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Biomedical subjects

N S Lewis

Publications and source records attributed to N S Lewis.

At least 19 recordsLinked to original sources
PubMed2026

Beyond in silico prediction: multi-omics to identify a pathogenic deep intronic HNRNPK variant in Au-Kline syndrome.

Pathogenic variants in HNRNPK are associated with autosomal dominant Au-Kline syndrome (AKS, Au-Kline-Okamoto syndrome, OMIM #616580). This syndrome is characterized by developmental delay and intellectual disability, hypotonia, and distinctive facial features. Despite the use of whole-genome sequencing (WGS) as a powerful diagnostic tool, we nearly dismissed a novel intronic variant (NM_031263.4(HNRNPK):c.214-55 T > A) affecting HNRNPK splicing and function. Although commonly used bioinformatic splice prediction tools, including SpliceAI and PDIVAS, yielded inconclusive results, Face2Gene analysis indicated a high phenotypic similarity to AKS. Characteristic facial features described by Choufani et al. [1] supported the clinical diagnosis of AKS. Subsequent functional studies demonstrated aberrant splicing with intron retention, and DNA methylation profiling revealed a positive HNRNPK-specific episignature. These insights and the de novo status support an evaluation as likely pathogenic. This case report supports the relevance of facial analysis and comprehensive variant validation strategies, particularly for deep intronic variants with ambiguous in silico splicing predictions.

Journal Article↗
PubMed2001

Detection and classification characteristics of arrays of carbon black/organic polymer composite chemiresistive vapor detectors for the nerve agent simulants dimethylmethylphosphonate and diisopropylmethylphosponate.

Arrays of conducting polymer composite vapor detectors have been evaluated for performance in the presence of the nerve agent simulants dimethylmethylphosphonate (DMMP) and diisopropylmethylphosponate (DIMP). Limits of detection for DMMP on unoptimized carbon black/ organic polymer composite vapor detectors in laboratory air were estimated to be 0.047-0.24 mg m(-3). These values are lower than the EC50 value (where EC50 is the airborne concentration sufficient to induce severe effects in 50% of those exposed for 30 min) for the nerve agents sarin (methylphosphonofluoridic acid, 1-methylethyl ester) and soman (methylphosphonofluoridic acid, 1,2,2-trimethylpropyl ester), which has been established as approximately 0.8 mg m(-3). Arrays of these vapor detectors were easily able to resolve signatures due to exposures to DMMP from those due to DIMP or due to a variety of other test analytes (including water, methanol, benzene, toluene, diesel fuel, lighter fluid, vinegar, and tetrahydrofuran) in a laboratory air background. In addition, DMMP at 27 mg m(-3) could be detected and differentiated from the signatures of the other test analytes in the presence of backgrounds of potential interferences, including water, methanol, benzene, toluene, diesel fuel, lighter fluid, vinegar, and tetrahydrofuran, even when these interferents were present in much higher concentrations than that of the DMMP or DIMP being detected.

Air↗
PubMed2001

Comparison of the performance of different discriminant algorithms in analyte discrimination tasks using an array of carbon black--polymer composite vapor detectors.

An array of 20 compositionally different carbon black--polymer composite chemiresistor vapor detectors was challenged under laboratory conditions to discriminate between a pair of extremely similar pure analytes (H2O and D2O), compositionally similar mixtures of pairs of compounds, and low concentrations of vapors of similar chemicals. Several discriminant algorithms were utilized, including k nearest neighbors (kNN, with k = 1), linear discriminant analysis (LDA, or Fisher's linear discriminant), quadratic discriminant analysis (QDA), regularized discriminant analysis (RDA, a hybrid of LDA and QDA), partial least squares, and soft independent modeling of class analogy (SIMCA). H2O and D2O were perfectly classified by most of the discriminants when a separate training and test set was used. As expected, discrimination performance decreased as the analyte concentration decreased, and performance decreased as the composition of the analyte mixtures became more similar. RDA was the overall best-performing discriminant, and LDA was the best-performing discriminant that did not require several cross-validations for optimization.

Journal Article↗
PubMed2001

Low power, lightweight vapor sensing using arrays of conducting polymer composite chemically-sensitive resistors.

Arrays of broadly responsive vapor detectors can be used to detect, identify, and quantify vapors and vapor mixtures. One implementation of this strategy involves the use of arrays of chemically-sensitive resistors made from conducting polymer composites. Sorption of an analyte into the polymer composite detector leads to swelling of the film material. The swelling is in turn transduced into a change in electrical resistance because the detector films consist of polymers filled with conducting particles such as carbon black. The differential sorption, and thus differential swelling, of an analyte into each polymer composite in the array produces a unique pattern for each different analyte of interest, Pattern recognition algorithms are then used to analyze the multivariate data arising from the responses of such a detector array. Chiral detector films can provide differential detection of the presence of certain chiral organic vapor analytes. Aspects of the spaceflight qualification and deployment of such a detector array, along with its performance for certain analytes of interest in manned life support applications, are reviewed and summarized in this article.

