Colored noise in spatially extended systems

We study the effects of time and space correlations of an external additive colored noise on the steady-state behavior of a time-dependent Ginzburg-Landau model. Simulations show the existence of nonequilibrium phase transitions controlled by both the correlation time and length of the noise. A Fokker-Planck equation and the steady probability density of the process are obtained by means of a theoretical approximation.

Glassiness in a model without energy barriers

We propose a microscopic model without energy barriers in order to explain some generic features observed in structural glasses. The statics can be exactly solved while the dynamics has been clarified using Monte Carlo calculations. Although the model has no thermodynamic transition, it captures some of the essential features of real glasses, i.e., extremely slow relaxation, time dependent hysteresis effects, anomalous increase of the relaxation time, and aging. This suggests that the effect of entropy barriers can be an important ingredient to account for the behavior observed in real glasses.

The 2013 Arvid Wretlind lecture: evolving concepts in parenteral nutrition.

Fifty years after the clinical introduction of total parenteral nutrition (TPN) the Arvid Wretlind lecture is an opportunity to critically analyse the evolution and changes that have marked its development and clinical use. The standard crystalline amino acid solutions, while devoid of side effects, remain incomplete regarding their composition (e.g. glutamine). Lipid emulsions have evolved tremendously and are now included in bi- and tri-compartmental feeding bags enabling a true "total" PN provided daily micronutrients are prescribed. The question of exact individual energy, macro- and micro-nutrient requirements is still unsolved. Many complications attributed to TPN are in fact the consequence of under- or over-feeding: the historical hyperalimentation concept is the main cause, along with the use of fixed weight based predictive equations (incorrect in 70% of the critically ill patients). In the late 80's many complications (hyperglycemia, sepsis, fatty liver, exacerbation of inflammation, mortality) were attributed to TPN leading to its near abandon in favour of enteral nutrition (EN). Enteral feeding, although desirable for many reasons, is difficult causing a worldwide recurrence of malnutrition by insufficient feed delivery. TPN indications have evolved towards its use either alone or in combination with EN: several controversial trials published 2011-13 have investigated TPN timing, an issue which is not yet resolved. The initiation time varies according to the country between admission (Australia and Israel), day 4 (Swiss) and day 7 (Belgium, USA). The most important issue may prove to be and individualized and time dependent prescription of feeding route, energy and substrates.

BK virus infection in hematopoietic stem cell transplant recipients: frequency, risk factors, and association with postengraftment hemorrhagic cystitis.

Blood samples from 132 consecutive hematopoietic stem cell transplant recipients were obtained and tested weekly for BK virus DNA by use of quantitative real-time PCR. Forty-four patients (33%) developed BK viremia at a median of 41 days (range, 9-91 days) after transplantation. Patients with hemorrhagic cystitis that occurred after platelet engraftment had higher levels of viremia than did patients without hemorrhagic cystitis (median, 9.7x10(3) vs. 0 copies/mL; P=.008) and patients with hemorrhagic cystitis that occurred before platelet engraftment (median, 9.7x10(3) vs. 0 copies/mL; P=.0006). BK viremia also was strongly associated with postengraftment hemorrhagic cystitis in a time-dependent analysis (P=.004).

Epac contributes to cardiac hypertrophy and amyloidosis induced by radiotherapy but not fibrosis.

BACKGROUND: Cardiac toxicity is a side-effect of anti-cancer treatment including radiotherapy and this translational study was initiated to characterize radiation-induced cardiac side effects in a population of breast cancer patients and in experimental models in order to identify novel therapeutic target. METHODS: The size of the heart was evaluated in CO-HO-RT patients by measuring the Cardiac-Contact-Distance before and after radiotherapy (48months of follow-up). In parallel, fibrogenic signals were studied in a severe case of human radiation-induced pericarditis. Lastly, radiation-induced cardiac damage was studied in mice and in rat neonatal cardiac cardiomyocytes. RESULTS: In patients, time dependent enhancement of the CCD was measured suggesting occurrence of cardiac hypertrophy. In the case of human radiation-induced pericarditis, we measured the activation of fibrogenic (CTGF, RhoA) and remodeling (MMP2) signals. In irradiated mice, we documented decreased contractile function, enlargement of the ventricular cavity and long-term modification of the time constant of decay of Ca(2+) transients. Both hypertrophy and amyloid deposition were correlated with the induction of Epac-1; whereas radiation-induced fibrosis correlated with Rho/CTGF activation. Transactivation studies support Epac contribution in hypertrophy stimulation and showed that radiotherapy and Epac displayed specific and synergistic signals. CONCLUSION: Epac-1 has been identified as a novel regulator of radiation-induced hypertrophy and amyloidosis but not fibrosis in the heart.

Metastability and front propagation in the first-order optical Fréedericksz transition

A general dynamical model for the first-order optical Fréedericksz transition incorporating spatial transverse inhomogeneities and hydrodynamic effects is discussed in the framework of a time-dependent Ginzburg-Landau model. The motion of an interface between two coexisting states with different director orientations is considered. A uniformly translating front solution of the dynamical equations for the motion of that interface is described.

Vascular Effects of RWJ-676070, a Selective Combined V-1a/V-2 Vasopressin Receptor Antagonist

In recent years, several vasopressin antagonists have been developed that block V-1 receptors either selectively or nonselectively.(1,2) To date, one combined V-1/V-2 antagonist (primarily a V-2 antagonist, as determined on the basis of human receptor binding data), conivaptan, has been approved for the treatment of euvolemic hyponatremia.(3,4) We have previously shown that the vascular properties of a vasopressin V-1 antagonist can be investigated safely and reliably in healthy subjects. We used the measurement of skin blood flow after intradermic injection of exogenous arginine vasopressin on a skin area prevasodilated with calcitonin gene-related peptide (CGRP).(3,5) This technique enables the documentation of the dose-dependent effects of vasopressin or vasopressin antagonists. In this study, we have characterized the V-1a pharmacodynamic profile of increasing doses of RWJ-676070, a new orally active dual V-1a/V-2 receptor antagonist, in healthy subjects.(5)

Na(+)-K(+)-ATPase gene expression during in vitro development of rat fetal forebrain.

The existence of at least three isoforms of Na(+)-K(+)-ATPase in adult brain tissues [alpha 1, kidney type; alpha 2 [or alpha(+)]; alpha 3] suggests that these genes might be regulated in a cell-specific and time-dependent manner during development. We have studied this question in serum-free aggregating cell cultures of mechanically dissociated rat fetal telencephalon. At the protein level, the relative rate of synthesis of the pool of alpha 1-, alpha 2-, and alpha 3-subunits increased approximately twofold over 15 days of culture, leading to a marked increase in the immunochemical pool of alpha-subunits as measured by a panspecific polyclonal antibody. Concomitantly, Na(+)-K(+)-ATPase enzyme-specific activity increased three- (lower forebrain) to sixfold (upper forebrain). The transcripts of all three alpha-isoforms and beta-subunit were detected in vitro in similar proportion to the level observed in vivo. alpha 3-mRNA (3.7 kb) was more abundant than alpha 1 (3.7 kb) or alpha 2 (5.3 and 3.4 kb). Cytosine arabinoside (0.4 microM) and cholera toxin (0.1 microM) were used to selectively eliminate glial cells or neurons, respectively. It was found that alpha 2-mRNA is predominantly transcribed in glial cell cultures, whereas alpha 3- and beta 1-mRNA (2.7, 2.3, and 1.8 kb) are predominant in neuronal cultures.

Effects of intranasal administration of synthetic (4-28)human atrial natriuretic peptide to normal volunteers.

The effects of intranasal administration of increasing doses of synthetic human natriuretic peptide (4-28 hANP) were studied in six healthy volunteers. The peptide was administered as a nasal spray at doses of 50, 100, 200, and 500 micrograms in ascending order at 48-h intervals. Vehicle was administered by the same route randomly between any two of the doses. Intranasal hANP administration had no effect on either blood pressure, heart rate (HR), or hematocrit. Diuresis did not change consistently, whereas natriuresis tended to rise with vehicle as well as with hANP administration. This was attributed to the infusion of isotonic saline during the experiment. There was no significant increase in plasma ANP levels after intranasal administration of any of the different doses. Thus, no evidence that the atrial natriuretic peptide tested (4-28 hANP) can cross the nasal mucosal barrier was found.

