Peter Weber - Profile on Academia.edu (original) (raw)

Papers by Peter Weber

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Neuron, Jan 3, 2015

Depression risk is exacerbated by genetic factors and stress exposure; however, the biological me... more Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation m...

PloS one, 2015

Genomic copy number variants (CNVs) have been implicated in multiple psychiatric disorders, but n... more Genomic copy number variants (CNVs) have been implicated in multiple psychiatric disorders, but not much is known about their influence on anxiety disorders specifically. Using next-generation sequencing (NGS) and two additional array-based genotyping approaches, we detected CNVs in a mouse model consisting of two inbred mouse lines showing high (HAB) and low (LAB) anxiety-related behavior, respectively. An influence of CNVs on gene expression in the central (CeA) and basolateral (BLA) amygdala, paraventricular nucleus (PVN), and cingulate cortex (Cg) was shown by a two-proportion Z-test (p = 1.6 x 10-31), with a positive correlation in the CeA (p = 0.0062), PVN (p = 0.0046) and Cg (p = 0.0114), indicating a contribution of CNVs to the genetic predisposition to trait anxiety in the specific context of HAB/LAB mice. In order to confirm anxiety-relevant CNVs and corresponding genes in a second mouse model, we further examined CD-1 outbred mice. We revealed the distribution of CNVs by ...

Long-term outcome after arterial ischemic stroke in children and young adults

Neurology, 2015

To compare long-term outcome of children and young adults with arterial ischemic stroke (AIS) fro... more To compare long-term outcome of children and young adults with arterial ischemic stroke (AIS) from 2 large registries. Prospective cohort study comparing functional and psychosocial long-term outcome (≥2 years after AIS) in patients who had AIS during childhood (1 month-16 years) or young adulthood (16.1-45 years) between January 2000 and December 2008, who consented to follow-up. Data of children were collected prospectively in the Swiss Neuropediatric Stroke Registry, young adults in the Bernese stroke database. Follow-up information was available in 95/116 children and 154/187 young adults. Median follow-up of survivors was 6.9 years (interquartile range 4.7-9.4) and did not differ between the groups (p = 0.122). Long-term functional outcome was similar (p = 0.896): 53 (56%) children and 84 (55%) young adults had a favorable outcome (modified Rankin Scale 0-1). Mortality in children was 14% (13/95) and in young adults 7% (11/154) (p = 0.121) and recurrence rate did not differ (p = 0.759). Overall psychosocial impairment and quality of life did not differ, except for more behavioral problems among children (13% vs 5%, p = 0.040) and more frequent reports of an impact of AIS on everyday life among adults (27% vs 64%, p < 0.001). In a multivariate regression analysis, low Pediatric NIH Stroke Scale/NIH Stroke Scale score was the most important predictor of favorable outcome (p < 0.001). There were no major differences in long-term outcome after AIS in children and young adults for mortality, disability, quality of life, psychological, or social variables.

PloS one, 2015

Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associate... more Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion. This was a prospective emergency-setting cross-sectional study of 161 children between six months and five years of age. Of these, 83 were diagnosed with febrile seizures, 69 had a febrile infection without seizures and nine had epileptic seizures not triggered by infection. Serum copeptin and prolactin levels were measured in addition to standard clinical, neurophysiological, and laboratory assessment. Clinical Trial Registration: NCT01884766. Circulating copeptin was significantly higher in children with febrile seizures (median [interquartile range] 18.9 pmol/L [8.5-36.6]) compared to febrile controls (5.6 pmol/L [4.1-9.4]; p <0.001), with no differences ...

Dihydropyrimidine Dehydrogenase Deficiency Caused by a Novel Genomic Deletion c.505_513del of DPYD

Nucleosides Nucleotides & Nucleic Acids, 2010

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of the pyrimi... more Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of the pyrimidine degradation pathway. In a patient presenting with convulsions, psychomotor retardation and Reye like syndrome, strongly elevated levels of uracil and thymine were detected in urine. No DPD activity could be detected in peripheral blood mononuclear cells. Analysis of the gene encoding DPD (DPYD) showed that the patient was

The ISME journal, 2015

Photosynthetic microbial mats are complex, stratified ecosystems in which high rates of primary p... more Photosynthetic microbial mats are complex, stratified ecosystems in which high rates of primary production create a demand for nitrogen, met partially by N₂ fixation. Dinitrogenase reductase (nifH) genes and transcripts from Cyanobacteria and heterotrophic bacteria (for example, Deltaproteobacteria) were detected in these mats, yet their contribution to N2 fixation is poorly understood. We used a combined approach of manipulation experiments with inhibitors, nifH sequencing and single-cell isotope analysis to investigate the active diazotrophic community in intertidal microbial mats at Laguna Ojo de Liebre near Guerrero Negro, Mexico. Acetylene reduction assays with specific metabolic inhibitors suggested that both sulfate reducers and members of the Cyanobacteria contributed to N₂ fixation, whereas (15)N₂ tracer experiments at the bulk level only supported a contribution of Cyanobacteria. Cyanobacterial and nifH Cluster III (including deltaproteobacterial sulfate reducers) sequence...

Frontiers in microbiology, 2014

Past studies of hydrogen cycling in hypersaline microbial mats have shown an active nighttime cyc... more Past studies of hydrogen cycling in hypersaline microbial mats have shown an active nighttime cycle, with production largely from Cyanobacteria and consumption from sulfate-reducing bacteria (SRB). However, the mechanisms and magnitude of hydrogen cycling have not been extensively studied. Two mats types near Guerrero Negro, Mexico-permanently submerged Microcoleus microbial mat (GN-S), and intertidal Lyngbya microbial mat (GN-I)-were used in microcosm diel manipulation experiments with 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), molybdate, ammonium addition, and physical disruption to understand the processes responsible for hydrogen cycling between mat microbes. Across microcosms, H2 production occurred under dark anoxic conditions with simultaneous production of a suite of organic acids. H2 production was not significantly affected by inhibition of nitrogen fixation, but rather appears to result from constitutive fermentation of photosynthetic storage products by oxygenic pho...

Science, 2007

High spatial-resolution secondaryion microprobespectrometry, synchrotron radiation Fourier-transf... more High spatial-resolution secondaryion microprobespectrometry, synchrotron radiation Fourier-transform infraredspectroscopy and polyacrylamide gel analysis demonstrate the intimateassociation of proteins with spheroidal aggregates of biogenic zincsulfide nanocrystals, an example of extracellular biomineralization.Experiments involving synthetic ZnS nanoparticles and representativeamino acids indicate a driving role for cysteine in rapid nanoparticleaggregation. These findings suggest that microbially-derivedextracellular proteins can limit dispersal of nanoparticulatemetal-bearing phases, such as the

1997 IEEE Ultrasonics Symposium Proceedings. An International Symposium (Cat. No.97CH36118), 1997

A new criterion, minimization of maximal weighted sidelobe, is applied together with a genetic se... more A new criterion, minimization of maximal weighted sidelobe, is applied together with a genetic search algorithm to the problem of element placement in a discrete linear lattice. By processing RF-data, the resulting 1D sparse arrays are compared experimentally with sparse periodic arrays and arrays found with a least square optimization criterion. The images show that algorithmically optimized layouts can be found with lateral resolution and contrast comparable to sparse periodic arrays.

To examine phylogenetic identity and metabolic activity of individual cells in complex microbial ... more To examine phylogenetic identity and metabolic activity of individual cells in complex microbial communi- ties, we developed a method which combines rRNA-based in situ hybridization with stable isotope imaging based on nanometer-scale secondary-ion mass spectrometry (NanoSIMS). Fluorine or bromine atoms were introduced into cells via 16S rRNA-targeted probes, which enabled phylogenetic identification of individual cells by NanoSIMS imaging. To overcome

Journal of Psychiatric Research, 2015

Very preterm children are at higher risk to develop behavioral and emotional problems, poor sleep... more Very preterm children are at higher risk to develop behavioral and emotional problems, poor sleep, and altered hypothalamic-pituitary-adrenocortical activity (HPAA). However, knowledge on objective sleep and HPAA as well as their role for the development of behavioral and emotional problems in very preterm children is limited. Fifty-eight very preterm children (<32nd gestational week) and 55 full-term children aged 6e10 years underwent one night of in-home polysomnographic sleep assessment. HPAA was assessed with four saliva samples in the morning (morning cortisol secretion) and four saliva samples in the evening (evening cortisol secretion). Parents completed the Strengths and Difficulties Questionnaire (SDQ) to assess children's behavioral and emotional problems and a subscale of the Children's Sleep Habits Questionnaire to assess sleep disordered breathing. Very preterm children showed more behavioral and emotional problems (SDQ total behavioral/emotional difficulties, emotional symptoms), poorer sleep (more nocturnal awakenings, more stage 2 sleep, less slow wave sleep), and faster decreasing evening cortisol secretion compared to full-term children. Across the whole sample, more stage 2 sleep and/or less slow wave sleep were associated with more SDQ total behavioral/ emotional difficulties, hyperactivity-inattention, and peer problems. Lower morning cortisol secretion and lower evening cortisol secretion were associated with more conduct problems. In very preterm children, increased SDQ total behavioral/emotional difficulties was partially explained by less restorative sleep including more stage 2 sleep and less slow wave sleep. This result points to the importance of restorative sleep for the behavioral and emotional development of very preterm children during middle childhood.

Direction-of-arrival of partial waves in wideband mobile radio channels for intelligent antenna concepts

Vehicular Technology, IEEE Conference, 1996

A method for wideband measurement and for post-processing of mobile radio channel impulse respons... more A method for wideband measurement and for post-processing of mobile radio channel impulse responses which include unambiguous information about the directions-of-arrival in the azimuth is introduced. Based on this method, measurement results for outdoor macrocellular environments are presented. These results are essential for assessing, developing, evaluating and optimizing adaptive directional antenna concepts for future mobile radio systems and for extending

The ISME Journal, 2012

Hydrogen (H 2 ) release from photosynthetic microbial mats has contributed to the 19 chemical evo... more Hydrogen (H 2 ) release from photosynthetic microbial mats has contributed to the 19 chemical evolution of Earth and could potentially be a source of renewable H 2 in the 20 future. However, the taxonomy of H 2 -producing microorganisms (hydrogenogens) in 21 these mats have not been previously determined. With combined biogeochemical and 22 595

The ISME Journal, 2007

Filamentous cyanobacteria are key players in global nutrient cycling, but the relationship betwee... more Filamentous cyanobacteria are key players in global nutrient cycling, but the relationship between C-and N-fixation and intercellular exchange of these elements remains poorly understood in many cyanobacteria. Using enriched H 13 CO 3 and 15 N 2 in incubations of Anabaena oscillarioides and high resolution nanometer-scale secondary ion mass spectrometry (NanoSIMS), we imaged the cellular distribution of recently assimilated C and N and observed that newly fixed nitrogen is rapidly exported from heterocysts and allocated to actively growing regions of vegetative cells. This approach allows characterization of cellular development (division, heterocyst differentiation), changes in individual cell composition, and cellular roles in metabolite exchange. (99 words) Some cyanobacteria are uniquely capable of fixing both dinitrogen (N 2 ) and CO 2 , deriving energy from oxygenic photosynthesis. These capabilities and the abundance of cyanobacteria in phytoplankton communities make these microorganisms keystone species in the global biogeochemical cycles of carbon and nitrogen. Under conditions of N limitation,

Proceedings of the National Academy of Sciences, 2009

The marine cyanobacterium Trichodesmium is ubiquitous in tropical and subtropical seas and is an ... more The marine cyanobacterium Trichodesmium is ubiquitous in tropical and subtropical seas and is an important contributor to global N and C cycling. We sought to characterize metabolic uptake patterns in individual Trichodesmium IMS-101 cells by quantitatively imaging 13 C and 15 N uptake with high-resolution secondary ion mass spectrometry (NanoSIMS). Trichodesmium fix both CO 2 and N2 concurrently during the day and are, thus, faced with a balancing act: the O 2 evolved during photosynthesis inhibits nitrogenase, the key enzyme in N 2 fixation. After performing correlated transmission electron microscopy (TEM) and NanoSIMS analysis on trichome thin-sections, we observed transient inclusion of 15 N and 13 C into discrete subcellular bodies identified as cyanophycin granules. We speculate that Trichodesmium uses these dynamic storage bodies to uncouple CO 2 and N2 fixation from overall growth dynamics. We also directly quantified both CO 2 and N 2 fixation at the single cell level using NanoSIMS imaging of whole cells in multiple trichomes. Our results indicate maximal CO 2 fixation rates in the morning, compared with maximal N2 fixation rates in the afternoon, bolstering the argument that segregation of CO 2 and N2 fixation in Trichodesmium is regulated in part by temporal factors. Spatial separation of N 2 and CO2 fixation may also have a role in metabolic segregation in Trichodesmium. Our approach in combining stable isotope labeling with NanoSIMS and TEM imaging can be extended to other physiologically relevant elements and processes in other important microbial systems.

Proceedings of the IEEE, 1991

This paper may be viewed as the culmination of a radar clutter classification research program th... more This paper may be viewed as the culmination of a radar clutter classification research program that has spanned over 15 years. In particular, we present the results of an experimental study aimed at the classification of radar clutter encountered on ground-based coherent scanning radar systems used for air traffic control. The clutter signals of interest are primarily those due to birds as well as clouds and weather systems. These two sources of radar returns represent potential hazards to aircraft safety. The aim of the clutter classifier is therefore to vector aircraft around such areas.

Acute disseminated encephalomyelitis review in 8 pediatric patients

Neuropediatrics, 2008

Neuromuscular Disorders, 2014

Mutations in A-type nuclear lamins are known to cause a variety of diseases, which can affect alm... more Mutations in A-type nuclear lamins are known to cause a variety of diseases, which can affect almost all organs of the human body including striated muscle. For lamin-related congenital muscular dystrophy two different phenotypes are known to date. Here, we describe a 3-year-old, white Caucasian girl with a novel de novo mutation in the LMNA gene with marked hypotonia of neck and trunk muscles with dropped head posture, loss of cervical lordosis and marked joint laxity. In addition to this novel mutation, the patient also had cerebral white matter lesions on MRI and cognitive impairment on developmental testing. This is only the second A-type lamin-related congenital muscular dystrophy patient in which white matter lesions are described. Thus, white matter involvement might be a feature in A-type lamin-related congenital muscular dystrophy, warranting screening of these patients for both white matter lesions and cognitive impairment.

Utility of neuropsychological testing for guiding treatment decisions in paediatric multiple sclerosis

Multiple Sclerosis Journal, 2013

In the past years, there has been growing awareness about childhood onset multiple sclerosis (MS)... more In the past years, there has been growing awareness about childhood onset multiple sclerosis (MS) and the relevance of psychosocial aspects such as cognitive disturbances, fatigue and depression in this population. We describe a case of a 16-year-old patient with relapsing-remitting multiple sclerosis (RRMS) who presented at our clinic with severe fatigue symptoms and who underwent repeated neuropsychological examinations. A sudden significant slowing indicated a new relapse while neurological examination did not. This case highlights the high sensitivity and clinical relevance of neuropsychological testing in patients with juvenile MS even in the context of treatment decisions.

Inhibition of Monoamine Oxidases by Functionalized Coumarin Derivatives: Biological Activities, QSARs, and 3D-QSARs

Journal of Medicinal Chemistry, 2000

A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A a... more A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC(50) values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3, 4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC(50) value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2)() = 0.72, r(2)() = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

Neuron, Jan 3, 2015

Depression risk is exacerbated by genetic factors and stress exposure; however, the biological me... more Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation m...

PloS one, 2015

Genomic copy number variants (CNVs) have been implicated in multiple psychiatric disorders, but n... more Genomic copy number variants (CNVs) have been implicated in multiple psychiatric disorders, but not much is known about their influence on anxiety disorders specifically. Using next-generation sequencing (NGS) and two additional array-based genotyping approaches, we detected CNVs in a mouse model consisting of two inbred mouse lines showing high (HAB) and low (LAB) anxiety-related behavior, respectively. An influence of CNVs on gene expression in the central (CeA) and basolateral (BLA) amygdala, paraventricular nucleus (PVN), and cingulate cortex (Cg) was shown by a two-proportion Z-test (p = 1.6 x 10-31), with a positive correlation in the CeA (p = 0.0062), PVN (p = 0.0046) and Cg (p = 0.0114), indicating a contribution of CNVs to the genetic predisposition to trait anxiety in the specific context of HAB/LAB mice. In order to confirm anxiety-relevant CNVs and corresponding genes in a second mouse model, we further examined CD-1 outbred mice. We revealed the distribution of CNVs by ...

Long-term outcome after arterial ischemic stroke in children and young adults

Neurology, 2015

To compare long-term outcome of children and young adults with arterial ischemic stroke (AIS) fro... more To compare long-term outcome of children and young adults with arterial ischemic stroke (AIS) from 2 large registries. Prospective cohort study comparing functional and psychosocial long-term outcome (≥2 years after AIS) in patients who had AIS during childhood (1 month-16 years) or young adulthood (16.1-45 years) between January 2000 and December 2008, who consented to follow-up. Data of children were collected prospectively in the Swiss Neuropediatric Stroke Registry, young adults in the Bernese stroke database. Follow-up information was available in 95/116 children and 154/187 young adults. Median follow-up of survivors was 6.9 years (interquartile range 4.7-9.4) and did not differ between the groups (p = 0.122). Long-term functional outcome was similar (p = 0.896): 53 (56%) children and 84 (55%) young adults had a favorable outcome (modified Rankin Scale 0-1). Mortality in children was 14% (13/95) and in young adults 7% (11/154) (p = 0.121) and recurrence rate did not differ (p = 0.759). Overall psychosocial impairment and quality of life did not differ, except for more behavioral problems among children (13% vs 5%, p = 0.040) and more frequent reports of an impact of AIS on everyday life among adults (27% vs 64%, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In a multivariate regression analysis, low Pediatric NIH Stroke Scale/NIH Stroke Scale score was the most important predictor of favorable outcome (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). There were no major differences in long-term outcome after AIS in children and young adults for mortality, disability, quality of life, psychological, or social variables.

PloS one, 2015

Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associate... more Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion. This was a prospective emergency-setting cross-sectional study of 161 children between six months and five years of age. Of these, 83 were diagnosed with febrile seizures, 69 had a febrile infection without seizures and nine had epileptic seizures not triggered by infection. Serum copeptin and prolactin levels were measured in addition to standard clinical, neurophysiological, and laboratory assessment. Clinical Trial Registration: NCT01884766. Circulating copeptin was significantly higher in children with febrile seizures (median [interquartile range] 18.9 pmol/L [8.5-36.6]) compared to febrile controls (5.6 pmol/L [4.1-9.4]; p <0.001), with no differences ...

Dihydropyrimidine Dehydrogenase Deficiency Caused by a Novel Genomic Deletion c.505_513del of DPYD

Nucleosides Nucleotides & Nucleic Acids, 2010

Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of the pyrimi... more Dihydropyrimidine dehydrogenase (DPD) deficiency is an autosomal recessive disorder of the pyrimidine degradation pathway. In a patient presenting with convulsions, psychomotor retardation and Reye like syndrome, strongly elevated levels of uracil and thymine were detected in urine. No DPD activity could be detected in peripheral blood mononuclear cells. Analysis of the gene encoding DPD (DPYD) showed that the patient was

The ISME journal, 2015

Photosynthetic microbial mats are complex, stratified ecosystems in which high rates of primary p... more Photosynthetic microbial mats are complex, stratified ecosystems in which high rates of primary production create a demand for nitrogen, met partially by N₂ fixation. Dinitrogenase reductase (nifH) genes and transcripts from Cyanobacteria and heterotrophic bacteria (for example, Deltaproteobacteria) were detected in these mats, yet their contribution to N2 fixation is poorly understood. We used a combined approach of manipulation experiments with inhibitors, nifH sequencing and single-cell isotope analysis to investigate the active diazotrophic community in intertidal microbial mats at Laguna Ojo de Liebre near Guerrero Negro, Mexico. Acetylene reduction assays with specific metabolic inhibitors suggested that both sulfate reducers and members of the Cyanobacteria contributed to N₂ fixation, whereas (15)N₂ tracer experiments at the bulk level only supported a contribution of Cyanobacteria. Cyanobacterial and nifH Cluster III (including deltaproteobacterial sulfate reducers) sequence...

Frontiers in microbiology, 2014

Past studies of hydrogen cycling in hypersaline microbial mats have shown an active nighttime cyc... more Past studies of hydrogen cycling in hypersaline microbial mats have shown an active nighttime cycle, with production largely from Cyanobacteria and consumption from sulfate-reducing bacteria (SRB). However, the mechanisms and magnitude of hydrogen cycling have not been extensively studied. Two mats types near Guerrero Negro, Mexico-permanently submerged Microcoleus microbial mat (GN-S), and intertidal Lyngbya microbial mat (GN-I)-were used in microcosm diel manipulation experiments with 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), molybdate, ammonium addition, and physical disruption to understand the processes responsible for hydrogen cycling between mat microbes. Across microcosms, H2 production occurred under dark anoxic conditions with simultaneous production of a suite of organic acids. H2 production was not significantly affected by inhibition of nitrogen fixation, but rather appears to result from constitutive fermentation of photosynthetic storage products by oxygenic pho...

Science, 2007

High spatial-resolution secondaryion microprobespectrometry, synchrotron radiation Fourier-transf... more High spatial-resolution secondaryion microprobespectrometry, synchrotron radiation Fourier-transform infraredspectroscopy and polyacrylamide gel analysis demonstrate the intimateassociation of proteins with spheroidal aggregates of biogenic zincsulfide nanocrystals, an example of extracellular biomineralization.Experiments involving synthetic ZnS nanoparticles and representativeamino acids indicate a driving role for cysteine in rapid nanoparticleaggregation. These findings suggest that microbially-derivedextracellular proteins can limit dispersal of nanoparticulatemetal-bearing phases, such as the

1997 IEEE Ultrasonics Symposium Proceedings. An International Symposium (Cat. No.97CH36118), 1997

A new criterion, minimization of maximal weighted sidelobe, is applied together with a genetic se... more A new criterion, minimization of maximal weighted sidelobe, is applied together with a genetic search algorithm to the problem of element placement in a discrete linear lattice. By processing RF-data, the resulting 1D sparse arrays are compared experimentally with sparse periodic arrays and arrays found with a least square optimization criterion. The images show that algorithmically optimized layouts can be found with lateral resolution and contrast comparable to sparse periodic arrays.

To examine phylogenetic identity and metabolic activity of individual cells in complex microbial ... more To examine phylogenetic identity and metabolic activity of individual cells in complex microbial communi- ties, we developed a method which combines rRNA-based in situ hybridization with stable isotope imaging based on nanometer-scale secondary-ion mass spectrometry (NanoSIMS). Fluorine or bromine atoms were introduced into cells via 16S rRNA-targeted probes, which enabled phylogenetic identification of individual cells by NanoSIMS imaging. To overcome

Journal of Psychiatric Research, 2015

Very preterm children are at higher risk to develop behavioral and emotional problems, poor sleep... more Very preterm children are at higher risk to develop behavioral and emotional problems, poor sleep, and altered hypothalamic-pituitary-adrenocortical activity (HPAA). However, knowledge on objective sleep and HPAA as well as their role for the development of behavioral and emotional problems in very preterm children is limited. Fifty-eight very preterm children (<32nd gestational week) and 55 full-term children aged 6e10 years underwent one night of in-home polysomnographic sleep assessment. HPAA was assessed with four saliva samples in the morning (morning cortisol secretion) and four saliva samples in the evening (evening cortisol secretion). Parents completed the Strengths and Difficulties Questionnaire (SDQ) to assess children's behavioral and emotional problems and a subscale of the Children's Sleep Habits Questionnaire to assess sleep disordered breathing. Very preterm children showed more behavioral and emotional problems (SDQ total behavioral/emotional difficulties, emotional symptoms), poorer sleep (more nocturnal awakenings, more stage 2 sleep, less slow wave sleep), and faster decreasing evening cortisol secretion compared to full-term children. Across the whole sample, more stage 2 sleep and/or less slow wave sleep were associated with more SDQ total behavioral/ emotional difficulties, hyperactivity-inattention, and peer problems. Lower morning cortisol secretion and lower evening cortisol secretion were associated with more conduct problems. In very preterm children, increased SDQ total behavioral/emotional difficulties was partially explained by less restorative sleep including more stage 2 sleep and less slow wave sleep. This result points to the importance of restorative sleep for the behavioral and emotional development of very preterm children during middle childhood.

Direction-of-arrival of partial waves in wideband mobile radio channels for intelligent antenna concepts

Vehicular Technology, IEEE Conference, 1996

A method for wideband measurement and for post-processing of mobile radio channel impulse respons... more A method for wideband measurement and for post-processing of mobile radio channel impulse responses which include unambiguous information about the directions-of-arrival in the azimuth is introduced. Based on this method, measurement results for outdoor macrocellular environments are presented. These results are essential for assessing, developing, evaluating and optimizing adaptive directional antenna concepts for future mobile radio systems and for extending

The ISME Journal, 2012

Hydrogen (H 2 ) release from photosynthetic microbial mats has contributed to the 19 chemical evo... more Hydrogen (H 2 ) release from photosynthetic microbial mats has contributed to the 19 chemical evolution of Earth and could potentially be a source of renewable H 2 in the 20 future. However, the taxonomy of H 2 -producing microorganisms (hydrogenogens) in 21 these mats have not been previously determined. With combined biogeochemical and 22 595

The ISME Journal, 2007

Filamentous cyanobacteria are key players in global nutrient cycling, but the relationship betwee... more Filamentous cyanobacteria are key players in global nutrient cycling, but the relationship between C-and N-fixation and intercellular exchange of these elements remains poorly understood in many cyanobacteria. Using enriched H 13 CO 3 and 15 N 2 in incubations of Anabaena oscillarioides and high resolution nanometer-scale secondary ion mass spectrometry (NanoSIMS), we imaged the cellular distribution of recently assimilated C and N and observed that newly fixed nitrogen is rapidly exported from heterocysts and allocated to actively growing regions of vegetative cells. This approach allows characterization of cellular development (division, heterocyst differentiation), changes in individual cell composition, and cellular roles in metabolite exchange. (99 words) Some cyanobacteria are uniquely capable of fixing both dinitrogen (N 2 ) and CO 2 , deriving energy from oxygenic photosynthesis. These capabilities and the abundance of cyanobacteria in phytoplankton communities make these microorganisms keystone species in the global biogeochemical cycles of carbon and nitrogen. Under conditions of N limitation,

Proceedings of the National Academy of Sciences, 2009

The marine cyanobacterium Trichodesmium is ubiquitous in tropical and subtropical seas and is an ... more The marine cyanobacterium Trichodesmium is ubiquitous in tropical and subtropical seas and is an important contributor to global N and C cycling. We sought to characterize metabolic uptake patterns in individual Trichodesmium IMS-101 cells by quantitatively imaging 13 C and 15 N uptake with high-resolution secondary ion mass spectrometry (NanoSIMS). Trichodesmium fix both CO 2 and N2 concurrently during the day and are, thus, faced with a balancing act: the O 2 evolved during photosynthesis inhibits nitrogenase, the key enzyme in N 2 fixation. After performing correlated transmission electron microscopy (TEM) and NanoSIMS analysis on trichome thin-sections, we observed transient inclusion of 15 N and 13 C into discrete subcellular bodies identified as cyanophycin granules. We speculate that Trichodesmium uses these dynamic storage bodies to uncouple CO 2 and N2 fixation from overall growth dynamics. We also directly quantified both CO 2 and N 2 fixation at the single cell level using NanoSIMS imaging of whole cells in multiple trichomes. Our results indicate maximal CO 2 fixation rates in the morning, compared with maximal N2 fixation rates in the afternoon, bolstering the argument that segregation of CO 2 and N2 fixation in Trichodesmium is regulated in part by temporal factors. Spatial separation of N 2 and CO2 fixation may also have a role in metabolic segregation in Trichodesmium. Our approach in combining stable isotope labeling with NanoSIMS and TEM imaging can be extended to other physiologically relevant elements and processes in other important microbial systems.

Proceedings of the IEEE, 1991

This paper may be viewed as the culmination of a radar clutter classification research program th... more This paper may be viewed as the culmination of a radar clutter classification research program that has spanned over 15 years. In particular, we present the results of an experimental study aimed at the classification of radar clutter encountered on ground-based coherent scanning radar systems used for air traffic control. The clutter signals of interest are primarily those due to birds as well as clouds and weather systems. These two sources of radar returns represent potential hazards to aircraft safety. The aim of the clutter classifier is therefore to vector aircraft around such areas.

Acute disseminated encephalomyelitis review in 8 pediatric patients

Neuropediatrics, 2008

Neuromuscular Disorders, 2014

Mutations in A-type nuclear lamins are known to cause a variety of diseases, which can affect alm... more Mutations in A-type nuclear lamins are known to cause a variety of diseases, which can affect almost all organs of the human body including striated muscle. For lamin-related congenital muscular dystrophy two different phenotypes are known to date. Here, we describe a 3-year-old, white Caucasian girl with a novel de novo mutation in the LMNA gene with marked hypotonia of neck and trunk muscles with dropped head posture, loss of cervical lordosis and marked joint laxity. In addition to this novel mutation, the patient also had cerebral white matter lesions on MRI and cognitive impairment on developmental testing. This is only the second A-type lamin-related congenital muscular dystrophy patient in which white matter lesions are described. Thus, white matter involvement might be a feature in A-type lamin-related congenital muscular dystrophy, warranting screening of these patients for both white matter lesions and cognitive impairment.

Utility of neuropsychological testing for guiding treatment decisions in paediatric multiple sclerosis

Multiple Sclerosis Journal, 2013

In the past years, there has been growing awareness about childhood onset multiple sclerosis (MS)... more In the past years, there has been growing awareness about childhood onset multiple sclerosis (MS) and the relevance of psychosocial aspects such as cognitive disturbances, fatigue and depression in this population. We describe a case of a 16-year-old patient with relapsing-remitting multiple sclerosis (RRMS) who presented at our clinic with severe fatigue symptoms and who underwent repeated neuropsychological examinations. A sudden significant slowing indicated a new relapse while neurological examination did not. This case highlights the high sensitivity and clinical relevance of neuropsychological testing in patients with juvenile MS even in the context of treatment decisions.

Inhibition of Monoamine Oxidases by Functionalized Coumarin Derivatives: Biological Activities, QSARs, and 3D-QSARs

Journal of Medicinal Chemistry, 2000

A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A a... more A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC(50) values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3, 4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC(50) value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2)() = 0.72, r(2)() = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.