Negative index fishnet with nanopillars formed by direct nano-imprint lithography

In this paper we demonstrate the ability to fabricate fishnets by nanoimprinting directly into a pre-deposited three layer metal–dielectric–metal stack, enabling us to pattern large areas in two minutes. We have designed and fabricated two different fishnet structures of varying dimensions using this method and measured their resonant wavelengths in the near-infrared at 1.45 μm and 1.88 μm. An important by-product of directly imprinting into the metal–dielectric stack, without separation from the substrate, is the formation of rectangular nanopillars that sit within the rectangular apertures between the fishnet slabs. Simulations complement our measurements and suggest a negative refractive index real part with a magnitude of 1.6. Further simulations suggest that if the fishnet were to be detached from the supporting substrate a refractive index real part of 5 and FOM of 2.74 could be obtained

Marketing's 60/20 Pareto Law

We confirm our 2007 conclusions concerning the Pareto Law. Our conclusions are now supported by many other data sets, and independent analyses. It’s wrong to talk about an 80/20 law in marketing. A brand’s heaviest 20% of buyers generally contribute not much more than half of a brand’s sales, and these same buyers will contribute less in the following time period. Indeed, even for stable brands half of last year’s heavy buyers will then not even qualify to be in the top 20%, while the people who were light or non-brand buyers last year will contribute more to sales this year than they did last year. The exact sales contribution of the top 20% (a brand’s Pareto share metric) depends on the time period and some other technical decisions made by the person calculating the metric, and brand size and some category characteristics. But it’s reasonable to expect that almost half of your brand’s sales will always come from your very lightest 80% of buyers. It is also apparent that growth comes largely from these light, very light/non-brand buyers and so it would be foolhardy to ignore them

Trimming of silicon-on-insulator ring-resonators via localized laser annealing

We propose a post-fabrication trimming method for the silicon-on-insulator photonic platform based on localised laser annealing of hydrogen silsesquioxane (HSQ) cladding. The technique is fast, does not degrade the device performance, does not require additional fabrication steps, and can therefore be implemented at minimal cost. Here we experimentally demonstrated how the spectrum of a ring resonator can be shifted by over 1 nm by annealing a section of the device as short as 30 µm, corresponding to a change in the effective refractive index of ∼10−2. Modifications of both the HSQ refractive index and its chemical structure as a function of the annealing temperature are also discussed. Trimming of multi-ring resonators indicate that this technique can be effectively used for post-fabrication reconfiguration of complex photonic circuits or to compensate for the fabrication tolerances of a typical CMOS process

Mapping the sensitivity of split ring resonators using a localized analyte

Split ring resonator (SRR) based metamaterials have frequently been demonstrated for use as optical sensors of organic materials. This is made possible by matching the wavelength of the SRR plasmonic resonance with a molecular resonance of a specific analyte, which is usually placed on top of the metal structure. However, systematic studies of SRRs that identify the regions that exhibit a high electric field strength are commonly performed using simulations. In this paper we demonstrate that areas of high electric field strength, termed “hot-spots,” can be found by localizing a small quantity of organic analyte at various positions on or near the structure. Furthermore, the sensitivity of the SRR to the localized analyte can be quantified to determine, experimentally, suitable regions for optical sensing

Distinct patterns of neurodegeneration after TBI and in Alzheimer's disease

INTRODUCTION: Traumatic brain injury (TBI) is a dementia risk factor, with Alzheimer's disease (AD) more common following injury. Patterns of neurodegeneration produced by TBI can be compared to AD and aging using volumetric MRI. METHODS: A total of 55 patients after moderate to severe TBI (median age 40), 45 with AD (median age 69), and 61 healthy volunteers underwent magnetic resonance imaging over 2 years. Atrophy patterns were compared. RESULTS: AD patients had markedly lower baseline volumes. TBI was associated with increased white matter (WM) atrophy, particularly involving corticospinal tracts and callosum, whereas AD rates were increased across white and gray matter (GM). Subcortical WM loss was shared in AD/TBI, but deep WM atrophy was TBI-specific and cortical atrophy AD-specific. Post-TBI atrophy patterns were distinct from aging, which resembled AD. DISCUSSION: Post-traumatic neurodegeneration 1.9-4.0 years (median) following moderate-severe TBI is distinct from aging/AD, predominantly involving central WM. This likely reflects distributions of axonal injury, a neurodegeneration trigger. HIGHLIGHTS: We compared patterns of brain atrophy longitudinally after moderate to severe TBI in late-onset AD and healthy aging. Patients after TBI had abnormal brain atrophy involving the corpus callosum and other WM tracts, including corticospinal tracts, in a pattern that was specific and distinct from AD and aging. This pattern is reminiscent of axonal injury following TBI, and atrophy rates were predicted by the extent of axonal injury on diffusion tensor imaging, supporting a relationship between early axonal damage and chronic neurodegeneration

