Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Outstation for x-ray powder diffraction at the Italian beamline at the European synchrotron.

LISA [Linea Italiana per la Spettroscopia di Assorbimento X, Italian beamline for X-ray Absorption Spectroscopy (XAS)] is the Italian CRG (Collaborating Research Group) beamline at the ESRF (European Synchrotron Radiation Facility) dedicated to XAS [d'Acapito et al., J. Synchrotron Radiat. 26, 551-558 (2019)]. In this work, a methodical test of the LISA beamline in performing diffraction measurements is carried out. Synchrotron x-ray diffraction measurements would complement absorption spectroscopy techniques with the long-range characterization of the material under investigation, while XAS provides the short-range element selective information.

The role of chemical and microstructural inhomogeneities on interface magnetism.

The study of interfacing effects arising when different magnetic phases are in close contact has led to the discovery of novel physical properties and the development of innovative technological applications of nanostructured magnetic materials. Chemical and microstructural inhomogeneities at the interfacial region, driven by interdiffusion processes, chemical reactions and interface roughness may significantly affect the final properties of a material and, if suitably controlled, may represent an additional tool to finely tune the overall physical properties. The activity at the Nanostructured Magnetic Materials Laboratory (nM2-Lab) at CNR-ISM of Italy is aimed at designing and investigating nanoscale-engineered magnetic materials, where the overall magnetic properties are dominated by the interface exchange coupling. In this review, some examples of recent studies where the chemical and microstructural properties are critical in determining the overall magnetic properties in core/shell nanoparticles, nanocomposites and multilayer heterostructures are presented.

The effect of long-range order on intermolecular interactions in organic semiconductors: zinc octaethyl porphyrin molecular thin film model systems.

In order to optimize the performance of devices based on porphyrin thin films it is of great importance to gain a physical understanding of the various factors which affect their charge transport and light-harvesting properties. In this work, we have employed a multi-technique approach to study vacuum deposited zinc octaethyl porphyrin (ZnOEP) thin films with different degrees of long-range order as model systems. An asymmetrical stretching of the skeletal carbon atoms of the porphyrin conformer has been observed and attributed to ordered molecular stacking and intermolecular interactions. For ordered films, a detailed fitting analysis of the X-ray absorption near edge structure (XANES) using the MXAN code establishes a symmetry reduction in the molecular conformer involving the skeletal carbon atoms of the porphyrin ring; this highlights the consequences of increased π-π stacking of ZnOEP molecules adopting the triclinic structure. The observed asymmetrical stretching of the π conjugation network of the porphyrin structure can have significant implications for charge transport and light harvesting, significantly influencing the performance of porphyrin based devices.

Temperature dependent local atomic displacements in NaSn2As2 system.

NaSn2As2 is mechanically exfoliable layered van der Waals (vdW) Zintl phase that is getting interesting due to its low thermal conductivity and recently observed superconductivity. Here, we have investigated the temperature dependent local structure of NaSn2As2 by a combined analysis of As K-edge and Sn K-edge extended x-ray absorption fine structure measurements. The system is intrinsically disordered with the interatomic distances largely consistent to those estimated by average structure measurements. The stretching force constants of different bond distances have been determined using temperature dependent mean square relative displacements. The Sn-As distance is the strongest bond in this system, having covalent nature, unlike the weaker interlayer distances which are characterized by vdW type bonding. Among them, As-Na distance is slightly weaker than Sn-Sn(i) below ∼200 K and tends to get stronger above this temperature. The anomalous behavior of As-Na bond suggests that the mechanical exfoliation in this system is likely to be temperature dependent. The anomaly in the interlayer atomic correlations may be due to a charge density wave-like instability around this temperature, indicated by earlier experiments. The local structure and disorder are discussed in relation to the physical properties of NaSn2As2.

The incorporation site of Er in nanosized CaF2.

The incorporation site of Er dopants inserted at high and low concentration (respectively 5 and 0.5 mol%) in nanoparticles of CaF2 is studied by x-ray absorption spectroscopy (XAS) at the Er L III edge. The experimental data are compared with the results of structural modeling based on density functional theory (DFT). DFT-based molecular dynamics is also used to simulate complete theoretical EXAFS spectra of the model structures. The result is that Er substitutes for Ca in the structure and in the low concentration case the dopant ions are isolated. At high concentration the rare earth ions cluster together binding Ca vacancies.

Local environment of metal ions in phthalocyanines: K-edge X-ray absorption spectra.

We report a detailed study of the K-edge X-ray absorption spectra of four transition metal phthalocyanines (MPc, M = Fe, Co, Cu and Zn). We identify the important single and multiple scattering contributions to the spectra in the extended energy range and provide a robust treatment of thermal damping; thus, a generally applicable model for the interpretation of X-ray absorption fine structure spectra is proposed. Consistent variations of bond lengths and Debye Waller factors are found as a function of atomic number of the metal ion, indicating a variation of the metal-ligand bond strength which correlates with the spatial arrangement and occupation of molecular orbitals. We also provide an interpretation of the near edge spectral features in the framework of a full potential real space multiple scattering approach and provide a connection to the local electronic structure.

Evidence for Germanene growth on epitaxial hexagonal (h)-AlN on Ag(1 1 1).

In this work, a structural analysis of Ge layers deposited by molecular beam epitaxy (MBE) on Ag(1 1 1) surfaces with and without an AlN buffer layer have been investigated by x-ray Absorption Spectroscopy (XAS) at the Ge-K edge. For the Ge layers deposited on h-AlN buffer layer on Ag(1 1 1) an interatomic Ge-Ge distance [Formula: see text] Å is found, typical of 2-Dimensional Ge layers and in agreement with the theoretical predictions for free standing low-buckled Germanene presented in literature. First principles calculations, performed in the density functional theory (DFT) framework, supported the experimental RHEED and XAS findings, providing evidence for the epitaxial 2-D Ge layer formation on h-AlN/Ag(1 1 1) template.

The role of the local chemical environment of Ag on the resistive switching mechanism of conductive bridging random access memories.

Conductive bridging random access memories (CBRAMs) are one of the most promising emerging technologies for the next generation of non-volatile memory. However, the lack of understanding of the switching mechanism at the nanoscale level prevents successful transfer to industry. In this paper, Ag/GeSx/W CBRAM devices are analyzed using depth selective X-ray Absorption Spectroscopy before and after switching. The study of the local environment around Ag atoms in such devices reveals that Ag is in two very distinct environments with short Ag-S bonds due to Ag dissolved in the GeSx matrix, and longer Ag-Ag bonds related to an Ag metallic phase. These experiments allow the conclusion that the switching process involves the formation of metallic Ag nano-filaments initiated at the Ag electrode. All these experimental features are well supported by ab initio molecular dynamics simulations showing that Ag favorably bonds to S atoms, and permit the proposal of a model at the microscopic level that can explain the instability of the conductive state in these Ag-GeSx CBRAM devices. Finally, the principle of the nondestructive method described here can be extended to other types of resistive memory concepts.

Ferromagnetic Mn-doped Si0.3Ge0.7 nanodots self-assembled on Si(100).

Densely packed epitaxial Mn-doped Si(0.3)Ge(0.7) nanodots self-assembled on Si(100) have been obtained. Their structural properties were studied using reflection high-energy electron diffraction, energy dispersive x-ray diffraction, atomic force microscopy, extended x-ray absorption fine structure measurements and high-resolution transmission electron microscopy. Mn(5)Ge(1)Si(2) crystallites embedded in Si(0.3)Ge(0.7) were found. They exhibit a ferromagnetic behaviour with a Curie temperature of about 225 K.

Localization of the dopant in Ge:Mn diluted magnetic semiconductors by x-ray absorption at the Mn K edge.

