Integrated High-Temporal-Resolution and High-Density Subretinal Prosthesis Using a Correlated Double-Sampling Technique.

This paper presents a 1600-pixel integrated neural stimulator with a correlated double-sampling readout (DSR) circuit for a subretinal prosthesis. The retinal stimulation chip inserted beneath the photoreceptor layer comprises an array of an active pixel sensor (APS) and biphasic pulse shaper. The DSR circuit achieves a high signal-to-noise ratio (SNR) of the APS with a short integration time to simultaneously improve the temporal and spatial resolutions of restored vision. This DSR circuit is adopted along with a 5 × 5-pixel tile, which reduces pixel size and improves the SNR by increasing the area occupied by storage capacitors. Moreover, a low-mismatch reference generator enables a low standard deviation between individual pulse shapers. The 1600-pixel retinal chip, fabricated using the 0.18 µm 1P6M CMOS process, occupies a total area of 4.3 mm × 3.3 mm and dissipates an average power of 3.4 mW; this was demonstrated by determining the stimulus current patterns corresponding to the illuminations of an LCD projector. Experimental results show that the proposed high-density stimulation array chip can achieve a high temporal resolution owing to its short integration time.

Interdisciplinary Health Care Evaluation Instruments: A Review of Psychometric Evidence.

Teamwork among health care professionals has been found to improve patient outcomes and reduce burnout. Surveys from individual team members are often used to measure the effectiveness of teamwork performance, as they provide an efficient way to capture various constructs of teamwork. This allows evaluators to better understand team functioning, areas of strength, and to identify potential areas for improvement. However, the majority of published surveys are yet to be validated. We conducted a review of psychometric evidence to identify instruments frequently used in practice and identified in the literature. The databases searched included MEDLINE, EMBASE, CINAHL, and PsycINFO. After excluding duplicates and irrelevant articles, 15 articles met the inclusion criteria for full assessment. Seven surveys were validated and most frequently identified in the literature. This review aims to facilitate the selection of instruments that are most appropriate for research and clinical practice. More research is required to develop surveys that better reflect the current reality of teamwork in our evolving health system, including a greater consideration for patient as team members. Additionally, more research is needed to encompass an increasing development of team assessment tools.

Ambient Light Rejection Integrated Circuit for Autonomous Adaptation on a Sub-Retinal Prosthetic System.

This paper introduces an ambient light rejection (ALR) circuit for the autonomous adaptation of a subretinal implant system. The sub-retinal implants, located beneath a bipolar cell layer, are known to have a significant advantage in spatial resolution by integrating more than a thousand pixels, compared to epi-retinal implants. However, challenges remain regarding current dispersion in high-density retinal implants, and ambient light induces pixel saturation. Thus, the technical issues of ambient light associated with a conventional image processing technique, which lead to high power consumption and area occupation, are still unresolved. Thus, it is necessary to develop a novel image-processing unit to handle ambient light, considering constraints related to power and area. In this paper, we present an ALR circuit as an image-processing unit for sub-retinal implants. We first introduced an ALR algorithm to reduce the ambient light in conventional retinal implants; next, we implemented the ALR algorithm as an application-specific integrated chip (ASIC). The ALR circuit was fabricated using a standard 0.35-µm CMOS process along with an image-sensor-based stimulator, a sensor pixel, and digital blocks. As experimental results, the ALR circuit occupies an area of 190 µm2, consumes a power of 3.2 mW and shows a maximum response time of 1.6 s at a light intensity of 20,000 lux. The proposed ALR circuit also has a pixel loss rate of 0.3%. The experimental results show that the ALR circuit leads to a sensor pixel (SP) being autonomously adjusted, depending on the light intensity.

Author Correction: How wind drives the correlation between leaf shape and mechanical properties.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

How localized force spreads on elastic contour feathers.

