Surface Bragg gratings of proteins patterned on integrated waveguides for (bio)chemical analysis.

The incorporation of biomacromolecules onto silicon waveguiding microstructures constitutes a growing trend that pushes towards compact and miniaturized biosensing systems. This paper presents the integration of one-dimensional periodic nanostructures of proteins on the surface of micrometric silicon waveguides for transducing binding events between biomacromolecules. The study demonstrates this new bioanalytical principle by experimental results and theoretical calculations, and proves that rib waveguides (1--1.6-µm width) together with protein gratings (495--515-nm period) display suitable spectral responses for this optical biosensing system. Protein assemblies of bovine serum albumin are fabricated on the surface of silicon nitride waveguides, characterized by electron microscopy, and their response is measured by optical frequency domain reflectometry along the fabrication process and the subsequent stages of the biorecognition assays. Detection and quantification limits of 0.3 and 3.7 µg·mL-1, respectively, of specific antibodies are inferred from experimental dose-response curves. Among other interesting features, the results of this study point towards new miniaturized and integrated sensors for label-free bioanalysis.

Discovery of tight-binding competitive inhibitors of dipeptidyl peptidase IV.

Dipeptidyl peptidase IV (DPP-IV, EC 3.4.14.5) is an abundant serine aminopeptidase that preferentially cleaves N-terminal Xaa-Pro or Xaa-Ala dipeptides from oligopeptides. Inhibitors of DPP-IV activity are used for treating type 2 diabetes mellitus and other diseases. DPP-IV is also involved in tumor progression. We identified four new non-peptide tight-binding competitive inhibitors of porcine DPP-IV by virtual screening and enzymatic assays. Molecular docking simulations supported the competitive behavior, and the selectivity of one of the compounds in the DPP-IV family. Since three of these inhibitors are also aminopeptidase N (APN) inhibitors, we tested their impact on APN+/DPP-IV+ and DPP-IV+ human tumor cells' viability. Using kinetic assays, we determined that HL-60 tumor cells express both APN and DPP-IV activities and that MDA-MB-231 tumor cells express DPP-IV activity. The inhibitors had a slight inhibitory effect on human HEK-293 cell viability but reduced the viability of APN+/DPP-IV+ and DPP-IV+ human tumor cells more potently. Remarkably, the intraperitoneal injection of these compounds inhibited DPP-IV activity in rat brain, liver, and pancreas. In silico studies suggested inhibitors binding to serum albumin contribute to blood-brain barrier crossing. The spectrum of action of some of these compounds may be useful for niche applications.

Advanced and versatile interferometric technique for the characterization of photonic integrated devices.

Adaptable and complex optical characterization of photonic integrated devices, permitting to unearth possible design and fabrication errors in the different workflow steps are highly desired in the community. Here, we propose a technique capable of resolving full optical amplitude and phase response, in both frequency and time domains, of a photonic integrated device. It relies on optical frequency domain interferometry and makes use of a novel integrated architecture; a 3-way interferometer enabling single input and single output detection. We derive the test structure design rules and provide extensive experimental validation in silicon nitride and silicon on insulator technologies, by testing relevant devices such as arrayed waveguide grating, Mach-Zehnder interferometers, and ring resonators. Horizontal and vertical chip coupling, different external setup arrangements, and the optical dispersion de-embedding inherent to the technique are demonstrated. Finally, we discuss why this characterization approach might lay the groundwork of a standard testing tool for photonic integrated devices.

Highly specific and rapid molecular detection of Candida glabrata in clinical samples.

The most common nosocomial fungal infections are caused by several species of Candida, of which Candida glabrata is the second most frequently isolated species from bloodstream infections. C. glabrata displays relatively high minimal inhibitory concentration values (MIC) to the antifungal fluconazole and is associated with high mortality rates. To decrease mortality rates, the appropriate treatment must be administered promptly. C. glabrata contains in its genome several non-identical copies of species-specific sequences. We designed three pairs of C. glabrata-specific primers for endpoint PCR amplification that align to these species-specific sequences and amplify the different copies in the genome. Using these primers, we developed a fast, sensitive, inexpensive, and highly specific PCR-based method to positively detect C. glabrata DNA in a concentration-dependent manner from mixes of purified genomic DNA of several Candida species, as well as from hemocultures and urine clinical samples. This tool can be used for positive identification of C. glabrata in the clinic.

