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Purpose Acoustic streaming induced by applying transcranial focused ultrasound (FUS) promotes localized advective solute transport in the brain and has recently garnered research interest for drug delivery and enhancement of brain waste clearance. The acoustic streaming behavior in brain tissue is difficult to model numerically and thus warrants an in vitro examination of the effects of using different sonication parameters, in terms of frequency, intensity, and pulse duration (PD). Methods Melamine and polyvinyl alcohol (PVA) foams were used to mimic the porous brain tissue, which contains leptomeningeal fenestrations and perivascular space, while agar hydrogel was used to emulate denser neuropil. FUS was delivered to these media, which were immersed in a phosphate-buffered saline containing toluidine blue O dye, across various frequencies (400, 500, and 600 kHz; applicable to transcranial delivery) in a pulsed mode at two different spatial-peak pulse-average intensities (3 and 4 W/cm2). Results Image analysis showed that the use of 400 kHz yielded the greatest dye infiltration in melamine foam, while sonication had no impact on infiltration in the agar hydrogel due to the dominance of diffusional transport. Using a fixed spatial-peak temporal-average intensity of 0.4 W/cm2 at 400 kHz, a PD of 75 ms resulted in the greatest infiltration depth in both melamine and PVA foams among the tested range (50-150 ms). Conclusion These findings suggest the existence of a specific frequency and PD that induce greater enhancement of solute/fluid movement, which may contribute to eventual in vivo applications in promoting waste clearance from the brain.

Purpose: Acoustic streaming induced by applying transcranial focused ultrasound (FUS) promotes localized advective solute transport in the brain and has recently garnered research interest for drug delivery and enhancement of brain waste clearance. The acoustic streaming behavior in brain tissue is difficult to model numerically and thus warrants an in vitro examination of the effects of using different sonication parameters, in terms of frequency, intensity, and pulse duration (PD). Methods: Melamine and polyvinyl alcohol (PVA) foams were used to mimic the porous brain tissue, which contains leptomeningeal fenestrations and perivascular space, while agar hydrogel was used to emulate denser neuropil. FUS was delivered to these media, which were immersed in a phosphate-buffered saline containing toluidine blue O dye, across various frequencies (400, 500, and 600 kHz; applicable to transcranial delivery) in a pulsed mode at two different spatialpeak pulse-average intensities (3 and 4 W/cm2). Results: Image analysis showed that the use of 400 kHz yielded the greatest dye infiltration in melamine foam, while sonication had no impact on infiltration in the agar hydrogel due to the dominance of diffusional transport. Using a fixed spatial-peak temporal-average intensity of 0.4 W/cm2 at 400 kHz, a PD of 75 ms resulted in the greatest infiltration depth in both melamine and PVA foams among the tested range (50-150 ms). Conclusion: These findings suggest the existence of a specific frequency and PD that induce greater enhancement of solute/fluid movement, which may contribute to eventual in vivo applications in promoting waste clearance from the brain. [ABSTRACT FROM AUTHOR]

Grooved liquid annular seals have a significant influence on the design of turbomachines. Corresponding lubrication film models need to account for the different friction behavior of the grooves compared to plain seals. However, there is a lack of reliable and validated models for this purpose. Thus, the applicability of a friction factor model is explored and a calibration method is presented. A single square groove is investigated by means of 96 steady-state RANS simulations for different operation conditions and groove geometries. The results are used to calibrate the friction model and successfully verify it in terms of the pressure drop over the groove. For validation, two full grooved seals with relatively large square grooves were investigated by experiment. The friction model was incorporated in a lubrication model and compared to the measurement data for the pressure difference and the resulting force for specified leakage and eccentricity. The model predictions for the pressure difference can be considered very good. The force predictions show significant deviation, but can be considered acceptable given the low force magnitudes and measurement uncertainty. The results offer a general validity to our friction model approach, assumptions and the calibration method. [ABSTRACT FROM AUTHOR]

The standard model of cosmology,, has been successful in describing many observations. With the improvement of the number and the accuracy of observations, some inconsistencies among key cosmological parameters of the model have emerged. Many alternative models are proposed to alleviate these tensions. On the other hand, some observations of peculiar velocity show higher values than expected in a universe which may contradict the cosmological principle. In this work, we used linear perturbation theory to measure bulk flow and parameter in two alternative cosmological models and XCDM. We compared measured bulk flows with the predictions and some observations. We did a analysis to see which model is preferred by data. We find that model predicts higher bulk flows and is more consistent with observational data but does not reduce tension. Bulk flows measured in the XCDM model are lower compared to . However, this model can reconcile tension.

