Wafer-scale, epitaxial growth of single layer hexagonal boron nitride on Pt(111)

Single-layer hexagonal boron nitride is produced on 2 inch Pt(111)/sapphire wafers. The growth with borazine vapor deposition at process temperatures between 1000 and 1300 K is in situ investigated by photoelectron yield measurements. The growth kinetics is slower at higher temperatures and follows a tanh2 law which better fits for higher temperatures. The crystal-quality of hexagonal boron nitride (h-BN)/Pt(111) is inferred from scanning low energy electron diffraction (x-y LEED). The data indicate a strong dependence of the epitaxy on the growth temperature. The dominant structure is an aligned coincidence lattice with 10 h-BN on 9 Pt(1 × 1) unit cells and follows the substrate twinning at the millimeter scale

Structural Basis for Dual-Inhibition Mechanism of a Non-Classical Kazal-Type Serine Protease Inhibitor from Horseshoe Crab in Complex with Subtilisin

Serine proteases play a crucial role in host-pathogen interactions. In the innate immune system of invertebrates, multi-domain protease inhibitors are important for the regulation of host-pathogen interactions and antimicrobial activities. Serine protease inhibitors, 9.3-kDa CrSPI isoforms 1 and 2, have been identified from the hepatopancreas of the horseshoe crab, Carcinoscorpius rotundicauda. The CrSPIs were biochemically active, especially CrSPI-1, which potently inhibited subtilisin (Ki = 1.43 nM). CrSPI has been grouped with the non-classical Kazal-type inhibitors due to its unusual cysteine distribution. Here we report the crystal structure of CrSPI-1 in complex with subtilisin at 2.6 Å resolution and the results of biophysical interaction studies. The CrSPI-1 molecule has two domains arranged in an extended conformation. These two domains act as heads that independently interact with two separate subtilisin molecules, resulting in the inhibition of subtilisin activity at a ratio of 1:2 (inhibitor to protease). Each subtilisin molecule interacts with the reactive site loop from each domain of CrSPI-1 through a standard canonical binding mode and forms a single ternary complex. In addition, we propose the substrate preferences of each domain of CrSPI-1. Domain 2 is specific towards the bacterial protease subtilisin, while domain 1 is likely to interact with the host protease, Furin. Elucidation of the structure of the CrSPI-1: subtilisin (1∶2) ternary complex increases our understanding of host-pathogen interactions in the innate immune system at the molecular level and provides new strategies for immunomodulation

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Remote doping of graphene on SiO2 with 5 keV x-rays in air

The transport properties of graphene change strongly in the presence of electric fields due to graphene's band structure. This makes graphene sensitive to charges in an insulator substrate. Graphene on SiO2/Si is studied under x-ray irradiation in ambient conditions. Using the metal oxide semiconductor structure of their samples, the authors observe remote doping due to the creation of positive charges in the oxide by the irradiation and relate them to resistance and Hall effect measurements performed on the graphene gate. The observed changes in conductivity, Hall charge carrier density, and the corresponding charge carrier mobility are consistent with expectations as well as recent experiments using graphene field effect transistors under ultrahigh vacuum conditions [P. Procházka et al. Sci. Rep. 7, 563 (2017)]. Furthermore, the stability of the effect under ambient conditions and its recovery using thermal annealing is demonstrated

The Winner Takes It All: Carbon Supersedes Hexagonal Boron Nitride with Graphene on Transition Metals at High Temperatures

The production of high-quality hexagonal boron nitride (h-BN) is essential for the ultimate performance of 2D materials-based devices, since it is the key 2D encapsulation material. Here, a decisive guideline is reported for fabricating high-quality h-BN on transition metals. It is crucial to exclude carbon from the h-BN related process, otherwise carbon prevails over boron and nitrogen due to its larger binding energy, thereupon forming graphene on metals after high-temperature annealing. The surface reaction-assisted conversion from h-BN to graphene with high-temperature treatments is demonstrated. The pyrolysis temperature Tp is an important quality indicator for h-BN/metals. When the temperature is lower than Tp, the quality of the h-BN layer is improved upon annealing. While the annealing temperature is above Tp, in case of carbon-free conditions, the h-BN disintegrates and nitrogen desorbs from the surface more easily than boron, eventually leading to clean metal surfaces. However, once the h-BN layer is exposed to carbon, graphene forms on Pt(111) in the high-temperature regime. This not only provides an indispensable principle (avoid carbon) for fabricating high-quality h-BN materials on transition metals, but also offers a straightforward method for the surface reaction-assisted conversion from h-BN to graphene on Pt(111)

The Winner Takes It All: Carbon Supersedes Hexagonal Boron Nitride with Graphene on Transition Metals at High Temperatures

The production of high-quality hexagonal boron nitride (h-BN) is essential for the ultimate performance of 2D materials-based devices, since it is the key 2D encapsulation material. Here, a decisive guideline is reported for fabricating high-quality h-BN on transition metals. It is crucial to exclude carbon from the h-BN related process, otherwise carbon prevails over boron and nitrogen due to its larger binding energy, thereupon forming graphene on metals after high-temperature annealing. The surface reaction-assisted conversion from h-BN to graphene with high-temperature treatments is demonstrated. The pyrolysis temperature Tp is an important quality indicator for h-BN/metals. When the temperature is lower than Tp, the quality of the h-BN layer is improved upon annealing. While the annealing temperature is above Tp, in case of carbon-free conditions, the h-BN disintegrates and nitrogen desorbs from the surface more easily than boron, eventually leading to clean metal surfaces. However, once the h-BN layer is exposed to carbon, graphene forms on Pt(111) in the high-temperature regime. This not only provides an indispensable principle (avoid carbon) for fabricating high-quality h-BN materials on transition metals, but also offers a straightforward method for the surface reaction-assisted conversion from h-BN to graphene on Pt(111)

Ar implantation beneath graphene on Ru(0001): Nanotents and “can-opener” effect

Exposing a monolayer of graphene on ruthenium (g/Ru(0001)) to low energy Ar+ ions leads to nanotent formation and “can-opener” effect, similar phenomena as observed for h-BN/Rh(111) targets (Cun, Iannuzzi, Hemmi, Roth, Osterwalder and Greber, 2013). Nanotents are extra protrusions in the sp2 monolayers beneath which atoms are immobilized at room temperature. Annealing the Ar+ implanted structures results in the “can-opener” effect, i.e., the formation of voids with a diameter of about 2 nm within the graphene layer. The voids preferentially settle in the “hill” regions of the g/Ru(0001) superstructure and thus display spacial selectivity. This provides a convenient method to control defect positions within graphene membranes with nanometer precision. The results are obtained by scanning tunneling microscopy, low energy electron diffraction and photoemission, and are backed with density functional theory calculations

Two-Nanometer voids in single-layer hexagonal Boron Nitride: Formation via the "Can-Opener" effect and annihilation by self-healing

The exposure of hexagonal boron nitride single layers to low energy ions leads to the formation of vacancy defects that are mobile at elevated temperatures. For the case of h-BN on rhodium, a superhoneycomb surface with 3 nm lattice constant (nanomesh), a concerted self-assembly of these defects is observed, where the “can-opener” effect leads to the cut-out of 2 nm “lids” and stable voids in the h-BN layer. These clean-cut voids repel each other, which enables the formation of arrays with a nearest neighbor distance down to about 8 nm. The density of voids depends on the Ar ion dose, and can reach 1012 cm–2. If the structures are annealed above 1000 K, the voids disappear and pristine h-BN nanomesh with larger holes is recovered. The results are obtained by scanning tunneling microscopy and density functional theory calculations