Birds can experience localized forces against their bodies due to impact against solid objects (like a branch or another bird) or water (during plunge-dives or landings). In this study, we hypothesize that densely packed contour feathers around the bird body would spread localized impact force while diving and maintaining plumage integrity. To test the hypothesis, we performed experiments with individual feathers and elastic beams, and developed a theoretical model to determine the response of feathers during the dive. First, we used a micro computed tomography scanner to characterize the internal structure of the contour feather from a northern gannet and calculate Young's modulus of feathers sampled from different parts of the body. This value was found to be of the order of 109 Pa for feathers from chest and belly. Second, we model the feathers as elastic beams taking into account their pre-curvature and non-uniform cross-section. Results from our experiments with polycarbonate beams suggest that the interaction of feathers on the skin patch redistributes the force, thereby reducing the impact on any particular area of the skin. Finally, a theoretical model of multiple overlaying feathers is proposed to quantify the spreading of impact force on the skin of the bird body which shows that the pressure on the skin at the impact point can be reduced by as much as three times the pressure if feathers had been absent.

Collaborative health research partnerships: a survey of researcher and knowledge-user attitudes and perceptions.

BACKGROUND: Integrated knowledge translation describes the process of partnered research between different stakeholders with the goal of producing research that ultimately achieves a greater impact when put into practice. A better understanding of research partnerships and integrated knowledge translation has implications for future partnerships and collaborative initiatives in practice. Our research describes and expands upon previous work done to identify barriers and attitudes toward collaboration in the context of research funding opportunities that required researcher-knowledge-user partnerships. METHODS: A survey was sent out to researchers funded by the Canadian Institutes of Health Research and knowledge-users who worked collaboratively on their research projects. There were two mirror versions of the survey, one for researchers and one for knowledge-users. Descriptive statistics, χ2 analysis and Mann-Whitney U analysis were used to understand the processes, barriers, perceived impact and sustainability of the partnerships. RESULTS: The results revealed that, although there were differences in the roles of researchers and knowledge-users, both groups felt very positive towards their partnerships. Some of the barriers identified as inhibiting effective partnerships were resource constraints (funding/time) and differences in contribution and involvement amongst team members. Despite these barriers, both researchers and knowledge-users felt that the partnership was not only sustainable, but also helped create an impact. CONCLUSIONS: Our results provide useful information for funding agencies launching opportunities requiring or encouraging collaborative research projects between researchers and knowledge-users.

An Intrafascicular Neural Interface With Enhanced Interconnection for Recording of Peripheral Nerve Signals.

For implantable devices, Parylene C (hereafter referred to as Parylene) has shown promising properties such as flexibility, biocompatibility, biostability, and good barrier properties. Parylene-based flexible interconnection cable (FIC) was previously developed to connect a flexible penetrating microelectrode array (FPMA) with a recording system. However, Parylene-based FIC was difficult to handle and prone to damage during the implantation surgery because of its low mechanical strength. To improve the mechanical properties of the FIC, we suggest a mechanically enhanced flexible interconnection cable (enhanced FIC) obtained using a combination of Parylene and polyimide. To investigate the long-term stability of the enhanced FIC, Parylene-only FIC, and enhanced FIC were tested and their mechanical properties were compared under an accelerated aging condition. During the course of six months of soaking, the maximum strength of the enhanced FIC remained twice as high as that of the Parylene-only FIC throughout the experiment, although the mechanical strength of both FICs decreased over time. To show the capability of the enhanced FIC in the context of nerve signal recording as a part of a neural interfacing device, it was assembled together with the FPMA and custom-made wireless recording electronics. We demonstrated the feasibility of the enhanced FIC in an in vivo application by recording acute nerve signals from canine sciatic nerves.

Fully Integrated Light-Sensing Stimulator Design for Subretinal Implants.

