Biophysical and biochemical characterization of a liposarcoma-derived recombinant MnSOD protein acting as an anticancer agent

A recombinant MnSOD (rMnSOD) synthesized by specific cDNA clones derived from a liposarcoma cell line was shown to have the same sequence as the wild-type MnSOD expressed in the human myeloid leukaemia cell line U937, except for the presence of the leader peptide at the N-terminus. These results were fully confirmed by the molecular mass of rMnSOD as evaluated by ES/MS analysis (26662.7 Da) and the nucleotide sequence of the MnSOD cDNA. The role of the leader peptide in rMnSOD was investigated using a fluorescent and/or 68Gallium-labelled synthetic peptide. The labelled peptide permeated MCF-7 cells and uptake could be inhibited in the presence of an excess of oestrogen. In vivo it was taken up by the tumour, suggesting that the molecule can be used for both therapy and diagnosis. The in vitro and in vivo pharmacology tests confirmed that rMnSOD is only oncotoxic for tumour cells expressing oestrogen receptors. Pharmacokinetic studies in animals performed with 125I- and 131I-labelled proteins confirmed that, when administered systemically, rMnSOD selectively reached the tumour, where its presence was unambiguously demonstrated by scintigraphic and PET scans. PCR analysis revealed that Bax gene expression was increased and the Bcl2 gene was down regulated in MCF7 cells treated with rMnSOD, which suggests that the protein induces a pro-apoptotic mechanism

Model-measurement comparison of mesospheric temperature inversions, and a simple theory for their occurrence

Mesospheric temperature inversions are well established observed phenomena, yet their properties remain the subject of ongoing research. Comparisons between Rayleigh-scatter lidar temperature measurements obtained by the University of Western Ontario's Purple Crow Lidar (42.9°N, 81.4°W) and the Canadian Middle Atmosphere Model are used to quantify the statistics of inversions. In both model and measurements, inversions occur most frequently in the winter and exhibit an average amplitude of ∼10 K. The model exhibits virtually no inversions in the summer, while the measurements show a strongly reduced frequency of occurrence with an amplitude about half that in the winter. A simple theory of mesospheric inversions based on wave saturation is developed, with no adjustable parameters. It predicts that the environmental lapse rate must be less than half the adiabatic lapse rate for an inversion to form, and it predicts the ratio of the inversion amplitude and thickness as a function of environmental lapse rate. Comparison of this prediction to the actual amplitude/thickness ratio using the lidar measurements shows good agreement between theory and measurements

The flow of plasma in the solar terrestrial environment

The overall goal of our NASA Theory Program was to study the coupling, time delays, and feedback mechanisms between the various regions of the solar-terrestrial system in a self-consistent, quantitative manner. To accomplish this goal, it will eventually be necessary to have time-dependent macroscopic models of the different regions of the solar-terrestrial system and we are continually working toward this goal. However, with the funding from this NASA program, we concentrated on the near-earth plasma environment, including the ionosphere, the plasmasphere, and the polar wind. In this area, we developed unique global models that allowed us to study the coupling between the different regions. These results are highlighted in the next section. Another important aspect of our NASA Theory Program concerned the effect that localized 'structure' had on the macroscopic flow in the ionosphere, plasmasphere, thermosphere, and polar wind. The localized structure can be created by structured magnetospheric inputs (i.e., structured plasma convection, particle precipitation or Birkland current patterns) or time variations in these input due to storms and substorms. Also, some of the plasma flows that we predicted with our macroscopic models could be unstable, and another one of our goals was to examine the stability of our predicted flows. Because time-dependent, three-dimensional numerical models of the solar-terrestrial environment generally require extensive computer resources, they are usually based on relatively simple mathematical formulations (i.e., simple MHD or hydrodynamic formulations). Therefore, another goal of our NASA Theory Program was to study the conditions under which various mathematical formulations can be applied to specific solar-terrestrial regions. This could involve a detailed comparison of kinetic, semi-kinetic, and hydrodynamic predictions for a given polar wind scenario or it could involve the comparison of a small-scale particle-in-cell (PIC) simulation of a plasma expansion event with a similar macroscopic expansion event. The different mathematical formulations have different strengths and weaknesses and a careful comparison of model predictions for similar geophysical situations provides insight into when the various models can be used with confidence

Improvements to a long-term Rayleigh-scatter lidar temperature climatology by using an optimal estimation method

Hauchecorne and Chanin (1980) developed a robust method to calculate middle-atmosphere temperature profiles using measurements from Rayleigh-scatter lidars. This traditional method has been successfully used to greatly improve our understanding of middle-atmospheric dynamics, but the method has some shortcomings regarding the calculation of systematic uncertainties and the vertical resolution of the retrieval. Sica and Haefele (2015) have shown that the optimal estimation method (OEM) addresses these shortcomings and allows temperatures to be retrieved with confidence over a greater range of heights than the traditional method. We have calculated a temperature climatology from 519 nights of Purple Crow Lidar Rayleigh-scatter measurements using an OEM. Our OEM retrieval is a first-principle retrieval in which the forward model is the lidar equation and the measurements are the level-0 count returns. It includes a quantitative determination of the top altitude of the retrieved temperature profiles, the evaluation of nine systematic plus random uncertainties, and the vertical resolution of the retrieval on a profile-by-profile basis. Our OEM retrieval allows for the vertical resolution to vary with height, extending the retrieval in altitude 5 to 10&thinsp;km higher than the traditional method. It also allows the comparison of the traditional method's sensitivity to two in-principle equivalent methods of specifying the seed pressure: using a model pressure seed versus using a model temperature combined with the lidar's density measurement to calculate the seed pressure. We found that the seed pressure method is superior to using a model temperature combined with the lidar-derived density. The increased altitude capability of our OEM retrievals allows for a comparison of the Rayleigh-scatter lidar temperatures throughout the entire altitude range of the sodium lidar temperature measurements. Our OEM-derived Rayleigh temperatures are shown to have improved agreement relative to our previous comparisons using the traditional method, and the agreement of the OEM-derived temperatures is the same as the agreement between existing sodium lidar temperature climatologies. This detailed study of the calculation of the new Purple Crow Lidar temperature climatology using the OEM establishes that it is both highly advantageous and practical to reprocess existing Rayleigh-scatter lidar measurements that cover long time periods, during which time the lidar may have undergone several significant equipment upgrades, while gaining an upper limit to useful temperature retrievals equivalent to an order of magnitude increase in power-aperture product due to the use of an OEM.</p

Cross Sectional and Longitudinal Fuzzy Clustering of the NUTS and Positioning of the Italian Regions with Respect to the Regional Competitiveness Index (RCI) Indicators with Contiguity Constraints

In socio-economical clustering often the empirical information is represented by time-varying data generated by indicators observed over time on a set of subnational (regional) units. Usually among these units may exist contiguity relations, spatial but not only.In this paper we propose a fuzzy clustering model of multivariate time-varying data, the longitudinal fuzzy C-Medoids clustering with contiguity constraints. The temporal aspect is dealt with by using appropriate measures of dissimilarity between time trajectories. The contiguity among units is dealt with adding a contiguity matrix as a penalization term in the clustering model.The cross sectional fuzzy C-Medoids clustering with contiguity constraints is obtained considering one instant of time. The model is applied to the classification of the European NUTS on the basis of the observed dynamics of the Basic, Efficiency and Innovation subindexes of the Regional Competitiveness Index (RCI) 2013 and 2016. The positioning of the Italian regions is analyzed through the values of the medoids of the clusters and shows the peculiarities of the regions with respect to the subindexes either in single times or in the dynamic. Two contiguity constraints, one based on the European Western, Southern, Central and Northern geographic areas and one on the level of GDP—taken into account in the computation of the RCI—are also introduced in the models

Ambulatory surgery for perianal Crohn’s disease. Study of feasibility

Background. One-third of Crohn’s disease (CD) patients present perianal fistula. The gold standard in the diagnosis and treatment of symptomatic perianal disease (PAD) in CD is the exploration of the anal canal and distal rectum under anesthesia (EUA). This procedure is mainly conducted as a day case surgery. Unfortunately, it is not always possible to proceed within the ideal timing and any delay may well represent a relevant clinical issue. The aim of this study was to evaluate the feasibility of outpatient treatment of symptomatic perianal fistulas in CD patients. Methods. All CD patients under regular follow-up at our inflammatory bowel disease referral center, presenting with symptomatic perianal fistulas, were offered surgical consultation. The data of patients were prospectively collected for three years (February 2014 to February 2017) for the purpose of the study. All clinical information, including previous EUA and/or records from MRI and endoscopic ultrasound, was included. Outpatient anal canal and distal rectum exploration and treatment (OE) were undertaken during the specialist surgical consultation. Fistulas were classified according to Parks’s classification; the type of outpatient treatment and compliance of patients were recorded. Pain was assessed by VAS at the time of the procedure and during the first control. Patients were followed up in the surgical clinic in relation to the study. Results. Ninety-two CD patients with symptomatic perianal fistulas had surgical consultation during the study period. OE was offered to all but 18 patients who fulfilled the exclusion criteria or had an extremely severe disease; six patients refused the OE (8.11%). Of the 68 patients undergoing OE, eleven (16.18%) had previous surgery for perianal disease. The OE was accomplished in sixty-one patients (89.71%), while in 7 patients, it was abandoned for scarce compliance. Nine patients (14.75%) underwent drainage of perianal abscess; in 3 of them, it was possible to probe the fistula tract, find the internal orifice, and pass a loose seton. Overall, setonage was performed in 50 patients (81.97%). Rectovaginal setons were placed in 3 patients and more than one seton (up to 3) in 6 cases. Fistulotomy was performed in 4 simple subcutaneous fistulous tracts. Concordance with the preoperative findings was found in 54 out of 61 patients. EUA was scheduled at the time of OE for the 7 patients who did not complete the procedure. All sixty-one patients who had the OE were followed up for a minimum of 12 months. Conclusions. This preliminary study indicates that OE in CD patients with symptomatic perianal fistulas is safe and feasible in a high-volume referral center. It might provide several benefits, including patients’ logistics, reduce or remove patients’ symptoms and discomfort, allow for a timely start of medical therapy, and avoid further complications

Provenance of white marbles from the Roman City of tauriana (Palmi, Reggio Calabria, Italy)

The work shows the results of an archaeometric study performed on fourteen white marble samples from the Roman city of Tauriana (Palmi, Reggio Calabria, Italy), belonging to different architectural elements of the Municipal Museum Complex and artifacts reused in the modern town. Samples were studied by optical microscopy (OM), x-ray powder diffraction (XRPD), and isotope ratio mass spectrometry (IRMS) of13C and18O with the aim to identify their provenance. The comparison between the collected data and the historical ones, concerning the ancient quarries of white marble of the Mediterranean area, allowed us to prove that most of the marbles used in the city of Tauriana were from the Apuan Alps Basin (Carrara) and, in few cases, from Minor Asia (Proconnesos, Aphrodisias, Docimium) and Greek (Thasos and Pentelic) quarries

Herlyn–Werner–Wunderlich syndrome: An “early” onset case report and review of Literature

AbstractHerlyn–Werner–Wunderlich syndrome (HWWS) is a rare congenital mullerian anomaly consisting of uterus didelphys, hemivaginal septum, and unilateral renal agenesis [1,2]. Most authors reported cases of Herlyn–Werner–Wunderlich syndrome with prepuberal or postpuberal onset with cyclical abdominal pain and a vaginal mass (3–8). Only six cases are reported in Literature with early onset of this syndrome under 5 years (9–14). Our case is about 3 years old girl, with all the features of this syndrome who came to our attention for lower abdominal mass. The aim of this article is to share our experience and focus the attention on the importance of high level of suspicion of HWWS in neonatal period to early diagnosis and treatment. The possible early presentation of this syndrome should be suspected in all neonates (females) with renal agenesia confirmed postnatally or with prenatal diagnosis. It is common, in fact, an error of evaluation with planning of removal of mass, that can damage patients in term of chance for a successful reproductive outcome. For all these reasons, our team consider HWWS as differential diagnosis in newborn with prenatal ultrasonography of a cystic mass behind the urinary bladder in the absence of a kidney and plan a pelvic ultrasound (with aim to identify an uterus, normal or dydhelfus, and presence or absence of pelvic mass), an examination under anesthesia and cystoscopy and vaginoscopy, if it is necessary. A high level of suspicion, indeed, is the key to early diagnosis