The replacement of the existing endcap calorimeter in the Compact Muon Solenoid (CMS) detector for the high-luminosity LHC (HL-LHC), scheduled for 2027, will be a high granularity calorimeter. It ...will provide detailed position, energy, and timing information on electromagnetic and hadronic showers in the immense pileup of the HL-LHC. The High Granularity Calorimeter (HGCAL) will use 120-, 200-, and 300-μm-thick silicon (Si) pad sensors as the main active material and will sustain 1 MeV neutron equivalent fluences up to about 1016neqcm−2. In order to address the performance degradation of the Si detectors caused by the intense radiation environment, irradiation campaigns of test diode samples from 8-inch and 6-inch wafers were performed in two reactors. Characterization of the electrical and charge collection properties after irradiation involved both bulk polarities for the three sensor thicknesses. Since the Si sensors will be operated at −30ˆC to reduce increasing bulk leakage current with fluence, the charge collection investigation of 30 irradiated samples was carried out with the infrared-TCT setup at −30ˆC. TCAD simulation results at the lower fluences are in close agreement with the experimental results and provide predictions of sensor performance for the lower fluence regions not covered by the experimental study. All investigated sensors display 60% or higher charge collection efficiency at their respective highest lifetime fluences when operated at 800 V, and display above 90% at the lowest fluence, at 600 V. The collected charge close to the fluence of 1016neqcm−2 exceeds 1 fC at voltages beyond 800 V.
One-sided depressurization is often employed in hydrate plug removal processes and has inherent risks associated with the high velocities that the plug achieves due to the pressure differential. In ...critical conditions, events such as pipeline ruptures may occur. Therefore, the need for detailed numerical studies to help reduce the risk of such operations is paramount. The present work devises a numerical methodology to predict the dynamics of plugs in transient two-phase flow conditions, coupled with a compositional model to determine the formation of the gas condensate. Different scenarios were examined to evaluate the impact on the plug displacement and flow variables due to the accumulation of a liquid slug at the plug head, as well as several operational conditions with different plug sizes, initial plug positions, and pressure differences. The effect of including an energy storage model in the insulating layers is also discussed. Results showed a negligible impact of the liquid formed at the plug’s head. However, a significant impact on the temperature distribution due to the energy stored at the insulating layers was observed without affecting the pressure and plug variables. It was also shown that for all cases a fast transient occurs at the beginning of the plug displacement when it reaches very high velocities, followed by a slower transient. Depending on the operational scenario, the plug stops before reaching the pipeline exit or can reach the exit with high velocity, indicating the need to explore different scenarios to design this type of operation.
Abstract
Hybrid pixel detectors require a reliable and cost-effective interconnect technology adapted to the pitch and die sizes of the respective applications. During the ASIC and sensor R&D phase, ...especially for small-scale applications, such interconnect technologies need to be suitable for the assembly of single dies, typically available from Multi-Project-Wafer submissions. Within the CERN EP R&D programme and the AIDAinnova collaboration, innovative hybridisation concepts targeting vertex-detector applications at future colliders are under development. Recent results of two novel interconnect methods for pixel pitches of 25 µm and 55 µm are presented in this contribution — an industrial fine-pitch SnAg solder bump-bonding process adapted to single-die processing using support wafers, as well as a newly developed in-house single-die interconnection process based on Anisotropic Conductive Film (ACF). The fine-pitch bump-bonding process is qualified with hybrid assemblies from a recent bonding campaign at Frauenhofer IZM. Individual CLICpix2 ASICs with 25 µm pixel pitch were bump-bonded to active-edge silicon sensors with thicknesses ranging from 50 µm to 130 µm. The device characterisation was conducted in the laboratory as well as during a beam test campaign at the CERN SPS beam-line, demonstrating an interconnect yield of about 99.7%. The ACF interconnect technology replaces the solder bumps by conductive micro-particles embedded in an epoxy film. The electro-mechanical connection between the sensor and ASIC is achieved via thermocompression of the ACF using a flip-chip device bonder. The required pixel pad topology is achieved with an in-house Electroless Nickel Immersion Gold (ENIG) plating process. This newly developed ACF hybridisation process is first qualified with the Timepix3 ASICs and sensors with 55 µm pixel pitch. The technology can be also used for ASIC-PCB/FPC integration, replacing wire bonding or large-pitch solder bumping techniques. This contribution introduces the two interconnect processes and presents preliminary hybridisation results with CLICpix2 and Timepix3 sensors and ASICs.
