Bounding Global Aerosol Radiative Forcing of Climate Change.

Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6 W m-2, or -2.0 to -0.4 W m-2 with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds.

Tigecycline resistance in clinical isolates of Enterococcus faecium is mediated by an upregulation of plasmid-encoded tetracycline determinants tet(L) and tet(M).

OBJECTIVES: Tigecycline represents one of the last-line therapeutics to combat multidrug-resistant bacterial pathogens, including VRE and MRSA. The German National Reference Centre for Staphylococci and Enterococci has received 73 tigecycline-resistant Enterococcus faecium and Enterococcus faecalis isolates in recent years. The precise mechanism of how enterococci become resistant to tigecycline remains undetermined. This study documents an analysis of the role of efflux pumps in tigecycline resistance in clinical isolates of Enterococcus spp. METHODS: Various tigecycline MICs were found for the different isolates analysed. Tigecycline-resistant strains were analysed with respect to genome and transcriptome differences by means of WGS and RT-qPCR. Genes of interest were cloned and expressed in Listeria monocytogenes for verification of their functionality. RESULTS: Detailed comparative whole-genome analyses of three isogenic strains, showing different levels of tigecycline resistance, revealed the major facilitator superfamily (MFS) efflux pump TetL and the ribosomal protection protein TetM as possible drug resistance proteins. Subsequent RT-qPCR confirmed up-regulation of the respective genes. A correlation of gene copy number and level of MIC was inferred from further qPCR analyses. Expression of both tet(L) and tet(M) in L. monocytogenes unequivocally demonstrated the potential to increase tigecycline MICs upon acquisition of either locus. CONCLUSIONS: Our results indicate that increased expression of two tetracycline resistance determinants, a tet(L)-encoded MFS pump and a tet(M)-encoded ribosomal protection protein, is capable of conferring tigecycline resistance in enterococcal clinical isolates.

Importance of charge fluctuations for the topological phase in SmB(6).

Typical Kondo insulators (KIs) can have a nontrivial Z_{2} topology because the energy gap opens at the Fermi energy (E_{F}) by a hybridization between odd- and even-parity bands. SmB_{6} deviates from such KI behavior, and it has been unclear how the insulating phase occurs. Here, we demonstrate that charge fluctuations are the origin of the topological insulating phase in SmB_{6}. Our angle-resolved photoemission spectroscopy results reveal that with decreasing temperature the bottom of the d-f hybridized band at the X[over ¯] point, which is predicted to have odd parity and is required for a topological phase, gradually shifts from below to above E_{F}. We conclude that SmB_{6} is a charge-fluctuating topological insulator.

Characterizing small supernumerary marker chromosomes with combination of multiple techniques.

Fourteen cases with constitutional small supernumerary marker chromosomes (sSMCs) were assessed by combination of diverse techniques including genome-wide high-resolution chromosomal microarray (CMA), chromosome banding analysis (G banding), fluorescence in situ hybridization (FISH), and quantitative real-time PCR (qPCR). Of the 14 sSMCs, 4 were complex sSMCs composed of genomic materials from more than one chromosome, 7 were simple sSMCs which contain only centromeric and/or pericentromeric regions from individual chromosomes, and the remaining 3 sSMCs contained inverted duplications. CMA precisely defined the breakpoints and genetic contents in 12 of the 14 sSMCs but failed to identify 2 of the 14 sSMCs due to lack of detectable euchromatin. In addition, CMA revealed unexpected genomic abnormalities in 2 cases. FISH techniques were necessary for the determination of the physical location, structure, formation mechanism, mosaic level, and origin of all these sSMCs. Our data emphasize the necessity to combine these methods for comprehensive characterization of sSMCs.

Water-driven microbial nitrogen transformations in biological soil crusts causing atmospheric nitrous acid and nitric oxide emissions.

Biological soil crusts (biocrusts) release the reactive nitrogen gases (Nr) nitrous acid (HONO) and nitric oxide (NO) into the atmosphere, but the underlying microbial process controls have not yet been resolved. In this study, we analyzed the activity of microbial consortia relevant in Nr emissions during desiccation using transcriptome and proteome profiling and fluorescence in situ hybridization. We observed that < 30 min after wetting, genes encoding for all relevant nitrogen (N) cycling processes were expressed. The most abundant transcriptionally active N-transforming microorganisms in the investigated biocrusts were affiliated with Rhodobacteraceae, Enterobacteriaceae, and Pseudomonadaceae within the Alpha- and Gammaproteobacteria. Upon desiccation, the nitrite (NO2-) content of the biocrusts increased significantly, which was not the case when microbial activity was inhibited. Our results confirm that NO2- is the key precursor for biocrust emissions of HONO and NO. This NO2- accumulation likely involves two processes related to the transition from oxygen-limited to oxic conditions in the course of desiccation: (i) a differential regulation of the expression of denitrification genes; and (ii) a physiological response of ammonia-oxidizing organisms to changing oxygen conditions. Thus, our findings suggest that the activity of N-cycling microorganisms determines the process rates and overall quantity of Nr emissions.

