Viscoelastic dynamics of a soft strip subject to a large deformation.

To produce sounds, we adjust the tension of our vocal folds to shape their properties and control the pitch. This efficient mechanism offers inspiration for designing reconfigurable materials and adaptable soft robots. However, understanding how flexible structures respond to a significant static strain is not straightforward. This complexity also limits the precision of medical imaging when applied to tensioned organs like muscles, tendons, ligaments and blood vessels among others. In this article, we experimentally and theoretically explore the dynamics of a soft strip subject to a substantial static extension, up to 180%. Our observations reveal a few intriguing effects, such as the resilience of certain vibrational modes to a static deformation. These observations are supported by a model based on the incremental displacement theory. This has promising practical implications for characterizing soft materials but also for scenarios where external actions can be used to tune properties.

Computing zero-group-velocity points in anisotropic elastic waveguides: Globally and locally convergent methods.

Dispersion curves of elastic waveguides exhibit points where the group velocity vanishes while the wavenumber remains finite. These are the so-called zero-group-velocity (ZGV) points. As the elastodynamic energy at these points remains confined close to the source, they are of practical interest for nondestructive testing and quantitative characterization of structures. These applications rely on the correct prediction of the ZGV points. In this contribution, we first model the ZGV resonances in anisotropic plates based on the appearance of an additional modal solution. The resulting governing equation is interpreted as a two-parameter eigenvalue problem. Subsequently, we present three complementary numerical procedures capable of computing ZGV points in arbitrary nondissipative elastic waveguides in the conventional sense that their axial power flux vanishes. The first method is globally convergent and guarantees to find all ZGV points but can only be used for small problems. The second procedure is a very fast, generally-applicable, Newton-type iteration that is locally convergent and requires initial guesses. The third method combines both kinds of approaches and yields a procedure that is applicable to large problems, does not require initial guesses and is likely to find all ZGV points. The algorithms are implemented in GEW ZGV computation (doi: 10.5281/zenodo.7537442).

Exhaled Propofol Concentrations Correlate With Plasma and Brain Tissue Concentrations in Rats.

BACKGROUND: Propofol can be measured in exhaled gas. Exhaled and plasma propofol concentrations correlate well, but the relationship with tissue concentrations remains unknown. We thus evaluated the relationship between exhaled, plasma, and various tissue propofol concentrations. Because the drug acts in the brain, we focused on the relationship between exhaled and brain tissue propofol concentrations. METHODS: Thirty-six male Sprague-Dawley rats were anesthetized with propofol, ketamine, and rocuronium for 6 hours. Animals were randomly assigned to propofol infusions at 20, 40, or 60 mg·kg·h (n = 12 per group). Exhaled propofol concentrations were measured at 15-minute intervals by multicapillary column-ion mobility spectrometry. Arterial blood samples, 110 µL each, were collected 15, 30, and 45 minutes, and 1, 2, 4, and 6 hours after the propofol infusion started. Propofol concentrations were measured in brain, lung, liver, kidney, muscle, and fat tissue after 6 hours. The last exhaled and plasma concentrations were used for linear regression analyses with tissue concentrations. RESULTS: The correlation of exhaled versus plasma concentrations (R = 0.71) was comparable to the correlation of exhaled versus brain tissue concentrations (R = 0.75) at the end of the study. In contrast, correlations between plasma and lung and between lung and exhaled propofol concentrations were poor. Less than a part-per-thousand of propofol was exhaled over 6 hours. CONCLUSIONS: Exhaled propofol concentrations correlate reasonably well with brain tissue and plasma concentrations in rats, and may thus be useful to estimate anesthetic drug effect. The equilibration between plasma propofol and exhaled gas is apparently independent of lung tissue concentration. Only a tiny fraction of administered propofol is eliminated via the lungs, and exhaled quantities thus have negligible influence on plasma concentrations.

Volutrauma Increases Exhaled Pentanal in Rats: A Potential Breath Biomarker for Ventilator-Induced Lung Injury.