Abstract
Hybrid pixel detectors require a reliable and cost-effective interconnect technology adapted to the pitch and die sizes of the respective applications. During the ASIC and sensor R&D phase, ...and in general for small-scale applications, such interconnect technologies need to be suitable for the assembly of single-dies, typically available from Multi-Project-Wafer submissions. Within the CERN EP R&D programme and the AIDAinnova collaboration, innovative hybridisation concepts targeting vertex-detector applications at future colliders are under development. This contribution presents recent results of a newly developed in-house single-die interconnection process based on Anisotropic Conductive Film (ACF). The ACF interconnect technology replaces the solder bumps with conductive particles embedded in an adhesive film. The electro-mechanical connection between the sensor and the read-out chip is achieved via thermo-compression of the ACF using a flip-chip device bonder. A specific pad topology is required to enable the connection via conductive particles and create cavities into which excess epoxy can flow. This pixel-pad topology is achieved with an in-house Electroless Nickel Immersion Gold (ENIG) plating process that is also under development within the project. The ENIG and ACF processes are qualified with the Timepix3 ASIC and sensors, with 55 µm pixel pitch and 14 µm pad diameter. The ACF technology can also be used for ASIC-PCB/FPC integration, replacing wire bonding or large-pitch solder bumping techniques. This contribution introduces the ENIG plating and ACF processes and presents recent results on Timepix3 hybrid assemblies.
Chagas' disease, caused by the protozoan Trypanosoma cruzi, represents a serious health problem in Latin America, and the available chemotherapy, which is based on 2 nitro-derivatives, is not ...satisfactory. In folk medicine, natural products including naphthoquinones have been employed for the treatment of different parasitic diseases. In the pursuit of alternative drugs for Chagas' disease, we investigated the mechanism of action of the triazolic naphthoquinone (TN; 2,2-dimethyl-3-(4-phenyl-1H-1,2,3-triazol-1-yl)-2,3-dihydronaphtho1,2-bfuran-4,5-dione), which is the most active compound against T. cruzi trypomastigotes among a series of naphthofuranquinones. TN was active against the 3 parasite forms producing a dose-dependent inhibitory effect. In epimastigotes, TN induced reservosome disruption, flagellar blebbing, Golgi disorganization, the presence of cytosolic concentric membrane structures and abnormal multiflagellar parasites. The treatment also led to the appearance of well-developed endoplasmic reticulum profiles surrounding organelles that associated with an increase in monodansylcadaverine labelling, suggesting autophagy as part of the TN mechanism of action. Interestingly, no ultrastructural damage was detected in the mitochondria of naphthoquinone-treated epimastigotes. Flow cytometric analysis demonstrated an impairment of mitosis, an increase in ROS production and the maintenance of mitochondrial membrane potential. TN could be a good starting point in the investigation of a chemotherapeutic approach for the treatment of Chagas' disease.
Swietenia macrophylla have been considered for the treatment of various diseases, including anticancer activity. This study aimed to investigate the anticancer activity of S. macrophylla leaves ...extract and its isolated compound towards human colorectal cancer cell line.
Hexanic extract of S. macrophylla leaves demonstrated relevant cytotoxicity only against colon cancer cell line HCT116.
Our results showed significant DNA damage and apoptosis after treatment with the hexanic extract of S. macrophylla. Moreover, no toxicity was noticed for the animal model. The isolated compound limonoid L1 showed potent cytotoxicity against cancer cell lines with IC50 at 55.87 μg mL−1. Limonoid L1 did not trigger any cell membrane rupture in the mice erythrocytes suggesting no toxicity. The antiproliferative effect of L1 was confirmed in colorectal cancer cells by clonogenic assay, inducing G2/M arrest, apoptosis, and DNA damage in cancer-type cells.
L1 reduced BCL2 and increased ATM, CHK2, TP53, ARF, CDK1, CDKN1A, and CASP3 in the colorectal cancer cell line. These findings suggest that limonoid L1 isolated from S. macrophylla can be a promising anticancer agent in managing colorectal cancer.