BIO bragg gratings on microfibers for label-free biosensing.

Discovering nanoscale phenomena to sense biorecognition events introduces new perspectives to exploit nanoscience and nanotechnology for bioanalytical purposes. Here we present Bio Bragg Gratings (BBGs), a novel biosensing approach that consists of diffractive structures of protein bioreceptors patterned on the surface of optical waveguides, and tailored to transduce the magnitude of biorecognition assays into the intensity of single peaks in the reflection spectrum. This work addresses the design, fabrication, and optimization of this system by both theoretical and experimental studies to explore the fundamental physicochemical parameters involved. Functional biomolecular gratings are fabricated by microcontact printing on the surface of tapered optical microfibers, and their structural features were characterized. The transduction principle is experimentally demonstrated, and its quantitative bioanalytical prospects are assessed in a representative immunoassay, based on patterned protein probes and selective IgG targets, in label-free conditions. This biosensing system involves appealing perspectives to avoid unwanted signal contributions from non-specific binding, herein investigated in human serum samples. The work also proves how the optical response of the system can be easily tuned, and it provides insights into the relevance of this feature to conceive multiplexed BBG systems capable to perform multiple label-free biorecognition assays in a single device.

Reconfigurable reflective arrayed waveguide grating using optimization algorithms.

In this paper we report the experimental realization of a reconfigurable reflective arrayed waveguide grating on silicon nitride technology, using optimization algorithms borrowed from machine learning applications. A dozen of band-shape responses, as well as a spectral resolution change, are demonstrated in the optical telecom C-band, alongside a proof of operation of the same device in the O-band. In the context of programmable and reconfigurable integrated photonics, this building block supports multi-wavelength/band spectral shaping of optical signals that can serve to multiple applications.

α1ACT Is Essential for Survival and Early Cerebellar Programming in a Critical Neonatal Window.

Postnatal cerebellar development is a precisely regulated process involving well-orchestrated expression of neural genes. Neurological phenotypes associated with CACNA1A gene defects have been increasingly recognized, yet the molecular principles underlying this association remain elusive. By characterizing a dose-dependent CACNA1A gene deficiency mouse model, we discovered that α1ACT, as a transcription factor and secondary protein of CACNA1A mRNA, drives dynamic gene expression networks within cerebellar Purkinje cells and is indispensable for neonatal survival. Perinatal loss of α1ACT leads to motor dysfunction through disruption of neurogenesis and synaptic regulatory networks. However, its elimination in adulthood has minimal effect on the cerebellum. These findings shed light on the critical role of α1ACT in facilitating neuronal development in both mice and humans and support a rationale for gene therapies for calcium-channel-associated cerebellar disorders. Finally, we show that bicistronic expression may be common to the voltage-gated calcium channel (VGCC) gene family and may help explain complex genetic syndromes.

Integrated Optic Sensing Spectrometer: Concept and Design.

In this paper the concept and design of an integrated optical device featuring evanescent field sensing and spectrometric analysis is presented. The device, termed integrated optics sensing spectrometer (IOSS), consists of a modified arrayed waveguide grating (AWG) which arms are engineered into two sets having different focal points. Half of the arms are exposed to the outer media, while the other half are left isolated, thus the device can provide both sensing and reference spectra. Two reference designs are provided for the visible and near-infrared wavelengths, aimed at the determination of the concentration of known solutes through absorption spectroscopy.

Integrated optical frequency domain reflectometry device for characterization of complex integrated devices.

Because of the demand for advanced measurement systems in the field of modern photonic integrated circuits, optical frequency domain reflectometry (OFDR) is a robust technique for characterizing design-to-fabrication deviations. In this paper we report an OFDR device where the interferometric part is monolithically integrated along with the device under test. We discuss the advantages in terms of compactness and performance, and the importance of the incorporated dispersion de-embedding mechanism. Experimental validation is carried out by interrogating an arrayed waveguide grating on a silicon nitride platform. The results establish the proposed device as a first step in the quest for a universal test structure for integrated devices.

