase from a local H(2)S reservoir produced by BSR (i.e., sedimentary biogenic pyrite, organo-sulfur compounds). Galena in discordant ore (-11.9 to -1.7%; -7.0 +/- 2.7%, n=12) tends to be depleted in (34)S compared with conformable ore (-24.7 to -2.8%, -11.7 +/- 6.2%, n=39). A similar trend is observed from fine-crystalline sphalerite I to coarse open-space filling sphalerite II. Some variation of the sulfide delta(34)S values is attributed to the inherent variability of bacterial sulfate reduction, including metabolic recycling in a locally partially closed system and contribution of H(2)S from hydrolysis of biogenic pyrite and thermal cracking of organo-sulfur compounds. The results suggest that the conformable orebodies originated by mixing of hydrothermal saline metal-rich fluid with H(2)S-rich pore waters during late burial diagenesis, while the discordant orebodies formed by mobilization of the earlier conformable mineralization.

Audit report on the Iowa Lottery Authority, a component unit of the State of Iowa, as of and for the year ended June 30, 2015

Audit report on the Iowa Lottery Authority, a component unit of the State of Iowa, as of and for the year ended June 30, 2015

Ville, tourisme et transport : la Compagnie du chemin de fer Lausanne-Ouchy (1869-1914)

Inauguré le 16 mars 1877, le chemin de fer entre Lausanne et le petit port touristique d'Ouchy constitue une entreprise aux dimensions techniques et financières pharaoniques. Premier funiculaire à câble de Suisse, le Lausanne-Ouchy est aussi le premier au monde à être équipé d'un système de traction hydraulique. L'objectif de cette contribution n'est toutefois pas d'analyser les conditions de réalisation de cet exploit technologique, mais la naissance et l'évolution d'une compagnie de transport étroitement liée à l'établissement du système touristique lausannois. La demande de mobilité créée par l'afflux d'étrangers et l'apport des milieux touristiques au capital sont en effet indispensables à la création et à la survie de l'entreprise, dont la santé financière reste longtemps problématique. En retour, le funiculaire modifie le système de transport régional et national, donnant d'importantes impulsions au développement touristique.

Audit report of Iowa State University of Science and Technology, Ames, Iowa, (Iowa State University) and its discretely presented component unit as of and for the years ended June 30, 2015 and 2014

Audit report of Iowa State University of Science and Technology, Ames, Iowa, (Iowa State University) and its discretely presented component unit as of and for the years ended June 30, 2015 and 2014

A Threat to a Virtual Hand Elicits Motor Cortex Activation

We report an experiment where participants observed an attack on their virtual body as experienced in an immersive virtual reality (IVR) system. Participants sat by a table with their right hand resting upon it. In IVR, they saw a virtual table that was registered with the real one, and they had a virtual body that substituted their real body seen from a first person perspective. The virtual right hand was collocated with their real right hand. Event-related brain potentials were recorded in two conditions, one where the participant"s virtual hand was attacked with a knife and a control condition where the knife only struck the virtual table. Significantly greater P450 potentials were obtained in the attack condition confirming our expectations that participants had a strong illusion of the virtual hand being their own, which was also strongly supported by questionnaire responses. Higher levels of subjective virtual hand ownership correlated with larger P450 amplitudes. Mu-rhythm event-related desynchronization in the motor cortex and readiness potential (C3C4) negativity were clearly observed when the virtual hand was threatened as would be expected, if the real hand was threatened and the participant tried to avoid harm. Our results support the idea that event-related potentials may provide a promising non-subjective measure of virtual embodiment. They also support previous experiments on pain observation and are placed into context of similar experiments and studies of body perception and body ownership within cognitive neuroscience.

Effects of verapamil and ryanodine on activity of the embryonic chick heart during anoxia and reoxygenation.

Perturbations of the trans-sarcolemmal and sarcoplasmic Ca2+ transport contribute to the abnormal myocardial activity provoked by anoxia and reoxygenation. Whether Ca2+ pools of the extracellular compartment and sarcoplasmic reticulum (SR) are involved to the same extent in the dysfunction of the anoxic-reoxygenated immature heart has not been investigated. Spontaneously contracting hearts isolated from 4-day-old chick embryos were submitted to repeated anoxia (1 min) followed by reoxygenation (5 min). Heart rate, atrioventricular propagation velocity, ventricular shortening, velocities of contraction and relaxation, and incidence of arrhythmias were studied, recorded continuously. Addition of verapamil (10 nM), which blocks selectively sarcolemmal L-type Ca2+ channels, was expected to protect against excessive entry of extracellular Ca2+, whereas addition of ryanodine (10 nM), which opens the SR Ca2+ release channel, was expected to increase cytosolic Ca2+ concentration. Verapamil (a) had no dromotropic effect by contrast to adult heart, (b) attenuated ventricular contracture induced by repeated anoxia, (c) shortened cardioplegia induced by reoxygenation, and (d) had remarkable antiarrhythmic properties during reoxygenation specially. On the other hand, ryanodine potentiated markedly arrhythmias both during anoxia and at reoxygenation. Thus despite its immaturity, the SR seems to be functional early in the developing chick heart and involved in the reversible dysfunction induced by anoxia-reoxygenation. Moreover, Ca2+ entry through L-type channels appears to worsen arrhythmias especially during reoxygenation. These findings show that the Ca2+-handling systems involved in irregular activity in immature heart, such as the embryonic chick heart, may differ from those in the adult.

