Controlling the formation and stability of ultra-thin nickel silicides : an alloying strategy for preventing agglomeration

The electrical contact of the source and drain regions in state-of-the-art CMOS transistors is nowadays facilitated through NiSi, which is often alloyed with Pt in order to avoid morphological agglomeration of the silicide film. However, the solid-state reaction between as-deposited Ni and the Si substrate exhibits a peculiar change for as-deposited Ni films thinner than a critical thickness of t(c) = 5 nm. Whereas thicker films form polycrystalline NiSi upon annealing above 450 degrees C, thinner films form epitaxial NiSi2 films that exhibit a high resistance toward agglomeration. For industrial applications, it is therefore of utmost importance to assess the critical thickness with high certainty and find novel methodologies to either increase or decrease its value, depending on the aimed silicide formation. This paper investigates Ni films between 0 and 15 nm initial thickness by use of "thickness gradients," which provide semi-continuous information on silicide formation and stability as a function of as-deposited layer thickness. The alloying of these Ni layers with 10% Al, Co, Ge, Pd, or Pt renders a significant change in the phase sequence as a function of thickness and dependent on the alloying element. The addition of these ternary impurities therefore changes the critical thickness t(c). The results are discussed in the framework of classical nucleation theory

Nomograms to predict survival and the risk for developing local or distant recurrence in patients with rectal cancer treated with optional short-term radiotherapy

Surgical oncolog

A semantic interoperability approach to support integration of gene expression and clinical data in breast cancer

[Abstract] Introduction. The introduction of omics data and advances in technologies involved in clinical treatment has led to a broad range of approaches to represent clinical information. Within this context, patient stratification across health institutions due to omic profiling presents a complex scenario to carry out multi-center clinical trials. Methods. This paper presents a standards-based approach to ensure semantic integration required to facilitate the analysis of clinico-genomic clinical trials. To ensure interoperability across different institutions, we have developed a Semantic Interoperability Layer (SIL) to facilitate homogeneous access to clinical and genetic information, based on different well-established biomedical standards and following International Health (IHE) recommendations. Results. The SIL has shown suitability for integrating biomedical knowledge and technologies to match the latest clinical advances in healthcare and the use of genomic information. This genomic data integration in the SIL has been tested with a diagnostic classifier tool that takes advantage of harmonized multi-center clinico-genomic data for training statistical predictive models. Conclusions. The SIL has been adopted in national and international research initiatives, such as the EURECA-EU research project and the CIMED collaborative Spanish project, where the proposed solution has been applied and evaluated by clinical experts focused on clinico-genomic studies.Instituto de Salud Carlos III, PI13/02020Instituto de Salud Carlos III, PI13/0028

Gemcitabine-induced TIMP1 attenuates therapy response and promotes tumor growth and liver metastasis in pancreatic cancer

Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in preclinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models. We identified potential pathways affected downstream of TIMP1 using the Illumina Human H12 array. Our findings were validated in both primary and metastatic models of pancreatic cancer. Gemcitabine increased inflammatory cytokines including TIMP1 in the KPC mouse model. TIMP1 was upregulated in patients with pancreatic intraepithelial neoplasias grade 3 and PDAC lesions relative to matched normal pancreatic tissue. In addition, TIMP1 played a role in tumor clonogenic survival and vascular density, while TIMP1 inhibition resensitized tumors to gemcitabine and radiotherapy. We observed a linear relationship between TIMP-1 expression, liver metastatic burden, and infiltration by CD11b+Gr1+ myeloid cells and CD4+CD25+FOXP3+ Tregs, whereas the presence of tumor cells was required for immune cell infiltration. Overall, our results identify TIMP1 upregulation as a resistance mechanism to gemcitabine and provide a rationale for combining chemo/radiotherapy with TIMP1 inhibitors in PDAC

The evolutionary state of Miras with changing pulsation periods

Context: Miras are long-period variables thought to be in the asymptotic giant branch (AGB) phase of evolution. In about one percent of known Miras, the pulsation period is changing. It has been speculated that this changing period is the consequence of a recent thermal pulse in these stars. Aims: We aim to clarify the evolutionary state of these stars, and to determine in particular whether or not they are in the thermally-pulsing (TP-)AGB phase. Methods: One important piece of information that has been neglected so far when determining the evolutionary state is the presence of the radio-active s-process element technetium (Tc). We obtained high-resolution, high signal-to-noise-ratio optical spectra of a dozen prominent Mira variables with changing pulsation period to search for this indicator of TPs and dredge-up. We also use the spectra to measure lithium (Li) abundances. Furthermore, we establish the evolutionary states of our sample stars by means of their present-day periods and luminosities. Results: Among the twelve sample stars observed in this programme, five were found to show absorption lines of Tc. BH Cru is found to be a carbon-star, its period increase in the past decades possibly having stopped by now. We report a possible switch in the pulsation mode of T UMi from Mira-like to semi-regular variability in the past two years. R Nor, on the other hand, is probably a fairly massive AGB star, which could be true for all meandering Miras. Finally, we assign RU Vul to the metal-poor thick disk with properties very similar to the short-period, metal-poor Miras. Conclusions: We conclude that there is no clear correlation between period change class and Tc presence. The stars that are most likely to have experienced a recent TP are BH Cru and R Hya, although their rates of period change are quite different.Comment: 11 pages, 7 figures, 2 tables; accepted for publication in A&