THE GEMINI NICI PLANET-FINDING CAMPAIGN: DISCOVERY OF A MULTIPLE SYSTEM ORBITING THE YOUNG A STAR HD 1160

We report the discovery of two low-mass companions to the young A0V star HD 1160 at projected separations of 81 +/- 5 AU (HD 1160 B) and 533 +/- 25 AU (HD 1160 C) by the Gemini NICI Planet-Finding Campaign. Very Large Telescope images of the system taken over a decade for the purpose of using HD 1160 A as a photometric calibrator confirm that both companions are physically associated. By comparing the system to members of young moving groups and open clusters with well-established ages, we estimate an age of 50(-40)(+50) Myr for HD 1160 ABC. While the UVW motion of the system does not match any known moving group, the small magnitude of the space velocity is consistent with youth. Near-IR spectroscopy shows HD 1160 C to be an M3.5 +/- 0.5 star with an estimated mass of 0.22(-0.04)(+0.03) M-circle dot, while NIR photometry of HD 1160 B suggests a brown dwarf with a mass of 33(-9)(+12) M-Jup. The very small mass ratio (0.014) between the A and B components of the system is rare for A star binaries, and would represent a planetary-mass companion were HD 1160 A to be slightly less massive than the Sun.

Discovery of the Persistent Luminescence Mechanism of CdSiO3:Tb3+

The persistent luminescence of CdSiO3:Tb3+ was investigated with photoluminescence, thermoluminescence (TL), synchrotron radiation X-ray absorption (XANES and EXAFS) and UV-VUV spectroscopies. Only the typical intraconfigurational 4f(8)-4f(8) transitions of the Tb3+ ion were observed with no traces of band emission in either the conventional UV excited or persistent luminescence spectra. The trap structure from TL with three traps from 0.65 to 0.85 eV is ideal for room-temperature persistent luminescence similar to, e.g., Sr2MgSi2O7:Eu2+,R3+. Despite the rather low band gap energy, 5.28 eV, the persistent luminescence from Tb3+ is produced only under UV irradiation due to the inauspicious position of the F-7(6) ground level deep in the band gap of CdSiO3. This confirms the role of electrons as the charge carriers in the mechanism of Tb3+ persistent luminescence. The XANES spectra indicated the presence of only the trivalent Tb3+ species, thus excluding the direct Tb3+ -> Tb-IV oxidation during the charging process of persistent luminescence. Eventually, a unique persistent luminescence mechanism for Tb3+ in CdSiO3 was constructed based on the comprehensive experimental data.

Discovery of hearing impairment by the family: seeing an idealized future collapse

OBJECTIVE: To portray the family experience when the discovery of hearing impairment in their child. METHODS: Qualitative research with Symbolic Interactionism and Grounded Theory as theoretical and methodological frameworks. Data collection instrument: semi-structured interview. The study included nine families (32 participants). RESULTS: The theme, "Seeing an idealized future collapse", shows that for the family, discovered the possibility of having a child with hearing loss is a moment that involves many negative feelings. CONCLUSION: Discover the hearing loss has a meaning of the expected loss of the perfect child, frustrated expectations and uncertain future. The family has been inadequately approached and the diagnosis has been made late, which requires immediate changes to the practices of professionals.

Computational investigation of the Plasmodium falciparum fatty acid biosynthetic pathway toward the discovery of novel antimalarials

The structural peculiarities of a protein are related to its biological function. In the fatty acid elongation cycle, one small carrier protein shuttles and delivers the acyl intermediates from one enzyme to the other. The carrier has to recognize several enzymatic counterparts, specifically interact with each of them, and finally transiently deliver the carried substrate to the active site. Carry out such a complex game requires the players to be flexible and efficiently adapt their structure to the interacting protein or substrate. In a drug discovery effort, the structure-function relationships of a target system should be taken into account to optimistically interfere with its biological function. In this doctoral work, the essential role of structural plasticity in key steps of fatty acid biosynthesis in Plasmodium falciparum is investigated by means of molecular simulations. The key steps considered include the delivery of acyl substrates and the structural rearrangements of catalytic pockets upon ligand binding. The ground-level bases for carrier/enzyme recognition and interaction are also put forward. The structural features of the target have driven the selection of proper drug discovery tools, which captured the dynamics of biological processes and could allow the rational design of novel inhibitors. The model may be perspectively used for the identification of novel pathway-based antimalarial compounds.

Nuclear structure studies in the xenon and radon region and the discovery of a new radon isotope by Penning trap mass spectrometry

Heutzutage gewähren hochpräzise Massenmessungen mit Penning-Fallen tiefe Einblicke in die fundamentalen Eigenschaften der Kernmaterie. Zu diesem Zweck wird die freie Zyklotronfrequenz eines Ions bestimmt, das in einem starken, homogenen Magnetfeld gespeichert ist. Am ISOLTRAP-Massenspektrometer an ISOLDE / CERN können die Massen von kurzlebigen, radioaktiven Nukliden mit Halbwertszeiten bis zu einigen zehn ms mit einer Unsicherheit in der Größenordnung von 10^-8 bestimmt werden. ISOLTRAP besteht aus einem Radiofrequenz-Quadrupol zum akkumulieren der von ISOLDE gelieferten Ionen, sowie zwei Penning-Fallen zum säubern und zur Massenbestimmung der Ionen. Innerhalb dieser Arbeit wurden die Massen von neutronenreichen Xenon- und Radonisotopen (138-146Xe und 223-229Rn) gemessen. Für elf davon wurde zum ersten Mal die Masse direkt bestimmt; 229Rn wurde im Zuge dieses Experimentes sogar erstmalig beobachtet und seine Halbwertszeit konnte zu ungefähr 12 s bestimmt werden. Da die Masse eines Nuklids alle Wechselwirkungen innerhalb des Kerns widerspiegelt, ist sie einzigartig für jedes Nuklid. Eine dieser Wechselwirkungen, die Wechselwirkung zwischen Protonen und Neutronen, führt zum Beispiel zu Deformationen. Das Ziel dieser Arbeit ist eine Verbindung zwischen kollektiven Effekten, wie Deformationen und Doppeldifferenzen von Bindungsenergien, sogenannten deltaVpn-Werten zu finden. Insbesondere in den hier untersuchten Regionen zeigen deltaVpn-Werte ein sehr ungewöhnliches Verhalten, das sich nicht mit einfachen Argumenten deuten lässt. Eine Erklärung könnte das Auftreten von Oktupoldeformationen in diesen Gebieten sein. Nichtsdestotrotz ist eine quantitative Beschreibung von deltaVpn-Werten, die den Effekt von solchen Deformationen berücksichtigt mit modernen Theorien noch nicht möglich.

