Influence of Titanium Additions on The Electrochemical Behaviour of NiCr/Ti Laser Cladded Coatings

In this research, the electrochemical evaluation of NiCr/Ti laser cladded coatings in simulated polymer electrolyte membrane fuel cells (PEMFCs) environment was investigated. The Laser Cladding technique was used to develop protective coatings on mild steel substrate using NiCr-based powders mixed with 12.5, 15, 17.5 and 20 wt.% Ti additions. The samples were tested at room temperature in Na2SO4 0.1M + 0.1 ppm F-. The potentiodynamic polarization curves are presented before and after the samples were subjected to accelerated stress tests, for 6 hours each, at +0.736 V (cathodic environment) and at -0.493 V (anodic environment). Afterwards, scanning electron microscopy (SEM) was used to investigate the effect of Ti addition in terms of morphology. Energy-dispersive X-ray spectroscopy (EDS) was performed for chemical evaluation of the surface after corrosion tests

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Meteorological data collected at the Tarlung reservoir, located in the centre of Romania

This data was obtained from the project CLISWELN funded by ERA4CS. ERA4CS is an ERA-NET initiated by JPI Climate, and CLISWELN is funded by BMBF (DE),UEFISCDI (RO), BMBWF and FFG (AT), and MINECO (ES), with co-funding from the European Union (Grant690462) The meteorological daily data registered outside and inside of the forest and consist of precipitations, air temperature, air humidity, photon flux, solar radiation, wind speed and direction and soil moisture. This data has been used in SWAT hydrological model

Efficient tumor targeting with high-affinity designed ankyrin repeat proteins: effects of affinity and molecular size

Slow-clearing, tumor-targeting proteins such as monoclonal antibodies typically exhibit high tumor accumulation but low tissue contrast, whereas intermediate-sized proteins such as scFvs show faster clearance but only moderate tumor accumulation. For both, tumor targeting does not seem to improve further above an optimal affinity. We show here that with very small high-affinity proteins such as designed ankyrin repeat proteins (DARPins), these limits can be overcome. We have systematically investigated the influence of molecular mass and affinity on tumor accumulation with DARPins with specificity for HER2 in SK-OV-3.ip nude mouse xenografts. DARPins with a mass of 14.5 kDa and affinities between 270 nmol/L and 90 pmol/L showed a strong correlation of tumor accumulation with affinity to HER2, with the highest affinity DARPin reaching 8% ID/g after 24 hours and 6.5% ID/g after 48 hours (tumor-to-blood ratio >60). Tumor autoradiographs showed good penetration throughout the tumor mass. Genetic fusion of two DARPins (30 kDa) resulted in significantly lower tumor accumulation, similar to values observed for scFvs, whereas valency had no influence on accumulation. PEGylation of the DARPins increased the circulation half-life, leading to higher tumor accumulation (13.4% ID/g after 24 hours) but lower tumor-to-blood ratios. Affinity was less important for tumor uptake of the PEGylated constructs. We conclude that two regimes exist for delivering high levels of drug to a tumor: small proteins with very high affinity, such as unmodified DARPins, and large proteins with extended half-life, such as PEGylated DARPins, in which the importance of affinity is less pronounced

Engineering an anti-HER2 biparatopic antibody with a multimodal mechanism of action

The receptor tyrosine kinase HER2 acts as oncogenic driver in numerous cancers. Usually, the gene is amplified, resulting in receptor overexpression, massively increased signaling and unchecked proliferation. However, tumors become frequently addicted to oncogenes and hence are druggable by targeted interventions. Here, we design an anti-HER2 biparatopic and tetravalent IgG fusion with a multimodal mechanism of action. The molecule first induces HER2 clustering into inactive complexes, evidenced by reduced mobility of surface HER2. However, in contrast to our earlier binders based on DARPins, clusters of HER2 are thereafter robustly internalized and quantitatively degraded. This multimodal mechanism of action is found only in few of the tetravalent constructs investigated, which must target specific epitopes on HER2 in a defined geometric arrangement. The inhibitory effect of our antibody as single agent surpasses the combination of trastuzumab and pertuzumab as well as its parental mAbs in vitro and it is effective in a xenograft model

3-Bromopyruvate as a potent anticancer therapy in honor and memory of the late Professor Andre Goffeau

3-Bromopyruvate (3BP) is a small, highly reactive molecule formed by bromination of pyruvate. In the year 2000, the antitumor properties of 3BP were discovered. Studies using animal models proved its high efficacy for anticancer therapy with no apparent side effects. This was also found to be the case in a limited number of cancer patients treated with 3BP. Due to the "Warburg effect," most tumor cells exhibit metabolic changes, for example, increased glucose consumption and lactic acid production resulting from mitochondrial-bound overexpressed hexokinase 2. Such alterations promote cell migration, immortality via inhibition of apoptosis, and less dependence on the availability of oxygen. Significantly, these attributes also make cancer cells more sensitive to agents, such as 3BP that inhibits energy production pathways without harming normal cells. This selectivity of 3BP is mainly due to overexpressed monocarboxylate transporters in cancer cells. Furthermore, 3BP is not a substrate for any pumps belonging to the ATP-binding cassette superfamily, which confers resistance to a variety of drugs. Also, 3BP has the capacity to induce multiple forms of cell death, by, for example, ATP depletion resulting from inactivation of both glycolytic and mitochondrial energy production pathways. In addition to its anticancer property, 3BP also exhibits antimicrobial activity. Various species of microorganisms are characterized by different susceptibility to 3BP inhibition. Among tested strains, the most sensitive was found to be the pathogenic yeast-like fungus Cryptococcus neoformans. Significantly, studies carried out in our laboratories have shown that 3BP exhibits a remarkable capacity to eradicate cancer cells, fungi, and algae.This study was supported by the Polish National Science Center (NCN), Preludium Grant UMO‐2015/19/N/NZ7/00956 (awarded to Katarzyna Niedźwiecka) and the Ministry of Science and Higher Edu cation (Poland) within of “Statutory Research 2018/S/IGM.” Coauthors P. L. P. and Y. H. K. express their gratitude to Mr. Paul Edelman, The Oncology Foundation, Single Cause and Single Cure Foundation, Compassion Center, Dr. Ed Miller, and The G. Yu Foundation for their continued interest and support for our cancer research

Engineering an anti-HER2 biparatopic antibody with a multimodal mechanism of action

HER2 acts an oncogenic driver in numerous cancers. Here, the authors design an anti-HER2 biparatopic and tetravalent IgG fusion with inhibitory effects in a xenograft model