Lack of association between beta-herpesvirus infection and bronchiolitis obliterans syndrome in lung transplant recipients in the era of antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV), human herpesvirus-6 and -7 (HHV-6 and -7) are beta-herpesviruses that commonly reactivate and have been proposed to trigger acute rejection and chronic allograft injury. We assessed the contribution of these viruses in the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. METHODS: Quantitative real-time polymerase chain reaction of bronchoalveolar lavage samples were performed for CMV, HHV-6 and -7 in a prospective cohort of lung transplant recipients. A time-dependent Cox regression analysis was used to correlate the risk of BOS and acute rejection in patients with and without beta-herpesviruses infection. RESULTS: Ninety-three patients were included in the study over a period of 3 years. A total of 581 samples from bronchoalveolar lavage were obtained. Sixty-one patients (65.6%) had at least one positive result for one of the beta-herpesviruses: 48 patients (51.6%) for CMV and 19 patients (20.4%) for both HHV-6 and -7. Median peak viral load was 3419 copies/mL for CMV, 258 copies/mL for HHV-6, and 665 copies/mL for HHV-7. Acute rejection (>or=grade 2) occurred in 46.2% and BOS (>or=stage 1) in 19.4% of the patients. In the Cox regression model the relative risk of acute rejection or BOS was not increased in patients with any beta-herpesviruses reactivation. Acute rejection was the only independently associated risk factor for BOS. CONCLUSIONS: In lung transplant recipients receiving prolonged antiviral prophylaxis, reactivation of beta-herpesviruses within the allograft was common. However, despite high viral loads in many patients, virus replication was not associated with the development of rejection or BOS.

Improving the Accuracy of Camber Predictions for Precast Pretensioned Concrete Beams, TR-625, 2015

The discrepancies between the designed and measured camber of precast pretensioned concrete beams (PPCBs) observed by the Iowa DOT have created challenges in the field during bridge construction, causing construction delays and additional costs. This study was undertaken to systematically identify the potential sources of discrepancies between the designed and measured camber from release to time of erection and improve the accuracy of camber estimations in order to minimize the associated problems in the field. To successfully accomplish the project objectives, engineering properties, including creep and shrinkage, of three normal concrete and four high-performance concrete mix designs were characterized. In parallel, another task focused on identifying the instantaneous camber and the variables affecting the instantaneous camber and evaluated the corresponding impact of this factor using more than 100 PPCBs. Using a combination of finite element analyses and the time-step method, the long-term camber was estimated for 66 PPCBs, with due consideration given to creep and shrinkage of concrete, changes in support location and prestress force, and the thermal effects. Utilizing the outcomes of the project, suitable long-term camber multipliers were developed that account for the time-dependent behavior, including the thermal effects. It is shown that by using the recommended practice for the camber measurements together with the proposed multipliers, the accuracy of camber prediction will be greatly improved. Consequently, it is expected that future bridge projects in Iowa can minimize construction challenges resulting from large discrepancies between the designed and actual camber of PPCBs during construction.

Effects of 2 different prior endurance exercises on whole-body fat oxidation kinetics: light vs. heavy exercise.

