Innovative technology for cancer risk analysis

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Measurements of Aerosol Size and Microphysical Properties: A Comparison Between Raman Lidar and Airborne Sensors

This manuscript compares measurements of aerosol size distributions and microphysical properties retrieved from the Raman lidar BASIL with those obtained from a series of aircraft sensors during HyMeX-SOP1. The attention is focused on a measurement session on 02 October 2012, with BASIL measurements revealing the presence of a lower aerosol layer extending up to 3.3 km and an elevated layer extending from 3.6 to 4.6 km. Aerosol size distribution and microphysical properties are determined from multi-wavelength particle backscattering and extinction profile measurements through a retrieval approach based on Tikhonov regularization. A good agreement is found between BASIL and the microphysical sensors' measurements for all considered aerosol size and microphysical properties. Specifically, BASIL and in-situ volume concentration values are in the range 2-5 mu m(3) cm(-3) in the lower layer and in the range 1-3.5 mu m(3) cm(-3) in the upper layer. Values of the effective radius values from BASIL and the in-situ sensors are in the range 0.2-0.6 mu m in both the lower and upper layer. Aerosol size distributions are determined at 2.2, 2.8, 4 and 4.3 km, with a good agreement between the Raman lidar and the microphysical sensors at all considered heights. We combined these size and microphysical results with Lagrangian back-trajectory analyses and chemical composition measurements. From this combination of datasets we conclude that aerosol particles below 3 km were probably originated by wildfires in North America and/or by anthropogenic activities in North-Eastern Europe, while aerosols above 3 km were also probably originated by wildfires in North America

Neutrophils, Crucial, or Harmful Immune Cells Involved in Coronavirus Infection: A Bioinformatics Study

The latest member of the Coronaviridae family, called SARS-CoV-2, causes the Coronavirus Disease 2019 (COVID-19). The disease has caused a pandemic and is threatening global health. Similar to SARS-CoV, this new virus can potentially infect lower respiratory tract cells and can go on to cause severe acute respiratory tract syndrome, followed by pneumonia and even death in many nations. The molecular mechanism of the disease has not yet been evaluated until now. We analyzed the GSE1739 microarray dataset including 10 SARS-positive PBMC and four normal PBMC. Co-expression network analysis by WGCNA suggested that highly preserved 833 turquoise module with genes were significantly related to SARS-CoV infection. ELANE, ORM2, RETN, BPI, ARG1, DEFA4, CXCL1, and CAMP were the most important genes involved in this disease according to GEO2R analysis as well. The GO analysis demonstrated that neutrophil activation and neutrophil degranulation are the most activated biological processes in the SARS infection as well as the neutrophilia, basophilia, and lymphopenia predicted by deconvolution analysis of samples. Thus, using Serpins and Arginase inhibitors during SARS-CoV infection may be beneficial for increasing the survival of SARS-positive patients. Regarding the high similarity of SARS-CoV-2 to SARS-CoV, the use of such inhibitors might be beneficial for COVID-19 patients

Atmospheric Boundary Layer Height: Inter-Comparison of Different Estimation Approaches Using the Raman Lidar as Benchmark

This work stems from the idea of improving the capability to measure the atmospheric boundary layer height (ABLH) in variable or unstable weather conditions or in the presence of turbulence and precipitation events. A new approach based on the use of rotational and roto-vibrational Raman lidar signals is considered and tested. The traditional gradient approach based on the elastic signals at wavelength 532 nm is also considered. Lidar data collected by the University of Basilicata Raman lidar (BASIL) within the Special Observation Period 1 (SOP 1) in Cardillargues (Ceveninnes-CV supersite) during the Hydrological Cycle in the Mediterranean Experiment (HyMeX) were used. Our attention was specifically focused on the data collected during the period 16-21 October 2012. ABLH estimates from the Raman lidar were compared against other innovative methods, such as the recently established Morphological Image Processing Approach (MIPA) and the temperature gradient technique applied to potential temperature obtained from radio-sounding data. For each considered methodology, a statistical analysis was carried out. In general, the results from the different methodologies are in good agreement. Some deviations have been observed in correspondence with quite unstable weather conditions

The unresolved case of sacral chordoma: from misdiagnosis to challenging surgery and medical therapy resistance.

PURPOSE: A sacral chordoma is a rare, slow-growing, primary bone tumor, arising from embryonic notochordal remnants. Radical surgery is the only hope for cure. The aim of our present study is to analyse our experience with the challenging treatment of this rare tumor, to review current treatment modalities and to assess the outcome based on R status. METHODS: Eight patients were treated in our institution between 2001 and 2011. All patients were discussed by a multidisciplinary tumor board, and an en bloc surgical resection by posterior perineal access only or by combined anterior/posterior accesses was planned based on tumor extension. RESULTS: Seven patients underwent radical surgery, and one was treated by using local cryotherapy alone due to low performance status. Three misdiagnosed patients had primary surgery at another hospital with R1 margins. Reresection margins in our institution were R1 in two and R0 in one, and all three recurred. Four patients were primarily operated on at our institution and had en bloc surgery with R0 resection margins. One had local recurrence after 18 months. The overall morbidity rate was 86% (6/7 patients) and was mostly related to the perineal wound. Overall, 3 out of 7 resected patients were disease-free at a median follow-up of 2.9 years (range, 1.6-8.0 years). CONCLUSION: Our experience confirms the importance of early correct diagnosis and of an R0 resection for a sacral chordoma invading pelvic structures. It is a rare disease that requires a challenging multidisciplinary treatment, which should ideally be performed in a tertiary referral center

