Monolithically Integrated Perovskite Semiconductor Lasers on Silicon Photonic Chips by Scalable Top-Down Fabrication.

Metal-halide perovskites are promising lasing materials for the realization of monolithically integrated laser sources, the key components of silicon photonic integrated circuits (PICs). Perovskites can be deposited from solution and require only low-temperature processing, leading to significant cost reduction and enabling new PIC architectures compared to state-of-the-art lasers realized through the costly and inefficient hybrid integration of III-V semiconductors. Until now, however, due to the chemical sensitivity of perovskites, no microfabrication process based on optical lithography (and, therefore, on existing semiconductor manufacturing infrastructure) has been established. Here, the first methylammonium lead iodide perovskite microdisc lasers monolithically integrated into silicon nitride PICs by such a top-down process are presented. The lasers show a record low lasing threshold of 4.7 µJcm-2 at room temperature for monolithically integrated lasers, which are complementary metal-oxide-semiconductor compatible and can be integrated in the back-end-of-line processes.

Graphene based on-chip variable optical attenuator operating at 855 nm wavelength.

This work reports on the fabrication and characterization of a graphene based variable optical attenuator integrated on a photonic Si3N4 waveguide and operating at 855 nm wavelength. The variable optical attenuator utilizes the gate voltage dependent optical absorption of a graphene layer, located in the evanescent field of the waveguide. A maximum attenuation of 17 dB is obtained at -3 V gate voltages for a device length of 700 µm. The measured voltage dependent absorption was found to be in good agreement with theoretical simulations, taking into account inter- and intra-band optical conductivity of graphene. An outlook is given on possible margins for increasing the operation speed and reducing the insertion loss of the device, using an optimized layout and improved fabrication processes.

Deficiency of PI3-Kinase catalytic isoforms p110γ and p110δ in mice enhances the IL-17/G-CSF axis and induces neutrophilia.

BACKGROUND: Phosphoinositide 3-kinase γ (PI3Kγ) and PI3Kδ are second messenger-generating enzymes with key roles in proliferation, differentiation, survival, and function of leukocytes. Deficiency of the catalytic subunits p110γ and p110δ of PI3Kγ and PI3Kδ in p110γ/δ-/- mice leads to defective B- and T-cell homeostasis. Here we examined the role of p110γ and p110δ in the homeostasis of neutrophils by analyzing p110γ-/-, p110δ-/- and p110γ/δ-/- mice. METHODS: Neutrophils and T cells in leukocyte suspensions from the bone marrow (BM), blood, spleen and lung were analyzed by flow cytometry. Serum concentrations of IL-17, of the neutrophilic growth factor G-CSF, and of the neutrophil mobilizing CXC chemokines CXCL1/KC and CXCL2/MIP-2 were measured by Bio-Plex assay. Production of G-CSF and CXCL1/KC by IL-17-stimulated primary lung tissue cells were determined by ELISA, whereas IL-17-dependent signaling in lung tissue cells was analyzed by measuring Akt phosphorylation using immunoblot. RESULTS: We found that in contrast to single knock-out mice, p110γ/δ-/- mice exhibited significantly elevated neutrophil counts in blood, spleen, and lung. Increased granulocytic differentiation stages in the bone marrow of p110γ/δ-/- mice were paralleled by increased serum concentrations of G-CSF, CXCL1/KC, and CXCL2/MIP-2. As IL-17 induces neutrophilia via the induction of G-CSF and CXC chemokines, we measured IL-17 and IL-17-producing T cells. IL-17 serum concentrations and frequencies of IL-17+ splenic T cells were significantly increased in p110γ/δ-/- mice. Moreover, IFN-γ+, IL-4+, and IL-5+ T cell subsets were drastically increased in p110γ/δ-/- mice, suggesting that IL-17+ T cells were up-regulated in the context of a general percentage increase of other cytokine producing T cell subsets. CONCLUSIONS: We found that p110γ/δ deficiency in mice induces complex immunological changes, which might in concert contribute to neutrophilia. These findings emphasize a crucial but indirect role of both p110γ and p110δ in the regulation of neutrophil homeostasis.

Controlled Generation of a p-n Junction in a Waveguide Integrated Graphene Photodetector.

With its electrically tunable light absorption and ultrafast photoresponse, graphene is a promising candidate for high-speed chip-integrated photonics. The generation mechanisms of photosignals in graphene photodetectors have been studied extensively in the past years. However, the knowledge about efficient light conversion at graphene p-n junctions has not yet been translated into high-performance devices. Here, we present a graphene photodetector integrated on a silicon slot-waveguide, acting as a dual gate to create a p-n junction in the optical absorption region of the device. While at zero bias the photothermoelectric effect is the dominant conversion process, an additional photoconductive contribution is identified in a biased configuration. Extrinsic responsivities of 35 mA/W, or 3.5 V/W, at zero bias and 76 mA/W at 300 mV bias voltage are achieved. The device exhibits a 3 dB bandwidth of 65 GHz, which is the highest value reported for a graphene-based photodetector.

SLy1 regulates T-cell proliferation during Listeria monocytogenes infection in a Foxo1-dependent manner.

Infection of mice with Listeria monocytogenes results in a strong T-cell response that is critical for an efficient defense. Here, we demonstrate that the adapter protein SLy1 (SH3-domain protein expressed in Lymphocytes 1) is essential for the generation of a fully functional T-cell response. The lack of SLy1 leads to reduced survival rates of infected mice. The increased susceptibility of SLy1 knock-out (KO) mice was caused by reduced proliferation of differentiated T cells. Ex vivo analyses of isolated SLy1 KO T cells displayed a dysregulation of Forkhead box protein O1 shuttling after TCR signaling, which resulted in an increased expression of cell cycle inhibiting genes, and therefore, reduced expansion of the T-cell population. Forkhead box protein O1 shuttles to the cytoplasm after phosphorylation in a protein complex including 14-3-3 proteins. Interestingly, we observed a similar regulation for the adapter protein SLy1, where TCR stimulation results in SLy1 phosphorylation and SLy1 export to the cytoplasm. Moreover, immunoprecipitation analyses revealed a binding of SLy1 to 14-3-3 proteins. Altogether, this study describes SLy1 as an immunoregulatory protein, which is involved in the generation of adaptive immune responses during L. monocytogenes infection, and provides a model of how SLy1 regulates T-cell proliferation.

SLy2 controls the antibody response to pneumococcal vaccine through an IL-5Rα-dependent mechanism in B-1 cells.

The adaptor protein SLy2 (Src homology domain 3 lymphocyte protein 2) is located on human chromosome 21 and was reported to be among a group of genes amplified in Down's syndrome (DS) patients. DS patients characteristically show an impaired immunity to pneumococcal infections. However, molecular mechanisms linking gene amplifications with specific DS phenotypes remain elusive. To investigate the effect of SLy2 gene amplification on the mammalian immune system, we studied SLy2 overexpressing transgenic-SLy2 (TG) mice. We found that baseline immunoglobulin M (IgM) levels as well as IgM responses following Pneumovax immunizations were reduced in TG mice. Moreover, B-1 cells, the major natural IgM-producing population in mice, were reduced in the peritoneal cavity of TG mice, while other immune cell compartments were unaltered. Mechanistically, SLy2 overexpression attenuated the expression of the IL-5 receptor α chain on B-1 cells, resulting in decreased B-1 cell numbers and decreased differentiation into Ab-secreting cells. Since B-1 cells essentially contribute to immunity against Streptococcus pneumoniae, the present study provides a novel molecular link between SLy2 expression and pneumococcal-specific IgM responses in vivo. These studies suggest that the adaptor protein SLy2 is a potential future target for immunomodulatory strategies for pneumococcal infections.

Infrared transparent graphene heater for silicon photonic integrated circuits.

Thermo-optical tuning of the refractive index is one of the pivotal operations performed in integrated silicon photonic circuits for thermal stabilization, compensation of fabrication tolerances, and implementation of photonic operations. Currently, heaters based on metal wires provide the temperature control in the silicon waveguide. The strong interaction of metal and light, however, necessitates a certain gap between the heater and the photonic structure to avoid significant transmission loss. Here we present a graphene heater that overcomes this constraint and enables an energy efficient tuning of the refractive index. We achieve a tuning power as low as 22 mW per free spectral range and fast response time of 3 µs, outperforming metal based waveguide heaters. Simulations support the experimental results and suggest that for graphene heaters the spacing to the silicon can be further reduced yielding the best possible energy efficiency and operation speed.

Graphene based low insertion loss electro-absorption modulator on SOI waveguide.

Graphene is considered a promising material for broadband opto-electronics because of its linear and gapless band structure. Its optical conductivity can be significantly tuned electrostatically by shifting the Fermi level. Using mentioned property, we experimentally demonstrate a graphene based electro-absorption modulator with very low insertion loss. The device is realized on a silicon on insulator (SOI) waveguide operating at 1550 nm wavelength. The modulator shows a modulation depth of 16 dB and an insertion loss of 3.3 dB, surpassing GeSi and previous graphene based absorption modulators and being comparable to silicon Mach-Zehnder interferometer based modulators.

Two-Dimensional Platinum Diselenide Waveguide-Integrated Infrared Photodetectors.

Low-cost, easily integrable photodetectors (PDs) for silicon (Si) photonics are still a bottleneck for photonic-integrated circuits (PICs), especially for wavelengths above 1.8 µm. Multilayered platinum diselenide (PtSe2) is a semi-metallic two-dimensional (2D) material that can be synthesized below 450 °C. We integrate PtSe2-based PDs directly by conformal growth on Si waveguides. The PDs operate at 1550 nm wavelength with a maximum responsivity of 11 mA/W and response times below 8.4 µs. Fourier-transform IR spectroscopy in the wavelength range from 1.25 to 28 µm indicates the suitability of PtSe2 for PDs far into the IR wavelength range. Our PtSe2 PDs integrated by direct growth outperform PtSe2 PDs manufactured by standard 2D layer transfer. The combination of IR responsivity, chemical stability, selective and conformal growth at low temperatures, and the potential for high carrier mobility makes PtSe2 an attractive 2D material for optoelectronics and PICs.

Interaction mining and skill-dependent recommendations for multi-objective team composition.

Web-based collaboration and virtual environments supported by various Web 2.0 concepts enable the application of numerous monitoring, mining and analysis tools to study human interactions and team formation processes. The composition of an effective team requires a balance between adequate skill fulfillment and sufficient team connectivity. The underlying interaction structure reflects social behavior and relations of individuals and determines to a large degree how well people can be expected to collaborate. In this paper we address an extended team formation problem that does not only require direct interactions to determine team connectivity but additionally uses implicit recommendations of collaboration partners to support even sparsely connected networks. We provide two heuristics based on Genetic Algorithms and Simulated Annealing for discovering efficient team configurations that yield the best trade-off between skill coverage and team connectivity. Our self-adjusting mechanism aims to discover the best combination of direct interactions and recommendations when deriving connectivity. We evaluate our approach based on multiple configurations of a simulated collaboration network that features close resemblance to real world expert networks. We demonstrate that our algorithm successfully identifies efficient team configurations even when removing up to 40% of experts from various social network configurations.

SLy2-deficiency promotes B-1 cell immunity and triggers enhanced production of IgM and IgG2 antibodies against pneumococcal vaccine.

BACKGROUND: Despite the benefits of existing vaccines, Streptococcus pneumoniae is still responsible for the greatest proportion of respiratory tract infections around the globe, thereby substantially contributing to morbidity and mortality in humans. B-1 cells are key players of bacterial clearance during pneumococcal infection and even provide long-lasting immunity towards S. pneumoniae. Previous reports strongly suggest an essential role of the immunoinhibitory adapter Src homology domain 3 lymphocyte protein 2 (SLy2) for B-1 cell-mediated antibody production. The objective of this study is to evaluate S. pneumoniae-directed B cell responses in the context of SLy2 deficiency. METHODS: B-1 cell populations were analyzed via flow cytometry before and after pneumococcal immunization of SLy2-deficient and wild-type control mice. Global and vaccine-specific immunoglobulin M (IgM) and IgG antibody titers were assessed by enzyme-linked immunosorbent assay. To investigate survival rates during acute pneumococcal lung infection, mice were intranasally challenged with S. pneumoniae (serotype 3). Complementary isolated splenic B cells were stimulated in vitro and their proliferative response was assessed by fluorescent staining. In vitro antibody secretion was quantified by LEGENDplex. RESULTS: We demonstrate increased frequencies of B-1 cells and elevated titers of preantigenic IgM in SLy2-deficient mice. In addition, these mice produce significantly more amounts of IgM and IgG2 upon pneumococcal vaccination. Knocking out SLy2 did not induce survival advantages in our murine model of acute pneumonia, indicating the presence of compensatory mechanisms. CONCLUSION: Our results reveal reinforced specific antibody responses towards pneumococcal polysaccharides and enhanced IgG2 secretion as a consequence of SLy2 deficiency, which could be relevant to the development of more efficient vaccines.