Air Conditioning↗
PubMed2000

An investigation of the concentration dependence and response to analyte mixtures of carbon black/insulating organic polymer composite vapor detectors.

The responses relative to an air background of carbon black/polymer composite vapor detectors have been determined as a function of the concentration of a homologous series of alcohols (n-CnH2n+1OH, 1 < or = n < or = 8), a homologous series of alkanes (n-CnH2n+2, 5 < or = n < or = 10 and n = 12, 14), and a set of diverse solvent vapors. In all cases, the steady-state relative differential resistance responses, delta R/Rb, of the carbon black/polymer composite vapor detectors were well-described by a linear relationship with respect to the analyte partial pressure, at least over the tested concentration range (P/P degree = 0.005-0.03, where P degree is the vapor pressure of the analyte). When two vapors in air were simultaneously presented to the detectors, the delta R/Rb response, relative to an air background, was the sum of the delta R/Rb values obtained when each analyte was exposed separately to the carbon black/polymer composite detectors under study. Similarly, when an analyte was exposed to the detectors on top of a background level of another analyte, the delta R/Rb values of the array of detectors were very close to those obtained when the test analyte was exposed to the detectors only in the presence of background air. The initial training requirements from the array response output data of such detectors are minimized because the delta R/Rb response pattern produced by the analyte of concern can be associated uniquely with that odor, under the conditions explored in this work.

Alcohols↗
PubMed2000

The use of 'electronic nose' sensor responses to predict the inhibition activity of alcohols on the cytochrome P-450 catalyzed p-hydroxylation of aniline.

A quantitative structure activity relationship (QSAR) has been formulated to describe the inhibitory action of a series of alcohols on the cytochrome P-450 catalyzed p-hydroxylation of aniline. The descriptors used in the QSAR are the responses of individual sensors in a polymer-based electronic nose, and are all easily generated experimental values. If the various electronic nose sensor response patterns for the family of test alcohols reflect differences in the chemical properties that are involved in the cytochrome P-450 inhibition process, it ought to be possible to correlate the differences in the electronic nose signals of these analytes with the differences in the cytochrome P-450 inhibition by these species. To evaluate this possibility, multiple linear regression was performed on data obtained from exposure of a series of test alcohols to 19 sensors of a conducting polymer composite electronic nose array. A genetic algorithm was then used to select the optimal set of sensors that best described the inhibitory activity of these alcohols within a linear regression model. The regression equation fit the inhibition data of 20 of the alcohols with an R of 0.995. This fit compares favorably with previously published QSARs on this system that have used log P (P triple bond octanol-water partition coefficient) along with steric parameters of the alcohols, and also compares favorably to QSARs formulated using theoretically calculated parameters.

Aniline Compounds↗
PubMed1998

Use of compatible polymer blends to fabricate arrays of carbon black-polymer composite vapor detectors.

Compatible blends of poly(vinyl acetate) and poly(methyl methacrylate) have been used to produce a series of electrically conducting carbon black composites whose resistance is sensitive to the nature and concentration of an analyte in the vapor phase. The dc electrical resistance response of the composites was found to be a nonlinear function of the mole fraction of poly(vinyl acetate) in the blend. These compatible blend composite detectors provided additional analyte discrimination information relative to a reference detector array that only contained composites formed using the pure polymer phases. The added discrimination power provided by the compatible blend detectors, and thus the added diversity of the enhanced detector array, was quantified through use of a statistical metric to assess the performance of detector arrays in various vapor classification tasks.

Carbon↗
PubMed1998

Trends in odor intensity for human and electronic noses: relative roles of odorant vapor pressure vs. molecularly specific odorant binding.

Response data were collected for a carbon black-polymer composite electronic nose array during exposure to homologous series of alkanes and alcohols. The mean response intensity of the electronic nose detectors and the response intensity of the most strongly driven set of electronic nose detectors were essentially constant for members of a chemically homologous odorant series when the concentration of each odorant in the gas phase was maintained at a constant fraction of the odorant's vapor pressure. A similar trend is observed in human odor detection threshold values for these same homologous series of odorants. Because the thermodynamic activity of an odorant at equilibrium in a sorbent phase is equal to the partial pressure of the odorant in the gas phase divided by the vapor pressure of the odorant and because the activity coefficients are similar within these homologous series of odorants for sorption of the vapors into specific polymer films, the data imply that the trends in detector response can be understood based on the thermodynamic tendency to establish a relatively constant concentration of sorbed odorant into each of the polymeric films of the electronic nose at a constant fraction of the odorant's vapor pressure. Similarly, the data are consistent with the hypothesis that the odor detection thresholds observed in human psychophysical experiments for the odorants studied herein are driven predominantly by the similarity in odorant concentrations sorbed into the olfactory epithelium at a constant fraction of the odorant's vapor pressure.

