A large-area organic transistor with 3D-printed sensing gate for noninvasive single-molecule detection of pancreatic mucinous cyst markers

Early diagnosis in a premalignant (or pre-invasive) state represents the only chance for cure in neoplastic diseases such as pancreatic-biliary cancer, which are otherwise detected at later stages and can only be treated using palliative approaches, with no hope for a cure. Screening methods for the purpose of secondary prevention are not yet available for these cancers. Current diagnostic methods mostly rely on imaging techniques and conventional cytopathology, but they do not display adequate sensitivity to allow valid early diagnosis. Next-generation sequencing can be used to detect DNA markers down to the physical limit; however, this assay requires labeling and is time-consuming. The additional determination of a protein marker that is a predictor of aggressive behavior is a promising innovative approach, which holds the potential to improve diagnostic accuracy. Moreover, the possibility to detect biomarkers in blood serum offers the advantage of a noninvasive diagnosis. In this study, both the DNA and protein markers of pancreatic mucinous cysts were analyzed in human blood serum down to the single-molecule limit using the SiMoT (single-molecule assay with a large transistor) platform. The SiMoT device proposed herein, which exploits an inkjet-printed organic semiconductor on plastic foil, comprises an innovative 3D-printed sensing gate module, consisting of a truncated cone that protrudes from a plastic substrate and is compatible with standard ELISA wells. This 3D gate concept adds tremendous control over the biosensing system stability, along with minimal consumption of the capturing molecules and body fluid samples. The 3D sensing gate modules were extensively characterized from both a material and electrical perspective, successfully proving their suitability as detection interfaces for biosensing applications. KRAS and MUC1 target molecules were successfully analyzed in diluted human blood serum with the 3D sensing gate functionalized with b-KRAS and anti-MUC1, achieving a limit of detection of 10 zM and 40 zM, respectively. These limits of detection correspond to (1 ± 1) KRAS and (2 ± 1) MUC1 molecules in the 100 μL serum sample volume. This study provides a promising application of the 3D SiMoT platform, potentially facilitating the timely, noninvasive, and reliable identification of pancreatic cancer precursor cysts

Modifying Anthocyanins Biosynthesis in Tomato Hairy Roots:A Test Bed for Plant Resistance to Ionizing Radiation and Antioxidant Properties in Space

Gene expression manipulation of specific metabolic pathways can be used to obtain bioaccumulation of valuable molecules and desired quality traits in plants. A single-gene approach to impact different traits would be greatly desirable in agrospace applications, where several aspects of plant physiology can be affected, influencing growth. In this work, MicroTom hairy root cultures expressing a MYB-like transcription factor that regulates the biosynthesis of anthocyanins in Petunia hybrida (PhAN4), were considered as a testbed for bio-fortified tomato whole plants aimed at agrospace applications. Ectopic expression of PhAN4 promoted biosynthesis of anthocyanins, allowing to profile 5 major derivatives of delphinidin and petunidin together with pelargonidin and malvidin-based anthocyanins, unusual in tomato. Consistent with PhAN4 features, transcriptomic profiling indicated upregulation of genes correlated to anthocyanin biosynthesis. Interestingly, a transcriptome reprogramming oriented to positive regulation of cell response to biotic, abiotic, and redox stimuli was evidenced. PhAN4 hairy root cultures showed the significant capability to counteract reactive oxygen species (ROS) accumulation and protein misfolding upon high-dose gamma irradiation, which is among the most potent pro-oxidant stress that can be encountered in space. These results may have significance in the engineering of whole tomato plants that can benefit space agriculture

A Single-Molecule Bioelectronic Portable Array for Early Diagnosis of Pancreatic Cancer Precursors

A cohort of 47 patients is screened for pancreatic cancer precursors with a portable 96-well bioelectronic sensing-array for single-molecule assay in cysts fluid and blood plasma, deployable at point-of-care (POC). Pancreatic cancer precursors are mucinous cysts diagnosed with a sensitivity of at most 80% by state-of-the-art cytopathological molecular analyses (e.g., KRASmut DNA). Adding the simultaneous assay of proteins related to malignant transformation (e.g., MUC1 and CD55) is deemed essential to enhance diagnostic accuracy. The bioelectronic array proposed here, based on single-molecule-with-a-large-transistor (SiMoT) technology, can assay both nucleic acids and proteins at the single-molecule limit-of-identification (LOI) (1% of false-positives and false-negatives). It comprises an enzyme-linked immunosorbent assay (ELISA)-like 8 × 12-array organic-electronics disposable cartridge with an electrolyte-gated organic transistor sensor array, and a reusable reader, integrating a custom Si-IC chip, operating via software installed on a USB-connected smart device. The cartridge is complemented by a 3D-printed sensing gate cover plate. KRASmut, MUC1, and CD55 biomarkers either in plasma or cysts-fluid from 5 to 6 patients at a time, are multiplexed at single-molecule LOI in 1.5 h. The pancreatic cancer precursors are classified via a machine-learning analysis resulting in at least 96% diagnostic-sensitivity and 100% diagnostic-specificity. This preliminary study opens the way to POC liquid-biopsy-based early diagnosis of pancreatic-cancer precursors in plasma

γ-irradiation effect on the mechanical properties of in situ specimens made of structural epoxy adhesive and comparison with adhesive bulk behavior

