24 research outputs found

    Assessing glyphosate in water, marine particulate matter, and sediments in the Lagoon of Venice

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    Lagoon water, suspended particulate matter, and sediment samples from seven sites at Lagoon of Venice were collected from 2019 to 2021 in order to study the presence of the herbicide glyphosate (N-(phosphonomethyl)glycine), among the most widely used agricultural chemicals worldwide, but its occurrence in lagoon water environment has not been deeply investigated. The sites were selected considering a supposed diversity of inputs and of pollution levels. An analytical method based on ion chromatography coupled with tandem mass spectrometry was optimized and validated for lagoon water, marine particulate matter, and sediment samples. Maximum concentrations of glyphosate were 260 and 7 ng L−1 for lagoon water and suspended particulate matter, respectively, and 15 ng g−1 for sediment, with some spatial and temporal fluctuations. Our results demonstrate that glyphosate content in the Venice Lagoon mainly depends on external forcing from river inlets and agricultural lagoon activities

    Phylogenetic conservation of Trop-2 across species—rodent and primate genomics model anti-Trop-2 therapy for pre-clinical benchmarks

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    A phylogenetic conservation analysis of Trop-2 across vertebrate species showed a high degree of sequence conservation, permitting to explore multiple models as pre-clinical benchmarks. Sequence divergence and incomplete conservation of expression patterns were observed in mouse and rat. Primate Trop-2 sequences were found to be 95%–100% identical to the human sequence. Comparative three-dimension primate Trop-2 structures were obtained with AlphaFold and homology modeling. This revealed high structure conservation of Trop-2 (0.66 ProMod3 GMQE, 0.80–0.86 ± 0.05 QMEANDisCo scores), with conservative amino acid changes at variant sites. Primate TACSTD2/TROP2 cDNAs were cloned and transfectants for individual ORF were shown to be efficiently recognized by humanized anti-Trop-2 monoclonal antibodies (Hu2G10, Hu2EF). Immunohistochemistry analysis of Macaca mulatta (rhesus monkey) tissues showed Trop-2 expression patterns that closely followed those in human tissues. This led us to test Trop-2 targeting in vivo in Macaca fascicularis (cynomolgus monkey). Intravenously injected Hu2G10 and Hu2EF were well tolerated from 5 to 10 mg/kg. Neither neurological, respiratory, digestive, urinary symptoms, nor biochemical or hematological toxicities were detected during 28-day observation. Blood serum pharmacokinetic (PK) studies were conducted utilizing anti-idiotypic antibodies in capture-ELISA assays. Hu2G10 (t1/2 = 6.5 days) and Hu2EF (t1/2 = 5.5 days) were stable in plasma, and were detectable in the circulation up to 3 weeks after the infusion. These findings validate primates as reliable models for Hu2G10 and Hu2EF toxicity and PK, and support the use of these antibodies as next-generation anti-Trop-2 immunotherapy tools

    Organic micropollutants in wet and dry depositions in the Venice Lagoon

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    Atmospheric transport is an important route by which pollutants are conveyed from the continents to both coastal and open sea. The role of aerosol deposition in the transport of polycyclic aromatic hydrocarbons (PAHs), polychlorobiphenyls (PCBs) and polybromodiphenyls ethers (PBDEs) to water and soil systems has been evaluated by measuring their concentrations in wet and dry depositions to the Venice Lagoon. The organic micropollutant flux data indicate that they contribute to the total deposition flux in different ways through wet and dry deposition, showing that the prevalent contribution derives from wet deposition. The fluxes calculated for PBDEs, showed the prevalence of 47, 99, 100 and 183 congeners, both in dry and wet fluxes. With regard to PCBs, the flux of PPCB for wet deposition is in the same order of magnitude of the diffusive flux at the air–water interface. The PAH fluxes obtained in the present study are similar to those obtained in previous studies on the atmospheric bulk deposition to the Venice Lagoon. The ratios between Phe/Ant and Fl/Py indicate that the pollutants sources are pyrolytic, deriving from combustion fuels

    Secreted Gal-3BP is a novel promising target for non-internalizing Antibody–Drug Conjugates

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    Abstract Galectin-3-binding protein (Gal-3BP) has been identified as a cancer and metastasis-associated, secreted protein that is expressed by the large majority of cancers. The present study describes a special type of non-internalizing antibody-drug-conjugates that specifically target Gal-3BP. Here, we show that the humanized 1959 antibody, which specifically recognizes secreted Gal-3BP, selectively localized around tumor but not normal cells. A site specific disulfide linkage with thiol-maytansinoids to unpaired cysteine residues of 1959, resulting in a drug-antibody ratio of 2, yielded an ADC product, which cured A375m melanoma bearing mice. ADC products based on the non-internalizing 1959 antibody may be useful for the treatment of several human malignancies, as the cognate antigen is abundantly expressed and secreted by several cancers, while being present at low levels in most normal adult tissues

    High Voltage Temperature Humidity Bias Test (THB) customized system and methodologies for reliability assessment of power semiconductor devices

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    High Volt­age Tem­per­a­ture Hu­mid­ity Bias Test (THB-HV) is cur­rently the state of the art test method for re­li­a­bil­ity eval­u­a­tion of power de­vices in high hu­mid­ity en­vi­ron­ments at high volt­age. These con­di­tions have be­come es­pe­cially sig­nif­i­cant in the case of power mod­ules for the au­to­mo­tive in­dus­try and other ap­pli­ca­tions in harsh en­vi­ron­ments. In this re­search work, a cus­tom sys­tem for ac­tive mon­i­tor­ing of THB-HV test­ing is de­vel­oped and cus­tomized, in or­der to eval­u­ate dif­fer­ent test­ing method­olo­gies, in­ter­cept de­vice degra­da­tion in real time, and al­low for a con­trolled and more ac­cu­rate fail­ure analy­sis of the DUTs

    Multilayer film passivation for enhanced reliability of power semiconductor devices

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    Automotive requirements are becoming ever more severe in terms of device operation under high stress and in harsh working conditions. In this context, passivation layers play a fundamental role in determining electrical performance and reliability. This study focuses on the primary and secondary passivation layers applied to the state-of-the-art power devices and their influence on reliability. Power diodes assembled in standard module packages are used as test vehicles, and high-voltage temperature humidity bias tests are performed to stress the structures. A complete failure mode analysis highlights the phenomena behind the degradation of the passivation layers. Different passivation schemes are evaluated through the application of specific inorganic and organic combinations of layers. Finally, a summary of the typical degradation mechanisms and interactions is presented
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