A multiple scale model for tumor growth

We present a physiologically structured lattice model for vascular tumor growth which accounts for blood flow and structural adaptation of the vasculature, transport of oxygen, interaction between cancerous and normal tissue, cell division, apoptosis, vascular endothelial growth factor release, and the coupling between these processes. Simulations of the model are used to investigate the effects of nutrient heterogeneity, growth and invasion of cancerous tissue, and emergent growth laws

The Migration of Elites in a Borderless World: Citizenship as an Incentive for Professionals and Managers?

Der Artikel geht der Frage nach, inwiefern die geöffneten Türen für die Immigration Hochqualifizierter in den OECD-Ländern tatsächlich zu einer verstärkten Migrationsbewegung führen. Die Analyse von Daten zu Eliten- und Hochqualifiziertenmigration in Ostasien, Europa und den USA führt zu dem Ergebnis, dass diese dem Muster einer „brain circulation“ folgt und die Staatsbürgerrechte dabei keine entscheidende Rolle spielen

BMW – Mastering the Crises with “New Efficiency?”

Purpose Make a contribution on company business models and typical reactions to economic crises. Design/methodology/approach Media-analysis-based case study. Findings Crisis is handled through drawing on a strategy deriving from the typical features of the company; through the crisis these features are even intensified. Research limitations/implications Multinational companies are complex and only transparent to a small degree; the empirical data therefore rests on a database with articles. Social implications Social implications can be seen at the BMW as a functioning example for social partnership as a form of economic embeddedness at the societal level

Hydrothermisch behandelte Lupinen zur Eiweißversorgung der Milchkuh

According to producer statements hydrothermal treatment of lupines increases the amount of rumen undegradable protein (UDP) from 20 % to 45 % and nXP values from 196 to 245 g/kg thus providing sufficient protein for dairy cows. To evaluate the effects of hydrothermal treatment on nutritive value of lupines, intestinal protein supply and lactation performance as well as economical and ecological efficiency, a nine months feeding trial was carried out at the Agricultural Centre Haus Riswick, Kleve. Two groups of 20 cows blocked by milk yield, parity and expected calving date were fed a forage diet of grass-clover and corn silage enriched with 3 kg of concentrates (46 % blue lupine, 41 % triticale, 10 % wheat bran, 2 % mineral feed, 1 % rape oil), sufficient for 25 kg ECM (DLG, 2001). Nutrient values per kg dry matter were as follows (control/experiment): 6,8 / 6,8 MJ NEL, 168 / 168 g XP, 144 / 148 g nXP, 3,9 / 3,2 g RNB. Nutritive value of lupines was determined by feeding wethers according to standard procedure (GfE, 1991). Protein fractions were analysed according to Shannak et al. (2000). Experimental groups varied only in lupine treatment (Börde Kraftkorn, Gröningen, GER). Yield of natural and energy corrected milk (ECM), milk fat and milk protein were higher in cows fed treated lupines (p <0,001). Urea nitrogen concentration was marginally lower compared to controls (p <0,001). Improvement of lactational performance was slightly higher during the first 100 days of lactation, but persisted during the whole lactational period. Body weight and condition were not affected by treatment. Improved lactational performance resulted in an overall better economic result

Repositioning the Catalytic Triad Aspartic Acid of Haloalkane Dehalogenase: Effects on Stability, Kinetics, and Structure

Haloalkane dehalogenase (DhlA) catalyzes the hydrolysis of haloalkanes via an alkyl-enzyme intermediate. The covalent intermediate, which is formed by nucleophilic substitution with Asp124, is hydrolyzed by a water molecule that is activated by His289. The role of Asp260, which is the third member of the catalytic triad, was studied by site-directed mutagenesis. Mutation of Asp260 to asparagine resulted in a catalytically inactive D260N mutant, which demonstrates that the triad acid Asp260 is essential for dehalogenase activity. Furthermore, Asp260 has an important structural role, since the D260N enzyme accumulated mainly in inclusion bodies during expression, and neither substrate nor product could bind in the active-site cavity. Activity for brominated substrates was restored to D260N by replacing Asn148 with an aspartic or glutamic acid. Both double mutants D260N+N148D and D260N+N148E had a 10-fold reduced kcat and 40-fold higher Km values for 1,2-dibromoethane compared to the wild-type enzyme. Pre-steady-state kinetic analysis of the D260N+N148E double mutant showed that the decrease in kcat was mainly caused by a 220-fold reduction of the rate of carbon-bromine bond cleavage and a 10-fold decrease in the rate of hydrolysis of the alkyl-enzyme intermediate. On the other hand, bromide was released 12-fold faster and via a different pathway than in the wild-type enzyme. Molecular modeling of the mutant showed that Glu148 indeed could take over the interaction with His289 and that there was a change in charge distribution in the tunnel region that connects the active site with the solvent. On the basis of primary structure similarity between DhlA and other α/β-hydrolase fold dehalogenases, we propose that a conserved acidic residue at the equivalent position of Asn148 in DhlA is the third catalytic triad residue in the latter enzymes.

The endothelial glycocalyx prefers albumin for evoking shear stress-induced, nitric oxide-mediated coronary dilatation

Background: Shear stress induces coronary dilatation via production of nitric oxide ( NO). This should involve the endothelial glycocalyx ( EG). A greater effect was expected of albumin versus hydroxyethyl starch ( HES) perfusion, because albumin seals coronary leaks more effectively than HES in an EG-dependent way. Methods: Isolated hearts ( guinea pigs) were perfused at constant pressure with Krebs-Henseleit buffer augmented with 1/3 volume 5% human albumin or 6% HES ( 200/0.5 or 450/0.7). Coronary flow was also determined after EG digestion ( heparinase) and with nitro-L-arginine ( NO-L-Ag). Results: Coronary flow ( 9.50 +/- 1.09, 5.10 +/- 0.49, 4.87 +/- 1.19 and 4.15 +/- 0.09 ml/ min/ g for `albumin', `HES 200', `HES 450' and `control', respectively, n = 5-6) did not correlate with perfusate viscosity ( 0.83, 1.02, 1.24 and 0.77 cP, respectively). NO-L-Ag and heparinase diminished dilatation by albumin, but not additively. Alone NO-L-Ag suppressed coronary flow during infusion of HES 450. Electron microscopy revealed a coronary EG of 300 nm, reduced to 20 nm after heparinase. Cultured endothelial cells possessed an EG of 20 nm to begin with. Conclusions: Albumin induces greater endothelial shear stress than HES, despite lower viscosity, provided the EG contains negative groups. HES 450 causes some NO-mediated dilatation via even a rudimentary EG. Cultured endothelial cells express only a rudimentary glycocalyx, limiting their usefulness as a model system. Copyright (c) 2007 S. Karger AG, Basel

Semiflexible polymer conformation, distribution and migration in microcapillary flows

The flow behavior of a semiflexible polymer in microchannels is studied using Multiparticle Collision Dynamics (MPC), a particle-based hydrodynamic simulation technique. Conformations, distributions, and radial cross-streamline migration are investigated for various bending rigidities, with persistence lengths Lp in the range 0.5 < Lp/Lr < 30. The flow behavior is governed by the competition between a hydrodynamic lift force and steric wall-repulsion, which lead to migration away from the wall, and a locally varying flow-induced orientation, which drives polymer away from the channel center and towards the wall. The different dependencies of these effects on the polymer bending rigidity and the flow velocity results in a complex dynamical behavior. However, a generic effect is the appearance of a maximum in the monomer and the center-of-mass distributions, which occurs in the channel center for small flow velocities, but moves off-center at higher velocities.Comment: in press at J. Phys. Condens. Matte

The influence of soil communities on the temperature sensitivity of soil respiration

