Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer

Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with ²¹²Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of ²¹²Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of ²¹²Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of ²¹²Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of ²¹²Pb-NG001.     

Element contents in leaves of four plant species (birch, mountain ash, fern and spruce) along anthropogenic and geogenic concentration gradients

Forty samples each of leaves of birch (Betula pubescens Ehrh.), European mountain ash (Sorbus aucuparia (L.)) and bracken fern (Pteridium aquilinum (L.) Kuhn) as well as spruce needles (Picea abies (L.) Karsten) were collected along a 120 km south-north transect running through Norway's largest city, Oslo. Concentrations of 25 chemical elements (Ag, Au, B, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, La, Mg, Mn, Mo, Na, Ni, P, Pb, S, Sb, Sr, Ti, and Zn) as well as loss on ignition for the 4 sample materials are reported. The decline of input of sea spray with distance from the coast, geology, pH and anthropogenic contamination all played a role for the observed element concentrations in the leaves. Although growing under exactly the same natural conditions each plant species displayed quite unique uptake characteristics. Plant-species dependency and individual differences in the reaction of the plant leaves to different element sources make the investigated species of very limited value as bioindicators of anthropogenic activities. Anthropogenic contamination influences plant-leaf element content within a limited distance ( approximately 20 km) from the source.     

An Improved On-line Contingency Screening for Power System Transient Stability Assessment

This paper presents a contingency screening method and a framework for its on-line implementation. The proposed method carries out contingency screening and on-line stability assessment with respect to first-swing transient stability. For that purpose, it utilizes the single machine equivalent method and aims at improving the prior developed contingency screening approaches. In order to determine vulnerability of the system with respect to a particular contingency, only one time-domain simulation needs to be performed. An early stop criteria is proposed so that in a majority of the cases the simulation can be terminated after a few hundred milliseconds of simulated system response. The method’s outcome is an assessment of the system’s stability and a classification of each considered contingency. The contingencies are categorized by exploiting parameters of an equivalent one machine infinite bus system. A novel island detection approach, appropriate for an on-line application since it utilizes efficient algorithms from graph theory and enables stability assessment of individual islands, is also introduced. The New England and New York system as well as the large-scale model of the Continental-European interconnected system are used to test the proposed method with respect to assessment accuracy and computation time.     

A sorption rate hypothesis for the increase in H2 permeability of palladium-silver (Pd-Ag) membranes caused by air oxidation

Hydrogen permeation measurements were performed at 300 °C for 25-μm cold-rolled Pd-Ag 25 wt% membranes before and after air oxidation at the same temperature as permeation. The air oxidation resulted in enhanced H₂ permeation through the membrane, as well as a roughening of the surface with the formation of surface grains and defects. The protruding grains can be leveled off by exposure to H₂ but the surface defects cannot. These microstructure changes are only on the membrane surfaces and do not create transmembrane defects that would allow permeation for gas species other than H₂. The H₂ permeability of the oxidized membrane increased by 25-90% compared to that of the as-received film at the same permeation condition, and the membranes retained perfect H₂ selectivity over N₂. The percent improvement of H₂ permeability decreases with increasing H₂ feed pressure. A new sorption kinetics hypothesis is proposed to elucidate the increase in H₂ permeability of Pd-Ag membranes caused by oxidation. H₂ solubility and sorption rate results were presented to test the new hypothesis. It is found that air oxidation does not change the H₂ solubility in Pd-Ag membranes, but enhances the H₂ sorption kinetics significantly. The extent of kinetics enhancement also decreases with increasing H₂ pressures. The much faster sorption equilibrium implies higher effective H₂ diffusivity at the Pd-Ag membrane surface for the oxidized sample and a higher transfer rate of atomic hydrogen from surface/sub-surface to the membrane bulk that contributes to the increase of H₂ permeability observed in experiments.     

SENSITIVITY ANALYSIS AND OPTIMIZATION OF ELASTIC-PLASTIC STRUCTURES

Elastic-plastic analysis problems formulated as quadratic programming problems involve energy functional and equilibrium and yield constraints that depend on the design, material and loading. In this paper we consider the problem of determining the variation of structural response with respect to variations of these parameters. A general result for discrete structures is presented and implications for optimal design are discussed.     

Eigenstructure and residuals in multivariable state-feedback design

In this paper it is shown that all residuals assignable by state feedback must belong to certain well-defined subspaces defined by the freely selectable closed-loop eigenvalues. These subspaces are straightforward to compute, and the computational requirements are modest. The applicability of this result is facilitated by the fact that fundamental control design objectives like I/O response and robustness can be expressed in terms of residuals. A design procedure is outlined and illustrated by an example. The method is applicable to square and non-square systems.