Physically Consistent Resolving Simulations of Turbulent Flows.

Usually applied simulation methods for turbulent flows as large eddy simulation (LES), wall-modeled LES (WMLES), and detached eddy simulation (DES) face significant challenges: they are characterized by improper resolution variations and essential practical simulation problems given by huge computational cost, imbalanced resolution transitions, and resolution mismatch. Alternative simulation methods are described here. By using an extremal entropy analysis, it is shown how minimal error simulation methods can be designed.

Acceleration of rises in the level of rivers induced by rising air temperatures in a cold climate.

The effects of climate change on water discharge in rivers in cold climates were investigated. To quantify the impacts of air temperature rises on the promotion of snowmelt and associated acceleration of a rise in the level of a river, 10 rivers on Hokkaido, northwestern Japan were chosen. Available data of daily water discharge for more than half a century by the Ministry of Land, Infrastructure, Transport and Tourism (MLIT) were correlated with air temperatures observed at the 8 weather stations operated by the Japan Meteorological Agency (JMA).

Effects of clay in a sandy soil on saturated/unsaturated pore water flow and dissolved chloride transport from road salt applications.

Saturated/unsaturated pore water flow induced by rainwater infiltration in a soil column composed of a mixture of Toyoura sand and a small amount of clay (kaolin minerals) and the rinsing rate (mass transfer) of dissolved NaCl accumulated in the pore system from previous road salt application were investigated by experiments and simulations. Experiments were conducted with variable kaolin minerals mass contents (mixing ratios) in the soil columns. Measured saturated hydraulic conductivity (K) diminished with increased clay contents, i.

Urinary Calprotectin loses specificity as tumour marker due to sterile leukocyturia associated with bladder cancer.

Background: Urinary Calprotectin, a mediator of the innate immune system, has been identified as a biomarker in bladder cancer. Our aim was to investigate the association between sterile leukocyturia and urinary Calprotectin in low-grade and high-grade bladder cancer.

Materials And Methods: We performed a prospective cross-sectional study including 52 patients with bladder cancer and 40 healthy controls.

Oxygen uptake prediction in rivers and streams: A stochastic approach.

Dissolved oxygen fluctuations in a river over a short period of time were assumed to be caused by the microbial growth dynamics, and a stochastic model was built for oxygen uptake. As a case study, biochemical oxygen demand (BOD) was measured in water from the Ura River, Oita River, and Otozu River flowing through the urban district of Oita, Japan. Water samples were taken from each river and partitioned into BOD bottles.

On the adhesion-cohesion balance and oxygen consumption characteristics of liver organoids.

Liver organoids (LOs) are of interest in tissue replacement, hepatotoxicity and pathophysiological studies. However, it is still unclear what triggers LO self-assembly and what the optimal environment is for their culture. Hypothesizing that LO formation occurs as a result of a fine balance between cell-substrate adhesion and cell-cell cohesion, we used 3 cell types (hepatocytes, liver sinusoidal endothelial cells and mesenchymal stem cells) to investigate LO self-assembly on different substrates keeping the culture parameters (e.

Applicability of second-generation upcyte® human hepatocytes for use in CYP inhibition and induction studies.

Human upcyte® hepatocytes are proliferating hepatocytes that retain many characteristics of primary human hepatocytes. We conducted a comprehensive evaluation of the application of second-generation upcyte® hepatocytes from four donors for inhibition and induction assays using a selection of reference inhibitors and inducers. CYP1A2, CYP2B6, CYP2C9, and CYP3A4 were reproducibly inhibited in a concentration-dependent manner and the calculated IC50 values for each compound correctly classified them as potent inhibitors.

Long-term culture and expansion of primary human hepatocytes.

Hepatocytes have a critical role in metabolism, but their study is limited by the inability to expand primary hepatocytes in vitro while maintaining proliferative capacity and metabolic function. Here we describe the oncostatin M (OSM)-dependent expansion of primary human hepatocytes by low expression of the human papilloma virus (HPV) genes E6 and E7 coupled with inhibition of epithelial-to-mesenchymal transition. We show that E6 and E7 expression upregulates the OSM receptor gp130 and that OSM stimulation induces hepatocytes to expand for up to 40 population doublings, producing 10 to 10 cells from a single human hepatocyte isolate.

