Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma

Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far. Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering. Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies. Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones

Vertical-external-cavity surface-emitting lasers and quantum dot lasers

The use of cavity to manipulate photon emission of quantum dots (QDs) has been opening unprecedented opportunities for realizing quantum functional nanophotonic devices and also quantum information devices. In particular, in the field of semiconductor lasers, QDs were introduced as a superior alternative to quantum wells to suppress the temperature dependence of the threshold current in vertical-external-cavity surface-emitting lasers (VECSELs). In this work, a review of properties and development of semiconductor VECSEL devices and QD laser devices is given. Based on the features of VECSEL devices, the main emphasis is put on the recent development of technological approach on semiconductor QD VECSELs. Then, from the viewpoint of both single QD nanolaser and cavity quantum electrodynamics (QED), a single-QD-cavity system resulting from the strong coupling of QD cavity is presented. A difference of this review from the other existing works on semiconductor VECSEL devices is that we will cover both the fundamental aspects and technological approaches of QD VECSEL devices. And lastly, the presented review here has provided a deep insight into useful guideline for the development of QD VECSEL technology and future quantum functional nanophotonic devices and monolithic photonic integrated circuits (MPhICs).Comment: 21 pages, 4 figures. arXiv admin note: text overlap with arXiv:0904.369

Submonolayer Quantum Dots for High Speed Surface Emitting Lasers

We report on progress in growth and applications of submonolayer (SML) quantum dots (QDs) in high-speed vertical-cavity surface-emitting lasers (VCSELs). SML deposition enables controlled formation of high density QD arrays with good size and shape uniformity. Further increase in excitonic absorption and gain is possible with vertical stacking of SML QDs using ultrathin spacer layers. Vertically correlated, tilted or anticorrelated arrangements of the SML islands are realized and allow QD strain and wavefunction engineering. Respectively, both TE and TM polarizations of the luminescence can be achieved in the edge-emission using the same constituting materials. SML QDs provide ultrahigh modal gain, reduced temperature depletion and gain saturation effects when used in active media in laser diodes. Temperature robustness up to 100 °C for 0.98 μm range vertical-cavity surface-emitting lasers (VCSELs) is realized in the continuous wave regime. An open eye 20 Gb/s operation with bit error rates better than 10−12has been achieved in a temperature range 25–85 °Cwithout current adjustment. Relaxation oscillations up to ∼30 GHz have been realized indicating feasibility of 40 Gb/s signal transmission

DNA methylation-based classification of sinonasal tumors

The diagnosis of sinonasal tumors is challenging due to a heterogeneous spectrum of various differential diagnoses as well as poorly defined, disputed entities such as sinonasal undifferentiated carcinomas (SNUCs). In this study, we apply a machine learning algorithm based on DNA methylation patterns to classify sinonasal tumors with clinical-grade reliability. We further show that sinonasal tumors with SNUC morphology are not as undifferentiated as their current terminology suggests but rather reassigned to four distinct molecular classes defined by epigenetic, mutational and proteomic profiles. This includes two classes with neuroendocrine differentiation, characterized by IDH2 or SMARCA4/ARID1A mutations with an overall favorable clinical course, one class composed of highly aggressive SMARCB1-deficient carcinomas and another class with tumors that represent potentially previously misclassified adenoid cystic carcinomas. Our findings can aid in improving the diagnostic classification of sinonasal tumors and could help to change the current perception of SNUCs

Nonlinear optics and saturation behavior of quantum dot samples under continuous wave driving

The nonlinear optical response of self-assembled quantum dots is relevant to the application of quantum dot based devices in nonlinear optics, all-optical switching, slow light and self-organization. Theoretical investigations are based on numerical simulations of a spatially and spectrally resolved rate equation model, which takes into account the strong coupling of the quantum dots to the carrier reservoir created by the wetting layer states. The complex dielectric susceptibility of the ground state is obtained. The saturation is shown to follow a behavior in between the one for a dominantly homogeneously and inhomogeneously broadened medium. Approaches to extract the nonlinear refractive index change by fringe shifts in a cavity or self-lensing are discussed. Experimental work on saturation characteristic of InGa/GaAs quantum dots close to the telecommunication O-band (1.24-1.28 mm) and of InAlAs/GaAlAs quantum dots at 780 nm is described and the first demonstration of the cw saturation of absorption in room temperature quantum dot samples is discussed in detail

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Dynamic Filamentation and Beam Quality of Quantum-Dot Lasers

We present a comparative study of numerical simulations and experiments on the spatiotemporal dynamics and emission characteristics of quantum-well and quantum-dot lasers of identical structure. They show that, in the quantum-dot laser, the strong localization of carrier inversion and the small amplitude-phase coupling enable a significant improvement of beam quality compared to quantum-well lasers of identical geometry. Near-field profiles and beam quality (M-2) parameters calculated on the basis of time-dependent effective Maxwell-Bloch equations into which the physical properties of the active media are included via space-dependent material parameters, effective time constants, and matrix elements are fully confirmed by experimental measurements. Together they indicate that, in the quantum-dot laser, the strong localization of carrier inversion and the small amplitude-phase coupling enable a significant improvement of beam quality compared with quantum-well lasers of identical geometry. (C) 2004 American Institute of Physics.</p

Dynamic Filamentation and Beam Quality of Quantum-Dot Lasers

We present a comparative study of numerical simulations and experiments on the spatiotemporal dynamics and emission characteristics of quantum-well and quantum-dot lasers of identical structure. They show that, in the quantum-dot laser, the strong localization of carrier inversion and the small amplitude-phase coupling enable a significant improvement of beam quality compared to quantum-well lasers of identical geometry. Near-field profiles and beam quality (M-2) parameters calculated on the basis of time-dependent effective Maxwell-Bloch equations into which the physical properties of the active media are included via space-dependent material parameters, effective time constants, and matrix elements are fully confirmed by experimental measurements. Together they indicate that, in the quantum-dot laser, the strong localization of carrier inversion and the small amplitude-phase coupling enable a significant improvement of beam quality compared with quantum-well lasers of identical geometry. (C) 2004 American Institute of Physics.</p

High-reliability MOCVD-grown quantum dot laser

4.7 W continuous-wave (CW) and 11.7 W quasi-CW output power have been demonstrated for laser diodes based on six-fold stacks of InGaAs/GaAs quantum dots. Lifetimes beyond 3000 h at 1.0 and 1.5 W output power and 50degreesC heatsink temperature were measured. The output power is limited by catastrophic optical mirror damage occurring at 19.5 MW/cm(2) on the front facet