Hoppers are widely used biomass handling devices that channel bulk biomass from storage to subsequent handling equipment. Jenike’s longstanding approach, based on the Mohr-Coulomb model, has been successfully used to design hoppers handling cohesionless granular materials such as grains and other agricultural produces. However, designing a hopper to ensure reliable biomass flow is found to be challenging due to cohesion, irregular particle shape, and bulk material elastoplasticity. This study aims to address the biomass handling engineering challenge with alternative constitutive material models concerning the flow behavior of bulk solids. Finite element modeling is an approach that allows for implementation of different material models, whose underlying constitutive theories assist in investigating the origin and manifestation of bulk mechanical behavior of granular materials. This study focuses on the incipient gravity hopper flow of two types of biomass feedstocks, i.e., ground corn stover and Douglas fir wood. Three widely used constitutive material models, i.e., Mohr-Coulomb model, modified Cam-Clay model, and Drucker-Prager/Cap model, are implemented. Using the flow pattern represented by the volume of biomass exhibiting more than 7% of axial strain (Kamath and Puri, 1999), the finite element model predicts that the bulk corn stover particulate material forms an arch, which represents a hampered transition from the static state to the dynamic flow-state out of the hopper, whereas bulk Douglas fir wood particulate material develops a reliable mass flow pattern. A laboratory scale hopper was used to experimentally determine the biomass flow conditions, which were subsequently compared with the predicted onset of flow by a finite element model (FEM). The developed FEM was found to correctly predict the initiation of mass flow for the milled Douglas fir wood, whereas corn stover was predicted to establish a strong core flow suggesting an unreliable handling characteristic. This observation aligns with the reported poor handling of milled corn stover.

Grooved liquid annular seals have a significant influence on the design of turbomachines. Corresponding lubrication film models need to account for the different friction behavior of the grooves compared to plain seals. However, there is a lack of reliable and validated models for this purpose. Thus, the applicability of a friction factor model is explored and a calibration method is presented. A single square groove is investigated by means of 96 steady-state RANS simulations for different operation conditions and groove geometries. The results are used to calibrate the friction model and successfully verify it in terms of the pressure drop over the groove. For validation, two full grooved seals with relatively large square grooves were investigated by experiment. The friction model was incorporated in a lubrication model and compared to the measurement data for the pressure difference and the resulting force for specified leakage and eccentricity. The model predictions for the pressure difference can be considered very good. The force predictions show significant deviation, but can be considered acceptable given the low force magnitudes and measurement uncertainty. The results offer a general validity to our friction model approach, assumptions and the calibration method.

Abstract Background Previous models of intracranial pressure (ICP) dynamics have not included flow of cerebral interstitial fluid (ISF) and changes in resistance to its flow when brain swelling occurs. We sought to develop a mathematical model that incorporates resistance to the bulk flow of cerebral ISF to better simulate the physiological changes that occur in pathologies in which brain swelling predominates and to assess the model’s ability to depict changes in cerebral physiology associated with cerebral edema. Methods We developed a lumped parameter model which includes a representation of cerebral ISF flow within brain tissue and its interactions with CSF flow and cerebral blood flow (CBF). The model is based on an electrical analog circuit with four intracranial compartments: the (1) subarachnoid space, (2) brain, (3) ventricles, (4) cerebral vasculature and the extracranial spinal thecal sac. We determined changes in pressure and volume within cerebral compartments at steady-state and simulated physiological perturbations including rapid injection of fluid into the intracranial space, hyperventilation, and hypoventilation. We simulated changes in resistance to flow or absorption of CSF and cerebral ISF to model hydrocephalus, cerebral edema, and to simulate disruption of the blood–brain barrier (BBB). Results The model accurately replicates well-accepted features of intracranial physiology including the exponential-like pressure–volume curve with rapid fluid injection, increased ICP pulse pressure with rising ICP, hydrocephalus resulting from increased resistance to CSF outflow, and changes associated with hyperventilation and hypoventilation. Importantly, modeling cerebral edema with increased resistance to cerebral ISF flow mimics key features of brain swelling including elevated ICP, increased brain volume, markedly reduced ventricular volume, and a contracted subarachnoid space. Similarly, a decreased resistance to flow of fluid across the BBB leads to an exponential-like rise in ICP and ventricular collapse. Conclusions The model accurately depicts the complex interactions that occur between pressure, volume, and resistances to flow in the different intracranial compartments under specific pathophysiological conditions. In modelling resistance to bulk flow of cerebral ISF, it may serve as a platform for improved modelling of cerebral edema and blood–brain barrier disruption that occur following brain injury.

