Linearly polarized emission from CdSe/CdS core-in-rod nanostructures: Effects of core position.

Semiconductor nanocrystals with an anisotropic morphology exhibit unique properties, most notably their linear polarization. The colloidal growth of semiconductor nanorods with core dots inside, also referred to as dot-in-rod (DIR) structure, has enabled the synthesis of anisotropic nanocrystals with better stability and controllable fluorescence polarization. In this study, we synthesize CdSe/CdS DIR nanocrystals, in which the position of the CdSe core particle can be controlled by using different ligand compositions during the CdS growth. Varying the core position within the DIR structure, e.g., from the center to the end of the DIR particles, results in a change in the degree of linear polarization. When the core is positioned at the center of the nanorod, the linear polarization turns out to be higher compared with tip-core DIRs. Time-resolved photoluminescence analysis reveals that the center-core DIRs have higher electron-hole interaction than tip-core DIRs because of weak uniaxial strain in center-core DIR that arises from lattice dislocations at the interface to relieve accumulated strain.

The KL genetic polymorphisms Associated with type 2 diabetes Mellitus.

Growing number of research studies have shown that an anti-ageing gene Klotho (KL) is closely associated with Type 2 Diabetes Mellitus (T2DM). In this study, the association is genetically analyzed with single nucleotide polymorphism (SNP) of KL found in T2DM case of an Asian cohort. KL SNP information was obtained from a big database of the Korean Association Resource (KARE) from which 20 KL SNPs were available. Statistical analyses were conducted based on the 3 genetic models, such as additive, dominant, and recessive. Of the 20 KL SNPs, 12 SNPs were found to be significantly associated with T2DM in both of additive and dominant models. Odds ratios of the KL SNPs indicate increased susceptibility to T2DM in additive and dominant models. Significant association of KL with T2DM was further analyzed using imputed KL SNPs from HapMap reference data of the Eastern population. The statistically significant KL SNPs including the imputed SNPs distributed evenly over the KL gene area. The results in this study suggest klotho is a major player in the development of T2DM and the KL SNPs found in the case could be a risk marker of T2DM in the cohort.

Polarized Electroluminescence Emission in High-Performance Quantum Rod Light-Emitting Diodes via the Langmuir-Blodgett Technique.

Due to their anisotropic structure, quantum rods (QRs) feature unique properties that differ from quantum dots, such as suppression of non-radiative Auger recombination and linearly polarized light emission. Despite many potential advantages, the progress of QR-based light-emitting diodes (QR-LEDs) is left behind due to the difficulty in aligning QRs. In this study, polarized electroluminescence emission is reported in high-performance QR-LEDs by employing the Langmuir-Blodgett (LB) technique. The adoption of the LB technique successfully produces a highly dense and smooth QR film with a high degree of alignment. As a result, the aligned QR films exhibit polarized photoluminescence emission with a degree of linear polarization of 2.1. Advantageous features of the LB technique, such as nondestructiveness, precise thickness control, and the nonnecessity of an additional matrix material, allow to fabricate QR-LEDs with the same procedure as the standard spin coating-based scheme. The device is fabricated via the LB technique, which shows excellent device performance, such as the low turn-on voltage of 1.8 V, peak luminance of 56 287 cd m-2 , and peak external quantum efficiency (EQE) of 10.33%. Furthermore, these devices clearly exhibit an indication of polarized electroluminescence emission, which opens new opportunities for QRs in display technologies.

A Meta-Analysis of the Associations Between the ATP-Binding Cassette Transporter ABCA1 R219K (rs2230806) Polymorphism and the Risk of Type 2 Diabetes in Asians.