In a screening of 65 derivatives of natural quinones using bloodstream trypomastigotes of Trypanosoma cruzi, the 3 naphthoimidazoles derived from beta-lapachone - N1, N2 and N3--were selected as the ...most active. Investigation of their mode of action led to the characterization of mitochondrion, reservosomes and DNA as their main targets, and stimulated further studies on death pathways. Ultrastructural analysis revealed both autophagic (autophagosomes) and apoptotic-like (membrane blebbing) phenotypes. Flow cytometry analysis showed, in N2-treated trypomastigotes, a small increase of phosphatidylserine exposure, and a large increase in the percentage of necrosis, caused by N1 or N2. These death phenotypes were not detected in treated epimastigotes. The strong increase in labelling of monodansyl cadaverine, the inhibition of the death process by wortmannin or 3-methyladenine, the overexpression of ATG genes in treated epimastigotes, together with ultrastructural evidence point to autophagy as the predominant phenotype induced by the naphthoimidazoles. However, there are other pathways occurring concomitantly with variable intensities, justifying the need to detail the molecular features involved.
The MALTA pixel chip is a 2 cm × 2 cm large monolithic pixel detector developed in the Tower 180 nm imaging process. The chip contains four CMOS transceiver blocks at its sides which allow ...chip-to-chip data transfer. The power pads are located mainly at the side edges on the chip which allows for chip-to-chip power transmission. The MALTA chip has been used to study module assembly using different interconnection techniques to transmit data and power from chip to chip and to minimize the overall material budget. Several 2-chip and 4-chip modules have been assembled using standard wire bonding, ACF (Anisotropic Conductive Films) and laser reflow interconnection techniques. These proceedings will summarize the experience with the different interconnection techniques and performance tests of MALTA modules with 2 and 4 chips tested in a cosmic muon telescope. They will also show first results on the effect of serial power tests on chip performance as well as the impact of the different interconnection techniques and the results of mechanical tests. Finally, a conceptual study for a flex based ultra-light weight monolithic pixel module based on the MALTA chip with minimum interconnections is presented.
Objectives: Investigation of the mode of action of the naphthoimidazole N1, obtained from the reaction of β-lapachone with benzaldehyde, which among 45 semi-synthetic derivatives of naphthoquinones ...isolated from Tabebuia sp. was one of the most active compounds against Trypanosoma cruzi trypomastigotes. Methods: Quantification of the effect of N1 against the proliferative forms of T. cruzi, and investigation of potential targets in the parasite using electron microscopy and flow cytometry techniques. Results: N1 presented the following order of activity: amastigotes > trypomastigotes > epimastigotes. The effect on intracellular forms was ∼25 times higher than on macrophages and heart muscle cells. N1-treated parasites presented an abnormal chromatin condensation and mitochondrial damage. In epimastigotes, alterations of reservosomes were observed, and in trypomastigotes, a decrease in the electron density of acidocalcisomes was observed. In epimastigotes, the naphthoimidazole inhibited the activity of succinate cytochrome c reductase. Labelling with rhodamine 123 or Acridine Orange was decreased in both forms treated with N1. Conclusions: The results suggest that epimastigotes, reservosomes, mitochondrion, and nucleus contain N1 targets. In trypomastigotes, in which reservosomes are absent, the organelles affected by the compound were also the mitochondrion and nucleus, as well as acidocalcisomes, in which the decrease in electron density could be due to the use of polyphosphate as an alternative energy supply.
The question of whether gold (Au) is more toxic as nanoparticles or in its ionic form remains unclear and controversial. The present work aimed to clarify the effects of 96 h exposure to 4, 80 and ...1600 μg·L−1 of 7 nm gold nanoparticles (AuNPs) – (citrate coated (cAuNPs) or polyvinylpyrrolidone coated (PVP-AuNPs)) – and ionic Au (iAu) on gilthead seabream (Sparus aurata). Effects at different levels of biological organization (behaviour, neurotransmission, biotransformation, oxidative stress/damage and genotoxicity) were assessed. cAuNPs induced oxidative stress and damage (lipid peroxidation increase), even at 4 μg·L−1, and reduced the ability of S. aurata to swim against a water flow at 1600 μg·L−1. Exposure to cAuNPs induced more adverse effects than exposure to PVP-AuNPs. All tested concentrations of Au (nano or ionic form) induced DNA breaks and cytogenetic damage in erythrocytes of S. aurata. Generally, iAu induced significantly more effects in fish than the nano form, probably associated with the significantly higher accumulation in the fish tissues. No fish mortality was observed following exposure to AuNPs, but mortality was observed in the group exposed to 1600 μg·L−1 of iAu.
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•Gold (nano or ionic form) induced lipid peroxidation and genotoxicity on fish.•Ionic gold induced more adverse effects than a nano form of the metal.•Citrate coated nanoparticles were more bioactive than PVP coated nanoparticles.
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