This paper presents a fully integrated photodiode-based low-power and low-mismatch stimulator for a subretinal prosthesis. It is known that a subretinal prosthesis achieves 1600-pixel stimulators on a limited single-chip area that is implanted beneath the bipolar cell layer. However, the high-density pixels cause high power dissipation during stimulation and high fabrication costs because of special process technologies such as the complementary metal-oxide semiconductor CMOS image sensor process. In addition, the many residual charges arising from the high-density pixel stimulation have deleterious effects, such as tissue damage and electrode corrosion, on the retina tissue. In this work, we adopted a switched-capacitor current mirror technique for the single-pixel stimulator (SPStim) that enables low power consumption and low mismatch in the subretinal device. The customized P+/N-well photodiode used to sense the incident light in the SPStim also reduces the fabrication cost. The 64-pixel stimulators are fabricated in a standard 0.35-µm CMOS process along with a global digital controller, which occupies a chip area of 4.3 × 3.2 mm² and are ex-vivo demonstrated using a dissected pig eyeball. According to measured results, the SPStim accomplishes a maximum biphasic pulse amplitude of 143 µA, which dissipates an average power of 167 µW in a stimulation period of 5 ms, and an average mismatch of 1.12 % between the cathodic and anodic pulses.

How wind drives the correlation between leaf shape and mechanical properties.

From a geometrical point of view, a non-sessile leaf is composed of two parts: a large flat plate called the lamina, and a long beam called the petiole which connects the lamina to the branch/stem. While wind is exerting force (e.g. drag) on the lamina, the petiole undergoes twisting and bending motions. To survive in harsh abiotic conditions, leaves may have evolved to form in different shapes, resulting from a coupling between the lamina geometry and the petiole mechanical properties. In this study, we measure the shape of laminae from 120 simple leaf species (no leaflets). Leaves of the same species are found to be geometrically similar regardless of their size. From tensile/torsional tests, we characterize the bending rigidity (EI) and the twisting rigidity (GJ) of 15 petioles of 4 species in the Spring/Summer: Red Oak (Quercus Rubra), American Sycamore (Platanus occidentalis), Yellow Poplar (Liriodendron tulipifera), and Sugar Maple (Acer saccharum). A twist-to-bend ratio EI/GJ is found to be around 4.3, within the range in previous studies conducted on similar species (EI/GJ = 2.7~8.0 reported in S. Vogel, 1992). In addition, we develop a simple energetic model to find a relation between geometrical shapes and mechanical properties (EI/GJ = 2LL/WC where LL is the laminar length and WC is the laminar width), verified with experimental data. Lastly, we discuss leaf's ability to reduce stress at the stem-petiole junction by choosing certain geometry, and also present exploratory results on the effect that seasons have on the Young's and twisting moduli.

Correction: Seasonal changes in morphology govern wettability of Katsura leaves.

[This corrects the article DOI: 10.1371/journal.pone.0202900.].

Seasonal changes in morphology govern wettability of Katsura leaves.

Deciduous broad-leaf trees survive and prepare for winter by shedding their leaves in fall. During the fall season, a change in a leaf's wettability and its impact on the leaf-fall are not well understood. In this study, we measure the surface morphology and wettability of Katsura leaves from the summer to winter, and reveal how leaf structural changes lead to wettability changes. The averaged contact angle of leaves decreases from 147° to 124° while the contact-angle hysteresis significantly increases by about 35°, which are attributed to dehydration and erosion of nano-wax. Due to such wettability changes, fall brown leaves support approximately 17 times greater water volume than summer leaves.

Sheet resistance characterization of locally anisotropic transparent conductive films made of aligned metal-enriched single-walled carbon nanotubes.

One-dimensional conductive fillers such as single-walled carbon nanotubes (SWNTs) can be aggregated and aligned during transparent conductive film (TCF) formation by the vacuum filtration method. The potential error of analysing the average sheet resistance of these anisotropic films, using the four-point probe in-line method and the conversion formula developed assuming uniform isotropic material properties, was systematically investigated by finite element analysis and experiments. The finite element analysis of anisotropic stripe-patterned TCFs with alternating low (ρ1) and high (ρ2) resistivities revealed that the estimated average sheet resistance approached ρ1/t when the probes were parallel to the aligned nanotubes. The thickness of the film is t. It was more close to ρ2/t when the probes were perpendicular to the aligned tubes. Indeed, TCFs fabricated by the vacuum filtration method using metal-enriched SWNTs exhibited highly anisotropic local regions where tubes were aggregated and aligned. The local sheet resistances of randomly oriented, aligned, and perpendicular tube regions of the TCF at a transmittance of 89.9% were 5000, 2.4, and 12 300 Ω â–¡(-1), respectively. Resistivities of the aggregated and aligned tube region (ρ1 = 1.2 × 10(-5) Ω cm) and the region between tubes (ρ2 = 6.2 × 10(-2) Ω cm) could be approximated with the aid of finite element analysis. This work demonstrates the potential error of characterizing the average sheet resistance of anisotropic TCFs using the four-point probe in-line method since surprisingly high or low values could be obtained depending on the measurement angle. On the other hand, a better control of aggregation and alignment of nanotubes would realize TCFs with a very small anisotropic resistivity and a high transparency.

