Can systemic administration of drag reducing agents reduce the risk of metastasizing after cancer surgery? A hydrodynamics based hypothesis

The human blood and lymphatic systems serve as transport media for circulating tumor cells. Hydrodynamic analysis suggests that the systemic administration of drag-reducing agents (DRA) in nanomolar concentrations may reduce the risk of metastasizing of circulating tumor cells. After testing this hypothesis on animal models, it could become a new complementary post-operative treatment for cancer patients or even replace classical cancer aftercare for patients with severe intolerance against chemo- or radio-therapy. Our approach is based on the following considerations:- Circulating tumor cells need for settling down a favorable environment in terms of nutrition and after settling also in its first stage of development an extra nutrient supply in order to survive and grow finally into the interstice.- The attachment of circulating tumor cells therefore tends to occur at sites in the human circulatory system characterized by localized turbulence, which enhances the mass transfer of nutrients, e.g., at sites of vessel branching and bending with plasma skimming.- Also restrictions to blood flow, such as plaques (atherosclerosis), red blood cell (RBC) rouleaux, and even tumor cells in its first stage of development attached to the inner vessel wall may produce local vortices that increase mass transfer, i.e., food supply.- DRA have the ability to smooth (laminarise) localized turbulence in the circulatory system and to reduce mass transfer. The systemic administration of DRA could therefore serve in a first step to defuse potential settling points, i.e., to make them harmless.- Depriving freshly settled down tumor cells of their required nutrient levels should therefore in a second step reduce the probability of creating metastatic tumors, and may even lead to its starvation-induced death before they grow into the interstice.In the first part of our essay we demonstrate how flow constrictions decrease the mean blood flow velocity, wall shear rates, and Reynolds numbers respectively, and increase the friction factor.Experimentally derived apparent viscosity data from literature will be used to determine the probability of RBC rouleaux formation. This is of importance since RBC rouleaux are typically associated with turbulent blood flow patterns. An increase in apparent viscosity at low flow rates will be attributed to the formation of RBC rouleaux.In part two we discuss the application of the Lockhart/Martinelli method to determine the pressure drop in blood vessels. The objective is to determine a mass transfer coefficient characterizing the mass transfer between the center and the wall of both healthy and constricted blood vessels. This coefficient indicates the nutrient supply available to tumor cells in its first stage of development under different flow conditions and shows the effect of administration of DRA.Our hydrodynamic approach contrasts with previous studies of the possible benefits of DRA administration, which were focused on improving blood supply. We emphasize the reduction of the mass transfer rate as a tool to withhold turbulence induced supplementary food supply to circulating tumor cells in the process of settling and in its first stage of development.Due to the hypothetical character of our approach and the possibility of unexpected side effects when administrating DRA (including their mechanical degradation products) animal models are indispensable before clinical trials

Causality and defect formation in the dynamics of an engineered quantum phase transition in a coupled binary Bose-Einstein condensate

Continuous phase transitions occur in a wide range of physical systems, and provide a context for the study of non-equilibrium dynamics and the formation of topological defects. The Kibble-Zurek (KZ) mechanism predicts the scaling of the resulting density of defects as a function of the quench rate through a critical point, and this can provide an estimate of the critical exponents of a phase transition. In this work we extend our previous study of the miscible-immiscible phase transition of a binary Bose-Einstein condensate (BEC) composed of two hyperfine states in which the spin dynamics are confined to one dimension [J. Sabbatini et al., Phys. Rev. Lett. 107, 230402 (2011)]. The transition is engineered by controlling a Hamiltonian quench of the coupling amplitude of the two hyperfine states, and results in the formation of a random pattern of spatial domains. Using the numerical truncated Wigner phase space method, we show that in a ring BEC the number of domains formed in the phase transitions scales as predicted by the KZ theory. We also consider the same experiment performed with a harmonically trapped BEC, and investigate how the density inhomogeneity modifies the dynamics of the phase transition and the KZ scaling law for the number of domains. We then make use of the symmetry between inhomogeneous phase transitions in anisotropic systems, and an inhomogeneous quench in a homogeneous system, to engineer coupling quenches that allow us to quantify several aspects of inhomogeneous phase transitions. In particular, we quantify the effect of causality in the propagation of the phase transition front on the resulting formation of domain walls, and find indications that the density of defects is determined during the impulse to adiabatic transition after the crossing of the critical point.Comment: 23 pages, 10 figures. Minor corrections, typos, additional referenc

Electrical half-wave rectification at ferroelectric domain walls

Ferroelectric domain walls represent multifunctional 2D-elements with great potential for novel device paradigms at the nanoscale. Improper ferroelectrics display particularly promising types of domain walls, which, due to their unique robustness, are the ideal template for imposing specific electronic behavior. Chemical doping, for instance, induces p- or n-type characteristics and electric fields reversibly switch between resistive and conductive domain-wall states. Here, we demonstrate diode-like conversion of alternating-current (AC) into direct-current (DC) output based on neutral 180$^{\circ}$ domain walls in improper ferroelectric ErMnO$_3$. By combining scanning probe and dielectric spectroscopy, we show that the rectification occurs for frequencies at which the domain walls are fixed to their equilibrium position. The practical frequency regime and magnitude of the output is controlled by the bulk conductivity. Using density functional theory we attribute the transport behavior at the neutral walls to an accumulation of oxygen defects. Our study reveals domain walls acting as 2D half-wave rectifiers, extending domain-wall-based nanoelectronic applications into the realm of AC technology

Collaborative development of predictive toxicology applications

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies