B-spline ADC: many-body ab initio theory for electron dynamics in strong laser fields

This thesis is focused on the development of an efficient first-principles theoretical and numerical method based on the many-electron algebraic diagrammatic construction [ADC(n)] schemes, in order to describe the correlated ionisation dynamics in atomic and molecular systems interacting with perturbative and non-perturbative laser fields. The first line of research has focused on the calculation of total singlephoton photoionisation cross-sections, applying the Stieltjes-Imaging theory to Lanczos pseudospectra of the ADC Hamiltonian in Gaussian basis. We have established the accuracy of this technique by comparing the ADCLanczos-Stieltjes ground-state cross-sections obtained using different levels of many-body theory to the experimental ones for a series of organic molecules. We have extended this method to excited states cross-sections showing that a theoretical modelling of photoionisation from excited states requires an intrinsically double excitation theory. However, above 80 eV photon energy all three methods lead to inaccurate results due to the limitations of the Gaussian basis to describe continuum wave-functions of ionised electrons. The second, main line of research, has therefore been dedicated to constructing and computationally optimising the first implementation of the single [ADC(1)] and double excitations [ADC(2)] schemes in the B-spline basis, which is able to accurately describe the strongly oscillating continuum orbitals. As first application of this new method, we have calculated the photoionisation cross-sections of noble gas atoms showing that the features that pose a challenge for the GTO calculations are reproduced in a very good agreement with the experiment. We also have developed a time-dependent version with which we have calculated the HHG spectra of Ar, reproducing the effect of the Cooper minimum, and CO2, quantitatively investigating the multi-channel effects on its dynamical minimum. Finally we have provided a numerical answer to the highly topical question of coherence and ionic wavepacket formation in short pulse photoionisation.Open Acces

The Holocene Evolution of the Volturno Coastal Plain (Northern Campania, Southern Italy): Implications for the Understanding of Subsidence Patterns

In the Mediterranean area, several alluvial coastal plains, developed after the Holocene transgression, are affected by subsidence. The Volturno alluvial‐coastal plain, along the eastern Tyrrhenian Sea (southern Italy) is characterized by subsidence rates determined through InSAR data analysis and ranging between 0 and <−20 mm/yr in an area of about 750 kmq across the Volturno River. Inside this area, the pattern of subsidence shows sites with apparently anomalous localized subsidence. To understand the driving mechanisms of this process, a lithostratigraphic reconstruction was provided focusing on the spatial distribution of the horizons considered weak by a geotechnical point of view; then, the subsidence map was overlain spatially with geological data in a Geographic Information System (GIS) environment. The spatial analysis highlighted the major ground deformation occurring within the outer boundary of the incised paleo‐valley, corresponding to the Holocene alluvial/transitional filling that overlies a compaction‐free Pleistocene basement. Inside this general trend, differential compaction was detected corresponding to the thick occurrence of clay and peat deposits, suggesting that the subsidence rate registered in the plain are due in part to the consolidation of primary settlements of soft and compressible soils that characterize the subsoil of these areas, and in large part to the secondary consolidation settlements

Investigating the antiparasitic potential of the marine sesquiterpene avarone, its reduced form avarol, and the novel semisynthetic thiazinoquinone analogue thiazoavarone

The chemical analysis of the sponge Dysidea avara afforded the known sesquiterpene quinone avarone, along with its reduced form avarol. To further explore the role of the thiazinoquinone scaffold as an antiplasmodial, antileishmanial and antischistosomal agent, we converted the quinone avarone into the thiazinoquinone derivative thiazoavarone. The semisynthetic compound, as well as the natural metabolites avarone and avarol, were pharmacologically investigated in order to assess their antiparasitic properties against sexual and asexual stages of Plasmodium falciparum, larval and adult developmental stages of Schistosomamansoni (eggs included), and also against promastigotes and amastigotes of Leishmania infantum and Leishmania tropica. Furthermore, in depth computational studies including density functional theory (DFT) calculations were performed. A toxic semiquinone radical species which can be produced starting both from quinone- and hydroquinone-based compounds could mediate the anti-parasitic effects of the tested compounds

Negative Feedback Regulation of Auxin Signaling by ATHB8/ACL5–BUD2 Transcription Module

ABSTRACT The role of auxin as main regulator of vascular differentiation is well established, and a direct correlation between the rate of xylem differentiation and the amount of auxin reaching the (pro)cambial cells has been proposed. It has been suggested that thermospermine produced by ACAULIS5 (ACL5) and BUSHY AND DWARF2 (BUD2) is one of the factors downstream to auxin contributing to the regulation of this process in Arabidopsis . Here, we provide an in-depth characterization of the mechanism through which ACL5 modulates xylem differentiation. We show that an increased level of ACL5 slows down xylem differentiation by negatively affecting the expression of homeodomain-leucine zipper ( HD–ZIP ) III and key auxin signaling genes. This mechanism involves the positive regulation of thermospermine biosynthesis by the HD–ZIP III protein ARABIDOPSIS THALIANA HOMEOBOX8 tightly controlling the expression of ACL5 and BUD2 . In addition, we show that the HD–ZIP III protein REVOLUTA contributes to the increased leaf vascularization and long hypocotyl phenotype of acl5 likely by a direct regulation of auxin signaling genes such as LIKE AUXIN RESISTANT2 ( LAX2 ) and LAX3 . We propose that proper formation and differentiation of xylem depend on a balance between positive and negative feedback loops operating through HD–ZIP III genes

MS Dereplication for Rapid Discovery of Structurally New or Novel Natural Products

In order to accelerate the isolation and characterisation of structurally new or novel natural products, it is crucial to develop efficient strategies that prioritise samples with greatest promise early in the workflow so that resources can be utilised in a more efficient and cost-effective manner. Two complementary approaches have been developed: One is based on targeted identification of known compounds held in a database based on high resolution MS and predicted LC retention time data [1]. The second is an MS metrics-based approach where the software algorithm calculates metrics for sample novelty, complexity, and diversity after interrogating databases of known compounds, and contaminants. These metrics are then used to prioritise samples for isolation and structure elucidation work [2]. Both dereplication approaches have been validated using natural product extracts resulting in the isolation and characterization of new or novel natural products

Contact relationships between mafic and syenitic alkaline rocks in Jabaquara Beach, northern sector of São Sebastião Island, SP

Contact relationships between syenitic rocks of the Serraria stock and plutonic to hypoabisal mafic rocks of the northern sector of the alkaline suite of São Sebastião Island are described here for the first time, allowing the indication of temporal relationships between different magmatic batches. The outcrops show a hololeucocratic syenitic variety hosting mega-, macro- and microxenoliths from different rocks forming agmatites. Five main rock units were described: alkali feldspar syenites, melasyenites, diabases, mafic cumulates (melagabbro/clinopyroxenite), and heterogeneous gabbros. Geochemically, the bimodal alkaline magmatism found on the island is well represented by the studied rocks. The sequence of magmatic events is as follows: emplacement and crystallization of basic alkaline magma batches in a magmatic chamber, forming a varieties of gabbroic cumulates, mainly olivine-bearing melagabbros and clinopyroxenites, and breccias with gabbroic matrix with evidences of textural reequilibrium by thermal action; new intrusions of alkaline basic magma batches, represented by diabase fragments, which also present textural reequilibrium (predominant granoblastic texture); syenitic magma intrusion in the mafic chamber, which fragmented the already partially or fully crystallized gabbro, carrying a large proportion of xenocrysts and xenoliths, and forming melasyenite; new syenitic magma intrusion, which fragmented the whole system forming an agmatite with megaxenoliths and microxenoliths of cumulative gabbro, diabase, agmatite with gabbroic matrix (heterogeneous gabbros) and melasyenite; pegmatite veins and dykes of quartz syenites crosscutting all lithotypes. All types sampled as xenoliths have some degree of recrystallization and chemical reaction with the final syenitic host magma. Relações de contato entre as rochas sieníticas do stock de Serraria e as rochas máficas plutônicas e hipoabissais do setor norte da suíte alcalina da Ilha de São Sebastião (Ilhabela) são descritas pela primeira vez, permitindo a indicação de relações temporais entre diferentes pulsos magmáticos. Os afloramentos apresentam variedade sienítica hololeucocrática hospedando mega-, macro- e microxenólitos de diferentes rochas, formando agmatitos. Cinco unidades principais são descritas: álcali feldspato sienitos, melassienitos, diabásios, cumulatos máficos (melagabros/clinopiroxenitos) e gabros heterogêneos. Geoquimicamente,o magmatismo alcalino bimodal encontrado na ilha é bem representado pelas rochas dos afloramentos estudados. A sequência de eventos magmáticos consiste em: colocação e cristalização de pulsos de magmas básicos alcalinos, em ambiente de câmara magmática, gerando as variedades gabroicas cumuláticas, principalmente melagabros e clinopiroxenitos com olivina, e brechas de matriz gábrica com evidências de reequilíbrio textural por ação de temperatura; intrusão de novos pulsos de magma básico alcalino, representados pelos fragmentos de diabásios, que apresentam também, reequilíbrio textural (textura granoblástica predominante); intrusão de pulso sienítico na câmara máfica que fragmentou o gabro já parcial ou totalmente cristalizado, transportando ampla proporção de xenocristais e xenólitos, o que gerou rochas classificadas como melassienitos; nova intrusão de pulso sienítico, que fragmenta todo o sistema formando um agmatito com megaxenólitos e microxenólitos de gabro cumuláticos, diabásios, agmatitos de matriz gabroica (gabros heterogêneos) e melassienitos; veios e diques de pegmatito e aplito de sienitos com quartzo cortam todos os litotipos. Todos os tipos amostrados como xenólitos apresentam algum grau de recristalização e de reação química com o magma sienítico final que os hospeda

The new small tyrosine-kinase inhibitor ARQ531 targets acute myeloid leukemia cells by disrupting multiple tumor-addicted programs

Tyrosine kinases have been implicated in promoting tumorigenesis of several human cancers. Exploiting these vulnerabilities has been shown to be an effective anti-tumor strategy as demonstrated for example by the Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, for treatment of various blood cancers. Here, we characterize a new multiple kinase inhibitor, ARQ531, and evaluate its mechanism of action in preclinical models of acute myeloid leukemia. Treatment with ARQ531, by producing global signaling pathway deregulation, resulted in impaired cell cycle progression and survival in a large panel of leukemia cell lines and patient-derived tumor cells, regardless of the specific genetic background and/or the presence of bone marrow stromal cells. RNA-seq analysis revealed that ARQ531 constrained tumor cell proliferation and survival through Bruton's tyrosine kinase and transcriptional program dysregulation, with proteasome-mediated MYB degradation and depletion of short-lived proteins that are crucial for tumor growth and survival, including ERK, MYC and MCL1. Finally, ARQ531 treatment was effective in a patient-derived leukemia mouse model with significant impairment of tumor progression and survival, at tolerated doses. These data justify the clinical development of ARQ531 as a promising targeted agent for the treatment of patients with acute myeloid leukemia

Electronic Quantum Coherence in Glycine Molecules Probed with Ultrashort X-ray Pulses in Real Time

Structural changes in nature and technology are driven by charge carrier motion. A process such as charge-directed reactivity that can be operational in radiobiology is more efficient, if energy transfer and charge motion proceeds along well-defined quantum mechanical pathways keeping the coherence and minimizing dissipation. The open question is: do long-lived electronic quantum coherences exist in complex molecules? Here, we use x-rays to create and monitor electronic wave packets in the amino acid glycine. The outgoing photoelectron wave leaves behind a positive charge formed by a superposition of quantum mechanical eigenstates. Delayed x-ray pulses track the induced electronic coherence through the photoelectron emission from the sequential double photoionization processes. The observed sinusoidal modulation of the detected electron yield as a function of time clearly demonstrates that electronic quantum coherence is preserved for at least 25 femtoseconds in this molecule of biological relevance. The surviving coherence is detected via the dominant sequential double ionization channel, which is found to exhibit a phase shift as a function of the photoelectron energy. The experimental results agree with advanced ab-initio simulations.Comment: 54 pages, 11 figure

A detailed investigation of single-photon laser enabled Auger decay in neon

Single-photon laser enabled Auger decay (spLEAD) is an electronic de-excitation process which was recently predicted and observed in Ne. We have investigated it using bichromatic phase-locked free electron laser radiation and extensive angle-resolved photoelectron measurements, supported by a detailed theoretical model. We first used separately the fundamental wavelength resonant with the Ne+ 2s?2p transition, 46.17 nm, and its second harmonic, 23.08 nm, then their phase-locked bichromatic combination. In the latter case the phase difference between the two wavelengths was scanned, and interference effects were observed, confirming that the spLEAD process was occurring. The detailed theoretical model we developed qualitatively predicts all observations: branching ratios between the final Auger states, their amplitudes of oscillation as a function of phase, the phase lag between the oscillations of different final states, and partial cancellation of the oscillations under certain conditions