Crucial Physical Dependencies of the Core-Collapse Supernova Mechanism

We explore with self-consistent 2D F{\sc{ornax}} simulations the dependence of the outcome of collapse on many-body corrections to neutrino-nucleon cross sections, the nucleon-nucleon bremsstrahlung rate, electron capture on heavy nuclei, pre-collapse seed perturbations, and inelastic neutrino-electron and neutrino-nucleon scattering. Importantly, proximity to criticality amplifies the role of even small changes in the neutrino-matter couplings, and such changes can together add to produce outsized effects. When close to the critical condition the cumulative result of a few small effects (including seeds) that individually have only modest consequence can convert an anemic into a robust explosion, or even a dud into a blast. Such sensitivity is not seen in one dimension and may explain the apparent heterogeneity in the outcomes of detailed simulations performed internationally. A natural conclusion is that the different groups collectively are closer to a realistic understanding of the mechanism of core-collapse supernovae than might have seemed apparent.Comment: 25 pages; 10 figure

Spectrum of germline pathogenic variants in brca1/2 genes in the apulian southern italy population: Geographic distribution and evidence for targeted genetic testing

BRCA1/2-associated hereditary breast and ovarian cancer is the most common form of hereditary breast and ovarian cancer and occurs in all ethnicities and racial populations. Different BRCA1/BRCA2 pathogenic variants (PVs) have been reported with a wide variety among populations. In this study, we retrospectively analyzed prevalence and geographic distribution of pathogenic germline BRCA1/2 variants in families from Apulia in southern Italy and evaluated the genotype–phenotype correlations. Data were collected from Oncogenetic Services present in Apulian hospitals and a shared database was built containing Apulian native probands (n = 2026) that had undergone genetic testing from 2004 to 2019. PVs were detected in 499 of 2026 (24.6%) probands and 68.5% of them (342 of 499) were in the BRCA1 gene. We found 65 different PVs in BRCA1 and 46 in BRCA2. There were 10 most recurrent PVs and their geographical distribution appears to be significantly specific for each province. We have assumed that these PVs are related to the historical and geopolitical changes that occurred in Apulia over time and/or to a “founder effect”. Broader knowledge of BRCA1/2 prevalence and recurring PVs in specific geographic areas could help establish more flexible genetic testing strategies that may enhance our ability to detect high-risk subjects

u-PAR expression in cancer associated fibroblast: new acquisitions in multiple myeloma progression

BACKGROUND: Multiple Myeloma (MM) is a B-cell malignancy in which clonal plasma cells progressively expand within the bone marrow (BM) as effect of complex interactions with extracellular matrix and a number of microenvironmental cells. Among these, cancer-associated fibroblasts (CAF) mediate crucial reciprocal signals with MM cells and are associated to aggressive disease and poor prognosis. A large body of evidence emphasizes the role of the urokinase plasminogen activator (u-PA) and its receptor u-PAR in potentiating the invasion capacity of tumor plasma cells, but little is known about their role in the biology of MM CAF. In this study, we investigated the u-PA/u-PAR axis in MM-associated fibroblasts and explore additional mechanisms of tumor/stroma interplay in MM progression. METHODS: CAF were purified from total BM stromal fraction of 64 patients including monoclonal gammopathy of undetermined significance, asymptomatic and symptomatic MM, as well as MM in post-treatment remission. Flow cytometry, Real Time PCR and immunofluorescence were performed to investigate the u-PA/u-PAR system in relation to the level of activation of CAF at different stages of the disease. Moreover, proliferation and invasion assays coupled with silencing experiments were used to prove, at functional level, the function of u-PAR in CAF. RESULTS: We found higher activation level, along with increased expression of pro-invasive molecules, including u-PA, u-PAR and metalloproteinases, in CAF from patients with symptomatic MM compared to the others stages of the disease. Consistently, CAF from active MM as well as U266 cell line under the influence of medium conditioned by active MM CAF, display higher proliferative rate and invasion potential, which were significantly restrained by u-PAR gene expression inhibition. CONCLUSIONS: Our data suggest that the stimulation of u-PA/u-PAR system contributes to the activated phenotype and function of CAF during MM progression, providing a biological rationale for future targeted therapies against MM

DECK: Distance and environment-dependent, coarse-grained, knowledge-based potentials for protein-protein docking

<p>Abstract</p> <p>Background</p> <p>Computational approaches to protein-protein docking typically include scoring aimed at improving the rank of the near-native structure relative to the false-positive matches. Knowledge-based potentials improve modeling of protein complexes by taking advantage of the rapidly increasing amount of experimentally derived information on protein-protein association. An essential element of knowledge-based potentials is defining the reference state for an optimal description of the residue-residue (or atom-atom) pairs in the non-interaction state.</p> <p>Results</p> <p>The study presents a new Distance- and Environment-dependent, Coarse-grained, Knowledge-based (DECK) potential for scoring of protein-protein docking predictions. Training sets of protein-protein matches were generated based on bound and unbound forms of proteins taken from the D<smcaps>OCKGROUND</smcaps> resource. Each residue was represented by a pseudo-atom in the geometric center of the side chain. To capture the long-range and the multi-body interactions, residues in different secondary structure elements at protein-protein interfaces were considered as different residue types. Five reference states for the potentials were defined and tested. The optimal reference state was selected and the cutoff effect on the distance-dependent potentials investigated. The potentials were validated on the docking decoys sets, showing better performance than the existing potentials used in scoring of protein-protein docking results.</p> <p>Conclusions</p> <p>A novel residue-based statistical potential for protein-protein docking was developed and validated on docking decoy sets. The results show that the scoring function DECK can successfully identify near-native protein-protein matches and thus is useful in protein docking. In addition to the practical application of the potentials, the study provides insights into the relative utility of the reference states, the scope of the distance dependence, and the coarse-graining of the potentials.</p