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Broadband Silicon-On-Insulator (SOI) directional couplers are designed based on a combination of curved and straight coupled waveguide sections. A design methodology based on the transfer matrix method (TMM) is used to determine the required coupler section lengths, radii, and waveguide cross-sections. A 50/50 power splitter with a measured bandwidth of 88 nm is designed and fabricated, with a device footprint of 20 μm × 3 μm. In addition, a balanced Mach-Zehnder interferometer is fabricated showing an extinction ratio of >16 dB over 100 nm of bandwidth.

We designed and simulated freestanding dielectric optical metasurfaces based on arrays of etched nanoholes in a silicon membrane. We showed 2π phase control and high forward transmission at mid-infrared (mid-IR) wavelengths around 4.2 μm by tuning the dimensions of the holes. We also identified the mechanisms responsible for high forward scattering efficiency and showed that these conditions are connected with the well-known Kerker conditions already proposed for isolated scatterers. A beam deflector was designed and optimized through sequential particle swarm and gradient descent optimization to maximize transmission efficiency and reduce unwanted grating orders. Such freestanding silicon nanohole array metasurfaces are promising for the realization of silicon-based mid-IR optical elements.

The minimisation of birefringence, or polarisation mode dispersion, is vital for simplifying and miniaturising photonic components. In this work, we present a systematic study of the slot waveguide geometries required for having zero birefringence (ZB). We show that the rail widths required for ZB are more strongly dependent on the height of the waveguide than on the slot separation. After which, we demonstrate that the ZB geometry is significantly affected by the slanting of the waveguide walls. This paper proceeds to show that within the range studied, one can fix the height, slot, slant angle, and bend radius, and still achieve ZB by varying the widths of both of the rails. Given a fabrication tolerance of 5 nm, we show that a coherence length on the order of a hundred microns can be achieved. We finish by showing that for straight and bent ZB waveguides, having symmetric rails is preferable due to higher tolerances and lower sensitivity to bending. Since any arbitrarily shaped slot waveguide is a combination of both single mode straight and bent waveguides, we have a toolbox from which we can achieve ZB for any given slot and height.

The optimal geometry of silicon-organic hybrid slot waveguides is investigated in the context of the efficiency of four-wave mixing (FWM), a χ(3) nonlinear optical process. We study the effect of slot and waveguide widths, as well as waveguide asymmetry on the two-photon absorption (TPA) figure of merit and the roughness scattering loss. The optimal waveguide core width is shown to be 220nm (symmetric) with a slot width of 120nm, at a fixed waveguide height of 220nm. We also show that state-of-the-art slot waveguides can outperform rib waveguides, especially at high powers, due to the high TPA figure-of-merit.

Using two-photon (Franson) interferometry, we measure the entanglement of photon pairs generated from an optically-pumped silicon photonic device consisting of a few coupled microring resonators. The pair-source chip operates at room temperature, and the InGaAs single-photon avalanche detectors (SPADs) are thermo-electrically cooled to 234K. Such a device can be integrated with other components for practical entangled photon-pair generation at telecommunications wavelengths.

Directly modulated semiconductor lasers are widely used, compact light sources in optical communications. Semiconductors can also be used to generate nonclassical light; in fact, CMOS-compatible silicon chips can be used to generate pairs of single photons at room temperature. Unlike the classical laser, the photon-pair source requires control over a two-dimensional joint spectral intensity (JSI) and it is not possible to process the photons separately, as this could destroy the entanglement. Here we design a photon-pair source, consisting of planar lightwave components fabricated using CMOS-compatible lithography in silicon, which has the capability to vary the JSI. By controlling either the optical pump wavelength, or the temperature of the chip, we demonstrate the ability to select different JSIs, with a large variation in the Schmidt number. Such control can benefit high-dimensional communications where detector-timing constraints can be relaxed by realizing a large Schmidt number in a small frequency range.

Silicon photonic four-wave mixing (FWM) devices intended for telecommunications applications must satisfy three requirements: achieve conversion efficiencies close to the detection threshold of typical receivers, while keeping pump power requirements modest and providing enough bandwidth for typical signal formats. Here, we report a continuous-wave FWM efficiency of -21.3  dB at 100 mW pump power and demonstrate wavelength conversion at 10 Gbps in a coupled-resonator optical-waveguide device.

