Positioning of self-assembled Ge islands on stripe-patterned Si (001) substrates

Self-assembled Ge islands were grown on stripe-patterned Si (001) substrates by solid source molecular beam epitaxy. The surface morphology obtained by atomic force microscopy (AFM) and cross-sectional transmission electron microscopy images (TEM) shows that the Ge islands are preferentially grown at the sidewalls of pure Si stripes along [-110] direction at 650o C or along the trenches, whereas most of the Ge islands are formed on the top terrace when the patterned stripes are covered by a strained GeSi buffer layer. Reducing the growth temperature to 600oC results in a nucleation of Ge islands both on the top terrace and at the sidewall of pure Si stripes. A qualitative analysis, based on the growth kinetics, demonstrates that the step structure of the stripes, the external strain field and the local critical wetting layer thickness for the islands formation contribute to the preferential positioning of Ge islands on the stripes.Comment: 10 pages, 7 figures, 1 table, the original paper is in print in J. Appl. Phy

Arrays of Individual DNA Molecules on Nanopatterned Substrates

Arrays of individual molecules can combine the advantages of microarrays and single-molecule studies. They miniaturize assays to reduce sample and reagent consumption and increase throughput, and additionally uncover static and dynamic heterogeneity usually masked in molecular ensembles. However, realizing single-DNA arrays must tackle the challenge of capturing structurally highly dynamic strands onto defined substrate positions. Here, we create single-molecule arrays by electrostatically adhering single-stranded DNA of gene-like length onto positively charged carbon nanoislands. The nanosites are so small that only one molecule can bind per island. Undesired adsorption of DNA to the surrounding non-target areas is prevented via a surface-passivating film. Of further relevance, the DNA arrays are of tunable dimensions, and fabricated on optically transparent substrates that enable singe-molecule detection with fluorescence microscopy. The arrays are hence compatible with a wide range of bioanalytical, biophysical, and cell biological studies where individual DNA strands are either examined in isolation, or interact with other molecules or cells

Antimicrobial Activity and Docking Study of Synthesized Xanthen-3-on Derivatives

Twelve previously synthesized biologically active 2,6,7-trihydroxy-9-aryl-3H-xanthen-3-one derivatives (1-12) were evaluated in vitro for their antimicrobial activity against four bacteria, S. aureus, B. subtilis P. aeruginosa and E. coli, and two fungi strains, C. albicans and S. cerevisiae. The most potent compound were derivatives 1 which possess hydroxyl group and bromine as substituent and 11 with bromine as substituent on phenyl ring. The results indicate that bromine increase antimicrobial activity of 2,6,7-trihydroxy-9-aryl-3-Hxanthen-3-one derivatives. Compound 7 with ethoxy substituent on phenyl ring showed the least activity against tested bacteria and fungi strains, which is in line with an earlier observation that ethoxy substitution decreases antimicrobial activity. The most and the least potent compounds were subjected to molecular docking simulations to preliminary find out the potential molecular target and at the same moment further support the experimental antimicrobial test of xanthen derivatives

Co-Immobilization of Proteins and DNA Origami Nanoplates to Produce High-Contrast Biomolecular Nanoarrays

The biofunctionalization of nanopatterned surfaces with DNA origami nanostructures is an important topic in nanobiotechnology. An unexplored challenge is, however, to co-immobilize proteins with DNA origami at pre-determined substrate sites in high contrast relative to the nontarget areas. The immobilization should, in addition, preferably be achieved on a transparent substrate to allow ultrasensitive optical detection. If successful, specific co-binding would be a step towards stoichiometrically defined arrays with few to individual protein molecules per site. Here, we successfully immobilize with high specificity positively charged avidin proteins and negatively charged DNA origami nanoplates on 100 nm-wide carbon nanoislands while suppressing undesired adsorption to surrounding nontarget areas. The arrays on glass slides achieve unprecedented selectivity factors of up to 4000 and allow ultrasensitive fluorescence read-out. The co-immobilization onto the nanoislands leads to layered biomolecular architectures, which are functional because bound DNA origami influences the number of capturing sites on the nanopatches for other proteins. The novel hybrid DNA origami-protein nanoarrays allow the fabrication of versatile research platforms for applications in biosensing, biophysics, and cell biology, and, in addition, represent an important step towards single-molecule protein arrays

