A comparison of theoretical MgVI emission line strengths with active-region observations from serts

R-matrix calculations of electron impact excitation rates in N-like Mg vi are used to derive theoretical electron-density-sensitive emission line ratios involving 2s(2)2p(3)-2s2p(4) transitions in the 269-403 Angstrom wavelength range. A comparison of these with observations of a solar active region, obtained during the 1989 flight of the Solar EUV Rocket Telescope and Spectrograph (SERTS), reveals good agreement between theory and observation for the 2s(2)2p(3) S-4-2s2p(4) P-4 transitions at 399.28, 400.67, and 403.30 Angstrom, and the 2s(2)2p(3) P-2-2s2p(4) D-2 lines at 387.77 and 387.97 Angstrom. However, intensities for the other lines attributed to Mg vi in this spectrum by various authors do not match the present theoretical predictions. We argue that these discrepancies are not due to errors in the adopted atomic data, as previously suggested, but rather to observational uncertainties or mis-identifications. Some of the features previously identified as Mg vi lines in the SERTS spectrum, such as 291.36 and 293.15 Angstrom, are judged to be noise, while others (including 349.16 Angstrom) appear to be blended.

Emission lines of Fe X in active region spectra obtained with the Solar Extreme-ultraviolet Research Telescope and Spectrograph

Fully relativistic calculations of radiative rates and electron impact excitation cross-sections for Fe X are used to derive theoretical emission-line ratios involving transitions in the 174-366 angstrom wavelength range. A comparison of these with solar active region observations obtained during the 1989 and 1995 flights of the Solar Extreme-ultraviolet Research Telescope and Spectrograph (SERTS) reveals generally very good agreement between theory and experiment. Several Fe X emission features are detected for the first time in SERTS spectra, while the 3s(2)3p(5) P-2(3/2)-3s(2)3p(4)(S-1)3d D-2(3/2) transition at 195.32 angstrom is identified for the first time (to our knowledge) in an astronomical source. The most useful Fe X electron density (N-e) diagnostic line ratios are assessed to be 175.27/174.53 and 175.27/177.24, which both involve lines close in wavelength and free from blends, vary by factors of 13 between N-e = 10(8) and 10(11) cm(-3), and yet show little temperature sensitivity. Should these lines not be available, then the 257.25/345.74 ratio may be employed to determine N-e, although this requires an accurate evaluation of the instrument intensity calibration over a relatively large wavelength range. However, if the weak 324.73 angstrom line of Fe X is reliably detected, the use of 324.73/345.74 or 257.25/324.73 is recommended over 257.25/345.74. Electron densities deduced from 175.27/174.53 and 175.27/177.24 for the stars Procyon and alpha Cen, using observations from the Extreme-Ultraviolet Explorer (EUVE) satellite, are found to be consistent and in agreement with the values of N-e determined from other diagnostic ratios in the EUVE spectra. A comparison of several theoretical extreme-ultraviolet Fe X line ratios with experimental values for a theta-pinch, for which the plasma parameters have been independently determined, reveals reasonable agreement between theory and observation, providing some independent support for the accuracy of the adopted atomic data.

Vasoactivity of AG014699, a clinically active small molecule inhibitor of poly(ADP-ribose) polymerase: a contributory factor to chemopotentiation in vivo?

Purpose: Poly(ADP-ribose) polymerase (PARP) plays an important role in DNA repair, and PARP inhibitors can enhance the activity of DNA-damaging agents in vitro and in vivo. AG014699 is a potent PARP inhibitor in phase II clinical development. However, the range of therapeutics with which AG014699 could interact via a DNA-repair based mechanism is limited. We aimed to investigate a novel, vascular-based activity of AG014699, underlying in vivo chemosensitization, which could widen its clinical application.

Experimental Design: Temozolomide response was analyzed in vitro and in vivo. Vessel dynamics were monitored using “mismatch” following the administration of perfusion markers and real-time analysis of fluorescently labeled albumin uptake in to tumors established in dorsal window chambers. Further mechanistic investigations used ex vivo assays of vascular smooth muscle relaxation, gut motility, and myosin light chain kinase (MLCK) inhibition.