Use of hand-to-hand impedancemetry to predict body composition of African women as measured by air displacement plethysmography.

OBJECTIVES: To test the validity of a simple, rapid, field-adapted, portable hand-held impedancemeter (HHI) for the estimation of lean body mass (LBM) and percentage body fat (%BF) in African women, and to develop specific predictive equations. DESIGN: Cross-sectional observational study. SETTINGS: Dakar, the capital city of Senegal, West Africa. SUBJECTS: A total sample of 146 women volunteered. Their mean age was of 31.0 y (s.d. 9.1), weight 60.9 kg (s.d. 13.1) and BMI 22.6 kg/m(2) (s.d. 4.5). METHODS: Body composition values estimated by HHI were compared to those measured by whole body densitometry performed by air displacement plethysmography (ADP). The specific density of LBM in black subjects was taken into account for the calculation of %BF from body density. RESULTS: : Estimations from HHI showed a large bias (mean difference) of 5.6 kg LBM (P<10(-4)) and -8.8 %BF (P<10(-4)) and errors (s.d. of the bias) of 2.6 kg LBM and 3.7 %BF. In order to correct for the bias, specific predictive equations were developed. With the HHI result as a single predictor, error values were of 1.9 kg LBM and 3.7 %BF in the prediction group (n=100), and of 2.2 kg LBM and 3.6 %BF in the cross-validation group (n=46). Addition of anthropometrical predictors was not necessary. CONCLUSIONS: The HHI analyser significantly overestimated LBM and underestimated %BF in African women. After correction for the bias, the body compartments could easily be estimated in African women by using the HHI result in an appropriate prediction equation with a good precision. It remains to be seen whether a combination of arm and leg impedancemetry in order to take into account lower limbs would further improve the prediction of body composition in Africans.

Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy.

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150 mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17 mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

The Wnt receptor FZD1 mediates chemoresistance in neuroblastoma through activation of the Wnt/beta-catenin pathway.

The development of chemoresistance represents a major obstacle in the successful treatment of cancers such as neuroblastoma (NB), a particularly aggressive childhood solid tumour. The mechanisms underlying the chemoresistant phenotype in NB were addressed by gene expression profiling of two doxorubicin (DoxR)-resistant vs sensitive parental cell lines. Not surprisingly, the MDR1 gene was included in the identified upregulated genes, although the highest overexpressed transcript in both cell lines was the frizzled-1 Wnt receptor (FZD1) gene, an essential component of the Wnt/beta-catenin pathway. FZD1 upregulation in resistant variants was shown to mediate sustained activation of the Wnt/beta-catenin pathway as revealed by nuclear beta-catenin translocation and target genes transactivation. Interestingly, specific micro-adapted short hairpin RNA (shRNAmir)-mediated FZD1 silencing induced parallel strong decrease in the expression of MDR1, another beta-catenin target gene, revealing a complex, Wnt/beta-catenin-mediated implication of FZD1 in chemoresistance. The significant restoration of drug sensitivity in FZD1-silenced cells confirmed the FZD1-associated chemoresistance. RNA samples from 21 patient tumours (diagnosis and postchemotherapy), showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance. Our data represent the first implication of the Wnt/beta-catenin pathway in NB chemoresistance and identify potential new targets to treat aggressive and resistant NB.

Effects of prior short multiple-sprint exercises with different intersprint recoveries on the slow component of oxygen uptake during high-intensity exercise.

This study compares the effects of two short multiple-sprint exercise (MSE) (6 × 6 s) sessions with two different recovery durations (30 s or 180 s) on the slow component of oxygen uptake ([Formula: see text]O(2)) during subsequent high-intensity exercise. Ten male subjects performed a 6-min cycling test at 50% of the difference between the gas exchange threshold and [Formula: see text]O(2peak) (Δ50). Then, the subjects performed two MSEs of 6 × 6 s separated by two intersprint recoveries of 30 s (MSE(30)) and 180 s (MSE(180)), followed 10 min later by the Δ50 (Δ50(30) and Δ50(180), respectively). Electromyography (EMG) activities of the vastus medialis and lateralis were measured throughout each exercise bout. During MSE(30), muscle activity (root mean square) increased significantly (p ≤ 0.04), with a significant leftward-shifted median frequency of the power density spectrum (MDF; p ≤ 0.01), whereas MDF was significantly rightward-shifted during MSE(180) (p = 0.02). The mean [Formula: see text]O(2) value was significantly higher in MSE(30) than in MSE(180) (p < 0.001). During Δ50(30), [Formula: see text]O(2) and the deoxygenated hemoglobin ([HHb]) slow components were significantly reduced (-27%, p = 0.02, and -34%, p = 0.003, respectively) compared with Δ50. There were no significant modifications of the [Formula: see text]O(2) slow component in Δ50(180) compared with Δ50 (p = 0.32). The neuromuscular and metabolic adaptations during MSE(30) (preferential activation of type I muscle fibers evidenced by decreased MDF and a greater aerobic metabolism contribution to the required energy demands), but not during MSE(180), may lead to reduced [Formula: see text]O(2) and [HHb] slow components, suggesting an alteration in motor units recruitment profile (i.e., change in the type of muscle fibers recruited) and (or) an improved muscle O(2) delivery during subsequent exercise.