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Background: The Botryosphaeriaceae are important plant pathogens, but also have the ability to establish asymptomatic infections that persist for extended periods in a latent state. In this study, we used comparative genome analyses to shed light on the genetic basis of the interactions of these fungi with their plant hosts. For this purpose, we characterised secreted hydrolytic enzymes, secondary metabolite biosynthetic gene clusters and general trends in genomic architecture using all available Botryosphaeriaceae genomes, and selected Dothideomycetes genomes., Results: The Botryosphaeriaceae genomes were rich in carbohydrate-active enzymes (CAZymes), proteases, lipases and secondary metabolic biosynthetic gene clusters (BGCs) compared to other Dothideomycete genomes. The genomes of Botryosphaeria, Macrophomina, Lasiodiplodia and Neofusicoccum, in particular, had gene expansions of the major constituents of the secretome, notably CAZymes involved in plant cell wall degradation. The Botryosphaeriaceae genomes were shown to have moderate to high GC contents and most had low levels of repetitive DNA. The genomes were not compartmentalized based on gene and repeat densities, but genes of secreted enzymes were slightly more abundant in gene-sparse regions., Conclusion: The abundance of secreted hydrolytic enzymes and secondary metabolite BGCs in the genomes of Botryosphaeria, Macrophomina, Lasiodiplodia, and Neofusicoccum were similar to those in necrotrophic plant pathogens and some endophytes of woody plants. The results provide a foundation for comparative genomic analyses and hypotheses to explore the mechanisms underlying Botryosphaeriaceae host-plant interactions., (© 2021. The Author(s).)

Little is known regarding mating strategies in the Botryosphaeriaceae. To understand sexual reproduction in this fungal family, the mating type genes of Botryosphaeria dothidea and Macrophomina phaseolina, as well as several species of Diplodia, Lasiodiplodia and Neofusicoccum were characterized from whole genome assemblies. Comparisons between the mating type loci of these fungi showed that the mating type genes are highly variable, but in most cases the organization of these genes is conserved. Of the species considered, nine were homothallic and seven were heterothallic. Mating type gene fragments were discovered flanking the mating type regions, which indicates both ongoing and ancestral recombination occurring within the mating type region. Ancestral reconstruction analysis further indicated that heterothallism is the ancestral state in the Botryosphaeriaceae and this is supported by the presence of mating type gene fragments in homothallic species. The results also show that at least five transitions from heterothallism to homothallism have taken place in the Botryosphaeriaceae. The study provides a foundation for comparison of mating type evolution between Botryosphaeriaceae and other fungi and also provides valuable markers for population biology studies in this family., (Copyright © 2018 Elsevier Inc. All rights reserved.)

For the assessment of small airway diseases, a noninvasive double-tracer gas single-breath washout (DTG-SBW) with sulfur hexafluoride (SF 6 ) and helium (He) as tracer components has been proposed. It is assumed that small airway diseases may produce typical ventilation inhomogeneities which can be detected within one single tidal breath, when using two tracer components. Characteristic parameters calculated from a relative molar mass (MM) signal of the airflow during the washout expiration phase are analyzed. The DTG-SBW signal is acquired by subtracting a reconstructed MM signal without tracer gas from the signal measured with an ultrasonic sensor during in- and exhalation of the double-tracer gas for one tidal breath. In this paper, a simple method to determine the reconstructed MM signal is presented. Measurements on subjects with and without obstructive lung diseases including the small airways have shown high reliability and reproducibility of this method.

Botryosphaeria dothidea is the type species of Botryosphaeria (Botryosphaeriaceae, Botryosphaeriales). Fungi residing in this order are amongst the most widespread and important canker and dieback pathogens of trees worldwide, with B. dothidea one of the most common species on a large number of hosts. Its taxonomic circumscription has undergone substantial change in the past decade, making it difficult to interpret the large volume of literature linked to the name B. dothidea. This pathogen profile synthesizes the current understanding of B. dothidea pertaining to its distribution, host associations and role as a pathogen in managed and natural woody environments. The prolonged latent infection or endophytic phase is of particular importance, as it implies that the fungus can easily pass undetected by quarantine systems in traded living plants, fruits and other plant parts. Infections typically become obvious only under conditions of host stress, when disease symptoms develop. This study also considers the knowledge emerging from the recently sequenced B. dothidea genome, elucidating previously unknown aspects of the species, including mating and host infection strategies. Despite more than 150 years of research on B. dothidea, there is clearly much to be learned regarding this global tree pathogen. This is increasingly important given the stresses imposed on various woody hosts as a result of climate change., Taxonomy: Botryosphaeria dothidea (Moug. ex Fr) Ces. & De Not, 1863. Kingdom Fungi, Phylum Ascomycota, Class Dothideomycetes, Order Botryosphaeriales, Family Botryosphaeriaceae, Genus Botryosphaeria, Species dothidea., Host Range: Confirmed on more than 24 host genera, including woody plants, such as Acacia (= Vachellia), Eucalyptus, Vitis and Pistachio., Disease Symptoms: Associated with twig, branch and stem cankers, tip and branch dieback, fruit rot, blue stain and plant death., Useful Websites: The Botryosphaeria site for detailed morphological descriptions (http://www.crem.fct.unl.pt/botryosphaeria_site/); Systematic Mycology and Microbiology Laboratory Fungal Database for all literature and associated hosts (https://nt.ars-grin.gov/fungaldatabases/); TreeBASE link for the combined ITS and TEF-1α tree (http://purl.org/phylo/treebase/phylows/study/TB2:S18906); DOE Joint Genome Institute, JGI Mycocosm for the Botryosphaeria dothidea genome (http://genome.jgi.doe.gov/Botdo1_1/Botdo1_1.home.html)., (© 2016 BSPP AND JOHN WILEY & SONS LTD.)

The diversity of Phytophthora spp. in rivers and riparian ecosystems has received considerable international attention, although little such research has been conducted in South Africa. This study determined the diversity of Phytophthora spp. within a single river in Gauteng province of South Africa. Samples were collected over 1 y including biweekly river baiting with Rhododendron indicum leaves. Phytophthora isolates were identified with phylogenetic analyses of sequences for the internal transcribed spacer (ITS) region of the ribosomal DNA and the mitochondrial cytochrome oxidase c subunit I (coxI) gene. Eight Phytophthora spp. were identified, including a new taxon, P. taxon Sisulu-river, and two hybrid species from Cooke's ITS clade 6. Of these, species from Clade 6 were the most abundant, including P. chlamydospora and P. lacustris. Species residing in Clade 2 also were encountered, including P. multivora, P. plurivora and P. citrophthora. The detection of eight species in this investigation of Phytophthora diversity in a single riparian river ecosystem in northern South Africa adds to the known diversity of this genus in South Africa and globally., (© 2015 by The Mycological Society of America.)

Surveys of Australian and South African rivers revealed numerous Phytophthora isolates residing in clade 6 of the genus, with internal transcribed spacer (ITS) gene regions that were either highly polymorphic or unsequenceable. These isolates were suspected to be hybrids. Three nuclear loci, the ITS region, two single copy loci (antisilencing factor (ASF) and G protein alpha subunit (GPA)), and one mitochondrial locus (cytochrome oxidase c subunit I (coxI)) were amplified and sequenced to test this hypothesis. Abundant recombination within the ITS region was observed. This, combined with phylogenetic comparisons of the other three loci, confirmed the presence of four different hybrid types involving the three described parent species Phytophthora amnicola, Phytophthora thermophila, and Phytophthora taxon PgChlamydo. In all cases, only a single coxI allele was detected, suggesting that hybrids arose from sexual recombination. All the hybrid isolates were sterile in culture and all their physiological traits tended to resemble those of the maternal parents. Nothing is known regarding their host range or pathogenicity. Nonetheless, as several isolates from Western Australia were obtained from the rhizosphere soil of dying plants, they should be regarded as potential threats to plant health. The frequent occurrence of the hybrids and their parent species in Australia strongly suggests an Australian origin and a subsequent introduction into South Africa., (Copyright © 2013 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.)

CHEK2 1100delC is a moderate-risk cancer susceptibility allele that confers a high breast cancer risk in a polygenic setting. Gene expression profiling of CHEK2 1100delC breast cancers may reveal clues to the nature of the polygenic CHEK2 model and its genes involved. Here, we report global gene expression profiles of a cohort of 155 familial breast cancers, including 26 CHEK2 1100delC mutant tumors. In line with previous work, all CHEK2 1100delC mutant tumors clustered among the hormone receptor-positive breast cancers. In the hormone receptor-positive subset, a 40-gene CHEK2 signature was subsequently defined that significantly associated with CHEK2 1100delC breast cancers. The identification of a CHEK2 gene signature implies an unexpected biological homogeneity among the CHEK2 1100delC breast cancers. In addition, all 26 CHEK2 1100delC tumors classified as luminal intrinsic subtype breast cancers, with 8 luminal A and 18 luminal B tumors. This biological make-up of CHEK2 1100delC breast cancers suggests that a relatively limited number of additional susceptibility alleles are involved in the polygenic CHEK2 model. Identification of these as-yet-unknown susceptibility alleles should be aided by clues from the 40-gene CHEK2 signature.

Breast cancer has for long been recognized as a highly diverse tumor group, but the underlying genetic basis has been elusive. Here, we report an extensive molecular characterization of a collection of 41 human breast cancer cell lines. Protein and gene expression analyses indicated that the collection of breast cancer cell lines has retained most, if not all, molecular characteristics that are typical for clinical breast cancers. Gene mutation analyses identified 146 oncogenic mutations among 27 well-known cancer genes, amounting to an average of 3.6 mutations per cell line. Mutations in genes from the p53, RB and PI3K tumor suppressor pathways were widespread among all breast cancer cell lines. Most important, we have identified two gene mutation profiles that are specifically associated with luminal-type and basal-type breast cancer cell lines. The luminal mutation profile involved E-cadherin and MAP2K4 gene mutations and amplifications of Cyclin D1, ERBB2 and HDM2, whereas the basal mutation profile involved BRCA1, RB1, RAS and BRAF gene mutations and deletions of p16 and p14ARF. These subtype-specific gene mutation profiles constitute a genetic basis for the heterogeneity observed among human breast cancers, providing clues for their underlying biology and providing guidance for targeted pharmacogenetic intervention in breast cancer patients.

Evidentiary traces may contain low quantities of DNA, and regularly incomplete short tandem repeat (STR) profiles are obtained. In this study, higher capillary electrophoresis injection settings were used to efficiently improve incomplete STR profiles generated from low-level DNA samples under standard polymerase chain reaction (PCR) conditions. The method involves capillary electrophoresis with higher injection voltage and extended injection time. STR peak heights increased six-fold. Inherent to the analysis of low-level DNA samples, we observed stochastic amplification artifacts, mainly in the form of allele dropout and heterozygous peak imbalance. Increased stutter ratios and allele drop-in were rarely seen. Upon STR typing of 10:1 admixed samples, the profile of the major component did not become overloaded when using higher injection settings as was observed upon elevated cycling. Thereby an improved profile of the minor component was obtained. For low-level DNA casework samples, we adhere to independent replication of the PCR amplification and boosted capillary electrophoresis.

Background: Identification of genes that are causally implicated in oncogenesis is a major goal in cancer research. An estimated 10-20% of cancer-related gene mutations result in skipping of one or more exons in the encoded transcripts. Here we report on a strategy to screen in a global fashion for such exon-skipping events using PAttern based Correlation (PAC). The PAC algorithm has been used previously to identify differentially expressed splice variants between two predefined subgroups. As genetic changes in cancer are sample specific, we tested the ability of PAC to identify aberrantly expressed exons in single samples., Principal Findings: As a proof-of-principle, we tested the PAC strategy on human cancer samples of which the complete coding sequence of eight cancer genes had been screened for mutations. PAC detected all seven exon-skipping mutants among 12 cancer cell lines. PAC also identified exon-skipping mutants in clinical cancer specimens although detection was compromised due to heterogeneous (wild-type) transcript expression. PAC reduced the number of candidate genes/exons for subsequent mutational analysis by two to three orders of magnitude and had a substantial true positive rate. Importantly, of 112 randomly selected outlier exons, sequence analysis identified two novel exon skipping events, two novel base changes and 21 previously reported base changes (SNPs)., Conclusions: The ability of PAC to enrich for mutated transcripts and to identify known and novel genetic changes confirms its suitability as a strategy to identify candidate cancer genes.

A single nucleotide polymorphism (SNP309T>G) in the intronic promoter of MDM2 was recently found to accelerate carcinogenesis in early-onset cancer cases. This cancer acceleration presumably was due to increased SP1 binding, resulting in enhanced MDM2 transcriptional activation by estrogens. We evaluated MDM2 SNP309 in 343 familial breast cancer cases with known mutation status for CHEK2 1100delC, BRCA1 and BRCA2. Cancer acceleration was indeed observed in early-onset familial breast cancer cases (diagnosed

Constitutive activation of the phosphatidylinositol-3-OH kinase (PI3K) and RAS signaling pathways are important events in tumor formation. This is illustrated by the frequent genetic alteration of several key players from these pathways in a wide variety of human cancers. Here, we report a detailed sequence analysis of the PTEN, PIK3CA, KRAS, HRAS, NRAS, and BRAF genes in a collection of 40 human breast cancer cell lines. We identified a surprisingly large proportion of cell lines with mutations in the PI3K or RAS pathways (54% and 25%, respectively), with mutants for each of the six genes. The PIK3CA, KRAS, and BRAF mutation spectra of the breast cancer cell lines were similar to those of colorectal cancers. Unlike in colorectal cancers, however, mutational activation of the PI3K pathway was mutually exclusive with mutational activation of the RAS pathway in all but 1 of 30 mutant breast cancer cell lines (P = 0.001). These results suggest that there is a fine distinction between the signaling activators and downstream effectors of the oncogenic PI3K and RAS pathways in breast epithelium and those in other tissues.

There is little experimental knowledge on the sequence dependent rate of hairpin formation in RNA. We have therefore designed RNA sequences that can fold into either of two mutually exclusive hairpins and have determined the ratio of folding of the two conformations, using structure probing. This folding ratio reflects their respective folding rates. Changing one of the two loop sequences from a purine- to a pyrimidine-rich loop did increase its folding rate, which corresponds well with similar observations in DNA hairpins. However, neither changing one of the loops from a regular non-GNRA tetra-loop into a stable GNRA tetra-loop, nor increasing the loop size from 4 to 6 nt did affect the folding rate. The folding kinetics of these RNAs have also been simulated with the program 'Kinfold'. These simulations were in agreement with the experimental results if the additional stabilization energies for stable tetra-loops were not taken into account. Despite the high stability of the stable tetra-loops, they apparently do not affect folding kinetics of these RNA hairpins. These results show that it is possible to experimentally determine relative folding rates of hairpins and to use these data to improve the computer-assisted simulation of the folding kinetics of stem-loop structures.

Germ line mutations of the BRCA1 gene confer a high risk of breast cancer and ovarian cancer to female mutation carriers. The BRCA1 protein is involved in the regulation of DNA repair. How specific tumor-associated mutations affect the molecular function of BRCA1, however, awaits further elucidation. Cell lines that harbor BRCA1 gene mutations are invaluable tools for such functional studies. Up to now, the HCC1937 cell line was the only human breast cancer cell line with an identified BRCA1 mutation. In this study, we identified three other BRCA1 mutants from among 41 human breast cancer cell lines by sequencing of the complete coding sequence of BRCA1. Cell line MDA-MB-436 had the 5396 + 1G>A mutation in the splice donor site of exon 20. Cell line SUM149PT carried the 2288delT mutation and SUM1315MO2 carried the 185delAG mutation. All three mutations were accompanied by loss of the other BRCA1 allele. The 185delAG and 5396 + 1G>A mutations are both classified as pathogenic mutations. In contrast with wild-type cell lines, none of the BRCA1 mutants expressed nuclear BRCA1 proteins as detected with Ab-1 and Ab-2 anti-BRCA1 monoclonal antibodies. These three new human BRCA1 mutant cell lines thus seem to be representative breast cancer models that could aid in further unraveling of the function of BRCA1.

Oligodendrogliomas are a specific subtype of brain tumor of which the majority responds favorably to chemotherapy. In this study, we made use of expression profiling to identify chemosensitive oligodendroglial tumors. Correlation of expression profiles to loss of heterozygosity on 1p and 19q, common chromosomal aberrations associated with response to treatment, identified 376, 64, and 60 differentially expressed probe sets associated with loss of 1p, 19q or 1p, and 19q, respectively. Correlation of expression profiles to the tumors' response to treatment identified 16 differentially expressed probe sets. Because transcripts associated with chemotherapeutic response were identified independent of common chromosomal aberrations, expression profiling may be used as an alternative approach to the tumors' 1p status to identify chemosensitive oligodendroglial tumors. Finally, we correlated expression profiles to survival of the patient after diagnosis and identified 103 differentially expressed probe sets. The observation that many genes are differentially expressed between long and short survivors indicates that the genetic background of the tumor is an important factor in determining the prognosis of the patient. Furthermore, these transcripts can help identify patient subgroups that are associated with favorable prognosis. Our study is the first to correlate gene expression with chromosomal aberrations and clinical performance (response to treatment and survival) in oligodendrogliomas. The differentially expressed transcripts can help identify patient subgroups with good prognosis and those that will benefit from chemotherapeutic treatments.

The mechanical properties of in vivo soft tissue are generally determined by palpation, ultrasound measurements (US), and magnetic resonance elastography (MRE). While it has been shown that US and MRE are capable of quantitatively measuring soft tissue elasticity, there is still some uncertainty about the reliability of quantitative MRE measurements. For this reason it was decided to determine in vitro how MRE measurements correspond with other quantitative methods of measuring characteristic elasticity values. This article presents the results of experiments with tissue-like agar-agar gel phantoms in which the wavelength of strain waves was measured by shear wave MR elastography and the resultant shear modulus was compared with results from mechanical compression tests with small gel specimens. The shear moduli of nine homogeneous gels with various agar-agar concentrations were investigated. The elasticity range of the gels covered the elasticity range of typical soft tissues. The systematic comparison between shear wave MRE and compression tests showed good agreement between the two measurement techniques., (Copyright 2003 Wiley-Liss, Inc.)

Many biologically active RNAs show a switch in their secondary structure, which is accompanied by changes in their function. Such changes in secondary structure often require trans-acting factors, e.g. RNA chaperones. However, several biologically active RNAs do not require trans-acting factors for this structural switch, which is therefore indicated here as a "self-induced switch". These self-induced structural switches have several characteristics in common. They all start from a metastable structure, which is maintained for some time allowing or blocking a particular function of the RNA. Hereafter, a structural element becomes available, e.g. during transcription, triggering a rapid transition into a stable conformation, which again is accompanied by either a gain or loss of function. A further common element of this type of switches is the involvement of a branch migration or strand displacement reaction, which lowers the energy barrier of the reaction sufficiently to allow rapid refolding. Here, we review a number of these self-induced switches in RNA secondary structure as proposed for several systems. A general model for this type of switches is presented, showing its importance in the biology of functionally active RNAs.

It has been shown that premature translation of the plasmid-mediated toxin in hok/sok of plasmid R1 and pnd/pndB of plasmid R483 is prevented during transcription of the hok and pnd mRNAs by the formation of metastable hairpins at the 5'-end of the mRNA. Here, an experimental approach is presented, which allows the accurate measurement of the refolding kinetics of the 5'-end RNA fragments in vitro without chemically modifying the RNA. The method is based on acid denaturation followed by a pH-jump to neutral pH as a novel way to trap kinetically favoured RNA secondary structures, allowing the measurement of a wide range of biologically relevant refolding rates, with or without the use of standard stopped-flow equipment. The refolding rates from the metastable to the stable conformation in both the hok74 and pnd58 5'-end RNA fragments were determined by using UV absorbance changes corresponding to the structural rearrangements. The measured energy barriers showed that the refolding path does not need complete unfolding of the metastable structures before the formation of the final structures. Two alternative models of such a pathway are discussed.

The present study examined whether alterations in the cardiac baroreceptor reflex in hypertension may be a function of constitutional differences associated with gender and age. These hypotheses were tested using a cross-sectional design that compared 20 normotensive and 21 hypertensive men and women of varying age for differences in baroreceptor reflex sensitivity and response latency for heart rate, obtained using a modified bolus phenylephrine (Oxford) method. Relative to their respective normotensive controls, baroreceptor reflex sensitivity was reduced in hypertensive men, but not in hypertensive women. Among normotensive subjects, men had greater baroreceptor reflex sensitivity than women. Independent from the effects associated with differences in blood pressure, age was not a significant predictor of reduction in baroreceptor reflex sensitivity. However, a combination of high blood pressure and older age was associated with a significant increase in baroreceptor reflex response time. In summary, gender and aging interacted with hypertension to alter two different aspects of the baroreceptor reflex. These results provide a preliminary indication that a decline in arterial baroreflex sensitivity may be more specific to hypertension in men than in women. Prolongation in baroreflex response latency in older hypertensive subjects also suggested that aging and hypertension may have a synergistic effect on cardiac parasympathetic function.

Programmed cell death by hok/sok of plasmid R1 and pnd/pndB of R483 mediates plasmid maintenance by killing of plasmid-free cells. It has been previously suggested that premature translation of the plasmid-mediated toxin is prevented during transcription of the hok and pnd mRNAs by the formation of metastable hairpins in the mRNA at the 5' end. Here, experimental evidence is presented for the existence of metastable structures in the 5' leader of the hok and pnd mRNAs in vitro. The kinetics of refolding from the metastable to the stable structure in the isolated fragments of the 5' ends of both the hok and pnd mRNAs could be estimated, in agreement with the structural rearrangement in this region, as predicted to occur during transcription and mRNA activation. The refolding rates of hok and pnd structures are slow enough to allow for the formation of downstream hairpin structures during elongation of the mRNAs, which thereby helps to stabilize the metastable structures. Thus, the kinetic refolding parameters of the hok and pnd mRNAs are consistent with the proposal that the metastable structures prevent premature translation and/or antisense RNA binding during transcription.

In cardiovascular reactivity studies, interpretations of the processes supporting the blood pressure response may become problematic when systolic blood pressure, diastolic blood pressure, and heart rate all increase in response to a behavioral challenge. Therefore, in addition to evaluating these cardiovascular responses, this study examined cardiac output, total peripheral resistance and systolic time intervals derived from impedance cardiogram, electrocardiogram and phonocardiogram recordings during a speech stressor, a mirror tracing task, and a foot cold pressor test. All of the behavioral stressors elicited increases in blood pressure and heart rate, with the largest changes occurring during the overt speech. Based on the examination of the response patterns of the underlying hemodynamic variables it would appear that, in both men and women, the blood pressure increase during the speech preparation period was supported by increased cardiac output; the speech itself resulted in a mixed pattern of increased cardiac output and total peripheral resistance; whereas, the mirror tracing and cold pressor tasks produced increased total peripheral resistance. Although men and women produced similar response patterns to the behavioral challenges, sex differences in the estimates of myocardial contractility were observed during rest. These results provide evidence that different behavioral stressors can produce a distinct yet integrated pattern of responses, whose differences may be revealed, when impedance cardiography is used, to derive sufficient response measures for assessing dynamic cardiovascular processes.

Our findings indicate that the impedance cardiogram spectrum extends from DC to 50 Hz. Any amplifier with an upper band limit less than 50 Hz can be expected to produce attenuation and distortion of the impedance cardiogram. This signal attenuation may be systematically enhanced under conditions of high heart rate when a greater proportion of signal energy will be in the upper frequency range of the impedance cardiogram spectrum. Therefore, the present study was designed to assess the influence of amplifier bandwidth on dZ/dtmax, stroke volume, and systolic time intervals (LVET, PEP, QZ, QX). Simultaneously measured delta Z and dZ/dt signals from two impedance cardiographs, with corner frequencies of 120 and 60 Hz for the delta Z and 50 and 15 Hz for dZ/dt channels, were contrasted over a broad range of heart rate (70-150 bpm). In addition to the analog dZ/dt signals obtained from the instruments, the delta Z signals were digitally converted to dZ/dt by off-line digital differentiation with a 50 Hz corner frequency. The results demonstrated that the measurements with the 15 Hz corner frequency, when compared with the 50 Hz corner frequency measurements, systematically attenuated the dZ/dtmax amplitude and stroke volume measurements as heart rate increased. The attenuation of dZ/dtmax and stroke volume ranged from about 13% to 26% as heart rate increased from 70 to 150 bpm. When the upper bandlimit was 50 Hz, the dZ/dt signal had greater resolution of waveform events and produced less prolonged systolic time intervals. The 15 Hz amplifier differentially influenced the B point, Z-peak and X minimum, having no apparent effect on the temporal location of the B point, but delaying the Z-peak about 21.7 ms and the X minimum about 7.4 ms. These findings indicate that impedance cardiographs with insufficient upper bandlimits will differentially influence ICG-derived measurements as heart rate varies.

Impedance cardiographic determination of clinically important cardiac parameters such as systolic time intervals, stroke volume, and related cardiovascular parameters has not yet found adequate application in clinical practice, since its theoretical basis remains controversial, and the precision of beat-to-beat parameter estimation has until recently suffered under severe shortcomings of available signal processing techniques. High levels of noise and motion artifacts deteriorate signal quality and result in poor event detection. To improve the precision of impedance cardiography, new techniques for event detection and parameter estimation have been developed. Specifically, matched filtering and various signal segmentation and decomposition techniques have been tested on impedance signals with various levels of artificially superimposed noise and on actual recordings from subjects in a laboratory study of cardiovascular response to a cognitive challenge. Substantial improvement in the precision of impedance cardiography was obtained using the newly developed signal processing techniques. In addition, some preliminary evidence from comparisons of the impedance cardiogram with invasive aortic electromagnetic flow measurement in anesthetized rabbits is presented to address questions relating to the origin of the impedance signal.