Identification of copy number variants on human chromosome 22 in patients with a variety of clinical findings.

The aims of this study were to create a copy number variant (CNV) profile of human chromosome 22 and to establish a genotype-phenotype correlation for patients with genomic abnormalities on chromosome 22. Thus, 1,654 consecutive pediatric patients with a diversity of clinical findings were evaluated by high-resolution chromosomal microarray analysis (CMA). We identified 25 individuals with abnormal CNVs on chromosome 22, representing 1.5% of the cases analyzed in this cohort. Meanwhile, we detected 1,298 benign CNVs on this chromosome in these individuals. Twenty-one of the 25 abnormal CNVs and the majority of the benign CNVs occurred through involvement of the 8 unstable genomic regions enriched with low copy repeats (LCR22A-H). The highly dynamic status of LCR22s within the 22q11 region facilitates the formation of diverse genomic abnormalities. This CNV profile provides a general perspective of the spectrum of chromosome 22 genomic imbalances and subsequently improves the CNV-phenotype correlations.

Linkage between growth retardation and pituitary cell morphology in a dystrophin-deficient pig model of Duchenne muscular dystrophy.

OBJECTIVE: Human patients with Duchenne muscular dystrophy (DMD) commonly exhibit a short stature, but the pathogenesis of this growth retardation is not completely understood. Due to the suspected involvement of the growth hormone/insulin-like growth factor 1 (GH/IGF1) system, controversial therapeutic approaches have been developed, including both GH- administration, as well as GH-inhibition. In the present study, we examined relevant histomorphological and ultrastructural features of adenohypophyseal GH-producing somatotroph cells in a porcine DMD model. METHODS: The numbers and volumes of immunohistochemically labelled somatotroph cells were determined in consecutive semi-thin sections of plastic resin embedded adenohypophyseal tissue samples using unbiased state-of-the-art quantitative stereological analysis methods. RESULTS: DMD pigs displayed a significant growth retardation, accounting for a 55% reduction of body weight, accompanied by a significant 50% reduction of the number of somatotroph cells, as compared to controls. However, the mean volumes of somatotroph cells and the volume of GH-granules per cell were not altered. Western blot analyses of the adenohypophyseal protein samples showed no differences in the relative adenohypophyseal GH-abundance between DMD pigs and controls. CONCLUSION: The findings of this study do not provide evidence for involvement of somatotroph cells in the pathogenesis of growth retardation of DMD pigs. These results are in contrast with previous findings in other dystrophin-deficient animal models, such as the golden retriever model of Duchenne muscular dystrophy, where increased mean somatotroph cell volumes and elevated volumes of intracellular GH-granules were reported and associated with DMD-related growth retardation. Possible reasons for the differences of somatotroph morphology observed in different DMD models are discussed.

The cannabinoid receptor-1 antagonist rimonabant inhibits platelet activation and reduces pro-inflammatory chemokines and leukocytes in Zucker rats.

BACKGROUND AND PURPOSE: We investigated the effect of rimonabant on inflammation and enhanced platelet reactivity in type 2 diabetic Zucker rats, an experimental model of impaired glucose tolerance and the metabolic syndrome. EXPERIMENTAL APPROACH: Rimonabant (10 mg kg(-1) by gavage) was fed for 2 weeks to 3-month-old male obese Zucker rats as an impaired glucose tolerance model and for 10 weeks to 6-month-old male obese Zucker rats as a model of the metabolic syndrome. RANTES (Regulated upon Activation, Normal T cell Expressed, and Secreted) and MCP-1 (monocyte chemotactic protein-1) serum levels were determined by ELISA. Leukocyte populations were quantitatively assessed using a veterinary differential blood cell counter. Platelet activation was assessed by flow-cytometry, platelet aggregation, and adhesion of isolated platelets to immobilized fibrinogen. KEY RESULTS: RANTES and MCP-1 serum levels were increased in obese vs lean Zucker rats and significantly reduced by long-term treatment with rimonabant, which slowed weight gain in rats with the metabolic syndrome. Neutrophils and monocytes were significantly increased in young and old obese vs lean Zucker rats and lowered by rimonabant. Platelet-bound fibrinogen was significantly enhanced in obese vs lean Zucker rats of both age, and was reduced by rimonabant. Platelets from obese rats were more sensitive to thrombin-induced aggregation and adhesion to fibrinogen, which were both attenuated by rimonabant therapy. CONCLUSIONS AND IMPLICATIONS: We demonstrate positive modulation of circulating neutrophil and monocyte numbers, reduced platelet activation and lower RANTES and MCP-1 levels by rimonabant in Zucker rats. This may potentially contribute to a reduction of cardiovascular risk.

