Hybrid photonic integration exploits complementary strengths of different material platforms, thereby offering superior performance and design flexibility in comparison to monolithic approaches. This applies in particular to multi-chip concepts, where components can be individually optimized and tested on separate dies before integration into more complex systems. The assembly of such systems, however, still represents a major challenge, requiring complex and expensive processes for high-precision alignment as well as careful adaptation of optical mode profiles. Here we show that these challenges can be overcome by in-situ nano-printing of freeform beam-shaping elements to facets of optical components. The approach is applicable to a wide variety of devices and assembly concepts and allows adaptation of vastly dissimilar mode profiles while considerably relaxing alignment tolerances to the extent that scalable, cost-effective passive assembly techniques can be used. We experimentally prove the viability of the concept by fabricating and testing a selection of beam-shaping elements at chip and fiber facets, achieving coupling efficiencies of up to 88 % between an InP laser and an optical fiber. We also demonstrate printed freeform mirrors for simultaneously adapting beam shape and propagation direction, and we explore multi-lens systems for beam expansion. The concept paves the way to automated fabrication of photonic multi-chip assemblies with unprecedented performance and versatility.

Proinflammatory cytokines are critically involved in the alteration of adipose tissue biology leading to deterioration of glucose homeostasis in obesity. Here we show a pronounced proinflammatory signature of adipose tissue macrophages in type 2 diabetic obese patients, mainly driven by increased NLRP3-dependent interleukin (IL)-1β production. IL-1β release increased with glycemic deterioration and decreased after gastric bypass surgery. A specific enrichment of IL-17- and IL-22-producing CD4+ T cells was found in adipose tissue of type 2 diabetic obese patients. Coculture experiments identified the effect of macrophage-derived IL-1β to promote IL-22 and IL-17 production by human adipose tissue CD4+ T cells. Reciprocally, adipose tissue macrophages express IL-17 and IL-22 receptors, making them sensitive to IL-17 and IL-22. IL-22 increased IL-1β release by inducing pro-IL-1β transcription through activation of C-Jun pathways in macrophages. In sum, these human data identified IL-1β and the T-cell cytokine IL-22 as key players of a paracrine inflammatory pathway previously unidentified in adipose tissue, with a pathological relevance to obesity-induced type 2 diabetes. These results provide an additional rationale for targeting IL-1β in obesity-linked type 2 diabetes and may have important implications for the conception of novel combined anti-IL-1β and anti-IL-22 immunotherapy in human obesity.

Strongly enhanced thermoelectric properties are predicted for graphene nanoribbons (GNRs) with optimized pattern. By means of nonequilibrium Green's function atomistic simulation of electron and phonon transport, we analyze the thermal and electrical properties of perfect GNRs as a function of their width and their edge orientation to identify a strategy likely to degrade the thermal conductance while retaining high electronic conductance and thermopower. An effect of resonant tunneling of electrons is detected in mixed GNRs consisting of alternate zigzag and armchair sections. To fully benefit from this effect and from strongly reduced phonon thermal conductance, a structure with armchair and zigzag sections of different widths is proposed. It is shown to provide a high thermoelectric factor of merit ZT exceeding unity at room temperature.

Adipose tissue contains a variety of immune cells, which vary in abundance and phenotype with obesity. The contribution of immune cell-derived factors to inflammatory, fibrotic and metabolic alterations in adipose tissue is not well established in human obesity. Human primary adipose tissue cells, including pre-adipocytes, endothelial cells and mature adipocytes, were used to investigate deregulation of cell- and pathway-specific gene profiles. Among factors known to alter adipose tissue biology, we focus on inflammatory (IL-1β and IL-17) and pro-fibrotic (TGF-β1) factors. rIL-1β and rIL-17 induced concordant pro-inflammatory transcriptional programs in pre-adipocytes and endothelial cells, with a markedly more potent effect of IL-1β than IL-17. None of these cytokines had significant effect on fibrogenesis-related gene expression, contrasting with rTGF-β1-induced up-regulation of extracellular matrix components and pro-fibrotic factors. In mature adipocytes, all three factors promoted down-regulation of genes functionally involved in lipid storage and release. IL-1β and IL-17 impacted adipocyte metabolic genes in relation with their respective pro-inflammatory capacity, while the effect of TGF-β1 occurred in face of an anti-inflammatory signature. These data revealed that IL-1β and IL-17 had virtually no effect on pro-fibrotic alterations but promote inflammation and metabolic dysfunction in human adipose tissue, with a prominent role for IL-1β.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex immune-mediated disease of the gastrointestinal tract that increases morbidity and negatively influences the quality of life. Intestinal mononuclear phagocytes (MNPs) have a crucial role in maintaining epithelial barrier integrity while controlling pathogen invasion by activating an appropriate immune response. However, in genetically predisposed individuals, uncontrolled immune activation to intestinal flora is thought to underlie the chronic mucosal inflammation that can ultimately result in IBD. Thus, MNPs are involved in fine-tuning mucosal immune system responsiveness and have a critical role in maintaining homeostasis or, potentially, the emergence of IBD. MNPs include monocytes, macrophages and dendritic cells, which are functionally diverse but highly complementary. Despite their crucial role in maintaining intestinal homeostasis, specific functions of human MNP subsets are poorly understood, especially during diseases such as IBD. Here we review the current understanding of MNP ontogeny, as well as the recently identified human intestinal MNP subsets, and discuss their role in health and IBD.

Light scattering by a two-dimensional photonic-crystal slab (PCS) can result in marked interference effects associated with Fano resonances. Such devices offer appealing alternatives to distributed Bragg reflectors and filters for various applications, such as optical wavelength and polarization filters, reflectors, semiconductor lasers, photodetectors, bio-sensors and non-linear optical components. Suspended PCS also have natural applications in the field of optomechanics, where the mechanical modes of a suspended slab interact via radiation pressure with the optical field of a high-finesse cavity. The reflectivity and transmission properties of a defect-free suspended PCS around normal incidence can be used to couple out-of-plane mechanical modes to an optical field by integrating it in a free-space cavity. Here we demonstrate the successful implementation of a PCS reflector on a high-tensile stress Si3N4 nanomembrane. We illustrate the physical process underlying the high reflectivity by measuring the photonic-crystal band diagram. Moreover, we introduce a clear theoretical description of the membrane scattering properties in the presence of optical losses. By embedding the PCS inside a high-finesse cavity, we fully characterize its optical properties. The spectrally, angular- and polarization-resolved measurements demonstrate the wide tunability of the membrane’s reflectivity, from nearly 0 to 99.9470±0.0025%, and show that material absorption is not the main source of optical loss. Moreover, the cavity storage time demonstrated in this work exceeds the mechanical period of low-order mechanical drum modes. This so-called resolved-sideband condition is a prerequisite to achieve quantum control of the mechanical resonator with light.

Natural killer (NK) cells are able to recognize and kill tumor cells, however whether they contribute to tumor immunosurveillance is still debated. Our previous studies demonstrated the presence of NK cells in human lung tumors. Their comparison with NK cells from non-tumoral lung tissues and with blood NK cells from the same individuals revealed a decreased expression of some NK receptors and impaired ex vivo cytotoxic functions occurring specifically in NK cells isolated from the tumor microenvironment. The aim of the present study was to characterize the transcriptional profile of such intratumoral NK cells, by comparative microarray analysis of sorted NK cells isolated from non-tumoral (Non-Tum-NK) and tumoral (Tum-NK) lung tissues of 12 Non-Small Cell Lung Cancer patients. Our results reveal a specific gene expression signature of Tum-NK cells particularly in activation processes and cytotoxicity, confirming that tumor environment induces modifications in NK cells biology. Indeed, intratumoral NK cells display higher expression levels of NKp44, NKG2A, Granzymes A and K, and Fas mRNA. A particular pattern of receptors involved in chemotaxis was also observed, with an overexpression of CXCR5 and CXCR6, and a lower expression of CX3CR1 and S1PR1 genes in Tum-NK as compared to Non-Tum-NK cells. The precise identification of the molecular pathways modulated in the tumor environment will help to decipher the role of NK cells in tumor immunosurveillance and will open future investigations to manipulate their antitumoral functions.

Mode-locked lasers find their use in a large number of applications, for instance, in spectroscopic sensing, distance measurements, and optical communication. To enable widespread use of mode-locked lasers, their on-chip integration is desired. In recent years, there have been multiple demonstrations of monolithic III-V and heterogeneous III-V-on-silicon mode-locked lasers. However, the pulse energy, noise performance, and stability of these mode-locked lasers are limited by the relatively high linear and nonlinear waveguide loss, and the high temperature sensitivity of said platforms. Here, we demonstrate a heterogeneous III-V-on-silicon-nitride (III-V-on-SiN) electrically pumped mode-locked laser. SiN’s low waveguide loss, negligible two-photon absorption at telecom wavelengths, and small thermo-optic coefficient enable low-noise mode-locked lasers with high pulse energies and excellent temperature stability. Our mode-locked laser emits at a wavelength of 1.6 μm, has a pulse repetition rate of 3 GHz, a high on-chip pulse energy of ≈2 pJ, a narrow RF linewidth of 400 Hz, and an optical linewidth <1 MHz. The SiN photonic circuits are fabricated on 200 mm silicon wafers in a CMOS pilot line and include an amorphous silicon waveguide layer for efficient coupling from the SiN to the III-V waveguide. The III-V integration is done by micro-transfer-printing, a technique that enables the transfer of thin-film devices in a massively parallel manner on a wafer scale.