A unitary picture of the structural properties of Mn(x)Ge(1-x) diluted alloys fabricated by either ion implantation or molecular beam epitaxy (MBE), at various growth temperatures (from 80 to about 623 K) and few per cent concentrations, is proposed. Analysis is based on synchrotron radiation x-ray absorption spectroscopy at the Mn K edge. When the growth temperature exceeds 330 K, the MBE samples show a high number of precipitated ferromagnetic nanoparticles, mainly Mn(5)Ge(3), nucleated from the previous occupation of interstitial tetrahedral sites. Efficient substitution is observed in the case of MBE samples made by alternate layers of GeMn alloys grown at T ≤ 433 K and undoped Ge thick layers. Similar good dilution properties are obtained by implanting Mn ions at low temperatures (80 K). Possible precursors to preferential mechanisms in the alloy formation are discussed on the basis of the present comparative study.

The evolution of the fraction of Er ions sensitized by Si nanostructures in silicon-rich silicon oxide thin films.

Photoluminescence (PL) and time-resolved PL experiments as a function of the elaboration process are performed on Er-doped silicon-rich silicon oxide (SRO:Er) thin films grown under NH(3) atmosphere. These PL measurements of the Er(3+) emission at 1.54 microm under non-resonant pumping with the Er f-f transitions are obtained for different Er(3+) concentrations, ranging from 0.05 to 1.4 at.%, and various post-growth annealing temperatures of the layers. High resolution transmission electron microscopy (HRTEM) and energy-filtered TEM (EFTEM) analysis show a high density of Si nanostructures composed of amorphous and crystalline nanoclusters varying from 2.7 x 10(18) to 10(18) cm(-3) as a function of the post-growth annealing temperature. Measurements of PL lifetime and effective Er excitation cross section for all the samples under non-resonant optical excitation with the Er(3+) atomic energy levels show that the number of Er(3+) ions sensitized by the silicon-rich matrix decreases as the annealing temperature is increased from 500 to 1050 degrees C. The origin of this effect is attributed to the reduction of the density of sensitizers for Er ions in the SRO matrix when the annealing temperature increases. Finally, extended x-ray absorption fine-structure spectroscopy (EXAFS) shows a strong correlation between the number of emitters and the mean local order around the erbium ions.

Setup for optimized grazing incidence x-ray absorption experiments on thin films on substrates.

We present a state-of-the-art experimental apparatus and a proper setup to perform x-ray absorption spectroscopy (XAS) experiments in grazing incidence mode. This geometry is appropriate for doped thin films or interfaces buried at moderate depth in a thick matrix, whenever the scattering and/or fluorescence from the matrix has to be strongly attenuated. Both the calculation and the experimental data demonstrate that the specific setup that consists in a grazing incidence and grazing collection geometry is extremely advantageous. In fact, with respect to the standard geometry used to perform XAS experiments in fluorescence mode, the present setup allows an enhancement in the interesting fluorescence signal from the surface layer without a corresponding increase in the elastic scattering contribution from the matrix. The sample holder especially designed for this kind of experiment can work in vacuum and at low temperature. An easy and quick automatic sample alignment procedure is detailed.

A new procedure for the quantitative analysis of extended x-ray absorption fine structure data in total reflection geometry.

A novel code for the analysis of extended x-ray absorption fine structure (EXAFS) data collected in total reflection mode (reflEXAFS) is presented. The procedure calculates the theoretical fine structure signals appearing in the reflectivity spectrum starting from the ab initio EXAFS calculations. These signals are then used in complex structural refinement (i.e., also including multiple scattering paths) with usual fitting programs of EXAFS data. A test case consisting in the analysis of a gold film collected at different incidence angles is presented in detail.

Controlled aggregation of magnetic ions in a semiconductor: an experimental demonstration.

The control on the distribution of magnetic ions into a semiconducting host is crucial for the functionality of magnetically doped semiconductors. Through a structural analysis at the nanoscale, we give experimental evidence that the aggregation of Fe ions in (Ga,Fe)N and consequently the magnetic response of the material are affected by the growth rate and doping with shallow impurities.

Local structure of [Cu(I)(CO)2]+ adducts hosted inside ZSM-5 zeolite probed by EXAFS, XANES and IR spectroscopies.