In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.

Measurement of Blood Coagulation Factor Synthesis in Cultures of Human Hepatocytes.

An important function of the liver is the synthesis and secretion of blood coagulation factors. Within the liver, hepatocytes are involved in the synthesis of most blood coagulation factors, such as fibrinogen, prothrombin, factor V, VII, IX, X, XI, XII, as well as protein C and S, and antithrombin, whereas liver sinusoidal endothelial cells produce factor VIII and von Willebrand factor. Here, we describe methods for the detection and quantification of most blood coagulation factors in hepatocytes in vitro.

Optimization of upcyte® human hepatocytes for the in vitro micronucleus assay.

"Upcyte(®) human hepatocytes" have the unique property of combining proliferation with the expression of drug metabolising activities. In our current study, we evaluated whether these cells would be suitable for early in vitro micronucleus (MN) tests. A treatment period of 96 h without a recovery period was most reliable for detecting MN formation in upcyte(®) hepatocytes from Donor 740.

Analysis of fatigue properties and failure mechanisms of Ti6Al4V in the very high cycle fatigue regime using ultrasonic technology and 3D laser scanning vibrometry.

Accelerated fatigue tests with Ti6Al4V were carried out using a 20kHz ultrasonic testing facility to investigate the cyclic deformation behavior in the Very High Cycle Fatigue (VHCF) regime in detail. Beside parameters like the ultrasonic generator power and the displacement of the specimen, a 3D laser scanning vibrometer was used to characterize the oscillation and fatigue behavior of the Ti-alloy. The course of the S-N(f) curve at the stress ratio R=-1 shows a significant decrease of the bearable stress amplitude and a change from surface to subsurface failures in the VHCF regime for more than 10⁷ cycles.

Generation of proliferating human hepatocytes using Upcyte® technology: characterisation and applications in induction and cytotoxicity assays.

1. We have developed a novel technique which causes primary human hepatocytes to proliferate by transducing them with genes that upregulate their proliferation. 2.

Non-linear effects on solute transfer between flowing water and a sediment bed.

A previously developed model of periodic pore water flow in space and time, and associated solute transport in a stream bed of fine sand is extended to coarse sand and fine gravel. The pore water flow immediately below the sediment/water interface becomes intermittently a non-Darcy flow. The periodic pressure and velocity fluctuations considered are induced by near-bed coherent turbulent motions in the stream flow; they penetrate from the sediment/water interface into the sediment pore system and are described by a wave number (χ) and a period (T) that are given as functions of the shear velocity (U(∗)) between the flowing water and the sediment bed.

SAFL Baffle retrofit for suspended sediment removal in storm sewer sumps.

Standard sumps (manholes) provide a location for pipe junctions and maintenance access in stormwater drainage systems. Standard sumps can also remove sand and silt particles from stormwater, but have a high propensity for washout of the collected sediment. With appropriate maintenance these sumps may qualify as a stormwater best management practice (BMP) device for the removal of suspended sediment from stormwater runoff.

Factor VIII-eGFP fusion proteins with preserved functional activity for the analysis of the early secretory pathway of factor VIII.

Considering the difficulty in detecting factor (F)VIII in vivo, fluorescently labelled FVIII protein provides a tool to analyse the intracellular localisation, bio distribution, and pharmacokinetics of the protein in living organisms. Here, we report the use of FVIII full length and B-domain deleted proteins, fused to enhanced green fluorescent protein (eGFP) at the C-terminus of the coagulation protein via a nine amino acid spanning linker. Comparison of the FVIII-eGFP fusion proteins to their unlabelled counterparts showed no impairment with respect to recombinant expression levels, intracellular processing, specific coagulant activity and decay at physiological temperature.

Modelling and expression studies of two novel mutations causing factor V deficiency.

Human coagulation factor V (FV), a non-enzymatic cofactor of the prothrombinase complex, is required for the rapid generation of thrombin. FV deficiency is a rare autosomal recessive bleeding disorder. We describe two novel mutations, Tyr91Asn and Asp2098Tyr, found in two probands with a residual FV activity of 51% and 4%, respectively.

