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Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in a single affected individual; in another, biopsy of skin lesions showed features of trichoblastoma. The combination of asymmetric clinical features, patchy skin manifestations, and neoplastic association previously led to the suggestion that this could be a mosaic condition, possibly involving hedgehog (Hh) signaling. Here, we show that CJS is caused by recurrent somatic mosaicism for a nonsynonymous variant in SMO (c.1234C>T [p.Leu412Phe]), encoding smoothened (SMO), a G-protein-coupled receptor that transduces Hh signaling. We identified eight mutation-positive individuals (two of whom had not been reported previously) with highly similar phenotypes and demonstrated varying amounts of the mutant allele in different tissues. We present detailed findings from brain MRI in three mutation-positive individuals. Somatic SMO mutations that result in constitutive activation have been described in several tumors, including medulloblastoma, ameloblastoma, and basal cell carcinoma. Strikingly, the most common of these mutations is the identical nonsynonymous variant encoding p.Leu412Phe. Furthermore, this substitution has been shown to activate SMO in the absence of Hh signaling, providing an explanation for tumor development in CJS. This raises therapeutic possibilities for using recently generated Hh-pathway inhibitors. In summary, our work uncovers the major genetic cause of CJS and illustrates strategies for gene discovery in the context of low-level tissue-specific somatic mosaicism.
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Anomalías Craneofaciales/etiología , Intestinos/anomalías , Mutación/genética , Anomalías Cutáneas/etiología , Receptor Smoothened/genética , Sindactilia/etiología , Preescolar , Anomalías Craneofaciales/patología , Femenino , Humanos , Lactante , Recién Nacido , Intestinos/patología , Masculino , Transducción de Señal , Anomalías Cutáneas/patología , Sindactilia/patologíaRESUMEN
Dowling-Degos disease (DDD) is an autosomal-dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation. We previously identified loss-of-function mutations in KRT5 but were only able to detect pathogenic mutations in fewer than half of our subjects. To identify additional causes of DDD, we performed exome sequencing in five unrelated affected individuals without mutations in KRT5. Data analysis identified three heterozygous mutations from these individuals, all within the same gene. These mutations, namely c.11G>A (p.Trp4*), c.652C>T (p.Arg218*), and c.798-2A>C, are within POGLUT1, which encodes protein O-glucosyltransferase 1. Further screening of unexplained cases for POGLUT1 identified six additional mutations, as well as two of the above described mutations. Immunohistochemistry of skin biopsies of affected individuals with POGLUT1 mutations showed significantly weaker POGLUT1 staining in comparison to healthy controls with strong localization of POGLUT1 in the upper parts of the epidermis. Immunoblot analysis revealed that translation of either wild-type (WT) POGLUT1 or of the protein carrying the p.Arg279Trp substitution led to the expected size of about 50 kDa, whereas the c.652C>T (p.Arg218*) mutation led to translation of a truncated protein of about 30 kDa. Immunofluorescence analysis identified a colocalization of the WT protein with the endoplasmic reticulum and a notable aggregating pattern for the truncated protein. Recently, mutations in POFUT1, which encodes protein O-fucosyltransferase 1, were also reported to be responsible for DDD. Interestingly, both POGLUT1 and POFUT1 are essential regulators of Notch activity. Our results furthermore emphasize the important role of the Notch pathway in pigmentation and keratinocyte morphology.
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Glucosiltransferasas/genética , Hiperpigmentación/genética , Mutación , Enfermedades Cutáneas Genéticas/genética , Enfermedades Cutáneas Papuloescamosas/genética , Adolescente , Adulto , Exoma , Femenino , Estudio de Asociación del Genoma Completo , Heterocigoto , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Masculino , Persona de Mediana Edad , Linaje , Conformación Proteica , Análisis de Secuencia de ADN , Piel/patología , Adulto JovenRESUMEN
The atom sets an ultimate scaling limit to Moore's law in the electronics industry. While electronics research already explores atomic scales devices, photonics research still deals with devices at the micrometer scale. Here we demonstrate that photonic scaling, similar to electronics, is only limited by the atom. More precisely, we introduce an electrically controlled plasmonic switch operating at the atomic scale. The switch allows for fast and reproducible switching by means of the relocation of an individual or, at most, a few atoms in a plasmonic cavity. Depending on the location of the atom either of two distinct plasmonic cavity resonance states are supported. Experimental results show reversible digital optical switching with an extinction ratio of 9.2 dB and operation at room temperature up to MHz with femtojoule (fJ) power consumption for a single switch operation. This demonstration of an integrated quantum device allowing to control photons at the atomic level opens intriguing perspectives for a fully integrated and highly scalable chip platform, a platform where optics, electronics, and memory may be controlled at the single-atom level.
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Sporadic sebaceous gland hyperplasia (SGH) is a benign skin lesion, with a high prevalence in the general population. Although SGH has been attributed to both extrinsic and intrinsic factors, the underlying genetic changes have not yet been characterized. Recently, HRAS and KRAS mutations have been identified in sebaceous naevus, a hamartoma sharing histological characteristics with SGH. Therefore we screened 43 SGH for activating mutations in RAS genes and other oncogenes. We identified a wide spectrum of mutually exclusive activating HRAS (8/43), KRAS (11/43) and EGFR mutations (7/31) in altogether 60% of the lesions investigated. A RAS and EGFR wildtype status was found in 15 normal sebaceous glands in the head and neck area. Our findings indicate that activating HRAS, KRAS and EGFR mutations play a major role in the pathogenesis of sporadic SGH. These results support the concept that SGH is a true benign neoplasm rather than a reactive hyperplasia.
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Receptores ErbB/genética , Mutación/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Enfermedades de las Glándulas Sebáceas/genética , Glándulas Sebáceas/metabolismo , Adolescente , Adulto , Biopsia , Análisis Mutacional de ADN , Femenino , Genes ras/genética , Cabeza , Humanos , Hiperplasia/genética , Inmunohistoquímica , Masculino , Persona de Mediana Edad , CuelloRESUMEN
A scheme for the direct conversion of millimeter and THz waves to optical signals is introduced. The compact device consists of a plasmonic phase modulator that is seamlessly cointegrated with an antenna. Neither high-speed electronics nor electronic amplification is required to drive the modulator. A built-in enhancement of the electric field by a factor of 35,000 enables the direct conversion of millimeter-wave signals to the optical domain. This high enhancement is obtained via a resonant antenna that is directly coupled to an optical field by means of a plasmonic modulator. The suggested concept provides a simple and cost-efficient alternative solution to conventional schemes where millimeter-wave signals are first converted to the electrical domain before being up-converted to the optical domain.
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We examine the possibility of optimizing the emission and the near-field signal of apertureless silver and gold tips by using an optimized non-periodic grating. In this context, we consider the emission of a single quantum emitter in close proximity to optimized tips. Additionally, we study the far-field coupling efficiency of a tightly focused beam to the near-field of the tip. The gain in performance is compared with unstructured tips and the comparison with a pure plasmonic excitation of an unstructured tip is discussed. The optimized, structured tips show a significant enhancement of the total decay rate, as a result of standing plasmonic waves between the grating and the tip apex, leading to a resonant behavior. The resonances can be explained well with a Fabry-Pérot model. Furthermore, the total decay rate of an emitter near a structured tip can also be decreased as compared to an unstructured tip, when the grating is shifted from the optimal resonant position. The proposed scheme represents an interesting novel nano-antenna, for which the resonance as well as the directivity can be controlled by the grating.
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Ultra-fast, continuously tunable true-time delays are key components in many microwave and optical communications subsystems. In this paper, we introduce and demonstrate a new implementation method of a continuously tunable true-time delay featuring a settling time in the order of tens of picoseconds. Our solution relies on the splitting and combining of complementary phased shifted spectra (CPSS). It works for large bandwidth signals, has a low complexity, offers moderate losses, and can be fully integrated.
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BACKGROUND: Sentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival. METHODS AND FINDINGS: We analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (nâ=â52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3-123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61-2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ≤3 had an increased risk of dying from melanoma compared to patients with DCCDâ=â0 (pâ=â0.04; hazard ratio 1.63, 95% CI 1.02-2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories. CONCLUSIONS: Cancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.
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Ganglios Linfáticos/patología , Melanoma/mortalidad , Melanoma/secundario , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/mortalidad , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Distribución de Chi-Cuadrado , Niño , Hibridación Genómica Comparativa , Femenino , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Melanoma/química , Melanoma/genética , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Neoplasias Cutáneas/química , Neoplasias Cutáneas/genética , Factores de Tiempo , Adulto JovenRESUMEN
CHILD syndrome is an acronym signifying congenital hemidysplasia with ichthyosiform nevus and limb defects. A 27-year-old woman presented with chronic verrucous and hyperkeratotic skin lesions involving the left genital area, left hand and left foot since childhood. The histopathologic findings were consistent with verruciform xanthoma. In correlation with the clinical picture of a linear lesion, the diagnosis of CHILD nevus was made. Subsequent genetic analysis identified a germline c.324C>T (p.A105V) NSDHL mutation and confirmed a diagnosis of CHILD syndrome. This syndrome can be associated with only minimal clinical symptoms. The anatomical distribution of the lesions, a static clinical course and the typical histopathologic features of a CHILD nevus can serve as the clue to a diagnosis of CHILD syndrome in such cases.
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Anomalías Múltiples/patología , Enfermedades Genéticas Ligadas al Cromosoma X/patología , Eritrodermia Ictiosiforme Congénita/patología , Deformidades Congénitas de las Extremidades/patología , Enfermedades de la Piel/patología , Xantomatosis/patología , 3-Hidroxiesteroide Deshidrogenasas/genética , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/terapia , Adulto , Diagnóstico Diferencial , Femenino , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Enfermedades Genéticas Ligadas al Cromosoma X/terapia , Humanos , Eritrodermia Ictiosiforme Congénita/diagnóstico , Eritrodermia Ictiosiforme Congénita/genética , Eritrodermia Ictiosiforme Congénita/terapia , Deformidades Congénitas de las Extremidades/diagnóstico , Deformidades Congénitas de las Extremidades/genética , Deformidades Congénitas de las Extremidades/terapia , Mutación Missense/genética , Nevo/patología , Nevo Pigmentado/patología , Síndrome , Resultado del TratamientoRESUMEN
Seborrheic keratosis (SK) represents a frequent epidermal skin tumor. Although lacking a malignant potential, these tumors reveal multiple oncogenic mutations. A previous study identified activating mutations in 89% of SK, particularly in FGFR3 and PIK3CA genes. The aim of this study was to identify further oncogenic mutations in human SK. Therefore, we screened for mutations in EGFR, FGFR2, PIK3R1, HRAS, KRAS, and NRAS genes using both Sanger sequencing of selected exons and a multiplex SNaPshot assay in 58 SK of 14 patients. We identified a somatic EGFR p.L858R mutation in 1 SK. Furthermore, the HRAS mutations p.G13R (2/58 SK) and p.Q61L (2/58 SK) were found. These mutations have not been described in human SK yet. In addition, 1 SK revealed the KRAS p.G12V mutation, which has already been reported in SK. No mutations were detected in FGFR2, PIK3R1, and NRAS genes. The results of this study suggest that activating mutations of EGFR, HRAS, and KRAS contribute to the pathogenesis of human SK, although at a lower frequency than FGFR3 and PIK3CA mutations. FGFR2, PIK3R1, and NRAS mutations obviously do not have a significant role in the development of SK.
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Biomarcadores de Tumor/genética , Receptores ErbB/genética , Queratosis Seborreica/genética , Mutación , Oncogenes , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Fosfatidilinositol 3-Quinasa Clase Ia , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Fosfatidilinositol 3-Quinasas/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
We investigate numerically a Scanning Near field Optical Microscope (SNOM) that uses a Parabolic Mirror (PM) to focus a radially polarized beam on a metallic tip. In order to overcome problems--like overestimated near fields or resonances--that arise when only considering finite tips, we have introduced a semi-infinite continuation of the tip, which incorporates the analytic solution of surface waves. For a realistic modeling the right description of the incident field is essential and we have complied with this requirement by a Bessel expansion of the focal fields, which is also applicable to an aplanatic objective. The established numerical model is used for an extensive study of model parameters like tip geometry, illumination directions and tip materials (Ag, Au, Al and Cu). Compared with a simplified inverted microscope configuration, the PM setup shows an increased field enhancement (factor of 2-2.5), which can be ascribed to the efficient coupling of the exciting field to tip surface plasmons.