The wind profile in the atmospheric stable boundary layer over complex terrain and heterogeneous surfaces: limitations of local similarity theory

L'indagine ha riguardato il profilo del vento nei primi 30 metri dello strato limite atmosferico stabile nell'ambito della teoria di similarità locale. Ad oggi, diversi esperimenti hanno confermato la validità della teoria per strati-limite su terreni livellati e superfici omogenee. Tali condizioni ideali sono però infrequenti nella realtà ed è perciò importante capire quali siano i limiti della similarità locale per strati-limite su terreni complessi e superfici disomogenee. Entrambe le condizioni sono presenti a Ny-Alesund (Svalbard, Norvegia) dove il Consiglio Nazionale delle Ricerche (CNR), nel 2009, ha installato una torre di 30 m, la Amudsen-Nobile Climate Change Tower (CCT), per lo studio dello strato-limite artico. Il lavoro di tesi ha riguardato misure di vento e turbolenza acquisite sulla CCT da maggio 2012 a maggio 2014. Il confronto tra le velocità del vento misurate dagli anemometri installati sulla CCT, ha rivelato criticità nel dato sonico manifestatesi con sovrastime sistematiche e maggiore erraticità rispetto alle misure provenienti dagli anemometri a elica. Un test condotto fra diversi metodi per il calcolo dei gradienti verticali della velocità del vento ha rivelato scarsa sensibilità dei risultati ottenuti al particolare metodo utilizzato. Lo studio ha riguardato i gradienti verticali adimensionali della velocità del vento nei primi 30-m dello strato limite stabile. Deviazioni significative tra i tra le osservazioni e i valori predetti dalla similarità locale sono state osservate in particolare per i livelli più distanti dal suolo e per valori crescenti del parametro di stabilità z/L (L, lunghezza di Obukhov locale). In particolare, si sono osservati gradienti adimensionali inferiori a quelli predetti dalle più usate relazioni di flusso-gradiente. Tali deviazioni, presenti perlopiù per z/L>0.1, sono state associate ad un effetto di accentuazione della turbolenza da parte delle irregolarità del terreno. Per condizioni meno stabili, z/L<0.1, scarti positivi tra i gradienti osservati e quelli attesi sono stati attribuiti alla formazione di strati limite interni in condizioni di vento dal mare verso la costa. Sono stati proposti diversi metodi per la stima dell'effetto della self-correlazione nella derivazione delle relazioni di flusso-gradiente, dovuta alla condivisione della variabile u*. La formula per il coefficiente lineare di self correlazione e le sue distribuzioni di probabilità empiriche sono state derivate e hanno permesso di stimare il livello di self-correlazione presente nel dataset considerato.

Natural products as leads for anticancer drug discovery: discovery of new chemotypes of microtubule stabilizers through reengineering of the epothilone scaffold

Epothilones are bacterial macrolides with potent microtubule-stabilizing and antiproliferative activity, which have served as successful lead structures for the discovery of several clinical candidates for cancer treatment. Overall, seven epothilone-type agents have been advanced to clinical evaluation in humans so far and one of these has been approved by the FDA in 2007 for clinical use in breast cancer patients. Notwithstanding these impressive numbers, however, the structural diversity represented by the collection of epothilone analogs that have been (or still are) investigated clinically is rather limited and their individual structures show little divergence from the original natural product leads. In contrast, we have elaborated a series of epothilone-derived macro-lactones, whose overall structural features significantly deviate from those of the natural epothilone scaffold and thus define new structural families of microtubule-stabilizing agents. Key elements of our hypermodification strategy are the change of the natural epoxide geometry from cis to trans, the incorporation of conformationally constrained side chains, the removal of the C(3)-hydroxyl group, and the replacement of C(12) with nitrogen. The latter modification leads to aza-macrolides that may be described as 'non-natural natural products'.

Computational Design and Experimental Discovery of an Anti-estrogenic Peptide Derived from Alpha-Fetoprotein

Breast cancer is the most common cancer among women, and tamoxifen is the preferred drug for estrogen receptor-positive breast cancer treatment. Many of these cancers are intrinsically resistant to tamoxifen or acquire resistance during treatment. Consequently, there is an ongoing need for breast cancer drugs that have different molecular targets. Previous work has shown that 8-mer and cyclic 9-mer peptides inhibit breast cancer in mouse and rat models, interacting with an unsolved receptor, while peptides smaller than eight amino acids did not. We show that the use of replica exchange molecular dynamics predicts the structure and dynamics of active peptides, leading to the discovery of smaller peptides with full biological activity. Simulations identified smaller peptide analogues with the same conserved reverse turn demonstrated in the larger peptides. These analogues were synthesized and shown to inhibit estrogen-dependent cell growth in a mouse uterine growth assay, a test showing reliable correlation with human breast cancer inhibition.