This work examines the effects of gamma-irradiation (up to 500 kGy) on the mechanical behavior of aluminum in situ specimens bonded with 3MTM Scotch-WeldTM EC-2216 B/A Gray, a commercial two-part epoxy adhesive. Shear tests were performed, from which failure data and incipient axial stiffness were obtained. The results were compared to those of dedicated finite element models that had been tuned with the previously obtained bulk cohesive properties of the adhesive. Analytic models to evaluate stress distribution in the adhesive and joints axial stiffness were applied to validate the developed models and to explain the relatively small stiffness variance (observed both in experimental and numerical analyses results) compared to that of the adhesive Young’s modulus. On the whole, the adhesive showed a good tolerance to radiation in the interval studied, as already observed for bulk specimens. Finite element models were found to be accurate in predicting of the stiffness for the entire deformative field, while they overestimated the failure loads and displacements also applying unconservative failure criteria. This is very likely due to the significant number of defects found on the fracture surfaces of bulk specimens

Radiation study of Lead Fluoride crystals

Lead fluoride (PbF2) crystals represent an excellent and relatively innovative choice for high resolution electromagnetic calorimeters with high granularity and fast timing for high intensity environments. For this reason two PbF2 crystals, sized 5 x 5 x 40 mm(3), were irradiated with Co-60 photons up to similar to 4 Mrad and with 14 MeV neutrons up to a 10(13) n/cm(2) total fluence. Their loss in transmittance was evaluated at different steps of the photon and neutron irradiation campaign, resulting in a total of 30% loss above 350 nm. With crystals always kept in dark conditions, natural and thermal annealing, as well as optical bleaching with 400 nm light, were performed on the irradiated specimens, resulting in a partial recovery of their original optical characteristics

Simple FFH pilot experiment model based on DTT-like machine

The global need for energy in the world is constantly increasing. Critical fission reactors have proved great efficiency in the energy production, but the fear of nuclear wastes and accidents due to an uncontrolled chain reaction makes these unpleasant to public. More safe fusion reactors, on the opposite, have lowefficiency. Hybrid reactors capable of using the advantages of both are studied, but not yet developed. In this paper, a simple fusion–fission pilot experiment model has been developed. A Tokamak with the same characteristics of DTT (Divertor Tokamak Test facility) has been considered as a reference machine for the fusion component. The fusion system has been coupled with a relatively simple low-power fission blanket configured into three different modes by using different fuels and materials. This model could be useful in order to investigate the properties of the fusion–fission hybrid coupling from a neutronic point of view

Large-area bio-electronic sensors for early detection of pancreatic-biliary cancer protein markers

Pancreatic-biliary cancer represents a challenge for clinicians since the detection is performed at later stages and treated with palliative approaches. A screening method for the early detection should be of paramount importance. The aim of this study is the detection of pancreatic mucinous cysts protein markers (MUC1) in human serum down to the physical limit, using an Electrolyte-gated FET based technology, namely the "Single-Molecule assay with a large Transistor" (SiMoT) platform. The structure and transistor components have been developed on plastic substrates. The 3D gate structure is compatible with an ELISA plate. The functionalization procedure is assessed independently through Surface Plasmon Resonance, enabling the real-time monitoring of the gold modification with antibodies essential for the assay

Mitochondrial carriers as new molecular targets for cancer treatement

The flux of a variety of metabolites, nucleotides and coenzymes across the inner membrane of mitochondria is catalysed by a nuclear-coded superfamily of secondary transport proteins called mitochondrial carriers (MCs) [1]. The importance of MCs is demonstrated by their wide distribution in all eukaryotes, their role in numerous metabolic pathways and cell functions with different tissuespecific expression patterns, and the identification of several diseases caused by alterations of their genes [2]. Until now, 22 MC subfamilies have been functionally characterized, mainly by transport assays upon heterologous gene expression, purification and reconstitution into liposomes [1]. In particular two well characterized MC subfamilies are known to play a crucial role in activating the mitochondrial apoptotic pathway, the first is the subfamily of the ADP/ATP carriers and the second is the subfamily of the citrate carrier. ADP/ATP carriers catalyze the efflux of ATP from the mitochondrial matrix in exchange for cytosolic ADP and their specific inhibition can lead the permeability transition pore opening in case of oxidative stress [3]. Citrate carrier catalyses the efflux of citrate from the mitochondrial matrix in exchange for cytosolic malate and plays a key role in inflammation [4,5]. Our data together with literature data let us suppose that these two MC subfamilies are promising molecular targets for cancer treatment. In particular basing on our knowledge of MC structure, translocation mechanism and substrate specificity [6] we are evaluating neuroendocrine cancer cell resistance to old MC inhibitors and we are screening chemical libraries to develop new specific drugs to be used for viability assays

BIL Chamber Tests in Roma Tre

The ATLAS group of INFN and Roma Tre University is responsible for the test and certification of 60 Barrel Inner Large MDT chambers for the ATLAS muon spectrometer. The gas distribution assembling techniques, the Quality Assurance and Quality Control (QA/QC) tests, the MDT read out and data acquisition at the cosmic ray stand and the standard analysis performed to certify the chambers performance are described. Our man power time estimate for each procedure is also reported. A section is dedicated to the procedures adopted to certify the chambers, together with a proposal for a “Chamber Certification Document” which should be used as a reference document for each assembled, equipped and tested chamber. Finally, a status report of the first 10% Roma Tre QA/QC test is provided