Molecular Auger Interferometry

We propose a theory of interferometric measurement of a normal Auger decay width in molecules. Molecular Auger interferometry is based on the coherent phase control of Auger dynamics in a two-colour (ω/2ω) laser field. We show that, in contrast to atoms, in oriented molecules of certain point groups (e.g. CH3F) the relative ω/2ω phase modulates the total ionisation yield. A simple analytical formula is derived for the extraction of the widths of Auger-active states from a molecular Auger interferogram, avoiding the need of either attosecond or high-resolution spectroscopy

Helicene grafting on halloysite nanotubes for drug delivery: layer structure, surface selectivity and pH triggered drug release

Halloysite nanotubes (HNTs) have recently emerged as promising candidates for targeted drug delivery [1]. HNTs are low-toxic and low-cost aluminosilicate clays with nanotubular structure, presenting a positively charged Al(OH)3 inner lumen and a negatively charged SiO2 outer surface, which can support a selective functionalization of the two surfaces. In this work, we investigated the loading and release mechanisms of the tetrathia[7]helicene (7-TH) derivative linked via an imine bond to HNTs. The 7-TH scaffold displays promising intercalation properties for DNA, with a high degree of enantioselective recognition [2]. Moreover, a 7-TH derivative showed potent inhibitory activity against telomerase, demonstrating the great potential of 7-TH as therapeutic cytotoxic molecules [2,3]. We analyzed functionalized HNTs as well as Al2O3 and SiO2 layers, as models of the inner and outer surfaces, by means of surface-sensitive synchrotron-based techniques (XPS, UPS and NEXAFS spectroscopies). The oxide surfaces were analyzed both before and after functionalization with helicene derivatives through a (3-aminopropyl)triethoxysilane (APTES) linker [4]. Furthermore, the effect of a treatment in acidic conditions was investigated to prove the release of the helicene moiety from the oxide carrier at the extracellular pH of tumor cells. The surface state and atomic ratios of key elements within the organic layer determined by XPS proved the successful coupling of the helicene aldehyde to the APTES-functionalized films, clarifying differences in the reactivity of the two oxides. The sulfur peak confirmed the results obtained on the model films, supporting the reliability of the two adopted model surfaces. Moreover, NEXAFS results provided indication of a preferential orientation of helicene moieties at the oxide surface, which is lacking in APTES-functionalized layers. A further confirmation of the complete release of helicene moieties upon treatment in mild acidic conditions was given by NEXAFS spectra, showing a random orientation of the C and N functional groups after the release treatment. Preliminary in vitro toxicity tests on cancer cell lines characterized by different extracellular pH values show data consistent with a pH-triggered release of the 7-TH moiety, as also supported by kinetics data about the release in various physiological conditions. Work is currently under way to achieve a selective functionalization of the inner and outer surfaces by orthogonal functionalization strategies

Nitridation of InP(1 0 0) surface studied by synchrotron radiation

The nitridation of InP(1 0 0) surfaces has been studied using synchrotron radiation photoemission. The samples were chemically cleaned and then ion bombarded, which cleaned the surface and also induced the formation of metallic indium droplets. The nitridation with a Glow Discharge Cell (GDS) produced indium nitride by reaction with these indium clusters. We used the In 4d and P 2p core levels to monitor the chemical state of the surface and the coverage of the species present. We observed the creation of In-N and P-N bonds while the In-In metallic bonds decrease which confirm the reaction between indium clusters and nitrogen species. A theoretical model based on stacked layers allows us to assert that almost two monolayers of indium nitride are produced. The effect of annealing on the nitridated layers at 450 $^\circ$C has also been analysed. It appears that this system is stable up to this temperature, well above the congruent evaporation temperature (370 $^\circ$C) of clean InP(1 0 0): no increase of metallic indium bonds due to decomposition of the substrate is detected as shown in previous works [L. Bideux, Y. Ould-Metidji, B. Gruzza, V. Matolin, Surf. Interface Anal. 34 (2002) 712] studying the InP(1 0 0) surfaces

Ultrafast relaxation of photoexcited superfluid He nanodroplets

The relaxation of photoexcited nanosystems is a fundamental process of light-matter interaction. Depending on the couplings of the internal degrees of freedom, relaxation can be ultrafast, converting electronic energy in a few fs, or slow, if the energy is trapped in a metastable state that decouples from its environment. Here, we study helium nanodroplets excited resonantly by femtosecond extreme-ultraviolet (XUV) pulses from a seeded free- electron laser. Despite their superfluid nature, we find that helium nanodroplets in the lowest electronically excited states undergo ultrafast relaxation. By comparing experimental pho- toelectron spectra with time-dependent density functional theory simulations, we unravel the full relaxation pathway: Following an ultrafast interband transition, a void nanometer-sized bubble forms around the localized excitation (He ) within 1 ps. Subsequently, the bubble collapses and releases metastable He at the droplet surface. This study highlights the high level of detail achievable in probing the photodynamics of nanosystems using tunable XUV pulses

Diffraction imaging of light induced dynamics in xenon-doped helium nanodroplets

We explore the light induced dynamics in superfluid helium nanodroplets with wide-angle scattering in a pump–probe measurement scheme. The droplets are doped with xenon atoms to facilitate the ignition of a nanoplasma through irradiation with near-infrared laser pulses. After a variable time delay of up to 800 ps, we image the subsequent dynamics using intense extreme ultraviolet pulses from the FERMI free-electron laser. The recorded scattering images exhibit complex intensity fluctuations that are categorized based on their characteristic features. Systematic simulations of wide-angle diffraction patterns are performed, which can qualitatively explain the observed features by employing model shapes with both randomly distributed as well as structured, symmetric distortions. This points to a connection between the dynamics and the positions of the dopants in the droplets. In particular, the structured fluctuations might be governed by an underlying array of quantized vortices in the superfluid droplet as has been observed in previous small-angle diffraction experiments. Our results provide a basis for further investigations of dopant–droplet interactions and associated heating mechanisms

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Slow interatomic Coulombic decay of multiply excited neon clusters

Ne clusters ( 3c5000 atoms) were resonantly excited (2p\u21923s) by intense free electron laser (FEL) radiation at FERMI. Such multiply excited clusters can decay nonradiatively via energy exchange between at least two neighboring excited atoms. Benefiting from the precise tunability and narrow bandwidth of seeded FEL radiation, specific sites of the Ne clusters were probed. We found that the relaxation of cluster surface atoms proceeds via a sequence of interatomic or intermolecular Coulombic decay (ICD) processes while ICD of bulk atoms is additionally affected by the surrounding excited medium via inelastic electron scattering. For both cases, cluster excitations relax to atomic states prior to ICD, showing that this kind of ICD is rather slow (picosecond range). Controlling the average number of excitations per cluster via the FEL intensity allows a coarse tuning of the ICD rate

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy