Polarized laser light scattering applied to surface morphology characterization of epitaxial III–V semiconductor layers

11 pages.-- PACS: 68.35.Bs; 81.05.Ea; 81.15.Hi; 78.35.+c; 78.66.FdIn this paper, we analyze typical morphologies of epitaxial III–V semiconductor layers by using a polarized laser light scattering technique. Crosshatched topographies, which are developed during heteroepitaxial growth, are studied. A sample with an intentionally high density of oval defects is also explored to establish how the laser light scattering pattern is affected by the presence of these defects, which are unavoidable in the epitaxial layers grown by molecular beam epitaxy. The former topographies produce a scattered light pattern that is highly anisotropic, with the intensity concentrated along two preferential directions; the latter defects give rise to a fairly isotropic pattern. Employing a perturbation-theoretical model, whose applicability and consistency are explicitly demonstrated by our results, the surface power spectral density is retrieved from the angle-resolved light scattering experimental data. For the samples exhibiting crosshatched topography, the scattering measurements provide information that allows us to model the roughness of the surface in terms of two quasi-one-dimensional, anisotropic components, and one two-dimensional, isotropic, long-range background. The root mean square heights and the typical lateral distances between ridges are obtained in quantitative agreement with the values extracted from the atomic force microscopy measurements. For the sample presenting oval defects, we consider their contribution to the surface power spectral density by means of a simple model of randomly distributed particles on a surface, and we compare the resulting power spectral density with typical behavior found in the literature for good-morphology GaAs layers. With the help of the ex situ information thus obtained, we also discuss the implementation of the light scattering technique for in situ monitoring during epitaxial growth.The authors wish to acknowledge the Spanish CICYT for financial support under Project No. TIC96-1020-C02. M.U.G. thanks the Consejería de Educación y Cultura de la Comunidad de Madrid for financial support. J.A.S.-G. acknowledges financial support from the Spanish DGESIC Grant No. PB97-1221.Spanish CICYTConsejería de Educación y Cultura de la Comunidad de MadridPeer reviewe

Nanocolumnar coatings on implants exhibiting antibacterial properties

Trabajo presentado en la 2nd International Conference on Nanomaterials Applied to Life Sciences 2020 (NALS 2020), celebrada en Madrid (España), del 29 al 31 de enero de 2020Addressing the problem of infection from the very first stage, i.e. inhibiting the formation of the bacterial biofilm, is a crucial step to prevent implant rejection. Nanocolumnar coatings exhibiting antibacterial properties have been fabricated by oblique deposition with magnetron sputtering [1]. The formation of nanocolumns (Fig.1) is the result of the effects of atomic shadowing when the atoms reach the surface along an inclined direction [2]. This technique is environmentally friendly: it is carried out at RT and does not involve chemical products (no recycling problems). Such methodology have been tested in a semiindustrial scale reactor, successfully coating in a single step the two sides of fixation plates for bone fractures [3]. Several in vitro experiments have been performed: analysis of bacterial adhesion and biofilm formation, analysis of osteoblast proliferation and mitochondrial activity, and osteoblasts–bacteria competitive growth scenarios, the latter also named “Race for the Surface” competition. In all these cases, the coatings show an opposite behavior toward osteoblast and bacterial proliferation [1,3]. Moreover, they are effective against Gram positive (S. aureus) and Gram negative (E. coli) bacteria [4]. Finally, when a synergic route is followed and the coatings are functionalized with Te nanorods, the antibacterial properties are enhanced, since Te adds contact-killing (Fig. 2), i.e. bactericidal effect, whilst the biocompatibility is preserved [4].MINECO and Fundación Domingo Martínez for funding. J.M.G.-M. thanks the Fulbright Commissio

Thin film nanostructuring at oblique angles by substrate patterning

It is demonstrated that, besides classical nanocolumnar arrays, the oblique angle geometry induces the growth of singular structures in the nanoscale when using wisely designed patterned substrates. Well-ordered array of crosses, cylindrical nanorods or hole structures arranged in square or hexagonal regular geometries are reported as examples, among others. The fundamental framework connecting substrate topography and film growth at oblique angles is presented, allowing the use of substrate patterning as a feasible thin film nanostructuring technique. A systematic analysis of the growth of TiO2 thin films on 4 different lithographic patterned substrates in 4 different scale lengths is also presented. A first conclusion is the existence of a height-based selective growth in the initial stages of the deposition, by which the film preferentially develops on top of the tallest substrate features. This behavior is maintained until the film reaches a critical thickness, the so-called Oblivion Thickness, above which the film topography becomes gradually independent of the substrate features. A general formula relating the spatial features of the pattern, the coarsening exponent and the Oblivion Thickness has been deduced.The authors thank the financial support from MCIN/AEI/10.13039/ 501100011033 projects PID2019-110430GB-C21, PID2020-112620GBI00, PID2020-114270RA-I00 and RTI2018-098117-B-C21 (also financed by FEDER Una manera de hacer europa), the Junta de Andalucía (PAIDI- 2020 through projects P18-RT-3480 and P18-RT-6079, and through its 2019 PhD Researcher Hiring Program), the CSIC (2019AEP161 and 201860E050), the Regional Government of Madrid (project IND2017/ IND-7668 and YEI contract PEJ-2019-AI/IND-14451 with support from FSE), the H2020-EU.1.2.1-FET OPEN program (grant 899352, project SOUNDofICE, and the EFRE Infra-Pro project ChAMP), and the University of Seville (VI PPIT-US). The work is supported by the Deutsche Forschungsgemeinschaft (DFG, grant Scha 632/24, “Tailored Disorder” and Scha 632/27, “DFGGer ¨atezentrum”). This work is also supported by the free state of Thuringia under grants 2015 FGI 0025 305 (FastμXRD) and B715-10009 (BioMacroNano2020), all co-financed by the European Union within the framework of the European Regional Development Fund (ERDF). The service from the MiNa Laboratory at IMN-CNM (CSIC), funded from CM (project S2018/NMT-4291 TEC2SPACE), MINECO (project CSIC13-4E- 1794) and EU (FEDER, FSE), is also acknowledged.Peer reviewe

Nanoestructuración a la Carta de Películas Delgadas en Geometría de Ángulo Oblicuo Mediante el Control Topográfico del Sustrato

Trabajo presentado en el XVI Congreso Nacional de Materiales CNMAT 2022, celebrado en Ciudad Real (España), del 28 de junio al 1 de julio de 2022La técnica de pulverización catódica operada en geometría de ángulo oblicuo es bien conocida por permitir el crecimiento de películas delgadas nanocolumnares sobre sustratos planos. En otro tipo de sustratos, e.g. rugosos o litografiados, la casuística es variada, apareciendo estructuras complejas y diversas, incluso para espesores del orden de la micra. Estos resultados sugieren la existencia de una fuerte conexión entre el crecimiento de la película y la topografía del sustrato, que podría utilizarse para obtener un mayor control nanoestructural. En esta presentación se analiza teórica y experimentalmente la relación entre ambos aspectos al utilizar la técnica de pulverización catódica a ángulo oblicuo. Se demuestra la posibilidad de crecer estructuras singulares como, por ejemplo, cruces nanopilares o incluso de huecos dentro de una matriz compacta, ordenados de acuerdo a un patrón regular con distancias típicas del orden de cientos de nanómetros (ver Figura 1). Se describe, por lo tanto, el marco conceptual que permitiría que las técnicas actuales de litografía superficial se puedan utilizar como técnicas efectivas de control nanoestructural de películas delgadas. Como resultado, se demuestran varios principios que definen los diferentes estadios de la deposición que servirían como guías para el diseño inteligente del sustrato e inducir crecimientos a la carta. Estos principios se han validado experimentalmente al crecer diferentes películas delgadas sobre un total de 16 sustratos litografiados con diferentes topografías, patrones y escalas típicas por debajo de la micra, así como en otros sustratos con rugosidad intrínseca sometidos a diferentes tipos de pulido

FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas.