A Code Division Design Strategy for Multiplexing Fiber Bragg Grating Sensing Networks.

In this paper, an encoding strategy is used to design specialized fiber Bragg grating (FBG) sensors. The encoding of each sensor requires two binary codewords to define the amplitude and phase patterns of each sensor. The combined pattern (amplitude and phase) makes each sensor unique and therefore two or more sensors can be identified under spectral overlapping. In this way, we add another dimension to the multiplexing of FBG sensors, obtaining an increase factor 'n' to enhance the number of sensors that the system can handle. A proof-of-concept scenario with three sensors was performed, including the manufacturing of the encoded sensors. Furthermore, an interrogation setup to detect the sensors central wavelength was proposed and its working principle was theoretically developed. Results show that total identification of the central wavelength is performed under spectral overlapping between the manufactured sensors, achieving a three-time improvement of the system capacity. Finally, the error due to overlapping between the sensors was assessed obtaining approximately 3 pm, which makes the approach suitable for use in real measurement systems.

Silicon Nitride Photonic Integration Platforms for Visible, Near-Infrared and Mid-Infrared Applications.

Silicon nitride photonics is on the rise owing to the broadband nature of the material, allowing applications of biophotonics, tele/datacom, optical signal processing and sensing, from visible, through near to mid-infrared wavelengths. In this paper, a review of the state of the art of silicon nitride strip waveguide platforms is provided, alongside the experimental results on the development of a versatile 300 nm guiding film height silicon nitride platform.

Mammalian Polycistronic mRNAs and Disease.

Our understanding of gene expression has come far since the 'one-gene one-polypeptide' hypothesis proposed by Beadle and Tatum. In this review, we address the gradual recognition that a growing number of polycistronic genes, originally discovered in viruses, are being identified within the mammalian genome, and that these may provide new insights into disease mechanisms and treatment. We carried out a systematic literature review identifying 13 mammalian genes for which there is evidence for polycistronic expression via translation through an internal ribosome entry site (IRES). Although the canonical mechanism of translation initiation has been studied extensively, here we highlight a process of noncanonical translation, IRES-mediated translation, that is a growing source for understanding complex inheritance, the elucidation of disease mechanisms, and the discovery of novel therapeutic targets. Identification of additional polycistronic genes may provide new insights into disease therapy and allow for new discoveries of both translational and disease mechanisms.

Increased postoperative complications after protective ileostomy closure delay: An institutional study.

AIM: To study the morbidity and complications associated to ileostomy reversal in colorectal surgery patients, and if these are related to the time of closure. METHODS: A retrospective analysis of 93 patients, who had undergone elective ileostomy closure between 2009 and 2013 was performed. Demographic, clinical and surgical variables were reviewed for analysis. All complications were recorded, and classified according to the Clavien-Dindo Classification. Statistical univariate and multivariate analysis was performed, setting a P value of 0.05 for significance. RESULTS: The patients had a mean age of 60.3 years, 58% male. The main procedure for ileostomy creation was rectal cancer (56%), and 37% had received preoperative chemo-radiotherapy. The average delay from creation to closure of the ileostomy was 10.3 mo. Postoperative complications occurred in 40% of the patients, with 1% mortality. The most frequent were ileus (13%) and wound infection (13%). Pseudomembranous colitis appeared in 4%. Increased postoperative complications were associated with delay in ileostomy closure (P = 0.041). Male patients had more complications (P = 0.042), mainly wound infections (P = 0.007). Pseudomembranous colitis was also associated with the delay in ileostomy closure (P = 0.003). End-to-end intestinal anastomosis without resection was significantly associated with postoperative ileus (P = 0.037). CONCLUSION: Although closure of a protective ileostomy is a fairly common surgical procedure, it has a high rate of complications, and this must be taken into account when the indication is made. The delay in stoma closure can increase the rate of complications in general, and specifically wound infections and colitis.