Alkylphenols in sediments of the Atlantic Rainforest south-west of São Paulo, Brazil.

Concentrations of technical 4-nonylphenol, 4-n-octylphenol, and 4-tert-octylphenol were investigated in surface water and sediment samples of four reservoirs southwest of São Paulo. Three of them (Takimoto 1, Takimoto 2, Pedro) were established in intensively cropped landscapes, one (Morro Grande) was surrounded by dense forests. Total alkylphenol concentrations in sediments generally ranged between 1 and 10 microgkg-1dw with 4-tert-octylphenol being the dominant alkylphenol. Because 4-tert-octylphenol concentration patterns at Takimoto 2, Pedro, and in the Morro Grande forest reservoir were found to be quite similar (upto 5 microgkg-1dw), this value is considered as the ubiquitous background level. In contrast, the Takimoto 1 sediments showed significantly higher 4-tert-octylphenol concentrations, possibly due to accelerated inputs from adjacent intensively cropped fields. Analysed alkylphenols were not detectable in water samples.

Registered Replication Report: Rand, Greene, and Nowak (2012).

In an anonymous 4-person economic game, participants contributed more money to a common project (i.e., cooperated) when required to decide quickly than when forced to delay their decision (Rand, Greene & Nowak, 2012), a pattern consistent with the social heuristics hypothesis proposed by Rand and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned to conditions and who met the protocol inclusion criteria (an intent-to-treat approach that included the 65.9% of participants in the time-pressure condition and 7.5% in the forced-delay condition who did not adhere to the time constraints), and we observed a difference in contributions of -0.37 percentage points compared with an 8.6 percentage point difference calculated from the original data. Analyzing the data as the original article did, including data only for participants who complied with the time constraints, the RRR observed a 10.37 percentage point difference in contributions compared with a 15.31 percentage point difference in the original study. In combination, the results of the intent-to-treat analysis and the compliant-only analysis are consistent with the presence of selection biases and the absence of a causal effect of time pressure on cooperation.

Three-dimensional electric field traps for manipulation of cells--calculation and experimental verification.

The forces acting on dielectric particles and living cells exposed to alternating and rotating fields generated by three-dimensional multi-electrode arrangements are investigated. Numerical procedures are described for the calculation of the electric field distribution and forces. The physical treatment considers electrodes of any shape and dielectric particles of complex structure. Particle and cell trapping are based on negative dielectrophoretic forces produced by high-frequency a.c. or rotating electric fields up to 400 MHz. Various multi-electrode systems were realised in commercially fabricated microelectrode systems, and tested for their ability to move and assemble microparticles or living cells without contact with the electrodes. The field distribution and accuracy of phase-controlled power application was tested using individual artificial particles trapped in the electric field cage. Position and trajectories of particle motion were measured. The paper gives an overview of electrode and field cage design in the microscale range.

Long-term outcome of survivors of cardiac arrest whose therapy is guided by electrophysiologic testing.

The long-term outcome of 217 consecutive survivors of cardiac arrest whose therapy was guided by electrophysiologic testing was analyzed. After electrophysiologic testing, 81 patients (37%) were classified as having no inducible arrhythmia and were treated without antiarrhythmic drugs; 23 received an implantable defibrillator. Of the 136 patients with inducible arrhythmia, the 51 (38%) who responded to serial drug testing were treated with the successful drug and the 85 (62%) with unsuccessful drug testing were treated with an implantable defibrillator (47 patients), amiodarone (36 patients) or drugs that were unsuccessful during testing (2 patients). The mean follow-up interval for all patients was 35 +/- 23 months. The actuarial incidence of sudden death and overall death was similar for patients whose arrhythmias were not inducible, drug responders and nonresponders. The actuarial incidence rate of recurrent arrhythmic events in nonresponders was 35 +/- 5% and 53 +/- 7% at 2 and 5 years, respectively. These values were significantly lower (and statistically similar to each other) in the other two patient groups: patients with noninducible arrhythmia (19 +/- 5% and 31 +/- 7%, respectively, p less than 0.05) and drug responders (13 +/- 5% and 23 +/- 8%, respectively, p less than 0.01). Patients with an implantable defibrillator who had recurrent arrhythmic events were significantly less likely to die suddenly than were patients without a defibrillator who had recurrent events (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of the automatic implantable cardioverter-defibrillator in prolonging survival in patients with severe underlying cardiac disease.

