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- Bavarian Center for Applied Energy Research (ZAE Bayern), 97074 Würzburg, Germany (1)
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- Genelux Corporation, San Diego Science Center, 3030 Bunker Hill Street, Suite 310, San Diego, California 92109, USA (1)
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- D-1250-2010 (1)
Background
Malignant pleural effusion (MPE) is associated with advanced stages of lung cancer and is mainly dependent on invasion of the pleura and expression of vascular endothelial growth factor (VEGF) by cancer cells. As MPE indicates an incurable disease with limited palliative treatment options and poor outcome, there is an urgent need for new and efficient treatment options.
Methods
In this study, we used subcutaneously generated PC14PE6 lung adenocarcinoma xenografts in athymic mice that developed subcutaneous malignant effusions (ME) which mimic pleural effusions of the orthotopic model. Using this approach monitoring of therapeutic intervention was facilitated by direct observation of subcutaneous ME formation without the need of sacrificing mice or special imaging equipment as in case of MPE. Further, we tested oncolytic virotherapy using Vaccinia virus as a novel treatment modality against ME in this subcutaneous PC14PE6 xenograft model of advanced lung adenocarcinoma.
Results
We demonstrated significant therapeutic efficacy of Vaccinia virus treatment of both advanced lung adenocarcinoma and tumor-associated ME. We attribute the efficacy to the virus-mediated reduction of tumor cell-derived VEGF levels in tumors, decreased invasion of tumor cells into the peritumoral tissue, and to viral infection of the blood vessel-invading tumor cells. Moreover, we showed that the use of oncolytic Vaccinia virus encoding for a single-chain antibody (scAb) against VEGF (GLAF-1) significantly enhanced mono-therapy of oncolytic treatment.
Conclusions
Here, we demonstrate for the first time that oncolytic virotherapy using tumor-specific Vaccinia virus represents a novel and promising treatment modality for therapy of ME associated with advanced lung cancer.
We study the structure formation of 1,4,5,8-naphthalenetetracarboxylicacid-
dianhydride (NTCDA) multilayer films on Ag(111) surfaces by energy dispersive near-edge x-ray absorption fine-structure spectroscopy (NEXAFS) and photoelectron spectroscopy. The time resolution of seconds of the method allows us to identify several sub-processes, which occur during the post-growth three-dimensional structural ordering, as well as their characteristic time scales. After deposition at low temperature the NTCDA molecules are preferentially flat lying and the films exhibit no long-range order. Upon annealing the molecules flip into an upright orientation followed by an aggregation in a transient phase which exists for several minutes. Finally, threedimensional islands are established with bulk-crystalline structure involving substantial mass transport on the surface and morphological roughening. By applying the Kolmogorov–Johnson–Mehl–Avrami model the activation energies of the temperature-driven sub-processes can be derived from the time evolution of the NEXAFS signal.
For determination of structures and structural dynamics of proteins organic fluorophores are a standard instrument. Intra- and intermolecular contact of biomolecular structures are determined in time-resolved and stationary fluorescence microscopy experiments by quenching of organic fluorophores due to Photoinduced Electron Transfer (PET) and dimerization interactions. Using PET we show in this work that end-to-end contact dynamics of serine-glycine peptides are slowed down by glycosylation. This slow down is due to a change in reaction enthalpy for end-to-end contact and is partly compensated by entropic effects. In a second step we test how dimerization of MR121 fluorophore pairs reports on end-to-end contact dynamics. We show that in aqueous solutions containing strong denaturants MR121 dimerization reports advantageously on contact dynamics for glycine-serine oligopeptides compared to the previously used MR121/tryptophane PET reporters. Then we analyze dimer interactions and quenching properties of different commercially available fluorophores being standards in Förster Resonance Energy Transfer (FRET) measurements. Distances in biomolecules are determinable using FRET, but for very flexible biomolecules the analysis of masurement data can be distorted if contact of the two FRET fluorophores is likely. We quantify how strong the quenching of fluorophore pairs with two different or two identical fluorophores is. Dimer spectra and association constants are quantified to estimate if fluophores are applicable in various applications, e.g. in FRET measurements with unstructured peptides and proteins.
Carbonaceous aerosols are responsible for large uncertainties in climate models, degraded visibility, and adverse health effects. The Carbonaceous Aerosols and Radiative Effects Study (CARES) was designed to study carbonaceous aerosols in the natural environment of the Central Valley, California, and learn more about their atmospheric formation and aging. This paper presents results from spectro-microscopic measurements of carbonaceous particles collected during CARES at the time of a pollution accumulation event (27-29 June 2010), when in situ measurements indicated an increase in the organic carbon content of aerosols as the Sacramento urban plume aged. Computer-controlled scanning electron microscopy coupled with an energy dispersive X-ray detector (CCSEM/EDX) and scanning transmission X-ray microscopy coupled with near-edge X-ray absorption spectroscopy (STXM/NEXAFS) were used to probe the chemical composition and morphology of individual particles. It was found that the mass of organic carbon on individual particles increased through condensation of secondary organic aerosol. STXM/NEXAFS indicated that the number fraction of homogenous organic particles lacking inorganic inclusions (greater than similar to 50 nm equivalent circular diameter) increased with plume age, as did the organic mass per particle. Comparison of the CARES spectro-microscopic dataset with a similar dataset obtained in Mexico City during the MILAGRO campaign showed that fresh particles in Mexico City contained three times as much carbon as those sampled during CARES. The number fraction of soot particles at the Mexico City urban site (ranging from 16.6 to 47.3 %) was larger than at the CARES urban site (13.4-15.7%), and the most aged samples from CARES contained fewer carbon-carbon double bonds. Differences between carbonaceous particles in Mexico City and California result from different sources, photochemical conditions, gas phase reactants, and secondary organic aerosol precursors. The detailed results provided by these spectro-microscopic measurements will allow for a comprehensive evaluation of aerosol process models used in climate research.
The discovery of the quantum spin Hall (QSH) state, and topological insulators in general, has sparked strong experimental efforts. Transport studies of the quantum spin Hall state have confirmed the presence of edge states, showed ballistic edge transport in micron-sized samples, and demonstrated the spin polarization of the helical edge states. While these experiments have confirmed the broad theoretical model, the properties of the QSH edge states have not yet been investigated on a local scale. Using scanning gate microscopy to perturb the QSH edge states on a submicron scale, we identify well-localized scattering sites which likely limit the expected nondissipative transport in the helical edge channels. In the micron-sized regions between the scattering sites, the edge states appear to propagate unperturbed, as expected for an ideal QSH system, and are found to be robust against weak induced potential fluctuations.
Silicon carbide light-emitting diode as a prospective room temperature source for single photons
(2013)
Generation of single photons has been demonstrated in several systems. However, none of them satisfies all the conditions, e.g. room temperature functionality, telecom wavelength operation, high efficiency, as required for practical applications. Here, we report the fabrication of light-emitting diodes (LEDs) based on intrinsic defects in silicon carbide (SiC). To fabricate our devices we used a standard semiconductor manufacturing technology in combination with high-energy electron irradiation. The room temperature electroluminescence (EL) of our LEDs reveals two strong emission bands in the visible and near infrared (NIR) spectral ranges, associated with two different intrinsic defects. As these defects can potentially be generated at a low or even single defect level, our approach can be used to realize electrically driven single photon source for quantum telecommunication and information processing.
The present thesis deals with the fabrication, optimization of growth process and characterization of silicon based materials with molecular beam epitaxy. Two material systems are investigated in the course of this work: silicon/silicon suboxide multilayer structures and mono manganese silicide thin films. Mono manganese silicide (MnSi) is grown on Si(111) substrates with an hydrogen passivated surface, that is prepared by wet chemical processes. The growth start is performed by deposition of an amorphous Mn wetting layer that is subsequently annealed to form a MnSi seed layer on which the MnSi molecular beam epitaxy (MBE) is achieved. An amorphous or a crystalline Si cap layer is deposited onto the MnSi film to finalize the growth process and protect the sample from oxidation. With Raman spectroscopy it is shown that the crystalline cap layer is in fact single crystalline silicon. Results of x-ray diffraction and Raman spectroscopy confirm the growth of mono manganese silicide in contrast to other existing manganese silicide phases. In addition, in-plane and out-of-plane residual strain, and twinning of the MnSi thin film is detected with x-ray diffraction of symmetric and asymmetric reflections. Orientation between the Si substrate and the MnSi film is determined with the parallel lattice planes MnSi(210) and Si(511). Transport measurements show a T^2 dependence of the resistivity below 30K and metallic behavior above, a magneto resistance of 0.9% and an unusual memory like effect of the resistance for an in-plane magnetic field sweep measurement. Silicon/Silicon suboxide (SiOx) multilayer structures are grown on Si(100) by interrupting the Si growth and oxidizing the surface with molecular oxygen. During oxidation the RHEED pattern changes from the Si(2x1) reconstruction to an amorphous pattern. When silicon growth is resumed a spotty RHEED pattern emerges, indicating a rough, three dimensional surface. The rough surface can be smoothed out with Si growth at substrate temperatures between 600°C and 700°C. Measurements with transmission electron microscopy show that a silicon suboxide layer of about 1nm embedded in single crystalline silicon is formed with the procedure. Multilayer structures are achieved by repeating the oxidation procedure when the Si spacer layer has a smooth and flat surface. The oxygen content of the suboxide layers can be varied between 7.6% and 26.8%, as determined with secondary ion mass spectrometry and custom-built simulations models for the x-ray diffraction. Structural stability of the multilayer structures is investigated by x-ray diffraction before and after rapid thermal annealing. For temperatures up to 1000°C the multilayer structures show no modification of the SiOx layer in x-ray diffraction.
A search is performed for WH production with a light Higgs boson decaying to hidden-sector particles resulting in clusters of collimated electrons, known as electron-jets. The search is performed with \(2.04 fb^{−1}\) of data collected in 2011 with the ATLAS detector at the Large Hadron Collider in proton–proton collisions at \(\sqrt {s}=7 TeV\) . One event satisfying the signal selection criteria is observed, which is consistent with the expected background rate. Limits on the product of the WH production cross section and the branching ratio of a Higgs boson decaying to prompt electron-jets are calculated as a function of a Higgs boson mass in the range from 100 to 140 GeV.
The large difference between the Planck scale and the electroweak scale, known as the hierarchy problem, is addressed in certain models through the postulate of extra spatial dimensions. A search for evidence of extra spatial dimensions in the diphoton channel has been performed using the full set of proton–proton collisions at \(\sqrt {s} = 7\) TeV recorded in 2011 with the ATLAS detector at the CERN Large Hadron Collider. This dataset corresponds to an integrated luminosity of \(4.9 fb^{−1}\). The diphoton invariant mass spectrum is observed to be in good agreement with the Standard Model expectation. In the context of the model proposed by Arkani–Hamed, Dimopoulos and Dvali, 95% confidence level lower limits of between 2.52 and 3.92 TeV are set on the ultraviolet cutoff scale MS depending on the number of extra dimensions and the theoretical formalism used. In the context of the Randall–Sundrum model, a lower limit of 2.06 (1.00) TeV at 95% confidence level is set on the mass of the lightest graviton for couplings of \(k/\overline {M}_{Pl} = 0.1 (0.01)\). Combining with the ATLAS dilepton searches based on the 2011 data, the 95% confidence level lower limit on the Randall–Sundrum graviton mass is further tightened to 2.23 (1.03) TeV for \(k/\overline {M}_{Pl} = 0.1 (0.01)\).
The ATLAS detector at the Large Hadron Collider is used to search for excited electrons and excited muons in the channel \(pp →ℓℓ^\ast→ℓℓ\gamma \), assuming that excited leptons are produced via contact interactions. The analysis is based on \(13 fb^{−1}\) of pp collisions at a centre-of-mass energy of 8 TeV. No evidence for excited leptons is found, and a limit is set at the 95% credibility level on the cross section times branching ratio as a function of the excitedlepton mass \(m_{ℓ^\ast}\) . For \(m_{ℓ^\ast}\) ≽0.8 TeV, the respective upper limits on \(\sigma B(ℓ→ ℓ\gamma)\) are 0.75 and 0.90 fb for the \(e^\ast\) and \(μ^\ast\) searches. Limits on \(\sigma B\) are converted into lower bounds on the compositeness scale \(\Lambda\). In the special case where \(\Lambda = m_{ℓ^\ast}\), excited-electron and excited-muon masses below 2.2 TeV are excluded.