BACKGROUND: Mechanical ventilation injures lungs, but there are currently no reliable methods for detecting early injury. We therefore evaluated whether exhaled pentanal, a lipid peroxidation product, might be a useful breath biomarker for stretch-induced lung injury in rats. METHODS: A total of 150 male Sprague-Dawley rats were investigated in 2 substudies. The first randomly assigned 75 rats to 7 hours of mechanical ventilation at tidal volumes of 6, 8, 12, 16, and 20 mL·kg-1. The second included 75 rats. A reference group was ventilated at a tidal volume of 6 mL·kg-1 for 10 hours 4 interventional groups were ventilated at a tidal volume of 6 mL·kg-1 for 1 hour, and then for 0.5, 1, 2, or 3 hours at a tidal volume of 16 mL.kg-1 before returning to a tidal volume of 6 mL·kg-1 for additional 6 hours. Exhaled pentanal was monitored by multicapillary column-ion mobility spectrometry. The first substudy included cytokine and leukocyte measurements in blood and bronchoalveolar fluid, histological assessment of the proportion of alveolar space, and measurements of myeloperoxidase activity in lung tissue. The second substudy included measurements of pentanal in arterial blood plasma, cytokine and leukocyte concentrations in bronchoalveolar fluid, and cleaved caspase 3 in lung tissue. RESULTS: Exhaled pentanal concentrations increased by only 0.5 ppb·h-1 (95% confidence interval [CI], 0.3-0.6) when rats were ventilated at 6 mL·kg-1. In contrast, exhaled pentanal concentrations increased substantially and roughly linearly at higher tidal volumes, up to 3.1 ppb·h-1 (95% CI, 2.3-3.8) at tidal volumes of 20 mL·kg-1. Exhaled pentanal increased at average rates between 1.0 ppb·h-1 (95% CI, 0.3-1.7) and 2.5 ppb·h-1 (95% CI, 1.4-3.6) after the onset of 16 mL·kg-1 tidal volumes and decreased rapidly by a median of 2 ppb (interquartile range [IQR], 0.9-3.2), corresponding to a 38% (IQR, 31-43) reduction when tidal volume returned to 6 mL·kg-1. Tidal volume, inspiratory pressure, and mechanical power were positively associated with pentanal exhalation. Exhaled and plasma pentanal were uncorrelated. Alveolar space decreased and inflammatory markers in bronchoalveolar lavage fluid increased in animals ventilated at high tidal volumes. Short, intermittent ventilation at high tidal volumes for up to 3 hours increased neither inflammatory markers in bronchoalveolar fluid nor the proportion of cleaved caspase 3 in lung tissue. CONCLUSIONS: Exhaled pentanal is a potential biomarker for early detection of ventilator-induced lung injury in rats.

Quantification of Volatile Aldehydes Deriving from In Vitro Lipid Peroxidation in the Breath of Ventilated Patients.

Exhaled aliphatic aldehydes were proposed as non-invasive biomarkers to detect increased lipid peroxidation in various diseases. As a prelude to clinical application of the multicapillary column-ion mobility spectrometry for the evaluation of aldehyde exhalation, we, therefore: (1) identified the most abundant volatile aliphatic aldehydes originating from in vitro oxidation of various polyunsaturated fatty acids; (2) evaluated emittance of aldehydes from plastic parts of the breathing circuit; (3) conducted a pilot study for in vivo quantification of exhaled aldehydes in mechanically ventilated patients. Pentanal, hexanal, heptanal, and nonanal were quantifiable in the headspace of oxidizing polyunsaturated fatty acids, with pentanal and hexanal predominating. Plastic parts of the breathing circuit emitted hexanal, octanal, nonanal, and decanal, whereby nonanal and decanal were ubiquitous and pentanal or heptanal not being detected. Only pentanal was quantifiable in breath of mechanically ventilated surgical patients with a mean exhaled concentration of 13 ± 5 ppb. An explorative analysis suggested that pentanal exhalation is associated with mechanical power-a measure for the invasiveness of mechanical ventilation. In conclusion, exhaled pentanal is a promising non-invasive biomarker for lipid peroxidation inducing pathologies, and should be evaluated in future clinical studies, particularly for detection of lung injury.

Differential Response of Pentanal and Hexanal Exhalation to Supplemental Oxygen and Mechanical Ventilation in Rats.

High inspired oxygen during mechanical ventilation may influence the exhalation of the previously proposed breath biomarkers pentanal and hexanal, and additionally induce systemic inflammation. We therefore investigated the effect of various concentrations of inspired oxygen on pentanal and hexanal exhalation and serum interleukin concentrations in 30 Sprague Dawley rats mechanically ventilated with 30, 60, or 93% inspired oxygen for 12 h. Pentanal exhalation did not differ as a function of inspired oxygen but increased by an average of 0.4 (95%CI: 0.3; 0.5) ppb per hour, with concentrations doubling from 3.8 (IQR: 2.8; 5.1) ppb at baseline to 7.3 (IQR: 5.0; 10.8) ppb after 12 h. Hexanal exhalation was slightly higher at 93% of inspired oxygen with an average difference of 0.09 (95%CI: 0.002; 0.172) ppb compared to 30%. Serum IL-6 did not differ by inspired oxygen, whereas IL-10 at 60% and 93% of inspired oxygen was greater than with 30%. Both interleukins increased over 12 h of mechanical ventilation at all oxygen concentrations. Mechanical ventilation at high inspired oxygen promotes pulmonary lipid peroxidation and systemic inflammation. However, the response of pentanal and hexanal exhalation varies, with pentanal increasing by mechanical ventilation, whereas hexanal increases by high inspired oxygen concentrations.

High average power transform limited picosecond laser with flexible repetition rate and pulse duration.

This Letter presents a pulsed, Fourier transform limited 1030 nm laser with a variable pulse duration between 47 and 733 ps resulting in a spectral bandwidth of roughly 1 to 10 GHz. The laser system is based on ytterbium-doped fiber amplifiers and acousto-optic and electro-optic modulation technology. The repetition rate can be set arbitrarily between 1 and 10 MHz. After three sequential amplifier stages, the average output power reaches a maximum of over 60 W. The particular fiber amplifier geometry allows to prevent the emergence of unwanted nonlinear effects. Due to its unique features, the laser system lends itself to a variety of applications wherever flexibility in terms of pulse duration and corresponding Fourier limited bandwidth are required, such as laser cooling at storage rings, lidar applications, or coherent molecular spectroscopy.

Simultaneous quantification of propofol, ketamine and rocuronium in just 10 µL plasma using liquid chromatography coupled with quadrupole mass spectrometry and its pilot application to a pharmacokinetic study in rats.

The combination of propofol, ketamine and rocuronium can be used for anesthesia of ventilated rats. However, reliable pharmacokinetic models of these drugs have yet to be developed in rats, and consequently optimal infusion strategies are also unknown. Development of pharmacokinetic models requires repeated measurements of drug concentrations. In small animals, samples must be tiny to avoid excessing blood extraction. We therefore developed a drug assay system using high-performance liquid chromatography coupled with quadrupole mass spectrometry that simultaneously determines the concentration of all three drugs in just 10 µL rat plasma. We established a plasma extraction protocol, using acetonitrile as the precipitating reagent. Calibration curves were linear with R2 = 0.99 for each drug. Mean recovery from plasma was 91-93% for propofol, 89-93% for ketamine and 90-92% for rocuronium. The assay proved to be accurate for propofol 4.1-8.3%, ketamine 1.9-7.8% and rocuronium -3.6-4.7% relative error. The assay was also precise; the intra-day precisions were propofol 2.0-4.0%, ketamine 2.7-2.9% and rocuronium 2.9-3.3% relative standard deviation. Finally, the method was successfully applied to measurement the three drugs in rat plasma samples. Mean plasma concentrations with standard deviations were propofol 2.0 µg/mL ±0.5%, ketamine 3.9 µg/mL ±1.0% and rocuronium 3.2 µg/mL ±0.8% during ventilation.

Calculating the full leaky Lamb wave spectrum with exact fluid interaction.

Lamb waves are elastodynamic guided waves in plates and are used for non-destructive evaluation, sensors, and material characterization. These applications rely on the knowledge of the dispersion characteristics, i.e., the frequency-dependent wavenumbers. The interaction of a plate with an adjacent fluid leads to a nonlinear differential eigenvalue problem with a square root term describing exchange of energy with the surrounding medium, e.g., via acoustic radiation. In this contribution, a spectral collocation scheme is applied to discretize the differential eigenvalue problem. A change of variable is performed to obtain an equivalent polynomial eigenvalue problem of fourth order, which is linear in state-space and can reliably be solved using modern numerical methods. Traditionally, the leaky Lamb wave problem has been solved by finding the roots of the characteristic equations, a numerically ill-conditioned problem. In contrast to root-finding, the approach described in this paper is inherently able to find all modes and naturally handles complex wavenumbers. The full phase velocity dispersion diagram and attenuation curves are presented and are shown to be in excellent agreement with solutions of the characteristic equation as well as computations made with a perturbation method. The procedure is applicable to anisotropic, viscoelastic, inhomogeneous, and layered plates coupled to an inviscid fluid.

