An electronic nose in the discrimination of patients with asthma and controls.

BACKGROUND: Exhaled breath contains thousands of volatile organic compounds (VOCs) that could serve as biomarkers of lung disease. Electronic noses can distinguish VOC mixtures by pattern recognition. OBJECTIVE: We hypothesized that an electronic nose can discriminate exhaled air of patients with asthma from healthy controls, and between patients with different disease severities. METHODS: Ten young patients with mild asthma (25.1 +/- 5.9 years; FEV(1), 99.9 +/- 7.7% predicted), 10 young controls (26.8 +/- 6.4 years; FEV(1), 101.9 +/- 10.3), 10 older patients with severe asthma (49.5 +/- 12.0 years; FEV(1), 62.3 +/- 23.6), and 10 older controls (57.3 +/- 7.1 years; FEV(1), 108.3 +/- 14.7) joined a cross-sectional study with duplicate sampling of exhaled breath with an interval of 2 to 5 minutes. Subjects inspired VOC-filtered air by tidal breathing for 5 minutes, and a single expiratory vital capacity was collected into a Tedlar bag that was sampled by electronic nose (Cyranose 320) within 10 minutes. Smellprints were analyzed by linear discriminant analysis on principal component reduction. Cross-validation values (CVVs) were calculated. RESULTS: Smellprints of patients with mild asthma were fully separated from young controls (CVV, 100%; Mahalanobis distance [M-distance], 5.32), and patients with severe asthma could be distinguished from old controls (CVV, 90%; M-distance, 2.77). Patients with mild and severe asthma could be less well discriminated (CVV, 65%; M-distance, 1.23), whereas the 2 control groups were indistinguishable (CVV, 50%; M-distance, 1.56). The duplicate samples replicated these results. CONCLUSION: An electronic nose can discriminate exhaled breath of patients with asthma from controls but is less accurate in distinguishing asthma severities. CLINICAL IMPLICATION: These findings warrant validation of electronic noses in diagnosing newly presented patients with asthma

A Novel Cre Recombinase Imaging System for Tracking Lymphotropic Virus Infection In Vivo

BACKGROUND:Detection, isolation, and identification of individual virus infected cells during long term infection are critical to advance our understanding of mechanisms of pathogenesis for latent/persistent viruses. However, current approaches to study these viruses in vivo have been hampered by low sensitivity and effects of cell-type on expression of viral encoded reporter genes. We have designed a novel Cre recombinase (Cre)-based murine system to overcome these problems, and thereby enable tracking and isolation of individual in vivo infected cells. METHODOLOGY/PRINCIPAL FINDINGS:Murine gammaherpesvirus 68 (MHV-68) was used as a prototypic persistent model virus. A Cre expressing recombinant virus was constructed and characterised. The virus is attenuated both in lytic virus replication, producing ten-fold lower lung virus titres than wild type virus, and in the establishment of latency. However, despite this limitation, when the sEGFP7 mouse line containing a Cre-activated enhanced green fluorescent protein (EGFP) was infected with the Cre expressing virus, sites of latent and persistent virus infection could be identified within B cells and macrophages of the lymphoid system on the basis of EGFP expression. Importantly, the use of the sEGFP7 mouse line which expresses high levels of EGFP allowed individual virus positive cells to be purified by FACSorting. Virus gene expression could be detected in these cells. Low numbers of EGFP positive cells could also be detected in the bone marrow. CONCLUSIONS/SIGNIFICANCE:The use of this novel Cre-based virus/mouse system allowed identification of individual latently infected cells in vivo and may be useful for the study and long-term monitoring of other latent/persistent virus infections

GoLoco motif proteins binding to Gαi1: insights from molecular simulations

Molecular dynamics simulations, computational alanine scanning and sequence analysis were used to investigate the structural properties of the Gαi1/GoLoco peptide complex. Using these methodologies, binding of the GoLoco motif peptide to the Gαi1 subunit was found to restrict the relative movement of the helical and catalytic domains in the Gαi1 subunit, which is in agreement with a proposed mechanism of GDP dissociation inhibition by GoLoco motif proteins. In addition, the results provide further insights into the role of the “Switch IV” region located within the helical domain of Gα, the conformation of which might be important for interactions with various Gα partners

Multispectral analysis of Northern Hemisphere temperature records over the last five millennia

Aiming to describe spatio-temporal climate variability on decadal-to-centennial time scales and longer, we analyzed a data set of 26 proxy records extending back 1,000–5,000 years; all records chosen were calibrated to yield temperatures. The seven irregularly sampled series in the data set were interpolated to a regular grid by optimized methods and then two advanced spectral methods—namely singular-spectrum analysis (SSA) and the continuous wavelet transform—were applied to individual series to separate significant oscillations from the high noise background. This univariate analysis identified several common periods across many of the 26 proxy records: a millennial trend, as well as oscillations of about 100 and 200 years, and a broad peak in the 40–70-year band. To study common NH oscillations, we then applied Multichannel SSA. Temperature variations on time scales longer than 600 years appear in our analysis as a dominant trend component, which shows climate features consistent with the Medieval Warm Period and the Little Ice Age. Statistically significant NH-wide peaks appear at 330, 250 and 110 years, as well as in a broad 50–80-year band. Strong variability centers in several bands are located around the North Atlantic basin and are in phase opposition between Greenland and Western Europe

Photocrosslinking of ferroelectric polymers and its application in three-dimensional memory arrays

\u3cp\u3eAn I-line photolithography process for ferroelectric polymers is developed. It is based on photocrosslinking using a bisazide photoinitiator. Patterned layers were realized down to 1-2μm resolution. Crosslinking yields a close-to-insoluble ferroelectric polymer network that counter intuitively has similar ferroelectric properties as a noncrosslinked film. The negative process is used to stack ferroelectric films on top of each other to make three-dimensional cross-bar arrays of nonvolatile ferroelectric capacitor memories.\u3c/p\u3

Gas sensing with self-assembled monolayer field-effect transistors

A new sensitive gas sensor based on a self-assembled monolayer field-effect transistor (SAMFET) was used to detect the biomarker nitric oxide. A SAMFET based sensor is highly sensitive because the analyte and the active channel are separated by only one monolayer. SAMFETs were functionalised for direct NO detection using iron porphyrin as a specific receptor. Upon exposure to NO a threshold voltage shift towards positive gate biases was observed. The sensor response was examined as a function of NO concentration. High sensitivity has been demonstrated by detection of ppb concentrations of NO. Preliminary measurements have been performed to determine the selectivity