Recent models represent gas (methane) migration in low-permeability media as a weighted sum of various contributions, each associated with a given flow regime. These models typically embed numerous chemical/physical parameters that cannot be easily and unambiguously evaluated via experimental investigations. In this context, modern sensitivity analysis techniques enable us to diagnose the behavior of a given model through the quantification of the importance and role of model input uncertainties with respect to a target model output. Here, we rely on two global sensitivity analysis approaches and metrics (i.e., variance-based Sobol' indices and moment-based AMA indices) to assess the behavior of a recent interpretive model that conceptualizes gas migration as the sum of a surface diffusion mechanism and two weighted bulk flow components. We quantitatively investigate the impact of (i) each uncertain model parameter and (ii) the type of their associated probability distribution on the evaluation of methane flow. We then derive the structure of an effective diffusion coefficient embedding all complex mechanisms of the model considered and allowing quantification of the relative contribution of each flow mechanism to the overall gas flow. Article Highlights: Relative importance of parameters driving gas flow in low-permeability media is assessed. The influence of parameter probability distribution on gas flow statistics is appraised. A simple effective diffusion model embedding major methane flow mechanisms is derived. [ABSTRACT FROM AUTHOR]

The glymphatic hypothesis proposes a mechanism for extravascular transport into and out of the brain of hydrophilic solutes unable to cross the blood–brain barrier. It suggests that there is a circulation of fluid carrying solutes inwards via periarterial routes, through the interstitium and outwards via perivenous routes. This review critically analyses the evidence surrounding the mechanisms involved in each of these stages. There is good evidence that both influx and efflux of solutes occur along periarterial routes but no evidence that the principal route of outflow is perivenous. Furthermore, periarterial inflow of fluid is unlikely to be adequate to provide the outflow that would be needed to account for solute efflux. A tenet of the hypothesis is that flow sweeps solutes through the parenchyma. However, the velocity of any possible circulatory flow within the interstitium is too small compared to diffusion to provide effective solute movement. By comparison the earlier classical hypothesis describing extravascular transport proposed fluid entry into the parenchyma across the blood–brain barrier, solute movements within the parenchyma by diffusion, and solute efflux partly by diffusion near brain surfaces and partly carried by flow along "preferred routes" including perivascular spaces, white matter tracts and subependymal spaces. It did not suggest fluid entry via periarterial routes. Evidence is still incomplete concerning the routes and fate of solutes leaving the brain. A large proportion of the solutes eliminated from the parenchyma go to lymph nodes before reaching blood but the proportions delivered directly to lymph or indirectly via CSF which then enters lymph are as yet unclear. In addition, still not understood is why and how the absence of AQP4 which is normally highly expressed on glial endfeet lining periarterial and perivenous routes reduces rates of solute elimination from the parenchyma and of solute delivery to it from remote sites of injection. Neither the glymphatic hypothesis nor the earlier classical hypothesis adequately explain how solutes and fluid move into, through and out of the brain parenchyma. Features of a more complete description are discussed. All aspects of extravascular transport require further study. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a three-compartmental semi-physiological model for analysis of uptake clearance and efflux from brain tissue of the hydrophilic markers sucrose and mannitol, compared to non-compartmental techniques presuming unidirectional uptake. Methods: Stable isotope-labeled [13C]sucrose and [13C]mannitol (10 mg/kg each) were injected as IV bolus into the tail vein of awake young adult mice. Blood and brain samples were taken after different time intervals up to 8 h. Plasma and brain concentrations were quantified by UPLC-MS/MS. Brain uptake clearance (Kin) was analyzed using either the single-time point analysis, the multiple time point graphical method, or by fitting the parameters of a three-compartmental model that allows for symmetrical exchange across the blood-brain barrier and an additional brain efflux clearance. Results: The three-compartment model was able to describe the experimental data well, yielding estimates for Kin of sucrose and mannitol of 0.068 ± 0.005 and 0.146 ± 0.020 μl.min−1.g−1, respectively, which were significantly different (p < 0.01). The separate brain efflux clearance had values of 0.693 ± 0.106 (sucrose) and 0.881 ± 0.20 (mannitol) μl.min−1.g−1, which were not statistically different. Kin values obtained by single time point and multiple time point analyses were dependent on the terminal sampling time and showed declining values for later time points. Conclusions: Using the three-compartment model allows determination of Kin for small molecule hydrophilic markers with low blood-brain barrier permeability. It also provides, for the first time, an estimate of brain efflux after systemic administration of a marker, which likely represents bulk flow clearance from brain tissue. [ABSTRACT FROM AUTHOR]