Antimicrobial Activity and Docking Study of Synthesized Xanthen-3-on Derivatives

Twelve previously synthesized biologically active 2,6,7-trihydroxy-9-aryl-3H-xanthen-3-one derivatives (1-12) were evaluated in vitro for their antimicrobial activity against four bacteria, S. aureus, B. subtilis P. aeruginosa and E. coli, and two fungi strains, C. albicans and S. cerevisiae. The most potent compound were derivatives 1 which possess hydroxyl group and bromine as substituent and 11 with bromine as substituent on phenyl ring. The results indicate that bromine increase antimicrobial activity of 2,6,7-trihydroxy-9-aryl-3-Hxanthen-3-one derivatives. Compound 7 with ethoxy substituent on phenyl ring showed the least activity against tested bacteria and fungi strains, which is in line with an earlier observation that ethoxy substitution decreases antimicrobial activity. The most and the least potent compounds were subjected to molecular docking simulations to preliminary find out the potential molecular target and at the same moment further support the experimental antimicrobial test of xanthen derivatives

Efficient room-temperature light-emitters based on partly amorphised Ge quantum dots in crystalline Si

Semiconductor light emitters compatible with standard Si integration technology (SIT) are of particular interest for overcoming limitations in the operating speed of microelectronic devices 1-3. Light sources based on group-IV elements would be SIT compatible but suffer from the poor optoelectronic properties of bulk Si and Ge. Here, we demonstrate that epitaxially grown Ge quantum dots (QDs) in a fully coherent Si matrix show extraordinary optical properties if partially amorphised by Ge-ion bombardment (GIB). The GIB-QDs exhibit a quasi-direct-band gap and show, in contrast to conventional SiGe nanostructures, almost no thermal quenching of the photoluminescence (PL) up to room-temperature (RT). Microdisk resonators with embedded GIB-QDs exhibit threshold-behaviour and super-linear increase of the integrated PL-intensity (IPL) with increasing excitation power Pexc which indicates light amplification by stimulated emission in a fully SIT-compatible group-IV nano-system

The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture

Contains fulltext : 220729.pdf (publisher's version ) (Open Access)The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14(+) DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system

Preclinical evaluation of the simultaneous inhibition of MCL-1 and BCL-2 with the combination of S63845 and venetoclax in multiple myeloma

This work was supported by the Spanish ISCIII-FIS and FEDER Funds (PI 15/00067 and PI 15/02156) and the Regional Health Council of Castilla y León (GRS 1604/A/17). EMA was supported by a grant from the Regional Education Council of Castilla y León co-financed by the European Social Fund

Selective BRAFV600E Inhibitor PLX4720, Requires TRAIL Assistance to Overcome Oncogenic PIK3CA Resistance

Documented sensitivity of melanoma cells to PLX4720, a selective BRAFV600E inhibitor, is based on the presence of mutant BRAFV600E alone, while wt-BRAF or mutated KRAS result in cell proliferation. In colon cancer appearance of oncogenic alterations is complex , since BRAF, like KRAS mutations, tend to co-exist with those in PIK3CA and mutated PI3K has been shown to interfere with the successful application of MEK inhibitors. When PLX4720 was used to treat colon tumours, results were not encouraging and herein we attempt to understand the cause of this recorded resistance and discover rational therapeutic combinations to resensitize oncogene driven tumours to apoptosis. Treatment of two genetically different BRAFV600E mutant colon cancer cell lines with PLX4720 conferred complete resistance to cell death. Even though p-MAPK/ ERK kinase (MEK) suppression was achieved, TRAIL, an apoptosis inducing agent, was used synergistically in order to achieve cell death by apoptosis in RKOBRAFV600E/PIK3CAH1047 cells. In contrast, for the same level of apoptosis in HT29BRAFV600E/PIK3CAP449T cells, TRAIL was combined with 17-AAG, an Hsp90 inhibitor. For cells where PLX4720 was completely ineffective, 17-AAG was alternatively used to target mutant BRAFV600E. TRAIL dependence on the constitutive activation of BRAFV600E is emphasised through the overexpression of BRAFV600E in the permissive genetic background of colon adenocarcinoma Caco-2 cells. Pharmacological suppression of the PI3K pathway further enhances the synergistic effect between TRAIL and PLX4720 in RKO cells, indicating the presence of PIK3CAMT as the inhibitory factor. Another rational combination includes 17-AAG synergism with TRAIL in a BRAFV600E mutant dependent manner to commit cells to apoptosis, through DR5 and the amplification of the apoptotic pathway. We have successfully utilised combinations of two chemically unrelated BRAFV600E inhibitors in combination with TRAIL in a BRAFV600E mutated background and provided insight for new anti-cancer strategies where the activated PI3KCA mutation oncogene should be suppressed