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.     

Trace element distributions between matte and slag in direct nickel matte smelting

ABSTRACT

Behaviour of trace elements in the nickel matte smelting was studied at 1673 K (1400°C) by equilibration-quenching techniques followed by direct phase analyses using electron probe X-ray microanalysis and laser ablation-inductively coupled plasma-mass spectrometry. The matte-slag samples at silica saturation were equilibrated with SO₂-CO-CO₂-Ar mixtures of fixed p_SO2, p_S2 and p_O2 in order to obtain a pre-determined oxidation degree for the sulphide matte, and thus to generate a targeted iron concentration of the nickel-copper–iron sulphide matte (Ni:Cu = 5, w/w), depending on the slag chemistry. The slag composition was varied from 0 to 2 wt-% K₂O and 0–10 wt-% MgO in silica saturation. The studied trace elements were Co, Ge, Pb, Se and Sn, but also the matte-to-slag distributions of the slag forming fluxing components Mg (MgO) and Si (SiO₂) were determined experimentally. Selenium was the only trace element studied which strongly enriched in the low-iron nickel mattes, and the deportment became larger when the sulphide matte depleted with iron. All the other trace elements behaved in the opposite way.     

The stiffness of laser stake welded T-joints in web-core sandwich structures

The purpose of this paper is to describe experiments carried out on laser stake welded T-joints of web-core steel sandwich structures. A special test setup was developed to measure the shear-induced rotation at the T-joint. The ratio of the shear force to rotation angle gave the joint stiffness. This stiffness was measured for specimens with two different face-plate thicknesses. The influence of weld thickness, root gap and occurrence of contact were further investigated with finite element simulations. Finally, the shear stiffness of the sandwich structure transverse to the web plate direction was determined using the experimentally obtained average joint stiffness value. The validation of the shear stiffness was carried out by considering a beam in four-point bending. The agreement between calculated deflection and stress and experimental results was found to be good.     

Self-organized pattern formation on silicon,stainless steel and zinc coated steel substrates

In this research, a self-organized pattern formation employing polystyrene/aluminum bilayer coatings on three different substrates was studied. Two new substrate materials, stainless steel and zinc coated steel for self-organization application were introduced. Influence of polystyrene molar mass on pattern formation was studied with five different polystyrene samples having molar masses between 27 and 247 × 10³ g/mol. Polystyrene/toluene solutions were applied onto the substrates using the spin coating technique and aluminum layer was created by chemical vapor deposition (CVD). Self-organized pattern formation was induced thermally, by heating the layered substrate/polystyrene/aluminum structures above the glass transition temperature of polystyrene. Sub-micron–micron sized wrinkles or island-like surface patterns were achieved on all substrates. The molar mass of polystyrene was found to have effect on the dimensions of the formed structures. It was also observed that the characteristic surface structure of substrates influences self-organization and thereby directs the structure formation.     

The transformative effect of top management governance choices on project team identity and relationship with the organization — An agency and stewardship approach

This study focuses on the relationship and identity changes within and between a project team and its organization following top management intervention in the context of a large international construction project. The study follows the project-as-practice orientation, examining the actions and behaviors of the project team through participant ethnography in the “praxis” of the project site over its entire duration. The longitudinal case allows the examination of the way the transition process established a new governance culture undermining the initial trust-based one and changed it from a virtual absence of mechanisms toward far more potent mechanisms of control, monitoring, and punishment. Simultaneously, the initial stewardship relationships and collectivist identity of the project team shifted toward agency relationships and individualistic identity. The triggers for the transformation process were identified as CEO succession, project failure, top management intervention driven changes in governance mechanisms, and perception of organizational betrayal of the project team.     

What company characteristics are associated with the adoption of social media?

ABSTRACT

In just one decade, social media have moved from being marginal phenomena to having three billion active monthly users globally in 2017. We use a large representative sample to study which company characteristics are associated with the early adoption of social media. Our findings suggest that digital orientation (outside social media), innovativeness, external collaboration in marketing and sales, and orientation towards consumer markets all increase a company’s probability of adopting social media. In addition, larger and younger companies are more likely to be early movers. Overall, business use of social media has only reached its early maturity; thus, it still has plenty of room to grow.