Chromatic dispersion compensation and Coherent Direct-Sequence OCDMA operation on a single super structured FBG.

We have proposed, fabricated and demonstrated experimentally a set of Coherent Direct Sequence-OCDMA en/decoders based on Super Structured Fiber Bragg Gratings (SSFBGs) which are able to compensate the fiber chromatic dispersion at the same time that they perform the en/decoding task. The proposed devices avoid the use of additional dispersion compensation stages reducing system complexity and losses. This performance was evaluated for 5.4, 11.4 and 16.8 km of SSMF. The twofold performance was verified in Low Reflectivity regime employing only one GVD compensating device at decoder or sharing out the function between encoder and decoder devices. Shared functionality requires shorter SSFBGs designs and also provides added flexibility to the optical network design. Moreover, dispersion compensated en/decoders were also designed into the High Reflectivity regime employing synthesis methods achieving more than 9 dB reduction of insertion loss for each device.

WDM-Coherent OCDMA over one single device based on short chip Super Structured Fiber Bragg Gratings.

We theoretically propose and demonstrate experimentally a Coherent Direct Sequence OCDMA en/decoder for multi-channel WDM operation based on a single device. It presents a broadband spectral envelope and a periodic spectral pattern that can be employed for en/decoding multiple sub-bands simultaneously. Multi-channel operation is verified experimentally by means of Multi-Band Super Structured Fiber Bragg Gratings with binary phase encoded chips fabricated with 1mm inter-chip separation that provides 4x100 GHz ITU sub-band separation at 1.25 Gbps. The WDM-OCDMA system verification was carried out employing simultaneous encoding of four adjacent sub-bands and two different OCDMA codes.

Tunable microwave photonic filter free from baseband and carrier suppression effect not requiring single sideband modulation using a Mach-Zenhder configuration.

We present a full theoretical and experimental analysis of a novel all-optical microwave photonic filter combining a mode-locked fiber laser and a Mach-Zenhder structure in cascade to a 2x1 electro-optic modulator. The filter is free from the carrier suppression effect and thus it does not require single sideband modulation. Positive and negative coefficients are obtained inherently in the system and the tunability is achieved by controlling the optical path difference of the Mach-Zenhder structure.

Microwave photonic filters using low-cost sources featuring tunability, reconfigurability and negative coefficients.

We propose and experimentally demonstrate two configurations of photonic filters for the processing of microwave signals featuring tunability, reconfigurability and negative coefficients based on the use of low cost optical sources. The first option is a low power configuration based on spectral slicing of a broadband source. The second is a high power configuration based on fixed lasers. Tunability, reconfigurability and negative coefficients are achieved by means of a MEMS cross-connect, a variable optical attenuator array and simple 2x2 switches respectively.

The cross waveguide grating: proposal, theory and applications.

In this paper a novel grating-like integrated optics device is proposed, the Cross Waveguide Grating (XWG). The device is based upon a modified configuration of a traditional Arrayed Waveguide Grating (AWG). The Arrayed Waveguides part is changed, as detailed along this document, giving the device both the ability of multi/demultiplexing and power splitting/coupling. Design examples and transfer function simulations show good agreement with the presented theory. Finally, some of the envisaged applications are outlined.

Optical microwave filter based on spectral slicing by use of arrayed waveguide gratings.

We have experimentally demonstrated a new optical signal processor based on the use of arrayed waveguide gratings. The structure exploits the concept of spectral slicing combined with the use of an optical dispersive medium. The approach presents increased flexibility from previous slicing-based structures in terms of tunability, reconfiguration, and apodization of the samples or coefficients of the transversal optical filter.

Microwave photonic filters with negative coefficients based on phase inversion in an electro-optic modulator.

We report on a novel technical approach to the implementation of photonic rf filters that is based on the pi phase inversion that a rf modulating signal suffers in an electro-optic Mach-Zehnder modulator, which depends on whether the positive or the negative linear slope of the signal's modulation transfer function is employed. Experimental evidence is provided of the implementation of filters with negative coefficients that shows excellent agreement with results predicted by the theory.