Interstitial fluid movement in the brain parenchyma has been suggested to contribute to sustaining the metabolism in brain parenchyma and maintaining the function of neurons and glial cells. The pulsatile hydrostatic pressure gradient may be one of the driving forces of this bulk flow. However, osmotic pressure-related factors have not been studied until now. In this prospective observational study, to elucidate the relationship between osmolality (mOsm/kg) in the serum and that in the cerebrospinal fluid (CSF), we simultaneously measured the serum and CSF osmolality of 179 subjects with suspected neurological conditions. Serum osmolality was 283.6 ± 6.5 mOsm/kg and CSF osmolality was 289.5 ± 6.6 mOsm/kg. Because the specific gravity of serum and CSF is known to be 1.024–1.028 and 1.004–1.007, respectively, the estimated average of osmolarity (mOsm/L) in the serum and CSF covered exactly the same range (i.e., 290.5–291.5 mOsm/L). There was strong correlation between CSF osmolality and serum osmolality, but the difference in osmolality between serum and CSF was not correlated with serum osmolality, serum electrolyte levels, protein levels, or quotient of albumin. In conclusion, CSF osmolarity was suggested to be equal to serum osmolarity. Osmolarity is not one of the driving forces of this bulk flow. Other factors such as hydrostatic pressure gradient should be used to explain the mechanism of bulk flow in the brain parenchyma. This study was approved by the Institutional Review Board of the Tohoku University Hospital (approval No. IRB No. 2015-1-257) on July 29, 2015.

Background: Previous models of intracranial pressure (ICP) dynamics have not included flow of cerebral interstitial fluid (ISF) and changes in resistance to its flow when brain swelling occurs. We sought to develop a mathematical model that incorporates resistance to the bulk flow of cerebral ISF to better simulate the physiological changes that occur in pathologies in which brain swelling predominates and to assess the model's ability to depict changes in cerebral physiology associated with cerebral edema. Methods: We developed a lumped parameter model which includes a representation of cerebral ISF flow within brain tissue and its interactions with CSF flow and cerebral blood flow (CBF). The model is based on an electrical analog circuit with four intracranial compartments: the (1) subarachnoid space, (2) brain, (3) ventricles, (4) cerebral vasculature and the extracranial spinal thecal sac. We determined changes in pressure and volume within cerebral compartments at steady-state and simulated physiological perturbations including rapid injection of fluid into the intracranial space, hyperventilation, and hypoventilation. We simulated changes in resistance to flow or absorption of CSF and cerebral ISF to model hydrocephalus, cerebral edema, and to simulate disruption of the blood–brain barrier (BBB). Results: The model accurately replicates well-accepted features of intracranial physiology including the exponential-like pressure–volume curve with rapid fluid injection, increased ICP pulse pressure with rising ICP, hydrocephalus resulting from increased resistance to CSF outflow, and changes associated with hyperventilation and hypoventilation. Importantly, modeling cerebral edema with increased resistance to cerebral ISF flow mimics key features of brain swelling including elevated ICP, increased brain volume, markedly reduced ventricular volume, and a contracted subarachnoid space. Similarly, a decreased resistance to flow of fluid across the BBB leads to an exponential-like rise in ICP and ventricular collapse. Conclusions: The model accurately depicts the complex interactions that occur between pressure, volume, and resistances to flow in the different intracranial compartments under specific pathophysiological conditions. In modelling resistance to bulk flow of cerebral ISF, it may serve as a platform for improved modelling of cerebral edema and blood–brain barrier disruption that occur following brain injury. [ABSTRACT FROM AUTHOR]

Powder processing and manufacturing operations are rate processes for which the bottleneck is cohesive powder flow. Diversity of material properties, particulate form, and sensitivity to environmental conditions, such as humidity and tribo-electric charging, make its prediction very challenging. However, this is highly desirable particularly when addressing a powder material for which only a small quantity is available. Furthermore, in a number of applications powder flow testing at low stress levels is highly desirable.Characterisation of bulk powder failure for flow initiation (quasi-static) is well established. However, bulk flow parameters are all sensitive to strain rate with which the powder is sheared, but in contrast to quasi-static test methods, there is no shear cell for characterisation of the bulk parameters in the dynamic regime. There are only a handful of instruments available for powder rheometry, in which the bulk resistance to motion can be quantified as a function of the shear strain rate, but the challenge is relating the bulk behaviour to the physical and mechanical properties of constituting particles. A critique of the current state of the art in characterisation and analysis of cohesive powder flow is presented, addressing the effects of cohesion, strain rate, fluid medium drag and particle shape.

The aim of the work is devoted to the substantiation of the choice of excipients while the development of Cardiosten tablets with a dry extract from a mixture of medicinal plant materials of cardiological action, taking into account the application of the mathematical planning of the experiment. Materials and methods. Using the method of mathematical planning of the experiment (MPE), the influence of auxiliary substances on the technological properties of the granules with dry extract “Cardiosten” and tablets obtained from these granules was investigated. Fillers, sorbents (moisture regulators), structure-forming substances (disintegrating agents), binding substances and calcium stearate as a powdering agent (antifriction substance) were used as excipients. All groups of excipients (except calcium stearate) were divided into levels of factors, which were investigated by the four-factor experiment method based on a Greek-Latin square. The following indicators of granules and tablets based on dry extract “Cardiosen” were used as responses: bulk density g/cm3; mass flow for tableting, s/100g; mass loss during wetting and granulation, %; disintegration of tablets, min., abrasion of tablets, % and resistance of tablets to crushing, N. Results. In the course of the conducted research, the dependence of all responses on the above factors was determined according to the technological parameters of the tablet mass and finished tablets. Based on the analysis of the most effective levels of factors that had the maximum effect on the responses, the following substances were selected as further objects: Prosolv HD 90 (vehicle), Neosorb –100 (sorbent), polyplasdon XL10 (structuring agent) and HPMC solution as a binder. Conclusions. Using the MPE method, the most optimal excipients were selected for the production of tablets with a dry extract content of “Cardiosten”. Based on the indicators of pelletized mass (bulk density, bulk flow, weight loss) and tablets (disintegration time of tablets, abrasion of tablets, resistance of tablets to crushing), the qualitative composition of auxiliary substances for the production of tablets by the method of wet granulation - Prosolv HD 90 (filler) was determined , Neosorb – 100 (sorbent), polyplasdon XL10 (structuring agent), HPMC solution (binding agent).

Abstract Background Periarterial spaces (PASs) are annular channels that surround arteries in the brain and contain cerebrospinal fluid (CSF): a flow of CSF in these channels is thought to be an important part of the brain’s system for clearing metabolic wastes. In vivo observations reveal that they are not concentric, circular annuli, however: the outer boundaries are often oblate, and the arteries that form the inner boundaries are often offset from the central axis. Methods We model PAS cross-sections as circles surrounded by ellipses and vary the radii of the circles, major and minor axes of the ellipses, and two-dimensional eccentricities of the circles with respect to the ellipses. For each shape, we solve the governing Navier–Stokes equation to determine the velocity profile for steady laminar flow and then compute the corresponding hydraulic resistance. Results We find that the observed shapes of PASs have lower hydraulic resistance than concentric, circular annuli of the same size, and therefore allow faster, more efficient flow of cerebrospinal fluid. We find that the minimum hydraulic resistance (and therefore maximum flow rate) for a given PAS cross-sectional area occurs when the ellipse is elongated and intersects the circle, dividing the PAS into two lobes, as is common around pial arteries. We also find that if both the inner and outer boundaries are nearly circular, the minimum hydraulic resistance occurs when the eccentricity is large, as is common around penetrating arteries. Conclusions The concentric circular annulus assumed in recent studies is not a good model of the shape of actual PASs observed in vivo, and it greatly overestimates the hydraulic resistance of the PAS. Our parameterization can be used to incorporate more realistic resistances into hydraulic network models of flow of cerebrospinal fluid in the brain. Our results demonstrate that actual shapes observed in vivo are nearly optimal, in the sense of offering the least hydraulic resistance. This optimization may well represent an evolutionary adaptation that maximizes clearance of metabolic waste from the brain.

Abstract Background Despite advances in in vivo imaging and experimental techniques, the nature of transport mechanisms in the brain remain elusive. Mathematical modelling verified using available experimental data offers a powerful tool for investigating hypotheses regarding extracellular transport of molecules in brain tissue. Here we describe a tool developed to aid in investigation of interstitial transport mechanisms, especially the potential for convection (or bulk flow) and its relevance to interstitial solute transport, for which there is conflicting evidence. Methods In this work, we compare a large body of published experimental data for transport in the brain to simulations of purely diffusive transport and simulations of combined convective and diffusive transport in the brain interstitium, incorporating current theories of perivascular influx and efflux. Results The simulations show (1) convective flow in the interstitium potentially of a similar magnitude to diffusive transport for molecules of interest and (2) exchange between the interstitium and perivascular space, whereby fluid and solutes may enter or exit the interstitium, are consistent with the experimental data. Simulations provide an upper limit for superficial convective velocity magnitude (approximately $$v$$ v = 50 μm min−1), a useful finding for researchers developing techniques to measure interstitial bulk flow. Conclusions For the large molecules of interest in neuropathology, bulk flow may be an important mechanism of interstitial transport. Further work is warranted to investigate the potential for bulk flow.

