High-resolution computational fluid dynamics detects flow instabilities in the carotid siphon: Implications for aneurysm initiation and rupture?

The carotid siphon is by nature a tortuous vessel segment with sharp bends and large area variations, and of relevance to the study of intracranial aneurysm initiation and rupture. The aim of this paper was to determine whether the siphon might harbor flow instabilities, if care is taken to resolve them. This study focused on five consecutive internal carotid artery (ICA) aneurysm cases from the open-source Aneurisk dataset. The aneurysm, always downstream of the siphon, was digitally removed using previously developed and verified tools. Computational fluid dynamic (CFD) models included long cervical segments upstream, and middle and anterior cerebral arteries downstream. High-resolution pulsatile simulations were performed using the equivalent of ~24$~24$ million linear tetrahedra on average (range 16-32 M) and 30,000 time-steps/cycle. Two of the five cases were laminar with mild flow instabilities right after peak systole. One of the cases experienced strong periodic vortex shedding at a frequency of around 100 Hz. The remaining two cases harbored higher frequency flow instabilities and complex 3D vortical structures, extending to the cerebral arteries downstream. Our findings suggest that the carotid siphon, a conduit to the majority of anterior intracranial aneurysms, may experience flow instabilities, consistent with in vitro reports, but seemingly at odds with the majority of CFD studies, which have been done at lower resolutions. This has obvious implications for elucidating the forces involved in aneurysm initiation; and propagation of flow instabilities into ICA or downstream aneurysms could also impact understanding of the forces involved in aneurysm rupture.     

Can cofactor-binding sites in proteins be flexible? Desulfovibrio desulfuricans flavodoxin binds FMN dimer

Flavodoxins catalyze redox reactions using the isoalloxazine moiety of the flavin mononucleotide (FMN) cofactor stacked between two aromatic residues located in two peptide loops. At high FMN concentrations that favor stacked FMN dimers in solution, isothermal titration calorimetric studies show that these dimers bind strongly to apo-flavodoxin from Desulfovibrio desulfuricans (30 degrees C, 20 mM Hepes, pH 7, K(D) = 5.8 microM). Upon increasing the temperature so the FMN dimers dissociate (as shown by (1)H NMR), only one-to-one (FMN-to-protein) binding is observed. Calorimetric titrations result in one-to-one binding also in the presence of phosphate or sulfate (30 degrees C, 13 mM anion, pH 7, K(D) = 0.4 microM). FMN remains dimeric in the presence of phosphate and sulfate, suggesting that specific binding of a divalent anion to the phosphate-binding site triggers ordering of the peptide loops so only one isoalloxazine can fit. Although the physiological relevance of FMN and other nucleotides as dimers has not been explored, our study shows that high-affinity binding to proteins of such dimers can occur in vitro. This emphasizes that the cofactor-binding site in flavodoxin is more flexible than previously expected.     

Can programmed cell death be induced in post-ejaculatory bull and stallion spermatozoa?

Apoptosis is common during spermatogenesis. Here, it was tested whether apoptosis could be induced in sperm after ejaculation. There were several lines of evidence to indicate that sperm are resistant to induction of apoptosis. First, incubation of bull sperm at temperatures characteristic of normothermia (38.5 °C) or heat shock (40 and 41 °C) for 4 h did not increase the proportion of sperm positive for the TUNEL reaction. There was also no reduction in mitochondrial polarity caused by exposure to 40 or 41 °C. Incubation at 38.5 °C (least-squares mean ± SEM = 4.0 ± 1.4%), 40 °C (6.2 ± 1.4%), and 41 °C (7.0 ± 1.4%) for 24 h did increase the proportion of sperm that were TUNEL positive slightly as compared to non-incubated control sperm (1.0 ± 1.4%). However, the increase in TUNEL labeling was not affected by incubation temperature and occurred even in the presence of the group II caspase inhibitor, z-DEVD-fmk. In addition, exposure of bull sperm to carbonyl cyanide 3-chlorophenylhydrazone (CCCP), which depolarizes mitochondrial membranes, did not increase TUNEL labeling. Stallion sperm were also resistant to increased TUNEL labeling in response to incubation at 41 °C for 4 h or exposure to CCCP. Western blotting was performed to determine whether failure of induction of apoptosis was due to aberrant caspase activation. Procaspase-9 was detected in bull sperm, but cleavage to caspase-9 was not induced by short-term aging at 38.5, 40, or 41 °C, or exposure to CCCP. Procaspase-3 was not detected in bull spermatozoa. In conclusion, post-ejaculatory bull and stallion sperm were resistant to induction of apoptosis; this resistance, at least in bulls, was due to refractoriness of mitochondria to heat shock-induced depolarization, lack of activation of procaspase-9, and an absence of procaspase-3.     

Can aspect ratio be used to categorize intra-aneurysmal hemodynamics?-A study of elastase induced aneurysms in rabbit

Clinical studies suggest that aneurysm aspect ratio (AR) is an important indicator of rupture likelihood. The importance of AR is hypothesized to arise from its influence on intra-aneurysmal hemodynamics. It has been conjectured that slower flow in high AR sacs leads to a cascade of biological activities that weaken the aneurysm wall (Ujiie et al.,1999). However, the connection between AR, hemodynamics and wall weakening has never been proven. Animal models of saccular aneurysms provide a venue for evaluating this conjecture. The focus of this work was to evaluate whether a commonly used elastase induced aneurysm model in rabbits is suitable for a study of this kind from a hemodynamic perspective. In particular, to assess whether hemodynamic factors in low and high AR sacs are statistically different. To achieve this objective, saccular aneurysms were created in 51 rabbits and pulsatile computational fluid dynamics (CFD) studies were performed using rabbit specific inflows. Distinct hemodynamics were found in the low AR (AR<1.8, n=25), and high AR (AR>2.2, n=18) models. A single, stable recirculation zone was present in all low AR aneurysms, whereas a second, transient recirculation zone was also found in the superior aspect of the aneurysm dome for all high AR cases. Aneurysms with AR between 1.8 and 2.2 displayed transitional flow patterns. Differences in values and distributions of hemodynamic parameters were found between low and high AR cases including time averaged wall shear stress, oscillatory shear index, relative residence time and non-dimensional inflow rate. This work lays the foundation for future studies of the dependence of growth and remodeling on AR in the rabbit model and provides a motivation for further studies of the coupling between AR and hemodynamics in human aneurysms.     

Can Ebola virus evolve to be less virulent in humans?

Understanding Ebola virus (EBOV) virulence evolution not only is timely but also raises specific questions because it causes one of the most virulent human infections and it is capable of transmission after the death of its host. Using a compartmental epidemiological model that captures three transmission routes (by regular contact, via dead bodies and by sexual contact), we infer the evolutionary dynamics of case fatality ratio on the scale of an outbreak and in the long term. Our major finding is that the virus's specific life cycle imposes selection for high levels of virulence and that this pattern is robust to parameter variations in biological ranges. In addition to shedding a new light on the ultimate causes of EBOV's high virulence, these results generate testable predictions and contribute to informing public health policies. In particular, burial management stands out as the most appropriate intervention since it decreases the of the epidemics, while imposing selection for less virulent strains.     

Can the modified Allen's test always detect sufficient collateral flow in the hand? A computational study

Blood flow in the largest arteries of the arm up to the digital arteries is numerically modelled using the one-dimensional equations of pressure and flow wave propagation in compliant vessels. The model can be applied to different anatomies of arterial networks and can simulate compression of arteries, these allowing us to simulate the modified Allen's test (MAT) and to assess its suitability for the detection of sufficient collateral flow in the hand if radial blood supply is interrupted. The test measures blood flow in the superficial palmar arch before and during compression of the radial artery. The absence of reversal flow in the palmar arch with the compression indicates insufficient collateral flow and is referred to as a positive MAT. This study shows that small calibres of the superficial palmar arch and insufficient compression of the radial artery can lead to false-positive results. Measurement of the drop in digital systolic pressures with compression of the radial artery has proved to be a more sensitive test to predict the presence of sufficient ulnar collateral flow in networks with small calibres of the superficial palmar arch. However, this study also shows that digital pressure measurements can fail in detecting enough collateral flow if the radial artery is insufficiently compressed.     

Can the modified Allen's test always detect sufficient collateral flow in the hand? A computational study

Blood flow in the largest arteries of the arm up to the digital arteries is numerically modelled using the one-dimensional equations of pressure and flow wave propagation in compliant vessels. The model can be applied to different anatomies of arterial networks and can simulate compression of arteries, these allowing us to simulate the modified Allen's test (MAT) and to assess its suitability for the detection of sufficient collateral flow in the hand if radial blood supply is interrupted. The test measures blood flow in the superficial palmar arch before and during compression of the radial artery. The absence of reversal flow in the palmar arch with the compression indicates insufficient collateral flow and is referred to as a positive MAT. This study shows that small calibres of the superficial palmar arch and insufficient compression of the radial artery can lead to false-positive results. Measurement of the drop in digital systolic pressures with compression of the radial artery has proved to be a more sensitive test to predict the presence of sufficient ulnar collateral flow in networks with small calibres of the superficial palmar arch. However, this study also shows that digital pressure measurements can fail in detecting enough collateral flow if the radial artery is insufficiently compressed.     

Can results from limnocorral experiments be transferred to in situ conditions?

In 1982–1984 eight limnocorral (LC) experiments, each lasting for two weeks, were performed in mesotrophic Lake Lucerne, Switzerland, to study the effects of biomanipulation (removal of crustaceans by 95 µm filter nets) on zooplankton — phytoplankton relationships and epilimnetic carbon and phosphorus fluxes. Seston concentrations and to a lesser extent primary production rates were reduced in control LCs through zooplankton grazing, and settling flux increased through fecal pellet production. But C and P regeneration were not significantly affected.We found several indications that the LCs, despite of their large size ( 70 m³, 3 m in diameter and 11 m long) were artificial systems when compared to the surrounding lake: The eddy diffusion was diminished by about one order of magnitude, nutrients depleted (but phosphorus was supplied to the LCs), the phyto- and zooplankton showed lower standing crops in the control LCs than in the lake, the phytoplankton showed a shift from nannoplankton to netplankton, the crustacean zooplankton was mostly limited in their vertical migration, and the POC and PP sedimentation rates were increased. Moreover, in our set of experiments we always found outliers, which may have been caused by the different in situ conditions at the beginning of the experiments, and further enhanced by the complexity of the enclosed system.The problems of the LC-technique, such as replicability, scaling (size and time) and data extrapolation are discussed. The impact of crustacean zooplankton on particulate matter, i.e. seston reduction and sedimentation enhancement, can be extrapolated on a qualitative rather than on a quantitative basis for the Lake Lucerne ecosystem.     

Can insecticide mixtures be considered to surmount neonicotinoid resistance in Bemisia tabaci?

Cotton whitefly, Bemisia tabaci is an important polyphagous pest worldwide. It is exposed to various chemical insecticides throughout the year, resulting in the rapid development of insecticide resistance. Mixtures of insecticides with distinct modes of action could enhance the toxicity of chemicals more effectively than sequences or rotations in resistant pest populations. Bioassays were conducted to study the efficacy of mixtures of neonicotinoid and ketoenol insecticides at different ratios against a laboratory susceptible (Lab-WB) and a neonicotinoid resistant (TMX-SEL) strain of B. tabaci Asia I. The results showed that mixtures of imidacloprid, acetamiprid, thiamethoxam or dinotefuran with spiromesifen at 1:1, 1:10 and 1:20 ratios and of imidacloprid, thiamethoxam or dinotefuran with spirotetramat at 1:1 ratio significantly increased (p < 0.05) toxicity to neonicotinoids in TMX-SEL strain. The combination indices of each tested neonicotinoids + ketoenols at 1:1 ratio and of acetamiprid + spiromesifen, and imidacloprid or dinotefuran + spirotetramat at 1:10 ratio for TMX-SEL strain were significantly below 1, suggesting synergistic interactions. The inhibitors PBO and DEF largely overcame resistance to the tested neonicotinoids, while none of the synergists significantly restored the susceptibility of B. tabaci to ketoenols. Increased activities of P450 monooxygenase and esterase were observed in TMX-SEL strain with an elevated 2.76 and 1.32-fold, respectively. Mixtures of neonicotinoids with spiromesifen or spirotetramat at a 1:1 ratio could be used to restore the neonicotinoid susceptibility in B. tabaci.     

Can root electrical capacitance be used to predict root mass in soil?

Background

Electrical capacitance, measured between an electrode inserted at the base of a plant and an electrode in the rooting substrate, is often linearly correlated with root mass. Electrical capacitance has often been used as an assay for root mass, and is conventionally interpreted using an electrical model in which roots behave as cylindrical capacitors wired in parallel. Recent experiments in hydroponics show that this interpretation is incorrect and a new model has been proposed. Here, the new model is tested in solid substrates.

Methods

The capacitances of compost and soil were determined as a function of water content, and the capacitances of cereal plants growing in sand or potting compost in the glasshouse, or in the field, were measured under contrasting irrigation regimes.

Key Results

Capacitances of compost and soil increased with increasing water content. At water contents approaching field capacity, compost and soil had capacitances at least an order of magnitude greater than those of plant tissues. For plants growing in solid substrates, wetting the substrate locally around the stem base was both necessary and sufficient to record maximum capacitance, which was correlated with stem cross-sectional area: capacitance of excised stem tissue equalled that of the plant in wet soil. Capacitance measured between two electrodes could be modelled as an electrical circuit in which component capacitors (plant tissue or rooting substrate) are wired in series.

Conclusions

The results were consistent with the new physical interpretation of plant capacitance. Substrate capacitance and plant capacitance combine according to standard physical laws. For plants growing in wet substrate, the capacitance measured is largely determined by the tissue between the surface of the substrate and the electrode attached to the plant. Whilst the measured capacitance can, in some circumstances, be correlated with root mass, it is not a direct assay of root mass.     

Can time-averaged flow boundary conditions be used to meet the clinical timeline for Fontan surgical planning?

Cardiovascular simulations have great potential as a clinical tool for planning and evaluating patient-specific treatment strategies for those suffering from congenital heart diseases, specifically Fontan patients. However, several bottlenecks have delayed wider deployment of the simulations for clinical use; the main obstacle is simulation cost. Currently, time-averaged clinical flow measurements are utilized as numerical boundary conditions (BCs) in order to reduce the computational power and time needed to offer surgical planning within a clinical time frame. Nevertheless, pulsatile blood flow is observed in vivo, and its significant impact on numerical simulations has been demonstrated. Therefore, it is imperative to carry out a comprehensive study analyzing the sensitivity of using time-averaged BCs. In this study, sensitivity is evaluated based on the discrepancies between hemodynamic metrics calculated using time-averaged and pulsatile BCs; smaller discrepancies indicate less sensitivity.The current study incorporates a comparison between 3D patient-specific CFD simulations using both the time-averaged and pulsatile BCs for 101 Fontan patients. The sensitivity analysis involves two clinically important hemodynamic metrics: hepatic flow distribution (HFD) and indexed power loss (iPL). Paired demographic group comparisons revealed that HFD sensitivity is significantly different between single and bilateral superior vena cava cohorts but no other demographic discrepancies were observed for HFD or iPL. Multivariate regression analyses show that the best predictors for sensitivity involve flow pulsatilities, time-averaged flow rates, and geometric characteristics of the Fontan connection. These predictors provide patient-specific guidelines to determine the effectiveness of analyzing patient-specific surgical options with time-averaged BCs within a clinical time frame.     

Can ecosystem functional recovery be traced to decomposition and nitrogen dynamics in estuaries of the Lower Laguna Madre,Texas?

The biggest incentive to attempt the restoration and protection of estuaries is their widely acknowledged ecological and economic importance. Assessing estuary health and recovery can most accurately come from examining ecosystem processes. The purpose of this study was to explore the potential of mass loss and nitrogen (N) dynamics during leaf litter decomposition, to detect signs of functional recovery in two estuarine systems in south Texas. Submerged litterbags with black mangrove (Avicennia germinans) leaves were retrieved at various dates over 320 days. Decomposition was about 50% slower in one of the recovering systems compared to a reference site. Nitrogen immobilization and release from decaying leaf litter also discriminated among sites. Nitrogen immobilization potentials ranged from 4.15 to 6.89 mgN/g leaf litter, with the reference site exhibiting the highest value and thus the highest potential to conserve N during litter decomposition. The reference site also had a N immobilization time twice as long as the recovering sites, and a slower net release after the immobilization, appearing again as the most conservative in this part of the N cycling, possibly pointing to a less disturbed, or more stable ecosystem. Overall, the N dynamics during decomposition of mangrove leaf litter were similar in both recovering sites, whereas the reference site had a more conservative nutrient dynamics with more N being retained for longer in decomposing litter, coupled with a slower net release. Metrics derived from N dynamics may provide a finer resolution assessment of functional recovery, than only decomposition metrics.     

Can Ca2+-dependent competence be repeatedly induced in the same Escherichia coli cells?

Summary With the help of devised multicycle consecutive transformation (MCT) it is shown that Ca²⁺-dependent competence can be repeatedly induced in the same population of Escherichia coli cells. The same fraction of cells is induced to competence and transformed during MCT. In contrast to the results on classical transformation with mixed DNA preparations, no double transformants are observed in MCT. The competent cells and transformants are found to be more fragile than nontransformed cells. The latter are represented presumably by the cells that have not absorbed exogenous plasmid DNA. The results suggest that there is strong interference between plasmid DNAs during MCT, and that the presence of exogenous DNA makes the cells more sensitive to the apparently harmful procedure of repeated competence induction.     

Could passive knee laxity be related to active gait mechanics? An exploratory computational biomechanical study using probabilistic methods

Improving total knee replacement (TKR) requires better understanding of the many factors influencing clinical outcomes. Recently, probabilistic studies have investigated the influence of variability for individual TKR activities. This study demonstrates conceptually how probabilistic studies might further provide a framework to explore relationships not just within but between multiple different activities, e.g. intra-operative passive laxity drawer loading and post-operative active gait. Two implants were compared using simulated ISO-gait and passive laxity loading, with factors including mal-positioning and soft-tissue constraint varied using Monte-Carlo analysis. The results illustrate that correlations between different activities can be quantified; this demonstration study suggests further research is justified (with detailed clinically representative models) to explore the relationship between passive and active mechanics for specific in vivo conditions. Probabilistics is a key enabling methodology for achieving this goal. In future, exploring correlations between different activities may facilitate a better holistic understanding of TKR function.     

Learning to forage in a regenerating patchy environment: Can it fail to be optimal?

The behaviour of animals foraging along closed traplines of regenerating patches of food has been simulated using a learning rule that determines when an animal should leave the patch at which it is currently feeding to search for another one. The rule causes the animal to stay at the patch as long as it is feeding faster than it remembers doing. The foraging behaviour of one animal, and of two or more animals together, feeding in traplines containing patches of the same and of differing types has been simulated, and in all cases the foraging behaviour generated by the rule allowed the animals to exploit the food very efficiently. The learning model is also responsible for indirect social interactions among animals sharing the same trapline because the feeding of each animal reduces the availability of food for the others. This causes a population of animals to disperse themselves, on average, among patches of food according to the ideal free distribution. The relationship between the learning model and conventional optimal foraging models is examined and it is shown that it is pointless to try to account for learned behaviour in the context of optimal foraging theory.     

Can occupancy patterns be used to predict distributions in widely separated geographic regions?

Occupancy models, that describe the presence and absence patterns of a species in a given area, are increasingly being used to predict the occurrence of the species in unsurveyed sites, as an aid to conservation planning. In this paper, we consider whether conclusions about local distributions derived from one landscape can be extrapolated to others. We found that habitat patchiness influenced the distribution and abundance of the host-specific moth Wheeleria spilodactylus in a similar way in two landscapes widely separated geographically. In both geographic regions, the spatial location (positive effect of connectivity), and quantity of resource (positive effect of host plant density) increased the likelihood that the moth would be present, consistent with the expectations of metapopulation dynamics. Though some biological attributes of the species appeared to be slightly different, including population density and the timing of the life cycle (phenology), occupancy patterns in one landscape accurately predict occupancy in the other landscape. Our results suggest that it maybe possible to make predictions from one landscape to another, even when the landscapes are widely separated.