EXAFS spectroscopy, analysed in the frame of the multiple scattering theory, has been able to determine the local structure of [Cu(CO)2]+ complexes hosted inside ZSM-5 channels upon contacting the activated zeolite with CO from the gas phase at room temperature. We found that the number of coordinated CO molecules (1.8 +/- 0.3) is in good agreement with the [Cu(CO)2]+ stoichiometry suggested by IR. The Cu-C distance obtained for the [Cu(CO)2]+ complex is 1.88 +/- 0.02 A, with a C-O distance (1.12 +/- 0.03 A). This work complements a previous one [C. Lamberti, G. Turnes Palomino, S. Bordiga, G. Berlier, F. D'Acapito and A. Zecchina, Angew. Chem. Int. Ed., 2000, 39, 2138], performed at liquid nitrogen temperature, where the structure of [Cu(CO)3]+ complexes was identified by combined EXAFS/XANES/IR spectroscopies. An increase of the Cu-C distance of 0.05 A by moving from [Cu(CO)2]+ to [Cu(CO)3]+ complexes has been observed, which is the local rearrangement needed to accommodate a third CO ligand in the first coordination shell of copper. EXAFS determined that the Cu-C-O bond angle is linear within the error bars (170 +/- 10 degrees), while IR and XANES indicate that intrazeolitic [Cu(CO)2]+ complexes have C2v symmetry. The experimentally obtained moieties are in good agreement with the values obtained with advanced quantum mechanical methods.

Risk for laparoscopic fenestration of liver cysts.

BACKGROUND: Laparoscopic fenestration is considered the best treatment for symptomatic simple liver cysts. Conversely, the laparoscopic approach for the management of hydatid simple liver cysts is not widely accepted because of the risk for severe complications. Despite improvement in imaging techniques, the probability of preoperatively mistaking a hydatid liver cyst for a simple liver cyst remains about 5%. Therefore, laparoscopic fenestration, planned for a liver cyst could be performed unintentionally for an undiagnosed hydatid liver cyst. METHODS: From January 2000 to January 2001, 15 patients with a diagnosis of liver cyst underwent laparoscopy for fenestration. In all cases preoperative serologic and imaging assessment had excluded hydatid liver cyst. To further exclude hydatid liver cyst, preliminary aspiration of the cyst with assessment of cystic fluid characteristics was performed. RESULTS: In two patients with presumedly simple liver cyst, hydatid liver cyst was diagnosed instead at laparoscopy by aspiration of cystic fluid. The procedure was converted to laparotomy with subtotal pericystectomy. CONCLUSIONS: The risk of misdiagnosing a hydatid liver cyst for a simple liver cyst, especially in the presence of a solitary cyst, should be considered before laparoscopic fenestration is performed. Intraoperative aspiration of cyst fluid before fenestration can minimize this risk, thus avoiding severe intraoperative and late complications.

Direct observation of charge order in an epitaxial NdNiO3 film.

The first direct observation of charge order of Ni(3+delta(')) and Ni(3-delta) by resonant x-ray scattering experiments in an epitaxial film of NdNiO3 is reported. A quantitative value of delta+delta(') = (0.45 +/- 0.04)e was obtained. The temperature dependence of the charge order deviates significantly from those of the magnetic moment and crystallographic structure. This might be an indication of a difference in their fluctuation time scales. These observations are discussed in terms of the temperature-driven metal-insulator transition in the RNiO3 family.

Curved optics for x-ray phase contrast imaging by synchrotron radiation.

Conventional radiographic techniques have strong limitations when low-absorption contrast samples are imaged. Phase contrast radiography has been shown to produce high-quality images of soft tissues. In this technique the recorded intensity patterns are related to gradients in the refractive index of the sample. A critical point of this new technique is the need to employ crystal analysers, which results in an appreciable reduction in the beam intensity and consequently in rather long exposure times. In this paper the use of focused beams is suggested to overcome this aspect. Biological samples with small structures and low absorption variations were imaged using both flat and curved monochromator crystals, demonstrating that the use of curved optics leads to a decrease in the exposure time with only a limited degradation of the spatial resolution. This opens up the possibility of using the phase contrast technique with laboratory sources.