Morphological asymmetry and habitat quality: using fleas and their rodent hosts as a novel experimental system.

Morphological asymmetry is widely used to measure developmental instability and higher levels of asymmetry often correlate with decreased mating success, increased inbreeding, increased stress and decreased habitat quality. We studied asymmetry and relationships between asymmetry and host identity in two flea species, host generalist Xenopsylla ramesis and host specialist Parapulex chephrenis, and asked: (1) what the level of asymmetry was in their femurs and tibiae; (2) which type of asymmetry predominates; and (3) whether fleas that fed on host species distantly related to their principal host species produced offspring that exhibited greater asymmetry compared with offspring of fleas that fed on their principal host species. We found fluctuating asymmetry in femurs and tibiae of X. ramesis and in the tibiae of P. chephrenis as well as significantly left-handed directional asymmetry in the femurs of P. chephrenis Host species identity significantly impacted asymmetry in leg segments of P. chephrenis but not in those of X. ramesis Offspring asymmetry increased when mother fleas fed on a host that was distantly related to the principal host. Fleas parasitizing multiple host species might compensate for developmental instability when utilizing a novel host species; therefore, host-switching events in host-specific parasites could be constrained by the relatedness between a novel and a principal host species.

Reproductive consequences of female size in haematophagous ectoparasites.

To test relationships between maternal size, egg size and size of new offspring, we studied (a) the effect of maternal size on egg size and number, and maternal survival after oviposition and (b) the effect of egg size on the duration of development and new imago size in three flea species (Xenopsylla ramesis, Synosternus cleopatrae, Parapulex chephrenis) with varying host and habitat specificity. In general, the number and size of eggs as well as total egg volume appeared to be independent of maternal body size. There was no trade-off between egg number and size. However, female body size was related to post-oviposition survival, with larger females surviving longer after oviposition than smaller females. In addition, females that produced more eggs died faster after oviposition in X. ramesis but not in the two other species. There were no significant size differences between eggs that developed into new imagoes and eggs that did not survive. Survivorship of male and female eggs did not differ; however, new adult females were significantly larger than new adult males. Female, but not male, new imagoes exhibited a significant positive relationship between egg size and duration of preimaginal development in all three species, with larger eggs developing faster than smaller eggs. In X. ramesis and S. cleopatrae, faster developing eggs also developed into larger new imagoes. We conclude that these patterns were largely consistent among the three flea species, suggesting that they result from the same mechanisms and are weakly affected by the ecological specialization of a given species.

Efficacy of midtrimester short cervix interventions is conditional on intraamniotic inflammation.

BACKGROUND: Midtrimester ultrasound is a valuable method for identifying asymptomatic women at risk for spontaneous preterm delivery (PTD). However, response to various treatments (cerclage, progestogen) has been variable in the clinical setting. It remains unclear how other biomarkers may be used to guide intervention strategies. OBJECTIVE: We applied an amniotic fluid inflammatory scoring system to determine if the degree of inflammation is associated with intervention efficacy in patients with midtrimester short cervix. STUDY DESIGN: Women carrying a singleton fetus between 16-24 weeks' gestation with a short cervix (≤25 mm) on transvaginal ultrasound underwent amniocentesis and were assigned to McDonald cerclage, no cerclage, or weekly 17-alpha hydroxyprogesterone caproate (17OHP-C). Our previously described inflammatory risk score (comprised of 14 inflammatory markers) was used to classify patients as high (score ≥8) or low (score <8) risk for inflammation. Gestational age at delivery was compared for each intervention and risk score status. Risk of delivering as a function of the remaining gestation was evaluated using modified Cox proportional hazards models with incorporation of methods to account for both left and right truncation bias. RESULTS: Ninety patients were included: 24 were in the nonintervention control group, 51 received cerclage, and 15 received 17OHP-C. Inflammation status at time of sampling influenced the efficacy of the treatment (P < .001). Compared to the nonintervention control group, in patients with low inflammation (score < 8), both cerclage (adjusted hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.28-6.37) and 17OHP-C (HR, 3.11; 95% CI, 1.04-9.30) were associated with increased hazard of PTD. In contrast, in patients with high inflammation (score ≥8) both cerclage (HR, 0.22; 95% CI, 0.08-0.65) and 17OHP-C (HR, 0.20; 95% CI, 0.05-0.81) were associated with lower hazard of delivering preterm. CONCLUSION: Cerclage placement or administration of 17OHP-C therapy for midtrimester short cervix for PTD prevention appears beneficial only in the subset of patients with high inflammation. Knowledge of the amniotic fluid inflammatory status may aid in guiding the appropriate therapy for women presenting with midtrimester short cervix who are at increased risk of PTD.

Effectiveness and short-term safety of modified sodium hyaluronic acid-carboxymethylcellulose at cesarean delivery: a randomized trial.

BACKGROUND: The rising cesarean birth rate has drawn attention to risks associated with repeat cesarean birth. Prevention of adhesions with adhesion barriers has been promoted as a way to decrease operative difficulty. However, robust data demonstrating effectiveness of such interventions are lacking. OBJECTIVE: We report data from a multicenter trial designed to evaluate the short-term safety and effectiveness of a modified sodium hyaluronic acid (HA)-carboxymethylcellulose (CMC) absorbable adhesion barrier for reduction of adhesions following cesarean delivery. STUDY DESIGN: Patients who underwent primary or repeat cesarean delivery were included in this multicenter, single-blinded (patient), randomized controlled trial. Patients were randomized into either HA-CMC (N = 380) or no treatment (N = 373). No other modifications to their treatment were part of the protocol. Short-term safety data were collected following randomization. The location and density of adhesions (primary outcome) were assessed at their subsequent delivery using a validated tool, which can also be used to derive an adhesion score that ranges from 0-12. RESULTS: No differences in baseline characteristics, postoperative course, or incidence of complications between the groups following randomization were noted. Eighty patients from the HA-CMC group and 92 controls returned for subsequent deliveries. Adhesions in any location were reported in 75.6% of the HA-CMC group and 75.9% of the controls (P = .99). There was no significant difference in the median adhesion score; 2 (range 0-10) for the HA-CMC group vs 2 (range 0-8) for the control group (P = .65). One third of the HA-CMC patients met the definition for severe adhesions (adhesion score >4) compared to 15.5% in the control group (P = .052). There were no significant differences in the time from incision to delivery (P = .56). Uterine dehiscence in the next pregnancy was reported in 2 patients in HA-CMC group vs 1 in the control group (P = .60). CONCLUSION: Although we did not identify any short-term safety concerns, HA-CMC adhesion barrier applied at cesarean delivery did not reduce adhesion formation at the subsequent cesarean delivery.

Bartonella, Rodents, Fleas and Ticks: a Molecular Field Study on Host-Vector-Pathogen Associations in Saxony, Eastern Germany.

Bartonellae cause zoonotic diseases and are transmitted by arthropods. Rodents are reservoirs for most Bartonella spp. As the knowledge about Bartonella in rodents and their parasitizing ectoparasites is scarce in Germany, this study's objectives were to investigate Bartonella spp. in small mammals and in their ectoparasites. A total of 79 small mammals (seven species) were captured and their ectoparasites collected at seven sites around Leipzig, Saxony, Germany, in 2010 and 2011. Altogether, 79 spleen samples, 135 fleas (five species) and 365 ticks (three species) were investigated for Bartonella spp. by PCR targeting the ITS 16S-23S rRNA region. In total, 52 (65.8 %) small mammals, 73 (54.1 %) fleas and 51 (16.3 %) ticks were positive for Bartonella spp. Most small mammals were positive for uncultured Bartonella sp. (n = 29) followed by Bartonella grahamii (n = 12), Bartonella taylorii (n = 8) and Bartonella sp. N40 (n = 3). Likewise, most fleas were positive for uncultured Bartonella sp. (n = 45) followed by B. grahamii (n = 14), B. taylorii (n = 8), B. sp. N40 (n = 5) and Bartonella elizabethae (n = 2). Most ticks were positive for B. sp. (n = 19) followed by B. grahamii (n = 10), Bartonella chomelii (n = 3), B. taylorii (n = 2) and B. sp. N40 (n = 1). This study's results suggest that rodents and fleas may be reservoirs and vectors, respectively. Zoonotic B. grahamii and B. elizabethae were found in rodents and their fleas. Therefore, humans may contract Bartonella infection by contact to wild rodents. Ticks seem of minor importance in transmitting Bartonella spp. found in fleas and rodents. However, ticks might be vectors of B. chomelii.

