Urinary Tract Tumor Organoids Reveal Eminent Differences in Drug Sensitivities When Compared to 2-Dimensional Culture Systems

Generation of organoids from urinary tract tumor samples was pioneered a few years ago. We generated organoids from two upper tract urothelial carcinomas and from one bladder cancer sample, and confirmed the expression of cytokeratins as urothelial antigens, vimentin as a mesenchymal marker, and fibroblast growth factor receptor 3 by immunohistochemistry. We investigated the dose response curves of two novel components, venetoclax versus {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, in comparison to the clinical standard cisplatin in organoids in comparison to the corresponding two-dimensional cultures. Normal urothelial cells and tumor lines RT4 and HT1197 served as controls. We report that upper tract urothelial carcinoma cells and bladder cancer cells in two-dimensional cultures yielded clearly different sensitivities towards venetoclax, {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, and cisplatin. Two-dimensional cultures were more sensitive at low drug concentrations, while organoids yielded higher drug efficacies at higher doses. In some two-dimensional cell viability experiments, colorimetric assays yielded different IC₅₀ toxicity levels when compared to chemiluminescence assays. Organoids exhibited distinct sensitivities towards cisplatin and to a somewhat lesser extent towards venetoclax or {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, respectively, and significantly different sensitivities towards the three drugs investigated when compared to the corresponding two-dimensional cultures. We conclude that organoids maintained inter-individual sensitivities towards venetoclax, {"type":"entrez-nucleotide","attrs":{"text":"S63845","term_id":"400540","term_text":"S63845"}}S63845, and cisplatin. The preclinical models and test systems employed may bias the results of cytotoxicity studies.     

Early detection of TUR(transurethral resection) syndrome--ethanol measurement in ventilated patients

A major complication of transurethral resection of the prostate (TURP) is the excessive absorption of irrigation solution resulting in hypervolemia and dilutional hyponatremia. Marking the irrigation fluid with ethanol is a method for the early detection of fluid absorption. Currently this method is being used in spontaneously breathing patients undergoing regional anaesthesia. The goal of this study was to determine whether this method is also reliable for patients undergoing general anaesthesia. Fifty-nine patients underwent TURP in either spinal anaesthesia (SPA), or general anaesthesia with semi-open (ITNO) and semi-closed (ITNC) systems. Plasma alcohol concentrations ([Eth]p), exhaled ethanol ([Eth]e), plasma sodium concentration ([Na+]), and central venous pressure (CVP) were measured. The irrigation fluid contained ethanol in an concentration of approx. 1%. We assumed that significant fluid absorption took place when [Eth]p exceeded 0.1/1000. Measurements were performed immediately prior to and during surgery at 10-minute intervals. [Eth]p correlated directly with [Eth]e for both forms of anaesthesia. [Eth]p and [Na+] correlated inversely both for SPA and ITNC. Changes in [Eth]p did not parallel changes in CVP. Clinically relevant episodes of fluid absorption were accompanied by the detection of exhaled ethanol in all groups. We conclude that measuring exhaled ethanol is a minimal invasive monitoring technique that allows the detection of significant fluid absorption in both spontaneously breathing as well as ventilated patients with sufficient sensitivity. The ethanol levels are not predictive of the sodium concentration both in SPA and general anaesthesia. Thus, additional determinations of [Na+] is recommended whenever [Eth]e exceeds 0.2/1000.     

A generalization of Gittus’ viscoplastic “mechanical equation of state” to multiaxial stress states

In this paper, a multiaxial generalization of the viscoplastic “mechanical equation of state” (MEOS) by Gittus is proposed that preserves the physical soundness of the theory. The concept of forward and backward mobility of dislocations is generalized to a concept of directional mobility by splitting the mobile dislocation density in an isotropic and a tensorial part, similar to the approach used in the Bodner unified viscoplastic model. It is shown that the formulation is equivalent to the original MEOS in the case of uniaxial loadings. The approach is easily applied to any uniaxial viscoplastic material model.     

Geometrically non‐linear damage interface based on regularized strong discontinuity

The contribution of this paper concerns the fracture modelling of an interface with a fixed internal material surface in the context of geometrically non‐linear kinematics. Typical applications are composite laminates and adhesive/frictional joints in general. In the model development, a key feature is the concept of regularized strong discontinuity, which provides a regular deformation gradient within the interface. The deformation gradient within the interface is formulated in a multiplicative structure with a continuous part and a discontinuous part, whereby the interface deformation is interpreted as a transformation between the material damaged configuration and the actual spatial configuration. In analogy with the continuum formulation of hyper‐inelasticity, a constitutive framework is defined for the relation between the induced material traction and the displacement jump vector, which are defined on the material damaged interface configuration. Within this framework, a simple, but yet still representative, model for the delamination problem is proposed on the basis of a damage–plasticity coupling for the interface. The model is calibrated analytically in the large deformation context with respect to energy dissipation in mode I so that a predefined amount of fracture energy is dissipated. The paper is concluded with a couple of numerical examples that display the properties of the interface. Copyright © 2002 John Wiley & Sons, Ltd.     

