Image potential states at chevron-shaped graphene nanoribbons /Au(111) interfaces

Image potential states (IPSs) have been observed for various adsorbed carbon structures, such as graphene or carbon nanotubes. Graphene nanoribbons (GNRs) are intriguing nanostructures with a significant band gap which promise applications in nanotechnology. In the present paper we employ two-photon photoemission (2PPE) to investigate the unoccupied electronic structure and particularly the IPS of chevron-shaped GNR which are synthesized in a thermally activated on-surface synthesis on Au(111). Angle- and time-resolved 2PPE are utilized to gain further insights into the properties of the IPS. Compared to the pristine surface, reduced effective masses between 0.6 and 0.8 electron masses are observed and the lifetimes of the IPS are below the experimental detection limit, which is in the femtosecond regime. Independent of the concentration of N dopant atoms introduced in the GNR we observe a constant binding energy with respect to the vacuum level of the system

Correlated Diffuse X-ray Scattering from Periodically Nano-Structured Surfaces

Laterally periodic nanostructures were investigated with grazing incidence small angle X-ray scattering. To support an improved reconstruction of nanostructured surface geometries, we investigated the origin of the contributions to the diffuse scattering pattern which is correlated to the surface roughness. Resonant diffuse scattering leads to a palm-like structure of intensity sheets. Dynamic scattering generates the so-called Yoneda band caused by a resonant scatter enhancement at the critical angle of total reflection and higher-order Yoneda bands originating from a subsequent diffraction of the Yoneda enhanced scattering at the grating. Our explanations are supported by modelling using a solver for the time-harmonic Maxwell's equations based on the finite-element method

Reconstructing Detailed Line Profiles of Lamellar Gratings from GISAXS Patterns with a Maxwell Solver

Laterally periodic nanostructures were investigated with grazing incidence small angle X-ray scattering (GISAXS) by using the diffraction patterns to reconstruct the surface shape. To model visible light scattering, rigorous calculations of the near and far field by numerically solving Maxwell's equations with a finite-element method are well established. The application of this technique to X-rays is still challenging, due to the discrepancy between incident wavelength and finite-element size. This drawback vanishes for GISAXS due to the small angles of incidence, the conical scattering geometry and the periodicity of the surface structures, which allows a rigorous computation of the diffraction efficiencies with sufficient numerical precision. To develop dimensional metrology tools based on GISAXS, lamellar gratings with line widths down to 55 nm were produced by state-of-the-art e-beam lithography and then etched into silicon. The high surface sensitivity of GISAXS in conjunction with a Maxwell solver allows a detailed reconstruction of the grating line shape also for thick, non-homogeneous substrates. The reconstructed geometrical line shape models are statistically validated by applying a Markov chain Monte Carlo (MCMC) sampling technique which reveals that GISAXS is able to reconstruct critical parameters like the widths of the lines with sub-nm uncertainty

Electronic structure changes during the surface-assisted formation of a graphene nanoribbon

High conductivity and a tunability of the band gap make quasi-one-dimensional graphene nanoribbons (GNRs) highly interesting materials for the use in field effect transistors. Especially bottom-up fabricated GNRs possess well-defined edges which is important for the electronic structure and accordingly the band gap. In this study we investigate the formation of a sub-nanometer wide armchair GNR generated on a Au(111) surface. The on-surface synthesis is thermally activated and involves an intermediate non-aromatic polymer in which the molecular precursor forms polyanthrylene chains. Employing angle-resolved two-photon photoemission in combination with density functional theory calculations we find that the polymer exhibits two dispersing states which we attribute to the valence and the conduction band, respectively. While the band gap of the non-aromatic polymer obtained in this way is relatively large, namely 5.25 ± 0.06 eV, the gap of the corresponding aromatic GNR is strongly reduced which we attribute to the different degree of electron delocalization in the two systems

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Elimusertib has anti-tumor activity in preclinical patient-derived pediatric solid tumor models