Hierarchical construction of self-standing anodized titania nanotube arrays and nanoparticles for efficient and cost-effective front-illuminated dye-sensitized solar cells.

We report on the influence of hierarchical structures, constructed via layer-by-layer assembly of self-standing titania nanotube arrays and nanoparticles, upon charge recombination and photoelectric performance of front-illuminated dye-sensitized solar cells. Both nanotubes and nanoparticles were produced by anodization rather than additionally employing other methods, providing low cost and great simplicity. Electrochemical impedance spectroscopy under AM 1.5 illumination indicates the construction of hybrid morphology has superior recombination characteristics and a longer electron lifetime than nanoparticulate systems. This enhancement with the incorporation of anodized titania nanoparticles with 1D architectures is unprecedented for solar cells. Owing to the better light harvesting efficiency, extended electron lifetime and desirable electron extraction, the short-circuit photocurrent density of solar cell is 18.89 mA cm(-2) with an overall power conversion efficiency of 8.80% and an incident photon-to-current conversion efficiency of 84.6% providing a very promising candidate for sustainable energy production with a high performance/cost ratio.

Local electrical characteristics of dielectrophoretically deposited carbon nanotubes.

Electrostatic force microscopy and scanning gate microscopy are employed to investigate the local electrical characteristics of single-walled carbon nanotube (SWCNT) devices that are fabricated by alternating current dielectrophoresis with high spatial resolutions. The results show good electrical anchoring of nanotubes to electrodes and absence of local gate dependence as well as global gate dependence while device resistance can be dominated by contact resistances among bundles of SWCNTs.

Transcriptional regulation of the Drosophila caudal homeobox gene by bHLH-PAS proteins.

Caudal-related homeobox transcription factors are involved in the definition of the anteroposterior axis and intestinal development. Recent reports indicate that dysregulation of CDX1 and CDX2, the human homologues of Drosophila caudal, are associated with several types of cancer. Very little is known, however, about the regulatory mechanisms that direct the caudal-related homeobox gene expression. In this study, we have identified the binding sites for bHLH-PAS proteins, referred to as CNS midline element (CME), in the 5'-flanking region of the Drosophila caudal gene. Analyses using transgenic flies carrying a caudal-lacZ fusion gene bearing a wild-type or mutant CME indicate that the CME sites are required for caudal gene expression in vivo. We also determined that the caudal promoter activity can be regulated by Trachealess (Trh)/Tango (Tgo) bHLH-PAS proteins, via the CME sites. Our results suggest that the Drosophila caudal gene is a target of the Trh/Tgo bHLH-PAS proteins.

Allele frequencies and haplotypes of the STR loci of the PowerPlex Y-system in southern populations from Korea.

In this study, 12 Y-specific STR loci--DYS391, DYS389 I, DYS439, DYS389 II, DYS438, DYS437, DYS19, DYS392, DYS393, DYS390, DYS385a/b--were analyzed in 259 unrelated males from the southern populations in Korea using the PowerPlex Y PCR system.

Identification of chicken nebulin isoforms of the 31-residue motifs and non-muscle nebulin.