The performance and stability of a low-bypass turbofan transonic axial compressor with a nonuniform inlet flow is a significant concern in recent times. In both military and commercial aircraft, serpentine ducts produce significant inlet swirl distortion. Moreover, the nonuniform inlet flow frequently acts upon aircraft gas-turbine engines causing deteriorating effects on the aircraft engine. High circumferential swirl flows and inlet flow angularity decrease the aerodynamic performance and the stall margin and increase the rotor blade loading. The current paper is aimed at the investigation of the flow field in the tip clearance region of low-bypass turbofan transonic compressor rotor under nonuniform circumferential flow conditions through numerical simulation using Ansys CFX. The mathematical models based on 1D Mean Line Code and Dynamic Turbine Engine Compressor Code (DYNTECC) are used to analyze the nonuniform inlet swirl flow of the compressor rotor. The mathematical model is limited to compute the multistage compressor characteristics for the compression system and the combustor of a turbine engine. For the single-stage swirl flow analysis current paper focuses on the CFD based results. The results based on CFD show that co-swirl patterns slightly improve the stability range of the compressor; counter-swirl flows diminish it. [ABSTRACT FROM AUTHOR]

Abstract Background In animal models, dissolved compounds in the subarachnoid space and parenchyma have been found to preferentially transport through the cortex perivascular spaces (PVS) but the transport phenomena involved are unclear. Methods In this study two hydraulic network models were used to predict fluid motion produced by blood vessel pulsations and estimate the contribution made to solute transport in PVS and parenchyma. The effect of varying pulse amplitude and timing, PVS dimensions, and tissue hydraulic conductivity on fluid motion was investigated. Results Periodic vessel pulses resulted in oscillatory fluid motion in PVS and parenchyma but no net flow over time. For baseline parameters, PVS and parenchyma peak fluid velocity was on the order of 10 μm/s and 1 nm/s, with corresponding Peclet numbers below 103 and 10−1 respectively. Peak fluid velocity in the PVS and parenchyma tended to increase with increasing pulse amplitude and vessel size, and exhibited asymptotic relationships with hydraulic conductivity. Conclusions Solute transport in parenchyma was predicted to be diffusion dominated, with a negligible contribution from convection. In the PVS, dispersion due to oscillating flow likely plays a significant role in PVS rapid transport observed in previous in vivo experiments. This dispersive effect could be more significant than convective solute transport from net flow that may exist in PVS and should be studied further.

Abstract Background Transport of solutes has been observed in the spaces surrounding cerebral arteries and veins. Indeed, transport has been found in opposite directions in two different spaces around arteries. These findings have motivated hypotheses of bulk flow within these spaces. The glymphatic circulation hypothesis involves flow of cerebrospinal fluid from the cortical subarachnoid space to the parenchyma along the paraarterial (extramural, Virchow–Robin) space around arteries, and return flow to the cerebrospinal fluid (CSF) space via paravenous channels. The second hypothesis involves flow of interstitial fluid from the parenchyma to lymphatic vessels along basement membranes between arterial smooth muscle cells. Methods This article evaluates the plausibility of steady, pressure-driven flow in these channels with one-dimensional branching models. Results According to the models, the hydraulic resistance of arterial basement membranes is too large to accommodate estimated interstitial perfusion of the brain, unless the flow empties to lymphatic ducts after only several generations (still within the parenchyma). The estimated pressure drops required to drive paraarterial and paravenous flows of the same magnitude are not large, but paravenous flow back to the CSF space means that the total pressure difference driving both flows is limited to local pressure differences among the different CSF compartments, which are estimated to be small. Conclusions Periarterial flow and glymphatic circulation driven by steady pressure are both found to be implausible, given current estimates of anatomical and fluid dynamic parameters.

Powder processing and manufacturing operations are rate processes for which the bottleneck is cohesive powder flow. Diversity of material properties, particulate form, and sensitivity to environmental conditions, such as humidity and tribo-electric charging, make its prediction very challenging. However, this is highly desirable particularly when addressing a powder material for which only a small quantity is available. Furthermore, in a number of applications powder flow testing at low stress levels is highly desirable. Characterisation of bulk powder failure for flow initiation (quasi-static) is well established. However, bulk flow parameters are all sensitive to strain rate with which the powder is sheared, but in contrast to quasi-static test methods, there is no shear cell for characterisation of the bulk parameters in the dynamic regime. There are only a handful of instruments available for powder rheometry, in which the bulk resistance to motion can be quantified as a function of the shear strain rate, but the challenge is relating the bulk behaviour to the physical and mechanical properties of constituting particles. A critique of the current state of the art in characterisation and analysis of cohesive powder flow is presented, addressing the effects of cohesion, strain rate, fluid medium drag and particle shape. [ABSTRACT FROM AUTHOR]

In turbopumps, the dynamic characteristics of the floating ring seal and rotor system are important, especially when the floating ring seal fails to lock up. To investigate the motion of the system with the unlocked floating ring seal, a dynamic model for the whirling system is established in this study. On the basis of the perturbation method, the nonlinear model is simplified into a steady whirling model superimposed with perturbation motion. The transient bulk flow model is improved to calculate the hydrodynamic force in the seal clearance. The results show that the floating ring seal is able to steadily follow the rotor whirling motion and reduce the rotor whirling amplitude when the friction is not enough to lock the seal. The perturbation motion is calculated and proved stable, as the direct rotordynamic coefficients of the floating ring seal are much larger than the cross-coupled coefficients. Further, the effects of the mass and the friction of the floating ring seal, the rotor whirling amplitude and the interaction between the seal and the rotor on the dynamic characteristics of the whirling system are investigated. [ABSTRACT FROM AUTHOR]

Highlights • Transit of Evans blue albumin from CSF to serum measured spectrophotometrically. • Transit of Evans blue from CSF to perivascular spaces visualized in real time. • Simultaneous quantitative and qualitative analysis of glymphatic flux. Abstract Background The glymphatic system is a proposed pathway for clearance of proteins and macromolecules from brain, and disrupted glymphatic flux is implicated in neurological disease. We capitalized on colorimetric, fluorescent, and protein-binding properties of Evans blue to evaluate glymphatic flux. New method Twenty-five μL of 1% Evans blue-labeled albumin (EBA) in artificial cerebrospinal fluid (aCSF) was injected into the intracisternal space of anesthetized postnatal day 17 rats. Serum was collected at various time points after injection (n = 37) and EBA was measured spectrophotometrically. In separate rats (n = 3), a cranial window was placed over the parietal cortex and EBA transit was evaluated using in vivo multiphoton microscopy. Separate rats (n = 6) were processed for immunohistochemistry to examine localization of EBA. In some rats, intracranial pressure (ICP) was increased via intracisternal injection of aCSF. Results EBA was detected in serum as early as 30 min, was maximal at 4 h, and was undetectable at 72 h after intracisternal injection. Using intra-vital microscopy and immunohistochemistry EBA could be tracked from CSF to perivascular locations. Consistent with removal via glymphatic flux, increasing ICP to 40 mmHg accelerated transit of EBA from CSF to blood. Comparison with existing methods Transit of EBA from CSF to serum could be quantified spectrophotometrically without radioactive labeling. Glymphatic flux could also be qualitatively evaluated using EBA fluorescence. Conclusion We present a novel technique for simultaneous quantitative and qualitative evaluation of glymphatic flux in rats. [ABSTRACT FROM AUTHOR]

The cellular mechanisms that ensure the selectivity and fidelity of secretory cargo protein transport from the endoplasmic reticulum (ER) to the Golgi are still not well understood. The p24 protein complex acts as a specific cargo receptor for GPI-anchored proteins by facilitating their ER exit through a specialized export pathway in yeast. In parallel, the p24 complex can also exit the ER using the general pathway that exports the rest of secretory proteins with their respective cargo receptors. Here, we show biochemically that the p24 complex associates at the ER with other cargo receptors in a COPII-dependent manner, forming high-molecular weight multireceptor complexes. Furthermore, live cell imaging analysis reveals that the p24 complex is required to retain in the ER secretory cargos when their specific receptors are absent. This requirement does not involve neither the unfolded protein response nor the retrograde transport from the Golgi. Our results suggest that, in addition to its role as a cargo receptor in the specialized GPI-anchored protein pathway, the p24 complex also plays an independent role in secretory cargo selectivity during its exit through the general ER export pathway, preventing the non-selective bulk flow of native secretory cargos. This mechanism would ensure receptor-regulated cargo transport, providing an additional layer of regulation of secretory cargo selectivity during ER export.

This paper presents a lock-up condition with rotor whirling motion to predict the lock-up area for floating ring seals in liquid turbopumps. To calculate the hydrodynamic forces with arbitrary rotor motion, bulk flow model is modified with explicitly considering the squeeze velocity and temporal inertia. Finite element method is implemented to solve the transient nonlinear model. The effect of lock-up position on leakage and rotordynamic coefficients of floating ring seals is studied and shows insensitivity to eccentricity within moderate eccentric area (<0.5), which indicates that predicting lock-up area with the lock-up condition is feasible for application. With circular trajectory of rotors, the effects of rotor whirling radius and friction force on lock-up area are investigated. The results show that the lock-up area shrinks toward rotor whirling center, with the increase in the rotor whirling radius and decrease in the friction force. Further, a coupled method of rotor trajectory and floating ring seal lock-up area is presented to consider the interaction between rotors and floating ring seals. The results show that the effect of the interaction on the lock-up area is almost negligible, as lock-up position of floating ring seals has little effect on rotor trajectory. In addition, the effect of the seal configuration on the lock-up area is studied. [ABSTRACT FROM AUTHOR]

A vascular access (VA) is used to facilitate hemodialysis in patients that suffer from end-stage renal disease. However, they suffer from high failure rates due to non-maturation and venous stenosis, with intimal hyperplasia (IH) the underlying cause of both conditions. Abnormal hemodynamic profiles, which arise following VA creation, are believed to lead to the development of IH. However, the exact physiological response that initiates this process is unknown. This review evaluates the different hemodynamic parameters that are hypothesised to correlate with the development of IH. Review studies that examine the correlation between hemodynamic parameters and the onset of IH using computational fluid dynamics. These studies are divided into groups depending on the type of analysis conducted; longitudinal studies, patient specific arteriovenous fistula (AVF) studies, arteriovenous graft studies, idealised AVF studies and studies that analyse the bulk flow. Studies that conduct longitudinal analysis identify an overall reduction in wall shear stress (WSS) as the VA matures. This is further associated with outward remodelling and the successful maturation of the VA. The majority of studies that conduct a transversal analysis find that low/oscillating shear is associated with the development of IH. However, a number of studies find a link between high shear and high spatial and temporal WSS gradients and the onset of IH. This review highlights the lack of unanimity between studies and emphasises the fact that the exact physiological response that leads to the development of IH remains unknown. This accentuates the need for a single, precise hypothesis capable of accurately predicting the onset of IH. If computational modelling is to assist in this process, the number of longitudinal studies conducted must increase. This will provide a better understanding of the effect that hemodynamic parameters have on the remodelling process and potentially identify a single/group of parameter/s that can accurately predict the onset of IH. [ABSTRACT FROM AUTHOR]

The mass and heat transfer mechanisms during radio frequency/vacuum (RF/V) drying of square-edged timber were analyzed and discussed in detail, and a new one-dimensional mathematical model to describe the transport phenomena of mass and heat during continuous RF/V drying was derived from conservation equations based on the mass and heat transfer theory of porous materials. The new model provided a relatively fast and efficient way to simulate vacuum drying behavior assisted by dielectric heating. Its advantages compared with the conventional models include: (1) Each independent variable has a separate control equation and is solved independently by converting the partial differential equation into a difference equation with the finite volume method; (2) The calculated data from different parts of the specimen can be displayed in the evolution curves, and the change law of the parameters can be better described. After analyzing the calculated results, most of the important phenomena observed during RF/V drying were adequately described by this model. [ABSTRACT FROM AUTHOR]

The Physiology Core Concept of flow down gradients is a major concept in physiology, as pressure gradients are the key driving force for the bulk flow of fluids in biology. However, students struggle to understand that this principle is foundational to the mechanisms governing bulk flow across diverse physiological systems (e.g., blood flow, phloem sap flow). Our objective was to investigate whether bulk flow items that differ in scenario context (i.e., taxa, amount of scientific terminology, living or nonliving system) or in which aspect of the pressure gradient is kept constant (i.e., starting pressure or pressure gradient) influence undergraduate students' reasoning. Item scenario context did not impact the type of reasoning students used. However, students were more likely to use the Physiology Core Concept of "flow down [pressure] gradients" when the pressure gradient was kept constant and less likely to use this concept when the starting pressure was kept constant. We also investigated whether item scenario context or which aspect of the pressure gradient is kept constant impacted how consistent students were in the type of reasoning they used across two bulk flow items on the same homework. Most students were consistent across item scenario contexts (76%) and aspects of the pressure gradient kept constant (70%). Students who reasoned using "flow down gradients" on the first item were the most consistent (86, 89%), whereas students using "pressures indicate (but don't cause) flow" were the least consistent (43, 34%). Students who are less consistent know that pressure is somehow involved or indicates fluid flow but do not have a firm grasp of the concept of a pressure gradient as the driving force for fluid flow. These findings are the first empirical evidence to support the claim that using Physiology Core Concept reasoning supports transfer of knowledge across different physiological systems. NEW & NOTEWORTHY These findings are the first empirical evidence to support the claim that using Physiology Core Concept reasoning supports transfer of knowledge across different physiological systems.

CrossTalk proposal: The glymphatic system supports convective exchange of cerebrospinal fluid and brain interstitial fluid that is mediated by perivascular aquaporin-4 The "glymphatic" system is a brain-wide network of perivascular pathways that supports exchange of cerebrospinal fluid (CSF) and brain interstitial fluid (ISF), contributing to the efflux of interstitial solutes including amyloid (Iliff I et al i ., [12], [11] I a i ,[13]). These studies demonstrate that AQP4 plays a key role in both the influx of CSF solutes into the brain parenchyma and the clearance of interstitial solutes from brain tissue. Groothius I et al i ., as well as a recent study, suggest a significant role for anaesthetics in modulating both CSF tracer influx and ISF solute efflux (Groothuis I et al i ., [7]; Hablitz I et al i ., [8]). [Extracted from the article]