Long Non-Coding RNA Profiling of Pediatric Medulloblastoma

BACKGROUND: Medulloblastoma (MB) is one of the most common malignant cancers in children. MB is primarily classified into four subgroups based on molecular and clinical characteristics as (1) WNT (2) Sonic-hedgehog (SHH) (3) Group 3 (4) Group 4. Molecular characteristics used for MB classification are based on genomic and mRNAs profiles. MB subgroups share genomic and mRNA profiles and require multiple molecular markers for differentiation from each other. Long non-coding RNAs (lncRNAs) are more than 200 nucleotide long RNAs and primarily involve in gene regulation at epigenetic and post-transcriptional levels. LncRNAs have been recognized as diagnostic and prognostic markers in several cancers. However, the lncRNA expression profile of MB is unknown. METHODS: We used the publicly available gene expression datasets for the profiling of lncRNA expression across MB subgroups. Functional analysis of differentially expressed lncRNAs was accomplished by Ingenuity pathway analysis (IPA). RESULTS: In the current study, we have identified and validated the lncRNA expression profile across pediatric MB subgroups and associated molecular pathways. We have also identified the prognostic significance of lncRNAs and unique lncRNAs associated with each MB subgroup. CONCLUSIONS: Identified lncRNAs can be used as single biomarkers for molecular identification of MB subgroups that warrant further investigation and functional validation

Improved Therapy for Medulloblastoma: Targeting Hedgehog and PI3K-mTOR Signaling Pathways in Combination with Chemotherapy

Aberrant activation and interactions of hedgehog (HH) and PI3K/AKT/mTOR signaling pathways are frequently associated with high-risk medulloblastoma (MB). Thus, combined targeting of the HH and PI3K/AKT/mTOR pathways could be a viable therapeutic strategy to treat high-risk patients. Therefore, we investigated the anti-MB efficacies of combined HH inhibitor Vismodegib and PI3K-mTOR dual-inhibitor BEZ235 together or combined individually with cisplatin against high-risk MB. Using non-MYC- and MYC-amplified cell lines, and a xenograft mouse model, the in vitro and in vivo efficacies of these therapies on cell growth/survival and associated molecular mechanism(s) were investigated. Results showed that combined treatment of Vismodegib and BEZ235 together, or with cisplatin, significantly decreased MB cell growth/survival in a dose-dependent-fashion. Corresponding changes in the expression of targeted molecules following therapy were observed. Results demonstrated that inhibitors not only suppressed MB cell growth/survival when combined, but also significantly enhanced cisplatin-mediated cytotoxicity. Of these combinations, BEZ235 exhibited a significantly greater efficacy in enhancing cisplatin-mediated MB cytotoxicity. Results also demonstrated that the MYC-amplified MB lines showed a higher sensitivity to combined therapies compared to non-MYC-amplified cell lines. Therefore, we tested the efficacy of combined approaches against MYC-amplified MB growing in NSG mice. In vivo results showed that combination of Vismodegib and BEZ235 or their combination with cisplatin, significantly delayed MB tumor growth and increased survival of xenografted mice by targeting HH and mTOR pathways. Thus, our studies lay a foundation for translating these combined therapeutic strategies to the clinical setting to determine their efficacies in high-risk MB patients

Detection of Organic Molecules using Asymmetric Plasmonic Nanostructures

We demonstrate the fabrication and characterization of an array of plasmonic metamaterial nanostructures based on asymmetric split H (ASH) resonators on a zinc selenide substrate that produce plasmonic resonances matched with the molecular vibrations of an organic material. Estrogenic hormones; 17β-Estradiol (E2) and Estrone (E1) were chosen as analytes for coupling with the plasmonic resonances. The experimental results show there is a good match with the molecular bond resonances of the C-H, C=O and C=C observed in estrogen and we have also shown that it is possible to differentiate the molecular bond resonance spectrum of E2 in a mixture with E1