Soil respiration represents a major carbon flux between terrestrial ecosystems and the atmosphere, and is expected to accelerate under climate warming. Despite its importance in climate change forecasts, however, our understanding of the effects of temperature on soil respiration (RS) is incomplete. Using a metabolic ecology approach we link soil biota metabolism, community composition and heterotrophic activity, to predict RS rates across five biomes. We find that accounting for the ecological mechanisms underpinning decomposition processes predicts climatological RS variations observed in an independent dataset (n = 312). The importance of community composition is evident because without it RS is substantially underestimated. With increasing temperature, we predict a latitudinal increase in RS temperature sensitivity, with Q10 values ranging between 2.33 ±0.01 in tropical forests to 2.72 ±0.03 in tundra. This global trend has been widely observed, but has not previously been linked to soil communities

Nutrient profiles of commercially produced complementary foods available in Cambodia, Indonesia and the Philippines

OBJECTIVE: To assess the nutritional suitability of commercially produced complementary foods (CPCF) marketed in three South-East Asian contexts. DESIGN: Based on label information declared on the products, nutrient composition and content of CPCF were assessed against the WHO Europe nutrient profile model (NPM). The proportion of CPCF that would require a 'high sugar' warning was also determined. SETTING: Khsach Kandal district, Cambodia; Bandung City, Indonesia; and National Capital Region, Philippines. PARTICIPANTS: CPCF products purchased in Cambodia (n 68) and Philippines (n 211) in 2020, and Indonesia (n 211) in 2017. RESULTS: Only 4·4 % of products in Cambodia, 10·0 % of products in Indonesia and 37·0 % of products in the Philippines fully complied with relevant WHO Europe NPM nutrient composition requirements. Sixteen per cent of CPCF in Cambodia, 27·0 % in Indonesia and 58·8 % in the Philippines contained total sugar content levels that would require a 'high sugar' warning. CONCLUSIONS: Most of the analysed CPCF were not nutritionally suitable to be promoted for older infants and young children based on their nutrient profiles, with many containing high levels of sugar and sodium. Therefore, it is crucial to introduce new policies, regulations and standards to limit the promotion of inappropriate CPCF in the South-East Asia region

3D Multi-Cell Simulation of Tumor Growth and Angiogenesis

We present a 3D multi-cell simulation of a generic simplification of vascular tumor growth which can be easily extended and adapted to describe more specific vascular tumor types and host tissues. Initially, tumor cells proliferate as they take up the oxygen which the pre-existing vasculature supplies. The tumor grows exponentially. When the oxygen level drops below a threshold, the tumor cells become hypoxic and start secreting pro-angiogenic factors. At this stage, the tumor reaches a maximum diameter characteristic of an avascular tumor spheroid. The endothelial cells in the pre-existing vasculature respond to the pro-angiogenic factors both by chemotaxing towards higher concentrations of pro-angiogenic factors and by forming new blood vessels via angiogenesis. The tumor-induced vasculature increases the growth rate of the resulting vascularized solid tumor compared to an avascular tumor, allowing the tumor to grow beyond the spheroid in these linear-growth phases. First, in the linear-spherical phase of growth, the tumor remains spherical while its volume increases. Second, in the linear-cylindrical phase of growth the tumor elongates into a cylinder. Finally, in the linear-sheet phase of growth, tumor growth accelerates as the tumor changes from cylindrical to paddle-shaped. Substantial periods during which the tumor grows slowly or not at all separate the exponential from the linear-spherical and the linear-spherical from the linear-cylindrical growth phases. In contrast to other simulations in which avascular tumors remain spherical, our simulated avascular tumors form cylinders following the blood vessels, leading to a different distribution of hypoxic cells within the tumor. Our simulations cover time periods which are long enough to produce a range of biologically reasonable complex morphologies, allowing us to study how tumor-induced angiogenesis affects the growth rate, size and morphology of simulated tumors