We fabricate a two-stage wavelength converter in silicon by cascading a microring wavelength mixer with a five-ring coupled-resonator filter. A p-i-n diode is incorporated into the microring for electronic carrier sweep-out, and microheaters are incorporated into the filter for tunability. The generated idler wavelength is effectively separated from the input pump and signal, with nearly 50 dB of suppression.

Anderson localization of light has been demonstrated in a few different dielectric materials and lithographically fabricated structures. However, such localization is difficult to control, and requires strong magnetic fields or nonlinear optical effects, and electronic control has not been demonstrated. Here, we show control of optical Anderson localization using charge carriers injected into more than 100 submicrometre-scale p-n diodes. The diodes are embedded into the cross-section of the optical waveguide and are fabricated with a technology compatible with the current electronics industry. Large variations in the output signal, exceeding a factor of 100, were measured with 1 V and a control current of 1 mA. The transverse footprint of our device is only 0.125 µm(2), about five orders of magnitude smaller than optical two-dimensional lattices. Whereas all-electronic localization has a narrow usable bandwidth, electronically controlled optical localization can access more than a gigahertz of bandwidth and creates new possibilities for controlling localization at radiofrequencies, which can benefit applications such as random lasers, optical limiters, imagers, quantum optics and measurement devices.

Leptin contributes to the pathogenesis of vascular repair and cardiovascular events. This study evaluated the molecular mechanism of EGCG in balloon injury-induced leptin expression. According to immunohistochemical and confocal analyses, leptin expression was increased and the aortic lumen exhibited narrowing after balloon injury. EGCG treatment attenuated leptin expression and diminished neointimal formation. The in vitro study showed that angiotensin II (Ang II) induced the migration and proliferation of cultured vascular smooth muscle cells (VSMCs), whereas treatment with EGCG, leptin siRNA, and c-Jun siRNA inhibited the migration and proliferation of VSMCs significantly. The EMSA shows that balloon injury increased AP-1-binding activity, and EGCG and c-Jun siRNA inhibited the AP-1-binding activity. Western blot and real-time RT-PCR analyses revealed similar results in intimal tissue samples. In summary, balloon injury induces leptin expression in the carotid artery of rats, and EGCG inhibits leptin expression through the JNK/AP-1 pathway and also attenuates neointimal formation.

Numerous studies suggest that in asymptomatic patients, routine follow-up CT is not indicated due to the insignificant findings found on these patients. A 53-year-old man, who denied any underlying disease before, underwent colonoscopy for routine health examination. Sudden onset of abdominal pain around left upper quarter was mentioned at our emergency department. Grade II spleen laceration was found on CT scan. Splenic injury was found few hours later on the day of colonoscopy. It might result from the extra tension between the spleen and splenic flexure which varies from different positions of patients.

Using a compact optically pumped silicon nanophotonic chip consisting of coupled silicon microrings, we generate photon pairs in multiple pairs of wavelengths around 1.55 μm. The wavelengths are tunable over several nanometers, demonstrating the capability to generate wavelength division multiplexed photon pairs at freely chosen telecommunications-band wavelengths.

CCN2 (connective tissue growth factor (CTGF/CCN2)) is a matricellular protein that utilizes integrins to regulate cell proliferation, migration and survival. The loss of CCN2 leads to perinatal lethality resulting from a severe chondrodysplasia. Upon closer inspection of Ccn2 mutant mice, we observed defects in extracellular matrix (ECM) organization and hypothesized that the severe chondrodysplasia caused by loss of CCN2 might be associated with defective chondrocyte survival. Ccn2 mutant growth plate chondrocytes exhibited enlarged endoplasmic reticula (ER), suggesting cellular stress. Immunofluorescence analysis confirmed elevated stress in Ccn2 mutants, with reduced stress observed in Ccn2 overexpressing transgenic mice. In vitro studies revealed that Ccn2 is a stress responsive gene in chondrocytes. The elevated stress observed in Ccn2-/- chondrocytes is direct and mediated in part through integrin α5. The expression of the survival marker NFκB and components of the autophagy pathway were decreased in Ccn2 mutant growth plates, suggesting that CCN2 may be involved in mediating chondrocyte survival. These data demonstrate that absence of a matricellular protein can result in increased cellular stress and highlight a novel protective role for CCN2 in chondrocyte survival. The severe chondrodysplasia caused by the loss of CCN2 may be due to increased chondrocyte stress and defective activation of autophagy pathways, leading to decreased cellular survival. These effects may be mediated through nuclear factor κB (NFκB) as part of a CCN2/integrin/NFκB signaling cascade.

