Inhibition of the RNA-dependent RNA-polymerase from SARS-CoV-2 by 6-chloropurine isoxazoline-carbocyclic monophosphate nucleotides

Isoxazoline-carbocyclic monophosphate nucleotides were designed and synthesized through the chemistry of nitrosocarbonyl intermediates and stable anthracenenitrile oxide. Docking and molecular dynamics studies were first conducted for determining the best candidate for polymerase SARS-CoV-2 inhibition. The setup phosphorylation protocol afforded the nucleotides available for the biological tests. Preliminary inhibition and cytotoxicity assays were then performed, and the results showed a moderate activity of the nucleotides accompanied by cytotoxicity

Cleareye In-Ground and In-Concrete DIV Inspections: FY11 Final Report

This report summarizes the results of a series of feasibility testing studies for in-ground and in-concrete imaging/detection technologies including radar imaging and acoustic time-of flight method. The objectives of this project are: (1) Design Information Verification (DIV) Tools for In-Concrete Inspections - To determine the feasibility of using holographic radar imaging (HRI), radar imaging, and acoustic time-of-flight (TOF) non-destructive evaluation technologies to detect, locate and identify pipes and voids embedded in standard-density and high-density concrete walls that typify those the IAEA will need to verify during field inspections; (2) DIV Tools for In-Ground Inspections - To determine the feasibility of using HRI and radar imaging non-destructive evaluation technologies to detect, locate, and identify objects buried at various depths made of various materials (metal, plastic, wood, and concrete) and representing geometries that typify those the IAEA will need to verify during field inspections; and (3) Based on the results of the studies, recommend the next steps needed to realize fieldable tools for in-concrete and in-ground inspections (including detection of deeply buried polyvinyl chloride [PVC] pipes) that employ the technologies shown to be feasible

Nuclear Energy Research Initiative Project No. 02 103 Innovative Low Cost Approaches to Automating QA/QC of Fuel Particle Production Using On Line Nondestructive Methods for Higher Reliability Final Project Report

This Nuclear Energy Research Initiative (NERI) project was tasked with exploring, adapting, developing and demonstrating innovative nondestructive test methods to automate nuclear coated particle fuel inspection so as to provide the United States (US) with necessary improved and economical Quality Assurance and Control (QA/QC) that is needed for the fuels for several reactor concepts being proposed for both near term deployment [DOE NE & NERAC, 2001] and Generation IV nuclear systems. Replacing present day QA/QC methods, done manually and in many cases destructively, with higher speed automated nondestructive methods will make fuel production for advanced reactors economically feasible. For successful deployment of next generation reactors that employ particle fuels, or fuels in the form of pebbles based on particles, extremely large numbers of fuel particles will require inspection at throughput rates that do not significantly impact the proposed manufacturing processes. The focus of the project is nondestructive examination (NDE) technologies that can be automated for production speeds and make either: (I) On Process Measurements or (II) In Line Measurements. The inspection technologies selected will enable particle “quality” qualification as a particle or group of particles passes a sensor. A multiple attribute dependent signature will be measured and used for qualification or process control decisions. A primary task for achieving this objective is to establish standard signatures for both good/acceptable particles and the most problematic types of defects using several nondestructive methods

AIRO Breast Cancer Group Best Clinical Practice 2022 Update

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations.Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders.Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine

Methodologies for “Wiring” Redox Proteins/Enzymes to Electrode Surfaces

The immobilization of redox proteins or enzymes onto conductive surfaces has application in the analysis of biological processes, the fabrication of biosensors, and in the development of green technologies and biochemical synthetic approaches. This review evaluates the methods through which redox proteins can be attached to electrode surfaces in a “wired” configuration, that is, one that facilitates direct electron transfer. The feasibility of simple electroactive adsorption onto a range of electrode surfaces is illustrated, with a highlight on the recent advances that have been achieved in biotechnological device construction using carbon materials and metal oxides. The covalent crosslinking strategies commonly used for the modification and biofunctionalization of electrode surfaces are also evaluated. Recent innovations in harnessing chemical biology methods for electrically wiring redox biology to surfaces are emphasized

The tumour suppressor CCDC6 is involved in ROS tolerance and neoplastic transformation by evading ferroptosis