Nebulin is a very large (M(r) 600-900kDa) actin-binding protein that is specific to skeletal muscle, and which is thought to act as a molecular template that regulates the length of sarcomere thin filaments. The 31-residue motif of nebulin contains a unique PEhXRVKXNQ consensus sequence. We have previously identified 11 different human nebulin isoforms of these 31-residue motifs. Here we present the identification of seven different isoforms (types II, III, IVa, IVb, V, VI, and X) of the 31-residue motifs in 15-day-old chicken embryo breast muscle. Isoform types II and III are also expressed in the brain, and type III is also detected in the heart, stomach, and liver. Chicken nebulin contains 11 copies of the 31-residue motif (R1a/b, R2, R3, R4, R5, R6, R7, R8, R9, R10, and R11), whereas human nebulin contains 13 copies. We confirmed the expression of nebulin in the heart, stomach, and brain in 15-day-old chicken embryos by immunofluorescence microscopy. The presence of nebulin in brain was further confirmed by in situ hybridization. These data suggest that there is even more diversity in nebulin isoforms than was previously known; this diversity likely contributes to the distinct actin filament architecture of different tissues.

An aqueous extract of Platycodi radix inhibits LPS-induced NF-kappaB nuclear translocation in human cultured airway epithelial cells.

We investigated the effects of aqueous extract from Platycodi radix (AEPR), a traditional drug used to treat acute lung inflammatory disease, on lipopolysaccharide (LPS)-induced inflammation in A549 human cultured airway epithelial cells. Nuclear factor-kappaB (NF-kappaB) and its inhibitory regulator, inhibitory kappaB (I-kappaB), play crucial roles in LPS-induced inflammatory response. We show that LPS-induced nuclear translocation of NF-kappaBp65 is inhibited by AEPR. LPS-induced expression of I-kappaBalpha, which is expressed by LPS-induced activation of NF-kappaB, is inhibited by AEPR as well. Besides LPS-induced expression of a group of genes, such as tumor necrosis factor-alpha (TNF-alpha), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), are repressed by AEPR. We also found that expression of heat shock protein 70 (Hsp70), which has an anti-inflammatory activity, is increased by AEPR plus LPS. These results suggest that AEPR may act as a therapeutic agent for inflammatory disease through regulating the activity of NF-kappaB and expression of inflammatory genes.

Incorporating genotyping uncertainty in haplotype inference for single-nucleotide polymorphisms.

The accuracy of the vast amount of genotypic information generated by high-throughput genotyping technologies is crucial in haplotype analyses and linkage-disequilibrium mapping for complex diseases. To date, most automated programs lack quality measures for the allele calls; therefore, human interventions, which are both labor intensive and error prone, have to be performed. Here, we propose a novel genotype clustering algorithm, GeneScore, based on a bivariate t-mixture model, which assigns a set of probabilities for each data point belonging to the candidate genotype clusters. Furthermore, we describe an expectation-maximization (EM) algorithm for haplotype phasing, GenoSpectrum (GS)-EM, which can use probabilistic multilocus genotype matrices (called "GenoSpectrum") as inputs. Combining these two model-based algorithms, we can perform haplotype inference directly on raw readouts from a genotyping machine, such as the TaqMan assay. By using both simulated and real data sets, we demonstrate the advantages of our probabilistic approach over the current genotype scoring methods, in terms of both the accuracy of haplotype inference and the statistical power of haplotype-based association analyses.

Redox regulation of DNA binding activity of DREF (DNA replication-related element binding factor) in Drosophila.

DREF [DRE (DNA replication-related element) binding factor] is an 80 kDa polypeptide homodimer which plays an important role in regulating cell proliferation-related genes. Both DNA binding and dimer formation activities are associated with residues 16-115 of the N-terminal region. However, the mechanisms by which DREF dimerization and DNA binding are regulated remain unknown. Here, we report that the DNA binding activity of DREF is regulated by a redox mechanism, and that the cysteine residues are involved in this regulation. Electrophoretic mobility shift analysis using Drosophila Kc cell extracts or recombinant DREF proteins indicated that the DNA binding domain is sufficient for redox regulation. Site-directed mutagenesis and transient transfection assays showed that Cys59 and/or Cys62 are critical both for DNA binding and for redox regulation, whereas Cys91 is dispensable. In addition, experiments using Kc cells indicated that the DNA binding activity and function of DREF are affected by the intracellular redox state. These findings give insight into the exact nature of DREF function in the regulation of target genes by the intracellular redox state.