Gastritis. Cause and significance]

Despite the high incidence and the increasing frequency gastritis is a true pathological process of the gastric mucosa. The importance of gastritis is not due to the symptoms but due to the altered reagibility of the stomach mucosa against exogenous and endogenous noxes. Two different forms fo chronic atrophic gastritis are to be distinguish concerning localization and etiology. Type A possibly is caused by an immunological process and is localized in the corpus mucosa. The more frequent typ B is localized in the antral mucosa and may be caused by exogen factors. None of these different forms of gastritis is a true precancerosis. However, dysplasia and enterocolic metaplasia which can appear in the course of chronic atrophic gastritis should be payed special attention because of a possible increased frequency of malignancy.     

Tests against stationary and explosive alternatives in vector autoregressive models

Abstract. The article proposes new tests for the number of unit roots in vector autoregressive models based on the eigenvalues of the companion matrix. Both stationary and explosive alternatives are considered. The limiting distributions of test statistics depend only on the number of unit roots. Size and power are investigated, and it is found that the new test against some stationary alternatives compares favourably with the widely used likelihood ratio test for the cointegrating rank. The powers are prominently higher against explosive than against stationary alternatives. Some empirical examples are provided to show how to use the new tests with real data.     

Surface charge sensitivity of silicon nanowires: size dependence

Silicon nanowires of different widths were fabricated in silicon on insulator (SOI) material using conventional process technology combined with electron-beam lithography. The aim was to analyze the size dependence of the sensitivity of such nanowires for biomolecule detection and for other sensor applications. Results from electrical characterization of the nanowires show a threshold voltage increasing with decreasing width. When immersed in an acidic buffer solution, smaller nanowires exhibit large conductance changes while larger wires remain unaffected. This behavior is also reflected in detected threshold shifts between buffer solutions of different pH, and we find that nanowires of width >150 nm are virtually insensitive to the buffer pH. The increased sensitivity for smaller sizes is ascribed to the larger surface/volume ratio for smaller wires exposing the channel to a more effective control by the local environment, similar to a surrounded gate transistor structure. Computer simulations confirm this behavior and show that sensing can be extended even down to the single charge level.     

GaAs/AlGaAs nanowire heterostructures studied by scanning tunneling microscopy

We directly image the interior of GaAs/AlGaAs axial and radial nanowire heterostructures with atomic-scale resolution using scanning tunneling microscopy. We show that formation of monolayer sharp and smooth axial interfaces are possible even by vapor-phase epitaxy. However, we also find that instability of the ternary alloys formed in the Au seed fundamentally limits axial heterostructure control, inducing large segment asymmetries. We study radial core-shell nanowires, imaging even ultrathin submonolayer shells. We demonstrate how large twinning-induced morphological defects at the wire surfaces can be removed, ensuring the formation of wires with atomically flat sides.     

Methyl Jasmonate-Induced Monoterpenes in Scots Pine and Norway Spruce Tissues Affect Pine Weevil Orientation

In large parts of Europe, insecticide-free measures for protecting conifer plants are desired to suppress damage by the pine weevil Hylobius abietis (L.). Treatment with methyl jasmonate (MeJA), a chemical elicitor already used in crop production, may enhance expression of chemical defenses in seedlings in conifer regenerations. However, in a previous experiment, MeJA treatment resulted in substantially better field protection for Scots pine (Pinus sylvestris L.) than for Norway spruce (Picea abies (L.) Karst.). Hypothesizing that the variations may be at least due partly to volatiles released by MeJA-treated seedlings and their effects on pine weevil orientation, we examined tissue extracts of seedlings (from the same batches as previously used) by two-dimensional GC-MS. We found that the MeJA treatment increased contents of the monoterpene (?)-β-pinene in phloem (the weevil’s main target tissue) of both tree species, however, the (?)-β-pinene/(?)-α-pinene ratio increased more in the phloem of P. sylvestris. We also tested the attractiveness of individual monoterpenes found in conifer tissues (needles and phloem) for pine weevils using an arena with traps baited with single-substance dispensers and pine twigs. Trap catches were reduced when the pine material was combined with a dispenser releasing (?)-β-pinene, (+)-3-carene, (?)-bornyl acetate or 1,8-cineole. However, (?)-α-pinene did not have this effect. Thus, the greater field protection of MeJA-treated P. sylvestris seedlings may be due to the selective induction of increases in contents of the deterrent (?)-β-pinene, in contrast to strong increases in both non-deterrent (?)-α-pinene and the deterrent (?)-β-pinene in P. abies seedlings.