Szidat's rule re-tested: relationships between flea and host phylogenetic clade ranks in four biogeographic realms.

We tested Szidat's rule (the more primitive the host, the more primitive the parasites it harbours) by analysing the relationships between phylogenetic clade ranks of fleas and their small mammalian hosts in four biogeographic realms (Afrotropics, Neotropics, Nearctic and Palearctic). From the host perspective, we tested the association between host clade rank and the mean clade rank of all fleas collected from this host. From the flea perspective, we tested the relationships between flea clade rank and the mean clade rank of hosts on which this flea was recorded. First, we tested whether the analysis of the relationships between host and flea clade ranks should be controlled for phylogenetic dependence among either host or flea species. Then, we tested for the associations between host and flea clade ranks separately for each realm using either a phylogenetic general least-squares analysis or an ordinary least-squares analysis. In all realms, the mean clade rank of fleas parasitic on a given host increased with an increase of this host's clade rank, and the mean clade rank of hosts recorded on a given flea increased with an increase of this flea's clade rank, suggesting that Szidat's rule, at least to some extent, holds for fleas.

Effects of parasite pressure on parasite mortality and reproductive output in a rodent-flea system: inferring host defense trade-offs.

Evaluating host resistance via parasite fitness helps place host-parasite relationships within evolutionary and ecological contexts; however, few studies consider both these processes simultaneously. We investigated how different levels of parasite pressure affect parasite mortality and reproductive success in relationship to host defense efforts, using the rodent Gerbillus nanus and the flea Xenopsylla conformis as a host-parasite system. Fifteen immune-naïve male rodents were infested with 20, 50, or 100 fleas for four weeks. During this time number of new imagoes produced per adult flea (our flea reproductive output metric), flea mortality, and change in circulating anti-flea immunoglobulin G (our measure of adaptive immune defense) were monitored. Three hypotheses guided this work: (1) increasing parasite pressure would heighten host defenses; (2) parasite mortality would increase and parasite reproductive output would decrease with increasing investment in host defense; and (3) hosts under high parasite pressure could invest in behavioral and/or immune responses. We predicted that at high infestation levels (a) parasite mortality would increase; (b) flea reproductive output per individual would decrease; and (c) host circulating anti-flea antibody levels would increase. The hypotheses were partially supported. Flea mortality significantly increased and flea reproductive output significantly decreased as flea pressure increased. Host adaptive immune defense did not significantly change with increasing flea pressure. Therefore, we inferred that investment in host behavioral defense, either alone or in combination with density-dependent effects, may be more efficient at increasing flea mortality and decreasing flea reproductive output than antibody production during initial infestation in this system.

Melatonin receptors mediate improvements of survival in a model of polymicrobial sepsis.

OBJECTIVES: Melatonin has been demonstrated to improve survival after experimental sepsis via antioxidant effects. Yet, recent evidence suggests that this protective capacity may also rely on melatonin receptor activation. Therefore, the present study was designed to investigate whether selective melatonin receptor-agonist ramelteon may influence survival and immune response in a model of polymicrobial sepsis in rats, wild-type and melatonin receptor MT1/MT2 double knockout mice. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats (200-250 g) and male C3H/HeN wild-type and MT1/MT2 receptor knockout mice (20-22 g). INTERVENTIONS: Animals underwent cecal ligation and incision and remained anesthetized for evaluation of survival for 12 hours (rats: n = 15 per group) or 15 hours (mice: n = 10 per group). Analysis of immune response by means of enzyme-linked immunosorbent assay was performed before and 5 hours after cecal ligation and incision (rats only; n = 5 per group). After induction of sepsis, animals were treated IV with vehicle, different doses of melatonin (rats: 0.01/0.1/1.0/10 mg/kg; mice: 1.0 mg/kg), ramelteon, melatonin receptor-antagonist luzindole, ramelteon + luzindole, or melatonin + luzindole (each 1.0 mg/kg). Sham controls underwent laparotomy but not cecal ligation and incision. MEASUREMENTS AND MAIN RESULTS: Compared with vehicle, administration of ramelteon or melatonin significantly improved median survival time in rats (sepsis/melatonin [0.1 mg/kg], 554 min, [1.0 mg/kg] 570 min, [10 mg/kg] 579 min; sepsis/ramelteon, 468 min; each p < 0.001 vs sepsis/vehicle, 303 min) and wild-type mice (sepsis/melatonin, 781 min; sepsis/ramelteon, 701 min; both p < 0.001 vs sepsis/vehicle, 435 min). This effect was completely antagonized by coadministration of luzindole in all groups. Melatonin, ramelteon, or luzindole had no significant effect on survival time in knockout mice. Significantly elevated concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-10 were observed 5 hours after cecal ligation and incision in rats (p < 0.05 vs baseline and corresponding sham); neither ramelteon nor melatonin treatment significantly affected immune response. CONCLUSIONS: Melatonin receptors mediate improvements of survival after polymicrobial sepsis in rats and mice; this effect appears to be independent from major alterations of cytokine release.

Notes on osculations and mode tracing in semi-analytical waveguide modeling.

The dispersion curves of (elastic) waveguides frequently exhibit crossings and osculations (also known as veering, repulsion, or avoided crossing). Osculations are regions in the dispersion diagram where curves approach each other arbitrarily closely without ever crossing before veering apart. In semi-analytical (undamped) waveguide models, dispersion curves are obtained as solutions to discretized parameterized Hermitian eigenvalue problems. In the mathematical literature, it is known that such eigencurves can exhibit crossing points only if the corresponding matrix flow (parameter-dependent matrix) is uniformly decomposable. We discuss the implications for the solution of the waveguide problem. In particular, we make use of a simple algorithm recently suggested in the literature for decomposing matrix flows. We also employ a method for mode tracing based on approximating the eigenvalue problem for individual modes by an ordinary differential equation that can be solved by standard procedures.

Beating resonance patterns and extreme power flux skewing in anisotropic elastic plates.

Elastic waves in anisotropic media can exhibit a power flux that is not collinear with the wave vector. This has notable consequences for waves guided in a plate. Through laser-ultrasonic experiments, we evidence remarkable phenomena due to slow waves in a single-crystal silicon wafer. Waves exhibiting power flux orthogonal to their wave vector are identified. A pulsed line source that excites these waves reveals a wave packet radiated parallel to the line. Furthermore, there exist precisely eight plane waves with zero power flux. These so-called zero-group-velocity modes are oriented along the crystal's principal axes. Time acts as a filter in the wave-vector domain that selects these modes. Thus, a point source leads to beating resonance patterns with moving nodal curves on the surface of the infinite plate. We observe this pattern as it emerges naturally after a pulsed excitation.

Characterization of lipoproteins in human placenta and fetal circulation as well as gestational changes in lipoprotein assembly and secretion in human and mouse placentas.

In the maternal circulation, apoB-containing low-density lipoproteins (LDL) and apoA1-containing high-density lipoproteins (HDL) transport lipids. The production of lipoproteins in the placenta has been suggested, but the directionality of release has not been resolved. We compared apolipoprotein concentrations and size-exclusion chromatography elution profiles of lipoproteins in maternal/fetal circulations, and in umbilical arteries/veins; identified placental lipoprotein-producing cells; and studied temporal induction of lipoprotein-synthesizing machinery during pregnancy. We observed that maternal and fetal lipoproteins are different with respect to concentrations and elution profiles. Surprisingly, concentrations and elution profiles of lipoproteins in umbilical arteries and veins were similar indicating their homeostatic control. Human placental cultures synthesized apoB100-containing LDL-sized and apoA1-containing HDL-sized particles. Immunolocalization techniques revealed that ApoA1 was present mainly in syncytiotrophoblasts. MTP, a critical protein for lipoprotein assembly, was in these trophoblasts. ApoB was in the placental stroma indicating that trophoblasts secrete apoB-containing lipoproteins into the stroma. ApoB and MTP expressions increased in placentas from the 2nd trimester to term, whereas apoA1 expression was unchanged. Thus, our studies provide new information regarding the timing of lipoprotein gene induction during gestation, the cells involved in lipoprotein assembly and the gel filtration profiles of human placental lipoproteins. Next, we observed that mouse placenta produces MTP, apoB100, apoB48 and apoA1. The expression of genes gradually increased and peaked in late gestation. This information may be useful in identifying transcription factors regulating the induction of these genes in gestation and the importance of placental lipoprotein assembly in fetal development.