The objective of the study was to investigate if hypoxia-inducible factor (HIF)-1α and connective tissue growth factor (CCN2) form a regulatory network in hypoxic nucleus pulposus (NP) cells. A decrease in CCN2 expression and proximal promoter activity was observed in NP cells after hypoxic culture. Analysis of both human and mouse CCN2 promoters using the JASPAR core database revealed the presence of putative hypoxia response elements. Transfection experiments showed that both promoter activities and CCN2 expression decreases in hypoxia in a HIF-1α-dependent fashion. Interestingly, deletion analysis and mutation of the hypoxia responsive elements individually or in combination resulted in no change in promoter activity in response to hypoxia or in response to HIF-1α, suggesting an indirect mode of regulation. Notably, silencing of endogenous CCN2 increased HIF-1α levels and its target gene expression, suggesting a role for CCN2 in controlling basal HIF-1α levels. On the other hand, treatment of cells with rCCN2 resulted in a decrease in the ability of HIF-1α transactivating domain to recruit co-activators and diminished target gene expression. Last, knockdown of CCN2 in NP cells results in a significant decrease in GAG synthesis and expression of AGGRECAN and COLLAGEN II. Immunohistochemical staining of intervertebral discs of Ccn2 null embryos shows a decrease in aggrecan. These findings reveal a negative feedback loop between CCN2 and HIF-1α in NP cells and demonstrate a role for CCN2 in maintaining matrix homeostasis in this tissue.

Integrated optical devices may replace bulk crystal or fiber based assemblies with a more compact and controllable photon pair and heralded single photon source and generate quantum light at telecommunications wavelengths. Here, we propose that a periodic waveguide consisting of a sequence of optical resonators can outperform conventional waveguides or single resonators and generate more than 1 Giga-pairs per second from a sub-millimeter-long room-temperature silicon device, pumped with only about 10 milliwatts of optical power. Furthermore, the spectral properties of such devices provide novel opportunities for chip-scale quantum light sources.

Silibinin is a flavonoid with antihepatotoxic properties and pleiotropic anticancer capabilities. This study investigated silibinin inhibition of cell invasion by down-regulating matrix metalloproteinase-2 (MMP-2) expression, via attenuation of activator protein-1 (AP-1) in IL-6-stimulated LoVo colon cancer cells. Western blot data showed that the expression of MMP-2 protein was reduced 1.6- or 1.7-fold over the control by treatment with silibinin or JNK inhibitor in the models. Similar results were revealed in zymography and confocal microscopy. Pretreatment with silibinin also abolished the binding activity of AP-1 and MMP-2 promoter activity via AP-1 binding, as observed by EMSA and luciferase assay. Finally, a [(3)H]-thymidine incorporation proliferation assay and cell migration assay demonstrated that silibinin inhibited IL-6-stimulated LoVo cell proliferation and invasion. Taken together, these data indicated that silibinin inhibits LoVo cell invasion with the reduction of MMP-2 presentation by attenuating AP-1 binding activity, suggesting a novel antimetastatic application for silibinin in colon cancer chemoprevention.

Constitutive activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway occurs commonly in cancer cells and endothelial cells, and contributes to angiogenesis. Wogonin is a compound with many biologically relevant properties. We previously reported that wogonin blocked IL-6-induced angiogenesis through suppression of VEGF expression, an important regulator of angiogenesis. However, the pathway involved in the suppressive effect of wogonin on IL-6-induced VEGF has not been completely clarified. This study aimed to investigate the molecular mechanisms participating in the suppression of wogonin on IL-6-induced VEGF in vitro, focusing on IL-6R/JAK1/STAT3/VEGF pathway. Both STAT3 siRNA and wogonin treatment resulted in an abolition of the expression of VEGF. Moreover, our data revealed that wogonin treatment after STAT3 knock-down did not further suppress VEGF expression. The addition of IL-6R siRNA or wogonin resulted in a decrease in the expression level of the phosphorylated JAK1 protein. Furthermore, wogonin significantly decreased the amount of phosphorylated STAT3. Finally, by EMSA, wogonin suppressed IL-6-induced STAT3 binding activity in a concentration-dependent manner. Taken together, our results show that wogonin suppresses IL-6-induced VEGF by modulating the IL-6R/JAK1/STAT3 signaling pathway. Based on this study, we suggest that wogonin may provide a new potential therapeutic option for treatment of IL-6-related pathological angiogenesis.

CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor β (TGFβ) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes.

Background: Along with obesity, physical inactivity, and family history of metabolic disorders, African American ethnicity is a risk factor for type 2 diabetes (T2D) in the United States. However, little is known about the differences in gene expression and transcriptomic profiles of blood in T2D between African Americans (AA) and Caucasians (CAU), and microarray analysis of peripheral white blood cells (WBCs) from these two ethnic groups will facilitate our understanding of the underlying molecular mechanism in T2D and identify genetic biomarkers responsible for the disparities., Results: A whole human genome oligomicroarray of peripheral WBCs was performed on 144 samples obtained from 84 patients with T2D (44 AA and 40 CAU) and 60 healthy controls (28 AA and 32 CAU). The results showed that 30 genes had significant difference in expression between patients and controls (a fold change of <-1.4 or >1.4 with a P value <0.05). These known genes were mainly clustered in three functional categories: immune responses, lipid metabolism, and organismal injury/abnormaly. Transcriptomic analysis also showed that 574 genes were differentially expressed in AA diseased versus AA control, compared to 200 genes in CAU subjects. Pathway study revealed that "Communication between innate and adaptive immune cells"/"Primary immunodeficiency signaling" are significantly down-regulated in AA patients and "Interferon signaling"/"Complement System" are significantly down-regulated in CAU patients., Conclusions: These newly identified genetic markers in WBCs provide valuable information about the pathophysiology of T2D and can be used for diagnosis and pharmaceutical drug design. Our results also found that AA and CAU patients with T2D express genes and pathways differently.

Objectives: The aim of the present study was to evaluate the performance of three indirect laryngoscopes, Truview EVO2 laryngoscope, Clarus Levitan fiberoptic stylet and AirwayScope AWS, in comparison with direct Macintosh laryngoscope (ML) when performed in normal and difficult airway scenarios., Methods: This prospective comparative study recruited 30 emergency physicians familiar with direct laryngoscopic intubation. Intubations were performed on manikin and were repeated twice for both scenarios. The primary end points were intubation time and rate of failed intubation. Glottis visualization was graded on Cormack and Lehane score and VAS., Results: In normal airway scenario: AWS had shortest intubation time (6.0 s) followed by ML (8.7 s); VAS score of ML and AWS was lower (easier to use) than the other two devices; Cormack and Lehane score was similar for all devices. In difficult airway scenario: AWS had shortest intubation time (5.9 s); VAS score of AWS was lower than the other three devices; TVL, FOS, AWS had better Cormack and Lehane score than ML. Intubation time, rate of failed intubation, and Cormack and Lehane score were similar between attempts in both scenarios. Learning effect was significant in FOS in both scenarios and in TVL in normal airway scenario., Conclusions: AWS performed best in normal and difficult airways. ML performed better than TVL and FOS in normal airways. Performances of ML, TVL and FOS were similar in difficult airways. Skills with AWS could be mastered rapidly. TVL and FOS required more practice to gain expertise., (© 2011 The Authors. EMA © 2011 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.)

We demonstrate four-wave mixing in silicon-on-insulator coupled-resonator optical waveguides consisting of 35 and 65 microring resonators, using a cw pump with coupled power below 20 mW and observed parametric conversion across more than 10 THz. The conversion efficiency is enhanced by +16 dB relative to a silicon straight waveguide of equivalent length, due to the slowing factor of the coupled-resonator structure., (© 2011 Optical Society of America)

We investigate diffraction of a white beam in a two-dimensional photonic crystal. Experimental and computational results for a halogen light source are presented. Applying equal-frequency surface analysis, we reproduce the experimental results by computer simulations. The white beam is modeled computationally as a sum of many circular rings; each ring is made up of many wavelength components. We also present computer simulations of the diffraction pattern for a fluorescent light source.

Abdominal abscess resulting from a perforated diverticulitis has never been reported as a cause of acute urinary retention. Our patient is the first case to be reported. Because of the atypical presentation, he was initially misdiagnosed and treated as having acute prostatitis. Emergency physicians should have a high index of suspicion. Detailed history, abdominal sonography, and digital examination are helpful in diagnosing this disease.