Results: AG014699 failed to sensitize SW620 cells to temozolomide in vitro but induced pronounced enhancement in vivo. AG014699 (1 mg/kg) improved tumor perfusion comparably with the control agents nicotinamide (1 g/kg) and AG14361 (forerunner to AG014699; 10 mg/kg). AG014699 and AG14361 relaxed preconstricted vascular smooth muscle more potently than the standard agent, hydralazine, with no impact on gut motility. AG014699 inhibited MLCK at concentrations that relaxed isolated arteries, whereas AG14361 had no effect.

Conclusion: Increased vessel perfusion elicited by AG014699 could increase tumor drug accumulation and therapeutic response. Vasoactive concentrations of AG014699 do not cause detrimental side effects to gut motility and may increase the range of therapeutics with which AG014699 could be combined with for clinical benefit.

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial:a double-blind, active and placebo-controlled study

The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial.

A comparison of theoretical Mg VI emission line strengths with active-region observations from SERTS

R-matrix calculations of electron impact excitation rates in N-like Mg VI are used to derive theoretical electron-density-sensitive emission line ratios involving 2s²2p³ - 2s2p⁴ transitions in the 269-403 Å wavelength range. A comparison of these with observations of a solar active region, obtained during the 1989 flight of the Solar EUV Rocket Telescope and Spectrograph (SERTS), reveals good agreement between theory and observation for the 2s²2p^{3 4}S - 2s2p ^{4 4}p transitions at 399.28, 400.67, and 403.30 Å, and the 2s²2p^{3 2}p - 2s2p^{4 2}D lines at 387.77 and 387.97 Å. However, intensities for the other lines attributed to Mg VI in this spectrum by various authors do not match the present theoretical predictions. We argue that these discrepancies are not due to errors in the adopted atomic data, as previously suggested, but rather to observational uncertainties or mis-identifications. Some of the features previously identified as Mg VI lines in the SERTS spectrum, such as 291.36 and 293.15 Å, are judged to be noise, while others (including 349.16 Å) appear to be blended.

Recueil de pièces originales et de copies concernant l'histoire de la maison de Nevers. De 1562 à 1625.

Contient : 1-3 Lettres, en italien, avec chiffres, de MARGUERITE PALEOLOGUE, duchesse DE MANTOUE, au duc de Nevers, Louis de Gonzague, son fils. De 1562 à 1564 ; 4-8 Lettres, en italien, de « FRANCESCO PUGIELLA » audit duc de Nevers. 1577 et 1578 ; 9 Lettre, en italien, d' « ASCANIO ANDREASI » audit duc de Nevers. « Di Casale, li 25 luglio 1589 » ; 10 Lettre, en italien, de « FRANCESCO PUGIELLA » audit duc de Nevers. « Di Roma, il 2e di marzo 1578 » ; 11 « Copia di 2 lettere scritte al Sor Lodovico Birago ». Paris, 23 et 25 décembre 1570. En italien ; 12 Billet, en italien, où l'on recommande d'annoncer au duc de Nevers que « la serma prencipessa di Mantova e sicuramente gravida » ; 13 « Copia del capo dell' instruttione del sermo Sr duca DI MANTOVA, fatta allo Stanghelino, per trattar coll' illmo et eccmo Sr duca di Nivers ». 1570. En italien ; 14 « Assegni fatti all' illma et eccma Sa duchessa di Mantova ». En italien. Copie ; 15 « Avisi di Genova, per lo eccmo Sr duca di Nevers ». Relatifs surtout à la Corse. En italien ; 16 Lettre de « PASQUALINO RASPOLLICHIO » au duc de Nevers, Charles de Gonzague. 1621. En italien ; 17 « Memoria di cose che ha da far fare il Sr duca di Nevers », Louis de Gonzague, concernant des recherches à faire pour établir ses droits à l'héritage laissé par sa mère, la duchesse de Mantoue, au Montferrat. En italien ; 18 Fragment d'une lettre, en italien, écrite au duc de Nevers par un de ses agents, le Sr GUAZZO ; 19 Obligation de 1,000 écus, souscrite au profit du comte Thomas Galeazzi par Claude Angier, marquis de Crapado. Mantoue, 28 mars 1622. En italien. Copie ; 20 Lettre du Sr « BARCHINO » à « Cesare » Ceppo, concernant les recherches à faire au nom de Louis de Gonzague, duc de Nevers, pour établir contre le duc de Mantoue, son frère, le compte de tutelle de Marguerite Paléologue, leur mère, décédée. En italien ; 21 Fragment de lettre écrite, en partie, en faveur d'Octave Landi, par le duc DE NEVERS à l'évêque de Cujavie. 1577. En latin. Minute ; 22 Autre fragment de lettre écrite par le duc DE NEVERS audit évêque de Cujavie, sur la fuite du roi de Pologne, Henri de Valois, et les conséquences de cet acte pour les Polonais. 1574. En latin. Minute ; 23-24 Documents concernant la recherche des textes destinés à établir les droits du duc de Nevers sur la succession de sa mère, Marguerite Paléologue, duchesse de Mantoue, et les empêchements mis par le duc de Mantoue à ces recherches. En italien ; 25 Mémoire concernant les éléments dont se compose la rente de 13,806 ducats 42 sous, attribuée à la duchesse de Mantoue, comme tutrice de son fils, le duc de Mantoue. En italien ; 26 Lettre d' « OTTAVIO LANDI » au duc de Nevers. Vienne, 31 juillet 1577. En italien ; 27 Nouvelles de Milan, 7 juin 1572, concernant les agissements du duc d'Albe, du côté de Valenciennes et de Cambrai. En italien ; 28 Fragment de lettre adressée par le Sr CEPPO au Sr Guazzo, agent du duc de Nevers à Milan. « 28 aprile 1572 ». En italien ; 29 Lettre de « FRANCESCO PUGIELLA,... al Sr cavalier Guazzo,... Di Casale, il 27 d'ottobre 1577 ». En italien ; 30 Lettre de « CAMILLO VOLTA,... al Sr Gio. Paolo Medici,... Di Casa, il di XXX di luglio del [15]70 ». En italien ; 31 Lettre d' « HIPPOLITO CAPILUPI,... al Sr duca di Nevers,... Di Malaca, il 20 di maggio 1593 ». En italien ; 32 Lettre de « FILIPPO PERSEI » à la duchesse de Nevers. Mantoue, 23 décembre 1591. En italien ; 33-34 Lettres de « FRANCESCO GONZAGA, vescovo di Mantova », à la duchesse de Nevers. Vervins, 18 et 17 mai 1598. En italien ; 35 Lettre de « FILIPPO PERSEI » à la duchesse de Nevers. « Della Cassina, li 12 di maggio 1598 ». En italien ; 36 Lettre de « VICENZO CALINO » au duc de Nevers. « Da Brescia, il di 4 d'ottobre 1594 ». En italien ; 37 Lettre de « PIETR' ANTONIO DE' BENEDETTI » au duc de Nevers. « Di Mantova, alli 29 giugno 1590 ». En italien ; 38 Lettre d' « HIPPOLITO CAPILUPI » au duc de Nevers. « Di Malaca, il 20 d'aprile 1593 ». En italien ; 39-40 Lettres de « TOMASO BOZZI » au duc de Nevers. Rome, 20 février 1593. En italien ; 41 Chiffre. Quelques lignes non chiffrées sont en italien ; 42 Lettre de CAMILLO « VOLTA,... Di Cona, a il 30 aprile 1589 ». En italien ; 43 « Memoriale del Sr BARCHINO al Sr cavalier Guazzo, per l'illmo et eccmo Sr duca di Nevers,... Li 29 giugno 1570 ». En italien ; 44 Avis de Gênes et de Milan. Juillet 1572. En italien ; 45 « Copia della risposta del Sr duca eccmo di Mantova, data li 14 di luglio, sopra il memoriale sporto dal cavaliere Guazzo per l'eccmo Sr duca di Nevers, li 28 di maggio 1572. P. M. CORNACCHIA ». En italien ; 46 Avis de Milan. 16 août 1572. En italien ; 47 Ordonnance du duc DE MANTOUE, adressée aux sénateurs du Montferrat. Il les charge de faire inscrire le duc de Nevers, son frère, sur les livres de la chambre des comptes du Montferrat, pour un revenu annuel de 2,000 écus, et pour le paiement immédiat de 9,000 écus dus audit duc de Nevers, le tout en exécution d'un article du testament de la duchesse de Mantoue, Marguerite Paléologue, mère desdits ducs de Mantoue et de Nevers. 1571. En italien. Copie ; 48 Acte par lequel le duc DE NEVERS déclare reprendre à son service le chevalier Guazzo. « In Parigi, febraio 1576 ». En italien. Copie ; 49 « Instruttione del Sr BARCHINO al Guissano, alli 12 di marzo del [15]70, per andar a Mantova ». En italien. Copie ; 50 « Copia d'una lettera scritta alli 22 di febraio dal Sr BARCHINO al Guissano,... 1570 ». En italien ; 51 Lettre adressée au duc de Nevers par un de ses agents, le Sr GUAZZO ? « Di Grana, li 14 di feb° 1577 ». En italien ; 52 Avis, en italien, daté de Milan, 4 juin 1572 ; 53 « Scritura chel' Sr duca » Guillaume de Gonzague, duc de Mantoue, « fece dare al' Volta in Mantova, il 30 de luglio, et quella che fu risposta, tutte due sopra uno foglio, l'una apresso l'altra, il 4 agosto, et mandata per il Basco à Mantova. Bagni, agosto 1571 ». En italien ; 54 « Sommario di quanto contiene la lettera del Sr duca di Mantova, scritta al Salvato, a di 29 di novembre del 1572 ». En italien ; 55 Lettre, en italien, du Sr « BARCHINO » au Sr « Guazzo,... Da Verale, alli X de giugno 1570 ». En italien ; 56 Avis de Milan. Juin 1572. En italien ; 57 « Instruttione per le cose necessarie a prodursi per le prove nelle cause allodiali ». En italien ; 58 Mémoire, en italien et sans date, contenant des nouvelles de Rome, sur la nomination de plusieurs évêques, sur les départements assignés à des cardinaux pour le gouvernement de l'état ecclésiastique, sur des visites et conférences des cardinaux avec le pape Urbain VIII, etc. Ces nouvelles paraissent être de l'année 1625, y étant question de la naissance de Marie, princesse d'Espagne, fille de Philippe IV

Active Microwave Imaging for Breast Cancer Detection

Active microwave imaging is explored as an imaging modality for early detection of breast cancer. When exposed to microwaves, breast tumor exhibits electrical properties that are significantly different from that of healthy breast tissues. The two approaches of active microwave imaging — confocal microwave technique with measured reflected signals and microwave tomographic imaging with measured scattered signals are addressed here. Normal and malignant breast tissue samples of same person are subjected to study within 30 minutes of mastectomy. Corn syrup is used as coupling medium, as its dielectric parameters show good match with that of the normal breast tissue samples. As bandwidth of the transmitter is an important aspect in the time domain confocal microwave imaging approach, wideband bowtie antenna having 2:1 VSWR bandwidth of 46% is designed for the transmission and reception of microwave signals. Same antenna is used for microwave tomographic imaging too at the frequency of 3000 MHz. Experimentally obtained time domain results are substantiated by finite difference time domain (FDTD) analysis. 2-D tomographic images are reconstructed with the collected scattered data using distorted Born iterative method. Variations of dielectric permittivity in breast samples are distinguishable from the obtained permittivity profiles.

Optimisation of recombinant production of active human cardiac SERCA2a ATPase

Methods for recombinant production of eukaryotic membrane proteins, yielding sufficient quantity and quality of protein for structural biology, remain a challenge. We describe here, expression and purification optimisation of the human SERCA2a cardiac isoform of Ca2+ translocating ATPase, using Saccharomyces cerevisiae as the heterologous expression system of choice. Two different expression vectors were utilised, allowing expression of C-terminal fusion proteins with a biotinylation domain or a GFP- His8 tag. Solubilised membrane fractions containing the protein of interest were purified onto Streptavidin-Sepharose, Ni-NTA or Talon resin, depending on the fusion tag present. Biotinylated protein was detected using specific antibody directed against SERCA2 and, advantageously, GFP-His8 fusion protein was easily traced during the purification steps using in-gel fluorescence. Importantly, talon resin affinity purification proved more specific than Ni-NTA resin for the GFP-His8 tagged protein, providing better separation of oligomers present, during size exclusion chromatography. The optimised method for expression and purification of human cardiac SERCA2a reported herein, yields purified protein (> 90%) that displays a calcium-dependent thapsigargin-sensitive activity and is suitable for further biophysical, structural and physiological studies. This work provides support for the use of Saccharomyces cerevisiae as a suitable expression system for recombinant production of multi-domain eukaryotic membrane proteins.

Correlation of the highest-energy cosmic rays with the positions of nearby active galactic nuclei

Data collected by the Pierre Auger Observatory provide evidence for anisotropy in the arrival directions of the cosmic rays with the highest-energies, which are correlated with the positions of relatively nearby active galactic nuclei (AGN) [Pierre Auger Collaboration, Science 318 (2007) 938]. The correlation has maximum significance for cosmic rays with energy greater than similar to 6 x 10(19) eV and AGN at a distance less than similar to 75 Mpc. We have confirmed the anisotropy at a confidence level of more than 99% through a test with parameters specified a priori, using an independent data set. The observed correlation is compatible with the hypothesis that cosmic rays with the highest-energies originate from extra-galactic sources close enough so that their flux is not significantly attenuated by interaction with the cosmic background radiation (the Greisen-Zatsepin-Kuz`min effect). The angular scale of the correlation observed is a few degrees, which suggests a predominantly light composition unless the magnetic fields are very weak outside the thin disk of our galaxy. Our present data do not identify AGN as the sources of cosmic rays unambiguously, and other candidate sources which are distributed as nearby AGN are not ruled out. We discuss the prospect of unequivocal identification of individual sources of the highest-energy cosmic rays within a few years of continued operation of the Pierre Auger Observatory. (C) 2008 Elsevier B.V. All rights reserved.

Sustainable production of biologically active molecules of marine based origin

The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. © 2013 Elsevier B.V.

Balancing Exploration and Exploitation: A New Algorithm for Active Machine Learning

Active machine learning algorithms are used when large numbers of unlabeled examples are available and getting labels for them is costly (e.g. requiring consulting a human expert). Many conventional active learning algorithms focus on refining the decision boundary, at the expense of exploring new regions that the current hypothesis misclassifies. We propose a new active learning algorithm that balances such exploration with refining of the decision boundary by dynamically adjusting the probability to explore at each step. Our experimental results demonstrate improved performance on data sets that require extensive exploration while remaining competitive on data sets that do not. Our algorithm also shows significant tolerance of noise.

PET/CT-guided biopsies of metabolically active bone lesions: applications and clinical impact

In a minority of cases a definite diagnosis and stage grouping in cancer patients is not possible based on the imaging information of PET/CT. We report our experience with percutaneous PET/CT-guided bone biopsies to histologically verify the aetiology of hypermetabolic bone lesions.

Antiestrogenic and anticancer activities of peptides derived from the active site of alpha-fetoprotein

Cyclo[EKTOVNOGN] (AFPep), a cyclic 9-amino acid peptide derived from the active site of alpha-fetoprotein, has been shown to prevent carcinogen-induced mammary cancer in rats and inhibit the growth of ER+ human breast cancer xenografts in mice. Recently, studies using replica exchange molecular dynamics predicted that the TOVN region of AFPep might form a dynamically stable putative Type I beta-turn, and thus be biologically active without additional amino acids. The studies presented in this paper were performed to determine whether TOVN and other small analogs of AFPep would inhibit estrogen-stimulated cancer growth and exhibit a broad effective-dose range. These peptides contained nine or fewer amino acids, and were designed to bracket or include the putative pharmacophoric region (TOVN) of AFPep. Biological activities of these peptides were evaluated using an immature mouse uterine growth inhibition assay, a T47D breast cancer cell proliferation assay, and an MCF-7 breast cancer xenograft assay. TOVN had very weak antiestrogenic activity in comparison to AFPep's activity, whereas TOVNO had antiestrogenic and anticancer activities similar to AFPep. OVNO, which does not form a putative Type I beta-turn, had virtually no antiestrogenic and anticancer activities. A putative proteolytic cleavage product of AFPep, TOVNOGNEK, significantly inhibited E2-stimulated growth in vivo and in vitro over a wider dose range than AFPep or TOVNO. We conclude that TOVNO has anticancer potential, that TOVNOGNEK is as effective as AFPep in suppressing growth of human breast cancer cells, and that it does so over a broader effective-dose range.