The ability of the automatic implantable cardioverter-defibrillator to prolong overall survival, particularly in patients with significantly depressed cardiac function, has not been well documented. Of 119 patients who received the implantable defibrillator in this institution, 40 had a left ventricular ejection fraction less than 30% (Group A) and 79 had an ejection fraction greater than or equal to 30% (Group B). For each group, cumulative survival was compared with the projected survival if the implantable defibrillator had not been used. Projected survival was based on the assumption that the first appropriate shock would have resulted in death without the defibrillator. For Group A, the 3 year cumulative survival rate was 67 +/- 12% versus a projected survival rate of 6 +/- 15% (p less than 0.001). For Group B, the 3 year cumulative survival rate was 96 +/- 3% versus a projected survival rate of 46 +/- 8% (p less than 0.001). Both the cumulative and projected survival rates for patients in Group A were significantly worse than for patients in Group B (p less than 0.01). The projected survival rates for both Groups A and B were comparable with the observed survival rate in similar patients treated without the implantable defibrillator. In summary, the implantable cardioverter-defibrillator significantly prolonged overall survival, even in patients with poor cardiac function. The technique of estimating projected survival appears to allow a realistic estimate of the reduction in mortality achieved by the defibrillator.

The chemistry of death--Adipocere degradation in modern graveyards.

The formation of adipocere slows further decomposition and preserves corpses for decades or even centuries. This resistance to degradation is a serious problem, especially with regard to the reuse of graves after regular resting times. We present results from an exhumation series in modern graveyards where coffins from water-saturated earth graves contained adipocere embedded in black humic material after resting times of about 30 years. Based on the assumption that this humic material resulted from in situ degradation of adipocere, its presence contradicts the commonly held opinion that adipocere decomposition only occurs under aerobic conditions. To test our hypothesis, we collected black humic material, adipocere as well as soil samples above and below coffins from representative graves (n=7). A comprehensive chemical analysis of the samples substantiated our in situ degradation theory. Element compositions and fatty acid mass spectra confirmed that the humic black material originated from the corpses. A van Krevelen diagram classified the excavated adipocere material as lipid, whereas the black humic material was closer to the carbohydrate region. Mass fragmentograms of the humic material revealed the presence of large amounts of saturated vs. unsaturated nC16 and nC18 fatty acids, which is typical for adipocere. In addition, the soil samples exhibited a lipid signature deriving primarily from plant waxes and root components (C20C32). Solid-state (13)C NMR spectra of adipocere displayed well-resolved signals of saturated aliphatic chains and a signal that corresponded to carboxylic acid groups. The NMR spectra of the black humic material revealed signals characteristic of long aliphatic chains. The intensities varied in relation to the state of degradation of the sample, as did the signals of oxidized aliphatic chains, acetals and ketals, aromatic structures, esters and amids. The analyses confirmed that the black humic material was indeed derived from adipocere, so the assumption is that the components detected must have developed from aliphatic fatty acids via a number of oxidation and condensation processes. We therefore propose the existence of chemical pathway(s) for the degradation of adipocere under poikiloaerobic conditions. Possible (biogeo)chemical reaction chains include (1) the autoxidation of fatty acids enhanced by haemoglobin, methaemoglobin and haemin, (2) the use of alternative electron acceptors, which leads to the formation of H2S that then reacts abiotically with iron (from haemoglobin), rendering iron sulphide, and (3) the Maillard reaction. These findings are another step forward in understanding the chemistry of buried corpses.

Lack of cell death enhancement after irradiation with monochromatic synchrotron X rays at the K-shell edge of platinum incorporated in living SQ20B human cells as cis-diamminedichloroplatinum (II).