Flexible Hall sensors based on graphene.

The excellent electronic and mechanical properties of graphene provide a perfect basis for high performance flexible electronic and sensor devices. Here, we present the fabrication and characterization of flexible graphene based Hall sensors. The Hall sensors are fabricated on 50 µm thick flexible Kapton foil using large scale graphene grown by chemical vapor deposition technique on copper foil. Voltage and current normalized sensitivities of up to 0.096 V VT(-1) and 79 V AT(-1) were measured, respectively. These values are comparable to the sensitivity of rigid silicon based Hall sensors and are the highest values reported so far for any flexible Hall sensor devices. The sensitivity of the Hall sensor shows no degradation after being bent to a minimum radius of 4 mm, which corresponds to a tensile strain of 0.6%, and after 1000 bending cycles to a radius of 5 mm.

Deficiency of the adaptor protein SLy1 results in a natural killer cell ribosomopathy affecting tumor clearance.

Individuals with robust natural killer (NK) cell function incur lower rates of malignancies. To expand our understanding of genetic factors contributing to this phenomenon, we analyzed NK cells from cancer resistant and susceptible strains of mice. We identified a correlation between NK levels of the X-chromosome-located adaptor protein SLy1 and immunologic susceptibility to cancer. Unlike the case for T or B lymphocytes, where SLy1 shuttles between the cytoplasm and nucleus to facilitate signal transduction, in NK cells SLy1 functions as a ribosomal protein and is located solely in the cytoplasm. In its absence, ribosomal instability results in p53-mediated NK cell senescence and decreased clearance of malignancies. NK defects are reversible under inflammatory conditions and viral clearance is not impacted by SLy1 deficiency. Our work defines a previously unappreciated X-linked ribosomopathy that results in a specific and subtle NK cell dysfunction leading to immunologic susceptibility to cancer.

Experimental verification of electro-refractive phase modulation in graphene.

Graphene has been considered as a promising material for opto-electronic devices, because of its tunable and wideband optical properties. In this work, we demonstrate electro-refractive phase modulation in graphene at wavelengths from 1530 to 1570 nm. By integrating a gated graphene layer in a silicon-waveguide based Mach-Zehnder interferometer, the key parameters of a phase modulator like change in effective refractive index, insertion loss and absorption change are extracted. These experimentally obtained values are well reproduced by simulations and design guidelines are provided to make graphene devices competitive to contemporary silicon based phase modulators for on-chip applications.

Highly air stable passivation of graphene based field effect devices.

The sensitivity of graphene based devices to surface adsorbates and charge traps at the graphene/dielectric interface requires proper device passivation in order to operate them reproducibly under ambient conditions. Here we report on the use of atomic layer deposited aluminum oxide as passivation layer on graphene field effect devices (GFETs). We show that successful passivation produce hysteresis free DC characteristics, low doping level GFETs stable over weeks though operated and stored in ambient atmosphere. This is achieved by selecting proper seed layer prior to deposition of encapsulation layer. The passivated devices are also demonstrated to be robust towards the exposure to chemicals and heat treatments, typically used during device fabrication. Additionally, the passivation of high stability and reproducible characteristics is also shown for functional devices like integrated graphene based inverters.

Integrated Ring Oscillators based on high-performance Graphene Inverters.

The road to the realization of complex integrated circuits based on graphene remains an open issue so far. Current graphene based integrated circuits are limited by low integration depth and significant doping variations, representing major road blocks for the success of graphene in future electronic devices. Here we report on the realization of graphene based integrated inverters and ring oscillators. By using an optimized process technology for high-performance graphene transistors with local back-gate electrodes we demonstrate that complex graphene based integrated circuits can be manufactured reproducibly, circumventing problems associated with doping variations. The fabrication process developed here is scalable and fully compatible with conventional silicon technology. Therefore, our results pave the way towards applications based on graphene transistors in future electronic devices.