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Diseño Asistido por Computadora , Lentes , Iluminación/instrumentación , Metales , Microscopía de Sonda de Barrido/instrumentación , Modelos Teóricos , Reconocimiento de Normas Patrones Automatizadas/métodos , Simulación por Computador , Diseño de Equipo , Análisis de Falla de Equipo , Microscopía de Sonda de Barrido/métodosRESUMEN
We demonstrate a reliable fabrication method to produce plasmonic dipole nanoantennas with gap values in the range of 3.5-20 nm. The method combines electron beam lithography to create gold nanorods and helium focused ion beam milling to cut the gaps. Results show a reproducibility within 1 nm. Scattering spectra of antennas show a red shift of resonance wavelengths and an increase of the intensity of resonance peaks with a decrease of the gap size, which is in agreement with finite element simulations. The measured refractive index sensitivity was about 250 nm per refractive index unit for antennas with gap values below 5 nm.
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BACKGROUND: Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations. METHODS: This study screened 72 KEN for activating mutations in RAS genes and other oncogenes. RESULTS: Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation. CONCLUSION: These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.
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Epidermis/patología , Genes ras , Queratinocitos/patología , Mosaicismo , Mutación , Nevo/genética , Neoplasias Cutáneas/genética , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Fosfatidilinositol 3-Quinasas/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Adulto JovenRESUMEN
Malignant tumors result from the accumulation of genetic alterations in oncogenes and tumor suppressor genes. Much less is known about the genetic changes in benign tumors. Seborrheic keratoses (SK) are very frequent benign human epidermal tumors without malignant potential. We performed a comprehensive mutational screen of genes in the FGFR3-RAS-MAPK and phosphoinositide 3-kinase (PI3K)-AKT pathways from 175 SK, including multiple lesions from each patient. SK commonly harbored multiple bona fide oncogenic mutations in FGFR3, PIK3CA, KRAS, HRAS, EGFR, and AKT1 oncogenes but not in tumor suppressor genes TSC1 and PTEN. Despite the occurrence of oncogenic mutations and the evidence for downstream ERK/MAPK and PI3K pathway signaling, we did not find induction of senescence or a DNA damage response. Array comparative genomic hybridization (aCGH) analysis revealed that SK are genetically stable. The pattern of oncogenic mutations and X chromosome inactivation departs significantly from randomness and indicates that spatially independent lesions from a given patient share a clonal relationship. Our findings show that multiple oncogenic mutations in the major signaling pathways involved in cancer are not sufficient to drive malignant tumor progression. Furthermore, our data provide clues on the origin and spread of oncogenic mutations in tissues, suggesting that apparently independent (multicentric) adult benign tumors may have a clonal origin.
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Queratosis Seborreica/genética , Queratosis Seborreica/patología , Mutación/genética , Oncogenes/genética , Apoptosis/genética , Biomarcadores de Tumor , Proliferación Celular , Senescencia Celular , Células Clonales , Análisis Mutacional de ADN , Pruebas Genéticas , Genoma Humano/genética , Genotipo , Humanos , Queratosis Seborreica/enzimología , Proteínas Quinasas Activadas por Mitógenos/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/metabolismo , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteínas Supresoras de Tumor/metabolismo , Proteínas ras/genéticaRESUMEN
During high-velocity atmospheric entries, space vehicles can be exposed to strong electromagnetic radiation from ionized gas in the shock layer. Glassy carbon (GC) and silicon carbide (SiC) are candidate thermal protection materials due to their high melting point and also their good thermal and mechanical properties. Based on data from shock tube experiments, a significant fraction of radiation at hypersonic entry conditions is in the frequency range from 215 to 415 THz. We propose and analyze SiC and GC photonic structures to increase the reflection of radiation in that range. For this purpose, we performed numerical optimizations of various structures using an evolutionary strategy. Among the considered structures are layered, porous, woodpile, inverse opal and guided-mode resonance structures. In order to estimate the impact of fabrication inaccuracies, the sensitivity of the reflectivity to structural imperfections is analyzed. We estimate that the reflectivity of GC photonic structures is limited to 38% in the aforementioned range, due to material absorption. However, GC material can be effective for photonic reflection of individual, strong spectral line. SiC on the other hand can be used to design a good reflector for the entire frequency range.