The small molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), elimusertib, is currently being tested clinically in various cancer entities in adults and children. Its preclinical anti-tumor activity in pediatric malignancies, however, is largely unknown. We here assessed the preclinical activity of elimusertib in 38 cell lines and 32 patient-derived xenograft (PDX) models derived from common pediatric solid tumor entities. Detailed in vitro and in vivo molecular characterization of the treated models enabled the evaluation of response biomarkers. Pronounced objective response rates were observed for elimusertib monotherapy in PDX, when treated with a regimen currently used in clinical trials. Strikingly, elimusertib showed stronger anti-tumor effects than some standard of care chemotherapies, particularly in alveolar rhabdomysarcoma PDX. Thus, elimusertib has strong preclinical anti-tumor activity in pediatric solid tumor models, which may translate to clinically meaningful responses in patients

Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells

Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity are still unresolved. Here we describe single-cell extrachromosomal circular DNA and transcriptome sequencing (scEC&T-seq), a method for parallel sequencing of circular DNAs and full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, we describe intercellular differences in ecDNA content while investigating their structural heterogeneity and transcriptional impact. Oncogene-containing ecDNAs were clonally present in cancer cells and drove intercellular oncogene expression differences. In contrast, other small circular DNAs were exclusive to individual cells, indicating differences in their selection and propagation. Intercellular differences in ecDNA structure pointed to circular recombination as a mechanism of ecDNA evolution. These results demonstrate scEC&T-seq as an approach to systematically characterize both small and large circular DNA in cancer cells, which will facilitate the analysis of these DNA elements in cancer and beyond

Sr/Ca ratios and oxygen isotopes from sclerosponges: Temperature history of the Carribean mixed layer and thermocline during the Little Ice Age

We investigate aragonitic skeletons of the Caribbean sclerosponge Ceratoporella nicholsoni from Jamaica, 20 m below sea level (mbsl), and Pedro Bank, 125 mbsl. We use d18O and Sr/Ca ratios as temperature proxies to reconstruct the Caribbean mixed layer and thermocline temperature history since 1400 A.D. with a decadal time resolution. Our age models are based on U/Th dating and locating of the radiocarbon bomb spike. The modern temperature difference between the two sites is used to tentatively calibrate the C. nicholsoni Sr/Ca thermometer. The resulting calibration points to a temperature sensitivity of Sr/Ca in C. nicholsoni aragonite of about -0.1 mmol/mol/K. Our Sr/Ca records reveal a pronounced warming from the early 19th to the late 20th century, both at 20 and 125 mbsl. Two temperature minima in the shallow water record during the late 17th and early 19th century correspond to the Maunder and Dalton sunspot minima, respectively. Another major cooling occurred in the late 16th century and is not correlatable with a sunspot minimum. The temperature contrast between the two sites decreased from the 14th century to a minimum in the late 17th century and subsequently increased to modern values in the early 19th century. This is interpreted as a long-term deepening and subsequent shoaling of the Caribbean thermocline. The major trends of the Sr/Ca records are reproduced in both specimens but hardly reflected in the d18O records

An intronic deletion in megakaryoblastic leukemia 1 is associated with hyperproliferation of B cells in triplets with Hodgkin lymphoma

Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together they regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom had been previously treated for Hodgkin lymphoma (HL). To investigate MKL1 and B-cell responses in the pathogenesis of HL, we generated Epstein-Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the patients with treated HL had a phenotype close to that of the healthy controls, cells from the undiagnosed triplet had increased MKL1 mRNA, increased MKL1 protein, and elevated expression of MKL1-dependent genes. This profile was associated with elevated actin content, increased cell spreading, decreased expression of CD11a integrin molecules, and delayed aggregation. Moreover, cells from the undiagnosed triplet proliferated faster, displayed a higher proportion of cells with hyperploidy, and formed large tumors in vivo. This phenotype was reversible by inhibiting MKL1 activity. Interestingly, cells from the triplet treated for HL in 1985 contained two subpopulations: one with high expression of CD11a that behaved like control cells and the other with low expression of CD11a that formed large tumors in vivo similar to cells from the undiagnosed triplet. This implies that pre-malignant cells had re-emerged a long time after treatment. Together, these data suggest that dysregulated MKL1 activity participates in B-cell transformation and the pathogenesis of HL