The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (P<0.05). FOXP1 knockdown in ABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL patients (n=150), reduced HLA-DRA (<90% frequency) expression correlated with inferior overall survival (P=0.0003) and progression-free survival (P=0.0012) and with non-GCB subtype stratified by the Hans, Choi or Visco-Young algorithms (all P<0.01). In non-GCB DLBCL cases with <90% HLA-DRA, there was an inverse correlation with the frequency (P=0.0456) and intensity (P=0.0349) of FOXP1 expression. We propose that FOXP1 represents a novel regulator of genes targeted by the class II MHC transactivator CIITA (MHC II and CD74) and therapeutically targeting the FOXP1 pathway may improve antigen presentation and immune surveillance in high-risk DLBCL patients

Involvement of miRNAs in the differentiation of human glioblastoma multiforme stem-like cells

Glioblastoma multiforme (GBM)-initiating cells (GICs) represent a tumor subpopulation with neural stem cell-like properties that is responsible for the development, progression and therapeutic resistance of human GBM. We have recently shown that blockade of NFκB pathway promotes terminal differentiation and senescence of GICs both in vitro and in vivo, indicating that induction of differentiation may be a potential therapeutic strategy for GBM. MicroRNAs have been implicated in the pathogenesis of GBM, but a high-throughput analysis of their role in GIC differentiation has not been reported. We have established human GIC cell lines that can be efficiently differentiated into cells expressing astrocytic and neuronal lineage markers. Using this in vitro system, a microarray-based high-throughput analysis to determine global expression changes of microRNAs during differentiation of GICs was performed. A number of changes in the levels of microRNAs were detected in differentiating GICs, including over-expression of hsa-miR-21, hsa-miR-29a, hsa-miR-29b, hsa-miR-221 and hsa-miR-222, and down-regulation of hsa-miR-93 and hsa-miR-106a. Functional studies showed that miR-21 over-expression in GICs induced comparable cell differentiation features and targeted SPRY1 mRNA, which encodes for a negative regulator of neural stem-cell differentiation. In addition, miR-221 and miR-222 inhibition in differentiated cells restored the expression of stem cell markers while reducing differentiation markers. Finally, miR-29a and miR-29b targeted MCL1 mRNA in GICs and increased apoptosis. Our study uncovers the microRNA dynamic expression changes occurring during differentiation of GICs, and identifies miR-21 and miR-221/222 as key regulators of this process

A cyclin-D1 interaction with BAX underlies its oncogenic role and potential as a therapeutic target in mantle cell lymphoma

The chromosomal translocation t(11;14)(q13;q32) leading to cyclin-D1 overexpression plays an essential role in the development of mantle cell lymphoma (MCL), an aggressive tumor that remains incurable with current treatment strategies. Cyclin-D1 has been postulated as an effective therapeutic target, but the evaluation of this target has been hampered by our incomplete understanding of its oncogenic functions and by the lack of valid MCL murine models. To address these issues, we generated a cyclin-D1-driven mouse model in which cyclin-D1 expression can be regulated externally. These mice developed cyclin-D1-expressing lymphomas capable of recapitulating features of human MCL. We found that cyclin-D1 inactivation was not sufficient to induce lymphoma regression in vivo; however, using a combination of in vitro and in vivo assays, we identified a novel prosurvival cyclin-D1 function in MCL cells. Specifically, we found that cyclin-D1, besides increasing cell proliferation through deregulation of the cell cycle at the G(1)-S transition, sequestrates the proapoptotic protein BAX in the cytoplasm, thereby favoring BCL2's antiapoptotic function. Accordingly, cyclin-D1 inhibition sensitized the lymphoma cells to apoptosis through BAX release. Thus, genetic or pharmacologic targeting of cyclin-D1 combined with a proapoptotic BH3 mimetic synergistically killed the cyclin-D1-expressing murine lymphomas, human MCL cell lines, and primary lymphoma cells. Our study identifies a role of cyclin-D1 in deregulating apoptosis in MCL cells, and highlights the potential benefit of simultaneously targeting cyclin-D1 and survival pathways in patients with MCL. This effective combination therapy also might be exploited in other cyclin-D1-expressing tumors