Biosensing Techniques↗
PubMed1995

A chemically diverse conducting polymer-based "electronic nose".

We describe a method for generating a variety of chemically diverse broadly responsive low-power vapor sensors. The chemical polymerization of pyrrole in the presence of plasticizers has yielded conducting organic polymer films whose resistivities are sensitive to the identity and concentration of various vapors in air. An array of such sensing elements produced a chemically reversible diagnostic pattern of electrical resistance changes upon exposure to different odorants. Principal component analysis has demonstrated that such sensors can identify and quantify different airborne organic solvents and can yield information on the components of gas mixtures.

Journal Article↗
PubMed1983

n-Type silicon photoelectrochemistry in methanol: Design of a 10.1% efficient semiconductor/liquid junction solar cell.

n-Type Si electrodes in MeOH solvent with 0.2 M (1-hydroxyethyl)ferrocene, 0.5 mM (1-hydroxyethyl)ferricenium, and 1.0 M LiClO(4) exhibit air mass 2 conversion efficiencies of 10.1% for optical energy into electricity. We observe open-circuit voltages of 0.53 V and short-circuit quantum efficiencies for electron flow of nearly unity. The fill factor of the cell does not decline significantly with increases in light intensity, indicating substantial reduction in efficiency losses in MeOH solvent compared to previous nonaqueous n-Si systems. Matte etch texturing of the Si surface decreases surface reflectivity and increases photocurrent by 50% compared to shiny, polished Si samples. The high values of the open-circuit voltage observed are consistent with the presence of a thin oxide layer, as in a Schottky metal-insulator-semiconductor device, which yields decreased surface recombination and increased values of open-circuit voltage and short-circuit current. The n-Si system was shown to provide sustained photocurrent at air mass 2 levels (20 mA/cm(2)) for charge through the interface of >2,000 C/cm(2). The n-Si/MeOH system represents a liquid junction cell that has exceeded the 10% barrier for conversion of optical energy into electricity.

Journal Article↗
PubMed1981

Electrochemical reduction of horse heart ferricytochrome c at chemically derivatized electrodes.

Platinum or gold electrodes derivatized with an N,N'-dialkyl-4,4'-bipyridinium reagent can be used to reduce horse heart ferricytochrome c, whereas reduction doses does not occur at the "naked" electrodes. From 3 to 17.7 millimoles per liter, the reduction of ferricytochrome c is mass transport-limited at electrode potentials more negative than about -0.6 volt against a saturated calomel reference electrode. Data for the photoreduction of ferricytochrome c at derivatized p-type silicon photocathodes show directly that the rate of reduction is mass transport-limited. Use of derivatized electrodes may allow convenient manipulation and analysis of biological molecules that do not ordinarily respond at conventional electrodes.

2,2'-Dipyridyl↗
PubMed1980

Synthesis and characterization of a photosensitive interface for hydrogen generation: Chemically modified p-type semiconducting silicon photocathodes.

p-Si photocathodes functionalized first with an N,N'-dialkyl-4,4'-bipyridinium redox reagent, (PQ(2+/+-))(surf), and then with a Pt precursor, PtCl(6) (2-), give significant efficiency (up to 5%) for photoelectrochemical H(2) generation with 632.8-nm light. Naked p-Si photocathodes give nearly zero efficiency, owing to poor H(2) evolution kinetics that are improved by the (PQ(2+/+-))(surf)/Pt modification. The mechanism of H(2) evolution from p-Si/(PQ(2+/+-))(surf)/Pt is first photoexcitation of electrons to the conduction band of Si followed by (PQ(2+))(surf) --> (PQ(+-))(surf) reduction. The dispersion of Pt then catalyzes H(2)O reduction to give H(2) and regeneration of (PQ(2+))(surf). The overall energy conversion efficiency rivals the best direct optical to chemical conversion systems reported to date.

Journal Article↗
PubMed1980

Hyperosmolality in the burn patient: analysis of an osmolal discrepancy.

In our study of 262 hospitalized flame burn patients, serum hyperosmolality, defined as having at least two reported osmolality values greater than 310 mOsm/kg, was observed in 15 patients (6%). From this group, nine patients were found to have an osmolal discrepancy (reported serum osmolality minus calculated serum osmolality). All patients in this group had a burn surface area greater than 35% TBS. The discrepancy between reported osmolality values of two patients from this group, determined by freezing point depression and vapor point analysis, suggested that a volatile substance was contributing to the osmolality. Further analysis by gas chromatography revealed propylene glycol as the agent accounting for most of the osmolal discrepancy. The only exposure to this polyalcohol was from the topical antibiotic cream (silver sulfadiazine) used in their treatment.

Adolescent↗