Coiled-coil domain containing 6 (CCDC6) is a tumour suppressor gene involved in apoptosis and DNA damage response. CCDC6 is known to be functionally impaired upon gene fusions, somatic mutations, and altered protein turnover in several tumours. Testicular germ cell tumours are among the most common malignancies in young males. Despite the high cure rate, achieved through chemotherapy and/or surgery, drug resistance can still occur. In a human cellular model of testis Embryonal Carcinoma, the deficiency of CCDC6 was associated with defects in DNA repair via homologous recombination and sensitivity to PARP1/2 inhibitors. Same data were obtained in a panel of murine testicular cell lines, including Sertoli, Spermatogonia and Spermatocytes. In these cells, upon oxidative damage exposure, the absence of CCDC6 conferred tolerance to reactive oxygen species affecting regulated cell death pathways by apoptosis and ferroptosis. At molecular level, the loss of CCDC6 was associated with an enhancement of the xCT/SLC7A11 cystine antiporter expression which, by promoting the accumulation of ROS, interfered with the activation of ferroptosis pathway. In conclusion, our data suggest that the CCDC6 downregulation could aid the testis germ cells to be part of a pro-survival pathway that helps to evade the toxic effects of endogenous oxidants contributing to testicular neoplastic growth. Novel therapeutic options will be discussed

Grandi dolii protostorici d’impasto dalla Calabria centromeridionale. Contributo allo studio cronotipologico, tecnologico e funzionale

Large protohistoric impasto dolia from Central-Southern Calabria. Contribution to the study of typology, chronology, technology and function - A high number of fragments of large protohistoric impasto pithoi has been found in several sites in the area, and mainly in Serre di Altilia (central Calabria). These fragments have been studied with other pithoi from Tropea (southern Calabria), in order to reconstruct their forms, typology, chronology, technology and function. It has been possible to define five types, with chronologies that may vary from the Final Bronze to the Early Iron Age, and with parallels in several sites of Southern Italy, in Sicily and at Lipari. Petrografic analyses on fragments from Central Calabria have shown a quite variable production, locally and/or regionally made. Chemical analyses have been also performed on two residue samples, in order to identify what kind of foodstuff was originally stored in these pithoi. The results of the analyses show the presence of terpenoid resins, such as Pistacia or Pinus, which may suggest the presence of wine

Technical Letter Report Assessment of Ultrasonic Phased Array Testing for Cast Austenitic Stainless Steel Pressurizer Surge Line Piping Welds and Thick Section Primary System Cast Piping Welds JCN N6398, Task 2A

Research is being conducted for the NRC at PNNL to assess the effectiveness and reliability of advanced NDE methods for the inspection of LWR components. The scope of this research encompasses primary system pressure boundary materials including cast austenitic stainless steels (CASS), dissimilar metal welds (DMWs), piping with corrosion-resistant cladding, weld overlays, and far-side examinations of austenitic piping welds. A primary objective of this work is to evaluate various NDE methods to assess their ability to detect, localize, and size cracks in coarse-grained steel components. This interim technical letter report (TLR) provides a synopsis of recent investigations at PNNL aimed at evaluating the capabilities of phased-array (PA) ultrasonic testing (UT) methods as applied to the inspection of CASS welds in nuclear reactor piping. A description of progress, recent developments and interim results are provided

Extraskeletal Ewing's sarcoma of the mediastinum: Case report

Background: Ewing sarcoma (ES) represents the second most common malignant bone tumor in children and young adults. ES is not a frequent finding in sites different from the skeletal. Common sites of appearance of ES are lower extremities, the pelvis, paravertebral spaces and head and neck. Primary extraskeletal ES located in the anterior mediastinum are very rare. These neoplasms should be discussed in specialized contests with a high volume of patients treated. Here, we present an uncommon mediastinal mass challenging in its characterization and management. Case description: A thirty-year-old woman performed a thoracic CT scan for dyspnea and persistent cough. Imaging showed a solid mass of 14 x 11 cm involving the left thorax with mediastinal deviation to the right side. Patient underwent an en bloc resection of the mass. Initial histological examination was suggestive for B3 thymoma/thymic carcinoma. Patient was then referred to our rare tumor reference center where a histological review excluded the diagnosis of thymic/thymoma neoplasms meanwhile a third revision assessed a diagnosis of ES. Patient refused adjuvant chemotherapy due to her desire of maternity and radiation therapy was not indicated because surgery was performed too many months earlier. A close follow-up was considered. After a few months the patient relapsed and first line chemotherapy was proposed. She reached a complete response at the first evaluation maintained also at the end of the protocol. In order to consolidate the obtained response, high dose chemotherapy followed by autologous stem cell transplantation (HDCT/ASCT) was suggested and the patient agreed. Conclusions: This case underlined that, potentially, ES can arise from any soft tissue site in the body, even in rare sites such as mediastinum. The evaluation of expert centers was critical to establish a correct diagnosis and therapeutic approach in this complex case. Taking into account the time lasting from the diagnosis and the aggressiveness of this kind of neoplasm, frequently relapsing, the patient after a multidisciplinary discussion was a candidate for a multimodal treatment