[Movement of a fluvial particle under the influence of coherent structures]. / Bewegung eines Einzelkorns unter dem Einfluss kohärenter Strukturen.

In a fundamental study the influence of coherent structures on the incipient motion of single fluvial grain was experimentally investigated. To fully characterize coherent structures, the three-dimensional velocity field must be known with high temporal resolution. Using a tr-3D PTV system (tr = time-resolved, PTV = particle tracking velocimetry) this could be achieved. The influence of hairpin vortices and counter-rotating longitudinal vortices (VLSM) on sediment transport has been postulated in several studies, but due to the missing 3D information, evidence has been lacking. In the present "Rolling Stones test series", the incipient motion of a single grain was investigated for smooth and rough beds. It could be shown for the first time that both hairpin vortices and VLSM trigger particle entrainment. Hairpin vortices could also be detected on rough beds, contrary to common hypotheses, and triggered particle movement. The long-term study should also find practical applications in the coming years and increase the accuracy of sediment transport calculations in rivers.

Evaluation of the potential stranding risk for aquatic organisms according to long-term morphological changes and grain size in alpine rivers impacted by hydropeaking.

Hydropeaking is one of the major hydropower-related disturbances of natural processes in river systems. The artificial flow fluctuations that are caused by the on-demand production of electricity are known for their severe impacts on aquatic ecosystems. These particularly affect those species and life stages that are not able to adjust their habitat selection to rapid up- and downramping rates. To date, the stranding risk has both experimentally and numerically mainly been investigated with variable hydropeaking graphs over stable river bathymetries. There is a lack of knowledge on how single, discrete peaking events vary concerning their impact on the stranding risk when the river morphology changes in the long-term perspective. The present study precisely addresses this knowledge gap by investigating morphological changes on the reach scale over a period of 20 years and the related variability of the lateral ramping velocity as a proxy for stranding risk. Two alpine gravel bed rivers impacted by hydropeaking over decades were tested by applying a one-dimensional and two-dimensional unsteady modelling approach. Both the Bregenzerach River and the Inn River exhibit alternating gravel bars on the reach scale. The results of the morphological development, however, showed different developments in the period 1995-2015. The Bregenzerach River displayed continuous aggradation (uplift of river bed) over the various selected submonitoring periods. In contrast, the Inn River showed continuous incision (erosion of river bed). The stranding risk exhibited high variability on a single cross-sectional basis. However, on the reach scale, no significant changes in stranding risk were calculated for either river reach. In addition, the impacts of river incision on the substrate composition were investigated. Here, in line with preceding studies, the results show that the coarsening of substrate increases the stranding risk and that especially the d90 (90 % finer of the grain size distribution) must be considered. The present study reveals that the quantified stranding risk of aquatic organisms is a function of the general morphological (bar) characteristics of the impacted river and both the morphological and grain size development have an impact on the potential stranding risk of aquatic organisms and should be considered in the revision of licences in the management of multi-stressed river systems.

Evaluation of re-depositing hydropower trapped sediments at large rivers to improve flood protection and aquatic habitats - Case study Danube/Austria.

Sedimentation in impoundments of run-of-river hydropower plants is an ongoing and progressing management issue for hydropower operators because of its consequences for e.g., the maintenance of flood protection and waterway parameters. Current practices in sediment management are often unsustainable, associated with high costs, and can pose risks for downstream biota (e.g. during flushing). The present study elaborated a conceptual model of a novel sediment management strategy for impounded river sections consisting of a current-state and deficit analysis, and the application of a novel sediment management practice, which was practically implemented at the study site at the Austrian Danube River. This novel practice consists of (i) local dredging of gravel at locations in the impoundment, which are problematic in terms of flood protection and waterway maintenance, and (ii) the re-deposition of dredged sediments by artificial placement of gravel structures. The present study included morphological analyses of the impounded section at the study site by applying the channel profile budget technique. The knowledge of the long-term morphological development served as a basis for the evaluation of the sediment management measures and for the elaboration of the conceptual model. The combination of the morphodynamic characteristics in the impoundment with the implementation of the novel sediment management practice helped to derive generalized statements for the potential implementation of the presented conceptual model in large rivers with similar impoundment characteristics. We further defined several aspects, which are related to sediment dynamics in impounded river sections, flood protection, waterway demands, and ecological criteria that require consideration for an efficient realization of the proposed conceptual model.

Putting patients at the center of kidney care transitions: PREPARE NOW, a cluster randomized controlled trial.