Asians have relatively low insulin secretion capacity and readily develop type 2 diabetes mellitus (T2DM) when insulin resistant. For that reason, insufficient insulin secretion is critical factor for Asians at the early stage of T2DM. ATP-binding cassette transporter1 (ABCA1) is a membrane protein responsible for cholesterol efflux and its function is also important for secreting insulin in pancreatic ß-cells. Given the importance of its role, different polymorphisms of ABCA1 gene might contribute differently to the development of T2DM. Here, we analyzed the association between a variant form of ABCA1 gene called ABCA1 rs2230806 and the prevalence of T2DM in a large sample size by pooling all of the case-control studies published. Relevant case-control studies were identified by searching PubMed, EMBASE, Cochrane Library, Korean scientific database, Chinese medical databases, and the Indian medical database. The association was evaluated using five genetic models such as the allelic (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) genetic models. Heterogeneity of each genetic model was determined by the I2 test. A total of eight studies (7 published studies and one data set from the Korean Genetic Epidemiology Study) were eligible, satisfying Hardy-Weinberg equilibrium and included 2755 T2DM patients (case) and 16 635 nondiabetic subjects (control). All subjects in the studies were Asians. Each genetic model exhibited heterogeneity. In all genetic models, ABCA1 rs2230806 had a significant association with prevalence of T2DM: AG (OR=0.78, 95% CI: 0.61-0.98), RG (OR=0.72, 95% CI: 0.51-1.03), DG (OR=0.73, 95% CI: 0.55-0.97), HMG (OR=0.62, 95% CI: 0.41-0.96), and HTG (OR=0.78, 95% CI: 0.61-0.99). There was no single study that changed the overall effects in allelic genetic model with random effects. No publication bias existed in any models except the RG model. In conclusion, middle-aged and elderly adults with the minor allele of ABCA1 rs2230806 will have a lower risk of T2DM. This is the first meta-analysis to evaluate the association in Asians.

Mimicking of a Transient Protein Binding in Mammalian Cells Using a Functionalized Magnetic Nanoparticle.

Identification of binding proteins is essential for uncovering biological mechanisms of functional small molecules and proteins, but if the binding is transient it may be quite difficult to find the binding proteins using cell extracts that is commonly used for target identification methods. Usually sticky proteins bind to bait molecule first as long as cell extracts are used. In such cases, it would be very difficult to find transient binding proteins. The best way to circumvent the non-specific bindings might be putting bait molecules into living cells and collects the baits after a certain period of incubation time. In here, we evaluated a new target identification method in living cells with magnetic nanoparticles. For the proof-of-concept, we reproduced a transient interaction between peroxisomal proteins and Pex5p, the peroxisome guiding protein. To that end, carboxyl group-functionalized magnetic nanoparticles were labeled with peroxisomal targeting signal 1 (PTS1) peptide to mimic peroxisomal proteins. The PTS1-labeled magnetic nanoparticles translocated into peroxisomes in the mammalian cells, during which they transiently interacted with Pex5p. These results were confirmed using a fluorescence microscope and "in cell pull-down" experiments. Conclusively, the transient interaction between peroxisomal proteins and Pex5p in cells was reproduced with the PTS1-labeled magnetic nanoparticles in living cells by showing its sequential translocation into peroxisomes and transient interaction with Pex5p in parallel. This result indicates that a magnetic nanoparticle can be a useful tool for analyzing dynamic change of interacting proteins to a functional molecule in living cells depending on circumstances the cells encounter.

Diminished Lipid Raft SNAP23 Increases Blood Pressure by Inhibiting the Membrane Fluidity of Vascular Smooth-Muscle Cells.

Synaptosomal-associated protein 23 (SNAP23) is involved in microvesicle trafficking and exocytosis in various cell types, but its functional role in blood pressure (BP) regulation has not yet been defined. Here, we found that lipid raft SNAP23 expression was much lower in vascular smooth-muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) than in those from normotensive Wistar-Kyoto (WKY) rats. This led us to investigate the hypothesis that this lower expression may be linked to the spontaneous hypertension found in SHR. The expression level of lipid raft SNAP23 and the fluidity in the plasma membrane of VSMCs were lower in SHR than in WKY rats. Cholesterol content in the VSMC membrane was higher, but the secreted cholesterols found in VSMC-conditioned medium and in the blood serum were lower in SHR than in WKY rats. SNAP23 knockdown in WKY rat VSMCs reduced the membrane fluidity and increased the membrane cholesterol level. Systemic overexpression of SNAP23 in SHR resulted in an increase of cholesterol content in their serum, a decrease in cholesterol in their aorta and the reduction of their BP. Our findings suggest that the low expression of the lipid raft SNAP23 in VSMCs might be a potential cause for the characteristic hypertension of SHR.

Detection of circulating tumor cell-specific markers in breast cancer patients using the quantitative RT-PCR assay.

BACKGROUND: Breast cancer is a highly prevalent disease among women worldwide. While the expression of certain proteins within breast cancer tumors is used to determine the prognosis and select therapies, additional markers need to be identified. Circulating tumor cells (CTCs) are constituent cells that have detached from a primary tumor to circulate in the bloodstream. CTCs are considered the main source of breast cancer metastases; therefore, detection of CTCs could be a promising diagnostic method for metastatic breast cancer. METHODS: In this study, the CircleGen CTC RT-qDx assay was used to analyze the mRNA expression levels of six CTC-specific markers including EpCAM, CK19, HER2, Ki67, hTERT, and vimentin with a total of 692 peripheral whole blood samples from 221 breast cancer patients and 376 healthy individuals. RESULTS: This assay showed high specificity with multiple markers; none of the healthy controls were detected positive, whereas 21.7 and 14 % of breast cancer patients were positive for EpCAM and CK19, respectively. Of the 221 breast cancer patients, 84 (38 %), 46 (20.8 %), 83 (37.6 %), and 39 (17.6 %) were positively for HER2, Ki67, hTERT, and vimentin mRNA, respectively. Of the 84 patients who were HER2 positive, nine (4 %) were also positive for EpCAM, CK19, Ki67, hTERT, and vimentin. Of the 139 breast cancer patients who were HER2 negative, 65 (29.1 %) were negative for EpCAM, CK19, Ki67, hTERT, and vimentin. Furthermore, the EpCAM-positive population decreased from 21.5 to 8.3 % after completion of anti-tumor treatment (TP4). Similarly, the CK19, HER2, hTERT, and vimentin positives also decreased from 13.9 to 9.5 %, from 37.7 to 21.4 %, from 37.2 to 33.3 %, and from 17.5 to 14.3 %, respectively, after completion of anti-tumor treatment. In contrast, the Ki67 positives increased from 20.6 to 41.7 % after completion of anti-tumor treatment. CONCLUSIONS: mRNA overexpression of six CTC-specific markers was detected by the CircleGen CTC RT-qDx assay with high specificity, and the obtained mRNA expression levels of CTC-specific markers might provide useful criteria to select appropriate anti-tumor treatment for breast cancer patients.

FXR-induced secretion of FGF15/19 inhibits CYP27 expression in cholangiocytes through p38 kinase pathway.

Cholangiocytes, bile duct lining cells, actively adjust the amount of cholesterol and bile acids in bile through expression of enzymes and channels involved in transportation and metabolism of the cholesterol and bile acids. Herein, we report molecular mechanisms regulating bile acid biosynthesis in cholangiocytes. Among the cytochrome p450 (Cyp) enzymes involved in bile acid biosynthesis, sterol 27-hydroxylase (Cyp27) that is the rate-limiting enzyme for the acidic pathway of bile acid biosynthesis expressed in cholangiocytes. Expression of other Cyp enzymes for the basic bile acid biosynthesis was hardly detected. The Cyp27 expression was negatively regulated by a hydrophobic bile acid through farnesoid X receptor (FXR), a nuclear receptor activated by bile acid ligands. Activated FXR exerted the negative effects by inducing an expression of fibroblast growth factor 15/19 (FGF15/19). Similar to its repressive function against cholesterol 7α-hydroxylase (Cyp7a1) expression in hepatocytes, secreted FGF15/19 triggered Cyp27 repression in cholangiocytes through interaction with its cognate receptor fibroblast growth factor receptor 4 (FGFR4). The involvements of FXR and FGFR4 for the bile acid-induced Cyp27 repression were confirmed in vivo using knockout mouse models. Different from the signaling in hepatocytes, wherein the FGF15/19-induced repression signaling is mediated by c-Jun N-terminal kinase (JNK), FGF15/19-induced Cyp27 repression in cholangiocytes was mediated by p38 kinase. Thus, the results collectively suggest that cholangiocytes may be able to actively regulate bile acid biosynthesis in cholangiocytes and even hepatocyte by secreting FGF15/19. We suggest the presence of cholangiocyte-mediated intrahepatic feedback loop in addition to the enterohepatic feedback loop against bile acid biosynthesis in the liver.

Evaluation of a quantitative RT-PCR assay to detect HER2 mRNA overexpression for diagnosis and selection of trastuzumab therapy in breast cancer tissue samples.

Breast cancer patients who have a positive result for HER2 overexpression are commonly treated with Herceptin, a HER2-targeted therapy. In the present study, the BrightGen HER2 RT-qDx (Syantra, Calgary, Canada), which is based on a one-tube nested RT-qPCR method that detects HER2 mRNA overexpression, was clinically evaluated in a total of 237 formalin-fixed paraffin-embedded (FFPE) tissue samples from breast cancer patients. Among the 38 HER2 positive samples, which were determined via IHC/FISH methods, 13 samples out of 16 (81.3%) that were IHC2+/FISH+ and 22 samples out of 22 (100%) that were IHC3+ have been decided positive for HER2 expression via the RT-qPCR method. The true positivity and false positivity results for the RT-qPCR were 92% (35/38) and 2% (1/65), respectively. The concordance between RT-qPCR and IHC results and RT-qPCR and IHC/FISH was 87.2% and 92.1%, respectively. Conclusively, the BrightGen HER2 RT-qDx may be a reliable and convenient method that can supplement traditional IHC and FISH methods for efficient use of trastuzumab.

Impact of Alternating-Current Operation on All-Inorganic Quantum Dot Light-Emitting Diodes.

In colloidal quantum dot light-emitting diodes (QD-LEDs), replacing organic hole transport layers (HTLs) with their inorganic counterparts is expected to yield distinct advantages due to their inherent material robustness. However, despite the promising characteristics of all-inorganic QD-LEDs, some challenges persist in achieving stable operation; for example, the electron overflow toward the inorganic HTL and charge accumulation within working devices return a temporal inconsistency in device characteristics. To address these challenges, we propose an operational approach that employs an alternating-current (AC) in all-inorganic QD-LEDs. We carry out comprehensive studies on the optoelectrical characteristics of all-inorganic QD-LEDs under direct-current (DC) or AC operation and demonstrate that AC operation can facilitate efficient charge carrier recombination within the QD emissive layer, leading to improved device efficiency and temporally invariant optoelectronic characteristics. Leveraging the intrinsic material robustness of inorganic charge transport layers (CTLs), our current study suggests a promising pathway toward enhancing the performance and stability of QD-LEDs, particularly for futuristic display applications.

Growth Control of InP/ZnSe Heterostructured Nanocrystals.

The morphology of heterostructured semiconductor nanocrystals (h-NCs) dictates the spatial distribution of charge carriers and their recombination dynamics and/or transport, which are the main performance indicators of photonic applications utilizing h-NCs. The inability to control the morphology of heterovalent III-V/II-VI h-NCs composed of heavy-metal-free elements hinders their practical use. As a case study of III-V/II-VI h-NCs, the growth control of ZnSe epilayers on InP NCs is demonstrated here. The anisotropic morphology in InP/ZnSe h-NCs is attributed to the facet-dependent energy costs for the growth of ZnSe epilayers on different facets of InP NCs, and effective chemical means for controlling the growth rates of ZnSe on different surface planes are demonstrated. Ultimately, this article capitalizes on the controlled morphology of InP/ZnSe h-NCs to expand their photophysical characteristics from stable and pure emission to environment-sensitive one, which will facilitate their use in a variety of photonic applications.

Strain-graded quantum dots with spectrally pure, stable and polarized emission.

Structural deformation modifies the bandgap, exciton fine structure and phonon energy of semiconductors, providing an additional knob to control their optical properties. The impact can be exploited in colloidal semiconductor quantum dots (QDs), wherein structural stresses can be imposed in three dimensions while defect formation is suppressed by controlling surface growth kinetics. Yet, the control over the structural deformation of QDs free from optically active defects has not been reached. Here, we demonstrate strain-graded CdSe-ZnSe core-shell QDs with compositionally abrupt interface by the coherent pseudomorphic heteroepitaxy. Resulting QDs tolerate mutual elastic deformation of varying magnitudes at the interface with high structural fidelity, allowing for spectrally stable and pure emission of photons at accelerated rates with near unity luminescence efficiency. We capitalize on the asymmetric strain effect together with the quantum confinement effect to expand emission envelope of QDs spanning the entire visible region and exemplify their use in photonic applications.

Liver X receptor ß and peroxisome proliferator-activated receptor δ regulate cholesterol transport in murine cholangiocytes.

UNLABELLED: Nuclear receptors (NRs) play crucial roles in the regulation of hepatic cholesterol synthesis, metabolism, and conversion to bile acids, but their actions in cholangiocytes have not been examined. In this study, we investigated the roles of NRs in cholangiocyte physiology and cholesterol metabolism and flux. We examined the expression of NRs and other genes involved in cholesterol homeostasis in freshly isolated and cultured murine cholangiocytes and found that these cells express a specific subset of NRs, including liver X receptor (LXR) ß and peroxisome proliferator-activated receptor (PPAR) δ. Activation of LXRß and/or PPARδ in cholangiocytes induces ATP-binding cassette cholesterol transporter A1 (ABCA1) and increases cholesterol export at the basolateral compartment in polarized cultured cholangiocytes. In addition, PPARδ induces Niemann-Pick C1-like L1 (NPC1L1), which imports cholesterol into cholangiocytes and is expressed on the apical cholangiocyte membrane via specific interaction with a peroxisome proliferator-activated response element (PPRE) within the NPC1L1 promoter. CONCLUSION: We propose that (1) LXRß and PPARδ coordinate NPC1L1/ABCA1-dependent vectorial cholesterol flux from bile through cholangiocytes and (2) manipulation of these processes may influence bile composition with important applications in cholestatic liver disease and gallstone disease, two serious health concerns for humans.

Mislocalization and inhibition of acetyl-CoA carboxylase 1 by a synthetic small molecule.

Chromeceptin is a synthetic small molecule that inhibits insulin-induced adipogenesis of 3T3-L1 cells and impairs the function of IGF2 (insulin-like growth factor 2). The molecular target of this benzochromene derivative is MFP-2 (multifunctional protein 2). The interaction between chromeceptin and MFP-2 activates STAT6 (signal transducer and activator of transcription 6), which subsequently induces IGF inhibitory genes. It was not previously known how the binding of chromeceptin with MFP-2 blocks adipogenesis and activates STAT6. The results of the present study show that the chromeceptin-MFP-2 complex binds to and inhibits ACC1 (acetyl-CoA carboxylase 1), an enzyme important for the de novo synthesis of malonyl-CoA and fatty acids. The formation of this ternary complex removes ACC1 from the cytosol and sequesters it in peroxisomes under the guidance of Pex5p (peroxisomal-targeting signal type 1 receptor). As a result, chromeceptin impairs fatty acid synthesis from acetate where ACC1 is a rate-limiting enzyme. Overexpression of malonyl-CoA decarboxylase or siRNA (small interfering RNA) knockdown of ACC1 results in STAT6 activation, suggesting a role for malonyl-CoA in STAT6 signalling. The molecular mechanism of chromeceptin may provide a new pharmacological approach to selective inhibition of ACC1 for biological studies and pharmaceutical development.

Coherent heteroepitaxial growth of I-III-VI2 Ag(In,Ga)S2 colloidal nanocrystals with near-unity quantum yield for use in luminescent solar concentrators.

Colloidal Ag(In,Ga)S2 nanocrystals (AIGS NCs) with the band gap tunability by their size and composition within visible range have garnered surging interest. High absorption cross-section and narrow emission linewidth of AIGS NCs make them ideally suited to address the challenges of Cd-free NCs in wide-ranging photonic applications. However, AIGS NCs have shown relatively underwhelming photoluminescence quantum yield (PL QY) to date, primarily because coherent heteroepitaxy has not been realized. Here, we report the heteroepitaxy for AIGS-AgGaS2 (AIGS-AGS) core-shell NCs bearing near-unity PL QYs in almost full visible range (460 to 620 nm) and enhanced photochemical stability. Key to the successful growth of AIGS-AGS NCs is the use of the Ag-S-Ga(OA)2 complex, which complements the reactivities among cations for both homogeneous AIGS cores in various compositions and uniform AGS shell growth. The heteroepitaxy between AIGS and AGS results in the Type I heterojunction that effectively confines charge carriers within the emissive core without optically active interfacial defects. AIGS-AGS NCs show higher extinction coefficient and narrower spectral linewidth compared to state-of-the-art heavy metal-free NCs, prompting their immediate use in practicable applications including displays and luminescent solar concentrators (LSCs).

Deactivation of STAT6 through serine 707 phosphorylation by JNK.

Signal transducer and activator of transcription 6 (STAT6), which plays a critical role in immune responses, is activated by interleukin-4 (IL-4). Activity of STAT family members is regulated primarily by tyrosine phosphorylations and possibly also by serine phosphorylations. Here, we report a previously undescribed serine phosphorylation of STAT6, which is activated by cell stress or by the pro-inflammatory cytokine, interleukin-1ß (IL-1ß). Our analyses suggest that Ser-707 is phosphorylated by c-Jun N-terminal kinase (JNK). Phosphorylation decreases the DNA binding ability of IL-4-stimulated STAT6, thereby inhibiting the transcription of STAT6-responsive genes. Inactivation of STAT6 by JNK-dependent Ser-707 phosphorylation may be one mechanism of controlling the balance between IL-1ß and IL-4 signals.

Incorporation of functionalized gold nanoparticles into nanofibers for enhanced attachment and differentiation of mammalian cells.

BACKGROUND: Electrospun nanofibers have been widely used as substrata for mammalian cell culture owing to their structural similarity to natural extracellular matrices. Structurally consistent electrospun nanofibers can be produced with synthetic polymers but require chemical modification to graft cell-adhesive molecules to make the nanofibers functional. Development of a facile method of grafting functional molecules on the nanofibers will contribute to the production of diverse cell type-specific nanofiber substrata. RESULTS: Small molecules, peptides, and functionalized gold nanoparticles were successfully incorporated with polymethylglutarimide (PMGI) nanofibers through electrospinning. The PMGI nanofibers functionalized by the grafted AuNPs, which were labeled with cell-adhesive peptides, enhanced HeLa cell attachment and potentiated cardiomyocyte differentiation of human pluripotent stem cells. CONCLUSIONS: PMGI nanofibers can be functionalized simply by co-electrospinning with the grafting materials. In addition, grafting functionalized AuNPs enable high-density localization of the cell-adhesive peptides on the nanofiber. The results of the present study suggest that more cell type-specific synthetic substrata can be fabricated with molecule-doped nanofibers, in which diverse functional molecules are grafted alone or in combination with other molecules at different concentrations.

Chemically-defined scaffolds created with electrospun synthetic nanofibers to maintain mouse embryonic stem cell culture under feeder-free conditions.

Embryonic stem cells (ESCs) are useful resources for drug discovery, developmental biology and disease studies. Cellular microenvironmental cues play critical roles in regulating ESC functions, but it is challenging to control them with synthetic components. Nanofibers hold a potential to create artificial cellular cues for controlling cell adhesion and cell-cell interactions. Mouse ESC (mESC) were cultured on electrospun nanofibers made from polymethylglutarimide (PMGI), which is a synthetic thermoplastic polymer stable under culture conditions. Both topology and the density of PMGI nanofibers were key factors. mESCs on nanofibers had a growth rate comparable to those cultured conventionally and retained their pluripotency. Furthermore, self-renewed ESCs differentiated into all three germ layers thereby providing a reliable way to expand mESCs without feeder cells.

Impact of Morphological Inhomogeneity on Excitonic States in Highly Mismatched Alloy ZnSe1-XTeX Nanocrystals.

ZnSe1-XTeX nanocrystals (NCs) are promising photon emitters with tunable emission across the violet to orange range and near-unity quantum yields. However, these NCs suffer from broad emission line widths and multiple exciton decay dynamics, which discourage their practicable use. Here, we explore the excitonic states in ZnSe1-XTeX NCs and their photophysical characteristics in relation to the morphological inhomogeneity of highly mismatched alloys. Ensemble and single-dot spectroscopic analysis of a series of ZnSe1-XTeX NC samples with varying Te ratios coupled with computational calculations shows that, due to the distinct electronegativity between Se and Te, nearest-neighbor Te pairs in ZnSe1-XTeX alloys create localized hole states spectrally distributed approximately 130 meV above the 1Sh level of homogeneous ZnSe1-XTeX NCs. This forms spatially separated excitons (delocalized electron and localized hole in trap), accounting for both inhomogeneous and homogeneous line width broadening with delayed recombination dynamics. Our results identify photophysical characteristics of excitonic states in NCs made of highly mismatched alloys and provide future research directions with potential implications for photonic applications.