Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. © 2012 American Chemical Society

A new strong-lensing model for the massive galaxy cluster PLCKG287.0+32.9

We present a new high-precision strong lensing model of PLCK G287.0+32.9, a massive lens galaxy cluster at z = 0.383, based on 153 spectroscopically and photometrically selected member galaxies and 47 secure multiple images of 12 background multiply-lensed sources. The total mass distribution derived from our model shows this cluster to be a very prominent gravitational lens with the third biggest Einstein radius of θE =43.4′′ ± 0.1′′ known to date

The Opportunities and Challenges of SME Manufacturing Automation: Safety and Ergonomics in Human–Robot Collaboration

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Early Release - Clinical Manifestations and Genomic Evaluation of Melioidosis Outbreak among Children after Sporting Event, Australia - Volume 29, Number 11—November 2023 - Emerging Infectious Diseases journal - CDC

Melioidosis, caused by the environmental gram-negative bacterium Burkholderia pseudomallei, usually develops in adults with predisposing conditions and in Australia more commonly occurs during the monsoonal wet season. We report an outbreak of 7 cases of melioidosis in immunocompetent children in Australia. All the children had participated in a single-day sporting event during the dry season in a tropical region of Australia, and all had limited cutaneous disease. All case-patients had an adverse reaction to oral trimethoprim/sulfamethoxazole treatment, necessitating its discontinuation. We describe the clinical features, environmental sampling, genomic epidemiologic investigation, and public health response to the outbreak. Management of this outbreak shows the potential benefits of making melioidosis a notifiable disease. The approach used could also be used as a framework for similar outbreaks in the future

Euclid: I. Overview of the Euclid mission

The current standard model of cosmology successfully describes a variety of measurements, but the nature of its main ingredients,dark matter and dark energy, remains unknown. Euclid is a medium-class mission in the Cosmic Vision 2015–2025 programme of theEuropean Space Agency (ESA) that will provide high-resolution optical imaging, as well as near-infrared imaging and spectroscopy,over about 14 000 deg² of extragalactic sky. In addition to accurate weak lensing and clustering measurements that probe structureformation over half of the age of the Universe, its primary probes for cosmology, these exquisite data will enable a wide range ofscience. This paper provides a high-level overview of the mission, summarising the survey characteristics, the various data-processingsteps, and data products. We also highlight the main science objectives and expected performance

Photocontrolled DNA binding of a receptor-targeted organometallic ruthenium(II) complex

A photoactivated ruthenium(II) arene complex has been conjugated to two receptor-binding peptides, a dicarba analogue of octreotide and the Arg-Gly-Asp (RGD) tripeptide. These peptides can act as “tumor-targeting devices” since their receptors are overexpressed on the membranes of tumor cells. Both ruthenium–peptide conjugates are stable in aqueous solution in the dark, but upon irradiation with visible light, the pyridyl-derivatized peptides were selectively photodissociated from the ruthenium complex, as inferred by UV–vis and NMR spectroscopy. Importantly, the reactive aqua species generated from the conjugates, [(η6-p-cym)Ru(bpm)(H2O)]2+, reacted with the model DNA nucleobase 9-ethylguanine as well as with guanines of two DNA sequences, 5′dCATGGCT and 5′dAGCCATG. Interestingly, when irradiation was performed in the presence of the oligonucleotides, a new ruthenium adduct involving both guanines was formed as a consequence of the photodriven loss of p-cymene from the two monofunctional adducts. The release of the arene ligand and the formation of a ruthenated product with a multidentate binding mode might have important implications for the biological activity of such photoactivated ruthenium(II) arene complexes. Finally, photoreactions with the peptide–oligonucleotide hybrid, Phac-His-Gly-Met-linker-p5′dCATGGCT, also led to arene release and to guanine adducts, including a GG chelate. The lack of interaction with the peptide fragment confirms the preference of such organometallic ruthenium(II) complexes for guanine over other potential biological ligands, such as histidine or methionine amino acids

Genetic Algorithm-based Optimization of Cutting Parameters in Turning Processes

AbstractAn optimization paradigm based on genetic algorithms (GA) for the determination of the cutting parameters in machining operations is proposed. In metal cutting processes, cutting conditions have an influence on reducing the production cost and time and deciding the quality of a final product. In order to find optimal cutting parameters during a turning process, the genetic algorithm has been used as an optimal solution finder. Process optimization has to yield minimum production time, while considering technological and material constrains

Formal Tools for Management of Manufacturing Systems: A Multi Agents System Approach

To overcome the consequences of the 2008 crisis on the real sector, especially manufacturing, Industry 4.0 gives guidelines to drive production by emphasizing technological innovations, such as industrial internet, cloud manufacturing, etc. The proposed paper focuses on cognitive manufacturing within the framework of the emergent synthesis paradigm. Specifically, the structuring process by which the manufacturing assets are organized to provide the finished goods is analyzed. The study is carried out by considering the analogies between manufacturing and other inventive processes supported by formal tools such as formal languages, semantic webs, and multi agent system