This study aimed to compare the effects of 2 different prior endurance exercises on subsequent whole-body fat oxidation kinetics. Fifteen men performed 2 identical submaximal incremental tests (Incr2) on a cycle ergometer after (i) a ∼40-min submaximal incremental test (Incr1) followed by a 90-min continuous exercise performed at 50% of maximal aerobic power-output and a 1-h rest period (Heavy); and (ii) Incr1 followed by a 2.5-h rest period (Light). Fat oxidation was measured using indirect calorimetry and plotted as a function of exercise intensity during Incr1 and Incr2. A sinusoidal equation, including 3 independent variables (dilatation, symmetry and translation), was used to characterize the fat oxidation kinetics and to determine the intensity (Fat(max)) that elicited the maximal fat oxidation (MFO) during Incr. After the Heavy and Light trials, Fat(max), MFO, and fat oxidation rates were significantly greater during Incr2 than Incr1 (p < 0.001). However, Δ (i.e., Incr2-Incr1) Fat(max), MFO, and fat oxidation rates were greater in the Heavy compared with the Light trial (p < 0.05). The fat oxidation kinetics during Incr2(Heavy) showed a greater dilatation and rightward asymmetry than Incr1(Heavy), whereas only a greater dilatation was observed in Incr2(Light) (p < 0.05). This study showed that although to a lesser extent in the Light trial, both prior exercise sessions led to an increase in Fat(max), MFO, and absolute fat oxidation rates during Incr2, inducing significant changes in the shape of the fat oxidation kinetics.

Atorvastatin-loaded hydrogel affects the smooth muscle cells of human veins.

Intimal hyperplasia (IH) is the major cause of stenosis of vein grafts. Drugs such as statins prevent stenosis, but their systemic administration has limited effects. We developed a hyaluronic acid hydrogel matrix, which ensures a controlled release of atorvastatin (ATV) at the site of injury. The release kinetics demonstrated that 100% of ATV was released over 10 hours, independent of the loading concentration of the hydrogel. We investigated the effects of such a delivery on primary vascular smooth muscle cells isolated from human veins. ATV decreased the proliferation, migration, and passage of human smooth muscle cells (HSMCs) across a matrix barrier in a similar dose-dependent (5-10 µM) and time-dependent manner (24-72 hours), whether the drug was directly added to the culture medium or released from the hydrogel. Expression analysis of genes known to be involved in the development of IH demonstrated that the transcripts of both the gap junction protein connexin43 (Cx43) and plasminogen activator inhibitor-1 (PAI-1) were decreased after a 24-48-hour exposure to the hydrogel loaded with ATV, whereas the transcripts of the heme oxygenase (HO-1) and the inhibitor of tissue plasminogen activator were increased. At the protein level, Cx43, PAI-1, and metalloproteinase-9 expression were decreased, whereas HO-1 was upregulated in the presence of ATV. The data demonstrate that ATV released from a hydrogel has effects on HSMCs similar to the drug being freely dissolved in the environment.

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.

Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating inflammatory signaling and response, oxidative/nitrative stress, and cell death.

Ischemia/reperfusion (I/R) is a pivotal mechanism of liver damage after liver transplantation or hepatic surgery. We have investigated the effects of cannabidiol (CBD), the nonpsychotropic constituent of marijuana, in a mouse model of hepatic I/R injury. I/R triggered time-dependent increases/changes in markers of liver injury (serum transaminases), hepatic oxidative/nitrative stress (4-hydroxy-2-nonenal, nitrotyrosine content/staining, and gp91phox and inducible nitric oxide synthase mRNA), mitochondrial dysfunction (decreased complex I activity), inflammation (tumor necrosis factor α (TNF-α), cyclooxygenase 2, macrophage inflammatory protein-1α/2, intercellular adhesion molecule 1 mRNA levels; tissue neutrophil infiltration; nuclear factor κB (NF-κB) activation), stress signaling (p38MAPK and JNK), and cell death (DNA fragmentation, PARP activity, and TUNEL). CBD significantly reduced the extent of liver inflammation, oxidative/nitrative stress, and cell death and also attenuated the bacterial endotoxin-triggered NF-κB activation and TNF-α production in isolated Kupffer cells, likewise the adhesion molecule expression in primary human liver sinusoidal endothelial cells stimulated with TNF-α and attachment of human neutrophils to the activated endothelium. These protective effects were preserved in CB(2) knockout mice and were not prevented by CB(1/2) antagonists in vitro. Thus, CBD may represent a novel, protective strategy against I/R injury by attenuating key inflammatory pathways and oxidative/nitrative tissue injury, independent of classical CB(1/2) receptors.