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Compuestos Inorgánicos de Carbono/química , Carbono/química , Radiación Cósmica , Protección Radiológica/instrumentación , Refractometría/instrumentación , Compuestos de Silicona/química , Nave Espacial/instrumentación , Atmósfera , Campos Electromagnéticos , Diseño de Equipo , Análisis de Falla de Equipo , Vidrio/química , Luz , Dispersión de RadiaciónRESUMEN
Line-defect photonic crystal waveguides exhibit severe propagation losses if they are implemented in semiconductor heterostructures with a weak refractive index contrast. We present, for what we believe is the first time, experimental structures for which we have evidence that fabrication imperfections are not the limiting factor in terms of propagation losses. We demonstrate a loss figure of 335±5 dB/cm, which is an improvement by a factor of about 2 with respect to state-of-the-art values. Simulations show that even lower losses can be obtained with different waveguide geometries. In other words, the dominant loss mechanism is related to the waveguide design, and losses are not expected to decrease upon further optimization of the fabrication process.
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Biosensing with nanoholes is one of the most promising applications of nanoplasmonic devices. The sensor properties, however, are complex due to coupled resonances through propagating and localized surface plasmons. This Full Paper demonstrates experimental and simulation studies on different plasmonic hole systems, namely various patterns of circular holes in gold films. In contrast to most previous work, here, the challenging situation of optically thin films is considered. The refractive-index-sensing properties, such as sensitive locations in the nanostructure and sensitive spectral features, are investigated. The multiple multipole program provides the complete field distribution in the nanostructure for different wavelengths. It is shown that the spectral feature most sensitive to refractive-index changes is the extinction minimum, rather than the maximum. The results are consistent with theory for perfect electrical conductors. The spectral response is investigated for molecular adsorption at different positions inside or outside a hole. Furthermore, the optical properties of nanohole arrays with long-range and short-range order are compared and found to demonstrate remarkable similarities. Our results help to predict the resonance wavelengths of nanoholes with arbitrary patterns, including short-range order. The results presented here are highly important since they extend and challenge several aspects of the current understanding of plasmon resonances in nanohole arrays. These theoretical models, simulation results, and experimental data together help provide the understanding necessary for the development of efficient biomolecular analysis tools based on metallic nanoholes.
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Técnicas Biosensibles/métodos , Metales/química , Nanoestructuras/química , Resonancia por Plasmón de Superficie/métodos , Oro/químicaRESUMEN
BACKGROUND: Epidermal nevi (EN) represent benign congenital skin lesions following the lines of Blaschko. They result from genetic mosaicism, and activating FGFR3 and PIK3CA mutations have been implicated. CASE PRESENTATION: We report a female patient with a systemic keratinocytic nevus also involving the oral mucosa. Molecular genetic analysis revealed a mosaicism of the FGFR3 hotspot mutation R248C in the EN lesions of the skin and of the oral mucosa. The detection of the R248C mutation in a proportion of blood leukocytes and a slight scoliosis suggest an EN syndrome. CONCLUSIONS: Our results show that activating FGFR3 mutations can also affect the oral mucosa and that extracutaneous manifestations of EN syndrome can be subtle. We highlight the theoretical risk of the patient having an offspring with thanatophoric dysplasia as gonadal mosaicism for the R248C mutation cannot be excluded.
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Epidermis/patología , Mucosa Bucal/patología , Mutación Missense/genética , Nevo/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Femenino , Humanos , MosaicismoRESUMEN
A Scanning Nearfield Optical Microscope (SNOM) tip with partial metallic cladding is presented. For its design, a very demanding 2D eigenvalue analysis of an optical waveguide with material and radiation losses is carried out by the Multiple Multipole Program (MMP) and by the Finite Element Method (FEM). These simulations require some special tricks that are outlined. The computed 2D MMP and FEM results are compared and discussed. This 2D analysis is followed by a full 3D FEM analysis of the SNOM tip. The obtained 3D results confirm the corresponding 2D predictions. Important conclusions regarding the guiding capabilities of the chosen structure and the efficiency of the applied numerical methods are presented.
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A multilayer approach (MA) and modified boundary conditions (MBC) are proposed as fast and efficient numerical methods for the design of 1D photonic structures with rough interfaces. These methods are applicable for the structures, composed of materials with an arbitrary permittivity tensor. MA and MBC are numerically validated on different types of interface roughness and permittivities of the constituent materials. The proposed methods can be combined with the 4x4 scattering matrix method as a field solver and an evolutionary strategy as an optimizer. The resulted optimization procedure is fast, accurate, numerically stable and can be used to design structures for various applications.