Increase of urban lake salinity by road deicing salt.

Over 317,000 tonnes of road salt (NaCl) are applied annually for road deicing in the Twin Cities Metropolitan Area (TCMA) of Minnesota. Although road salt is applied to increase driving safety, this practice influences environmental water quality. Thirteen lakes in the TCMA were studied over 46 months to determine if and how they respond to the seasonal applications of road salt.

A novel HSP90 chaperone complex regulates intracellular vesicle transport.

Heat shock protein 90 (HSP90) is considered a specialized molecular chaperone that controls the folding of cell-regulatory proteins such as steroid receptors and kinases. However, its high abundance is suggestive of a more general function in other fundamental processes. Here, we show that HSP90 is required for vesicular protein transport in the cell.

The chimeric cytokine Hyper-IL-6 enhances the efficiency of lentiviral gene transfer in hepatocytes both in vitro and in vivo.

Lentiviral vectors have been used for gene transfer into the liver but their ability to efficiently transduce quiescent hepatocytes remains controversial. Lentivirus-mediated gene transfer is more efficient in cycling cells. We determine the effect of H-IL6 in the lentiviral transduction.

Sedimentary microbial oxygen demand for laminar flow over a sediment bed of finite length.

Dead organic material accumulated on the bed of a lake, reservoir or wetland often provides the substrate for substantial microbial activity as well as chemical processes that withdraw dissolved oxygen (DO) from the water column. A model to estimate the actual DO profile and the "sedimentary oxygen demand (SOD)" must specify the rate of microbial or chemical activity in the sediment as well as the diffusive supply of DO from the water column through the diffusive boundary layer into the sediment. Most previous experimental and field studies have considered this problem with the assumptions that the diffusive boundary layer is (a) turbulent and (b) fully developed.

Molecular to fluid dynamics: the consequences of stochastic molecular motion.

The derivation of fluid dynamic equations from molecular equations is considered. This is done on the basis of a stochastic model for the molecular motion which can be obtained by a projection of underlying deterministic equations. The stochastic model is used to derive fluid dynamic equations where the molecular stress tensor and heat flux appear as unknowns.

Diffusive boundary layer development above a sediment-water interface.

A model to estimate the entry length to a fully developed diffusive boundary layer above a sediment bed, such as those found in lakes, reservoirs, rivers, and estuaries, is presented. The model is used to determine how the length of a sediment bed in mass-transfer experiments influences the measured vertical diffusive flux at the sediment-water interface. A nondimensional local mass flux is introduced in the form of a Sherwood number (Sh) and expressed as a function of both the distance from the leading edge of the sediment bed (x) and the Schmidt number (Sc).

Confocal microscopy analysis of native, full length and B-domain deleted coagulation factor VIII trafficking in mammalian cells.

In mammalian cells, factor VIII (FVIII) secretion depends upon its interaction with chaperones of the endoplasmic reticulum (ER) and requires a unique ATP-dependent step to dissociate aggregates formed within the ER. To further elucidate mechanisms which might account for the inefficient secretion of recombinant FVIII (rFVIII), we have analyzed the pathways of recombinant full length (rFVIII-FL) and B-domain deleted (rFVIII Delta B) FVIII and compared these to the secretion route of native FVIII in primary hepatocytes. Using confocal laser scanning microscopy in combination with a pulse chase of a known secretion marker, we describe the trafficking route of FVIII, which upon release from the ER--where it colocalizes with calnexin--is transported to the Golgi complex in vesicular-tubular transport complexes (VTCs) which could be further identified as being COP I coated.

Unsteady diffusional mass transfer at the sediment/water interface: Theory and significance for SOD measurement.

Dissolved oxygen uptake at a sediment/water interface (SOD) is controlled by mass transport and/or biochemical reactions in two adjacent boundary layers: the diffusive boundary layer delta(D) in the water and the penetration depth delta in the sediment. Either one of those boundary layers or both can be controlling. The transition from sediment control to water control is a function of shear velocity at the sediment/water interface (U(*)) and biochemical activity rate (micro(0)) in the sediment.