In this paper we describe the results of experiments using synchrotron radiation to trigger the Auger effect in living human cancer cells treated with a widely used chemotherapy drug: cis-diamminedichloroplatinum (II) (cisplatin). The experiments were carried out at the ID17 beamline of the European Synchrotron Radiation Facility, which produces a high-fluence monochromatic beam that is adjustable from 20 to 80 keV. Cisplatin was chosen as the carrier of platinum atoms in the cells because of its alkylating-like activity and the irradiation was done with monochromatic beams above and below the platinum K-shell edge (78.39 keV). Cell survival curves were comparable with those obtained for the same cells under conventional irradiation conditions. At a low dose of cisplatin (0.1 microM, 48 h), no difference was seen in survival when the cells were irradiated above and below the K-shell edge of platinum. Higher cisplatin concentrations were investigated to enhance the cellular platinum content. The results with 1 microM cisplatin for 12 h showed no difference when the cells were irradiated with beams above or below the platinum K-shell edge with the exception of the higher cell death resulting from drug toxicity. The intracellular content of platinum was significant, as measured macroscopically by inductively coupled plasma mass spectrometry. Its subcellular localization and particularly its presence in the cell nucleus were verified by microscopic synchrotron X-ray fluorescence. This was the first known attempt at K-shell edge photon activation of stable platinum in living cells with a platinum complex used for chemotherapy. Its evident toxicity in these cells leads us to put forth the hypothesis that cisplatin toxicity can mask the enhancement of cell death induced by the irradiation above the K-shell edge. However, K-shell edge photon activation of stable elements provides a powerful technique for the understanding of the biological effects of Auger processes. Further avenues of development are discussed.

Genetic transformation of various species of Enterococcus by electroporation.

A transformation system for Enterococcus faecalis was developed which uses untreated (i.e., non-protoplasted) cells and the electroporation technique. The optimized protocol resulted in transformation efficiencies of up to 4 x 10(6) transformants per microgram of plasmid DNA. All strains of E. faecalis tested could be transformed by this method, albeit with differing transformation efficiencies. Using the protocol optimized for E. faecalis we successfully transformed Enterococcus faecium, E. hirae, E. malodoratus and E. mundtii.

Objective comparison of image quality and dose between conventional and synchrotron radiation mammography.

The shape of the energy spectrum produced by an x-ray tube has a great importance in mammography. Many anode-filtration combinations have been proposed to obtain the most effective spectrum shape for the image quality-dose relationship. On the other hand, third generation synchrotrons such as the European Synchrotron Radiation Facility in Grenoble are able to produce a high flux of monoenergetic radiation. It is thus a powerful tool to study the effect of beam energy on image quality and dose in mammography. An objective method was used to evaluate image quality and dose in mammography with synchrotron radiation and to compare them to standard conventional units. It was performed systematically in the energy range of interest for mammography through the evaluation of a global image quality index and through the measurement of the mean glandular dose. Compared to conventional mammography units, synchrotron radiation shows a great improvement of the image quality-dose relationship, which is due to the beam monochromaticity and to the high intrinsic collimation of the beam, which allows the use of a slit instead of an anti-scatter grid for scatter rejection.

Imaging lobular breast carcinoma: comparison of synchrotron radiation DEI-CT technique with clinical CT, mammography and histology.

Different modalities for imaging cancer-bearing breast tissue samples are described and compared. The images include clinical mammograms and computed tomography (CT) images, CT images with partly coherent synchrotron radiation (SR), and CT and radiography images taken with SR using the diffraction enhanced imaging (DEI) method. The images are evaluated by a radiologist and compared with histopathological examination of the samples. Two cases of lobular carcinoma are studied in detail. The indications of cancer are very weak or invisible in the conventional images, but the morphological changes due to invasion of cancer become pronounced in the images taken by the DEI method. The strands penetrating adipose tissue are seen clearly in the DEI-CT images, and the histopathology confirms that some strands contain the so-called 'Indian file' formations of cancer cells. The radiation dose is carefully measured for each of the imaging modalities. The mean glandular dose (MGD) for 50% glandular breast tissue is about 1 mGy in conventional mammography and less than 0.25 mGy in projection DEI, while in the clinical CT imaging the MGD is very high, about 45 mGy. The entrance dose of 95 mGy in DEI-CT imaging gives rise to an MGD of 40 mGy, but the dose may be reduced by an order of magnitude, because the contrast is very large in most images.

First human transvenous coronary angiography at the European Synchrotron Radiation Facility.

The first operation of the European Synchrotron Radiation Facility (ESRF) medical beamline is reported in this paper. The goal of the angiography project is to develop a reduced risk imaging technique, which can be used to follow up patients after coronary intervention. After the intravenous injection of a contrast agent (iodine) two images are produced with monochromatic beams, bracketing the iodine K-edge. The logarithmic subtraction of the two measurements results in an iodine enhanced image, which can be precisely quantified. A research protocol has been designed to evaluate the performances of this method in comparison with the conventional technique. Patients included in the protocol have previously undergone angioplasty. If a re-stenosis is suspected, the patient is imaged both at the ESRF and at the hospital with the conventional technique, within the next few days. This paper reports the results obtained with the first patients. To date, eight patients have been imaged and excellent image quality was obtained.

Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent.

Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter.