Here, we use a novel growth scheme to overcome this roadblock and directly grow on-chip InGaAs nanopillar lasers, demonstrating the potency of bottom-up nano-optoelectronic integration. Unique helically-propagating cavity modes are employed to strongly confine light within subwavelength nanopillars despite low refractive index contrast between InGaAs and silicon. These modes thereby provide an avenue for engineering on-chip nanophotonic devices such as lasers. Nanopillar lasers are as-grown on silicon, offer tiny footprints and scalability, and are thereby particularly suited to high-density optoelectronics. They may ultimately form the basis of the missing monolithic light sources needed to bridge the existing gap between photonic and electronic circuits. 2Since the first laser demonstrated that stimulated emission processes in an optical medium can implement a powerful, coherent light source 1 , the field of photonics has witnessed an explosion of applications in telecommunications, lighting, displays, medicine, and optical physics amongst others. Integration of photonic and electronic devices to leverage the advantages of both has subsequently attracted great interest. In particular, integration of optical interconnects onto silicon (Si) chips has become critical as ongoing miniaturization of Si logic elements has incurred a bottleneck in inter-and intra-chip communications 2,3 . Efforts towards creating on-chip light sources for optical interconnects have included engineering silicon and germanium for optical gain 4-6 and stimulated Raman scattering 7-9 . Concurrently, III-V lasers have been heterogeneously bonded onto silicon substrates [10][11][12] . However, numerous challenges face these approaches. Wafer bonding have low yields because of a stringent surface flatness requirement down to the atomic scale, while group IV emitters must overcome an indirect band gap that offers exceedingly inefficient radiation. Monolithic growth of high-performance III-V lasers on silicon thereby remains a "holy grail" for cost-effective, massively scalable, and streamlined fabrication of on-chip light sources.The fundamental roadblock facing monolithic integration up to now has been a large mismatch of lattice constants and thermal expansion coefficients between III-V materials and The nanopillar-based laser is schematically depicted in Figure 1A. shows the hexagonal cross-section of the nanopillar, which results from its unique single crystal wurtzite structure 15 . As we will later show, the as-grown nanopillar structure provides a natural optical cavity supporting unique resonances that have not been observed before to the best of our knowledge. As such, nanopillars do not require additional top-down processing to form on-chip optical cavities. Instead, they provide a viable bottom-up approach towards integrating light sources and resonators onto a silicon chip.Importantly, nanopillars possess several critical advantages for optoelectronic integration onto silicon. They grow at a low temperature of 400 °C, which is dra...

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Purpose: Lenalidomide has significant activity in myelodysplastic syndromes, multiple myeloma, and non-Hodgkin's lymphoma (NHL). In previous studies, natural killer (NK) cell expansion by lenalidomide was shown to enhance the cytotoxic effect of rituximab. This study assessed the ability of lenalidomide to enhance antibody-dependent cellular cytotoxicity (ADCC) in rituximab-treated NHL cell lines and primary tumor cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) in vitro. Experimental Design: An in vitro ADCC system was used to assess the ability of lenalidomide to enhance human NK cell and monocyte function in response to rituximab. Results: Lenalidomide directly enhanced IFN-g production via Fc-g receptor-mediated signaling in response to IgG. It was also a potent enhancer of NK cell-mediated and monocyte-mediated tumor cell ADCC for a variety of rituximab-treated NHL cell lines in vitro, an effect that was dependent on the presence of antibody and either interleukin-2 or interleukin-12. Lenalidomide also enhanced the ability of NK cells to kill primary tumor cells derived from three patients with B-CLL who have been treated previously with fludarabine plus cyclophosphamide. Enhanced NK cell ADCC was associated with enhanced granzyme B and Fas ligand expression and could be inhibited by a granzyme B inhibitor and partially inhibited by antibody to FasL. Enhanced NK cell Fc-g receptor signaling is associated with enhanced phosphorylated extracellular signal-related kinase levels leading to enhanced effector function. Conclusions: These findings suggest that lenalidomide has the potential to enhance the rituximab-induced killing of NHL cell lines and primary B-cell chronic lymphocytic leukemia cells via a NK cell-mediated and monocyte-mediated ADCC mechanism in vitro, providing a strong rationale for the combination of lenalidomide with IgG1 antibodies to target tumor-specific antigens in patients with cancer.

This study evaluated the long-term safety and efficacy of dapagliflozin as an adjunct to adjustable insulin in patients with type 1 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS DEPICT-1 (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) was a randomized (1:1:1), double-blind, placebo-controlled phase 3 study of dapagliflozin 5 mg and 10 mg in patients with type 1 diabetes (HbA 1c 7.5-10.5% [58-91 mmol/mol]) (NCT02268214). The results of the 52-week study, consisting of the 24-week short-term and 28-week extension period, are reported here. RESULTS Of the 833 patients randomized into the study, 708 (85%) completed the 52-week study. Over 52 weeks, dapagliflozin 5 mg and 10 mg led to clinically significant reductions in HbA 1c (difference vs. placebo [95% CI] 20.

Lenalidomide (Revlimid; CC-5013) and pomalidomide (CC-4047) are IMiDs proprietary drugs having immunomodulatory properties that have both shown activity in cancer clinical trials; lenalidomide is approved in the United States for a subset of MDS patients and for treatment of patients with multiple myeloma when used in combination with dexamethasone. These drugs exhibit a range of interesting clinical properties, including anti-angiogenic, anti-proliferative, and pro-erythropoietic activities although exact cellular target(s) remain unclear. Also, anti-inflammatory effects on LPS-stimulated monocytes (TNF-alpha is decreased) and costimulatory effects on anti-CD3 stimulated T cells, (enhanced T cell proliferation and proinflammatory cytokine production) are observed. These drugs also cause augmentation of NK-cell cytotoxic activity against tumour-cell targets. Having shown that pomalidomide confers T cell-dependent adjuvant-like protection in a preclinical whole tumour-cell vaccine-model, we now show that lenalidomide and pomalidomide strongly inhibit T-regulatory cell proliferation and suppressor-function. Both drugs inhibit IL-2-mediated generation of FOXP3 positive CTLA-4 positive CD25high CD4+ T regulatory cells from PBMCs by upto 50%. Furthermore, suppressor function of pre-treated T regulatory cells against autologous responder-cells is abolished or markedly inhibited without drug related cytotoxicity. Also, Balb/C mice exhibit 25% reduction of lymph-node T regulatory cells after pomalidomide treatment. Inhibition of T regulatory cell function was not due to changes in TGF-beta or IL-10 production but was associated with decreased T regulatory cell FOXP3 expression. In conclusion, our data provide one explanation for adjuvant properties of lenalidomide and pomalidomide and suggest that they may help overcome an important barrier to tumour-specific immunity in cancer patients.