Care for patients transitioning from chronic kidney disease to kidney failure often falls short of meeting patients' needs. The PREPARE NOW study is a cluster randomized controlled trial studying the effectiveness of a pragmatic health system intervention, 'Patient Centered Kidney Transition Care,' a multi-component health system intervention designed to improve patients' preparation for kidney failure treatment. Patient-Centered Kidney Transition Care provides a suite of new electronic health information tools (including a disease registry and risk prediction tools) to help providers recognize patients in need of Kidney Transitions Care and focus their attention on patients' values and treatment preferences. Patient-Centered Kidney Transition Care also adds a 'Kidney Transitions Specialist' to the nephrology health care team to facilitate patients' self-management empowerment, shared-decision making, psychosocial support, care navigation, and health care team communication. The PREPARE NOW study is conducted among eight [8] outpatient nephrology clinics at Geisinger, a large integrated health system in rural Pennsylvania. Four randomly selected nephrology clinics employ the Patient Centered Kidney Transitions Care intervention while four clinics employ usual nephrology care. To assess intervention effectiveness, patient reported, biomedical, and health system outcomes are collected annually over a period of 36 months via telephone questionnaires and electronic health records. The PREPARE NOW Study may provide needed evidence on the effectiveness of patient-centered health system interventions to improve nephrology patients' experiences, capabilities, and clinical outcomes, and it will guide the implementation of similar interventions elsewhere. TRIAL REGISTRATION: NCT02722382.

Longitudinal assessment of hydropeaking impacts on various scales for an improved process understanding and the design of mitigation measures.

Hydropeaking is one of the main pressures on the aquatic ecology in alpine rivers. Beside studies on abiotic process and biotic response on the local scale there is a lack in process understanding on the reach scale. Especially longitudinal changes of hydropeaking impacts based on retention processes have not been studied yet. Thus, based on unsteady one-dimensional and two-dimensional depth averaged modelling it was targeted to investigate possible changes in vertical ramping velocity for the discussion of possible mitigation measures at the local scale. Here, we compared artificial and natural sheltering habitats in terms of peak flow. Additionally, the hydropeaking assessment on various river scales was supported by an evaluation of tributaries in an alpine river system. Based on the modelling results and the discussion of the impact assessment of hydropeaking in different case studies we state, that on the first 5km downstream of the turbine outlet a significant decrease in vertical ramping velocity occurs. In this reach, habitat improvements should focus on increasing retention processes considering the higher risk of stranding for juvenile fish and macroinvertebrates. For morphological mitigation measures at the local scale, it turned out that self-formed, near-natural morphology should be targeted in terms of mitigation measure design compared to artificial sheltering habitats. Abundance and biomass of macroinvertebrates are directly linked to substrate variability in self-formed sheltering habitats downstream of gravel bars. Moreover, we ascertained that tributaries are able to contribute to the 'ecological potential' in multi-stressed hydropeaking rivers by providing spawning and rearing habitats for fish. However, for a sustainable improvement of the aquatic environment on all relevant scales, both sediment and flood dynamics have to be considered as important drivers to establish self-formed sheltering habitats in terms of hydropeaking.

Habitat use and tolerance levels of macroinvertebrates concerning hydraulic stress in hydropeaking rivers - A case study at the Ziller River in Austria.

Artificial flow fluctuations due to the operation of hydropower plants, frequently described as hydropeaking, result in a constant decrease of biomass of specific macrozoobenthos (MZB) taxa. For the presented case study, we assessed three reaches in the Ziller River catchment. At each sampling reach we performed the Multi-Habitat-Sampling (MHS) method with a Water Framework Directive (WFD) compliant AQEM/MHS net according to the Austrian guideline. Additionally, a hydraulic-specific sampling was conducted with a modified Box (Surber) sampler. As a basis for predictive habitat modelling of the MZB fauna, we measured abiotic parameters like mean (v40) and bottom-near (vbottom) flow rate or water depth respectively, for each box sample. In addition, the choriotope type, representing grain size classes, was determined. One of the main results is, that the national status assessment was not capable to reflect the impact of pulse release at the investigated river stretches on the basis of status classes. Moreover, we figured out that 1) habitats of stagnophilic macroinvertebrate taxa are minimized in channelized stretches affected by hydropeaking, leading to heavy quantitative losses for populations, becoming apparent in significant decreases in total individual numbers and biomass for many taxa. 2) The minor respond of the ecological status class in affected stretches by applying the WFD compliant national assessment method for macroinvertebrates owes to the tolerance of rheobiont or rheophilic taxa commonly classified as indicators for good conditions regarding saprobity or degradation score. 3) A development of a stressor-specific sampling design is required as the MHS method largely ignores vulnerable habitats. 4) The habitat suitability of selected species provides efficient expertise for impact assessment and mitigation measure design in terms of predictive habitat modelling.

Evaluation of hydropeaking impacts on the food web in alpine streams based on modelling of fish- and macroinvertebrate habitats.

Hydropeaking as a result of peak-load electricity production has been identified as one of the most significant pressures in alpine streams. Scouring of macroinvertebrates leads to downstream transport of aquatic organisms (catastrophic drift). Additionally, invertebrates are affected by periodic drying of wetted area during the dewatering of gravel bars and exposed areas along the banks. Even though fish are physiologically better adapted to switch to suitable habitats, artificial flow fluctuations may be followed by lethal stranding and quick alteration in habitat quantity and quality. Nevertheless, the interactions between pressures on fish and macroinvertebrates in terms of hydropeaking have not been investigated so far. The aim of this paper is to evaluate effects of flow fluctuations on potential epibenthic feeding grounds. Therefore, we evaluated changes in habitat distribution resulting from rapid flow fluctuations in river reaches with different river morphological characteristics, for five different macroinvertebrate taxa. Additionally, microhabitats for brown trout at two different life stages were calculated using representative peaking events (seasonal analysis) based on mid- to long term times series. Moreover, GIS-analysis allowed the evaluation of hydropeaking impacts (interaction) on both, macroinvertebrates and fish. In this study, it could be documented that feeding from the benthos for juvenile and subadult brown trout is inhibited during peak flow and is therefore reduced to times of base flow. Moreover, potential benthic feeding areas occurring at base flow have been found to increase with the level of morphological heterogeneity within analyzed river reaches. Likewise, hydrological sensitivity testing in terms of reducing ∆Q at different levels was performed and revealed that possible positive effects required heterogeneous river morphology as a precondition. However, this approach might be applied for estimating the impacts of hydrological mitigation measures in hydropeaked rivers concerning physical condition and/or growth rate of salmonids considering the river morphology of the investigated stream.

Acute placebo-controlled sleep laboratory studies and clinical follow-up with pramipexole in restless legs syndrome.

In a single-blind, placebo-controlled crossover trial, the acute efficacy of the dopamine agonist pramipexole was investigated in 11 restless legs syndrome (RLS) patients by sleep laboratory methods, with a clinical follow-up for 4 weeks. In 3 nights (pre-treatment, placebo and drug night), objective sleep quality was determined by polysomnography (PSG), subjective sleep and awakening quality by rating scales, objective awakening quality by psychometry. Clinical follow-up consisted of completion of the International RLS Study Group (IRLSSG) Scale, Zung Depression (SDS) and Anxiety (SAS) Scale, Quality of Life Index, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Concerning acute effects, an omnibus significance test for PSG variables demonstrated a global difference between placebo and pramipexole, but none between pre-treatment and placebo. Pramipexole 0.27 mg significantly decreased the target variable periodic leg movements (PLM)/h of sleep as well as all other RLS/PLM variables and improved objective sleep efficiency and subjective sleep quality as compared with placebo. In sleep architecture, sleep stages S1 and S2 and stage shifts increased, while slow-wave sleep and SREM decreased. After 4 weeks of therapy, the total scores of the IRLSSG questionnaire, sleep quality and daytime sleepiness, depression and quality of life also improved. Thus, acute pramipexole markedly reduced PLM measures and slightly improved objective and subjective sleep quality. Follow-up ratings showed a moderate improvement of RLS and sleep quality, and to a lesser extent of daytime sleepiness, depression and quality of life. The psychopathological findings as well as acute sleep architecture changes are reminiscent of those seen after activating antidepressants.

EEG mapping, psychometric, and polysomnographic studies in restless legs syndrome (RLS) and periodic limb movement disorder (PLMD) patients as compared with normal controls.

OBJECTIVES: Investigation of daytime brain function, psychopathology, and objective and subjective sleep and awakening quality in restless legs syndrome (RLS) and periodic limb movement disorder (PLMD). METHODS: Thirty-three RLS and 26 PLMD patients free of psychotropic drugs were studied as compared with age- and sex-matched normal controls, utilizing electroencephalographic (EEG) mapping and clinical evaluations by the Zung Self-Rating Depression (SDS) and Anxiety Scale (SAS), the Quality of Life Index, the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale. In a subsample of 12 RLS patients, 12 PLMD patients, and 12 controls, objective and subjective sleep and awakening quality were evaluated in two sleep laboratory nights (adaptation and baseline night). RESULTS: Scores of the PSQI, SDS, and SAS were found increased in both patient groups; RLS patients showed reduced quality of life, while in the PLMD group daytime sleepiness was increased. EEG mapping demonstrated findings characteristic of major depression in RLS patients and of generalized anxiety disorder in PLMD patients. Polysomnography showed a significant deterioration of sleep efficiency only for RLS patients, while nocturnal awakenings were increased in both patient groups. Concerning sleep architecture, both groups exhibited increased S1 and stage shifts and decreased S2, while only PLMD patients showed an increase in S4. The PLM/(h TST), the PLM/(h wake) and the PLMS-arousal index were significantly increased in both patient groups as compared with controls. Subjective sleep and awakening quality and thymopsychic measures were deteriorated in RLS. Morning mental performance and fine motor activity were deteriorated in both groups, reaction time only in RLS, numerical memory and attention variability only in PLMD. CONCLUSION: EEG mapping revealed neurophysiological correlates of depression and anxiety in RLS and PLMD, respectively, which were confirmed by self-ratings of symptoms.

Interrelationships among biological activity, disulfide bonds, secondary structure, and metal ion binding for a chemically synthesized 34-amino-acid peptide derived from alpha-fetoprotein.

A 34-amino-acid peptide has been chemically synthesized based on a sequence from human alpha-fetoprotein. The purified peptide is active in anti-growth assays when freshly prepared in pH 7.4 buffer at 0.20 g/l, but this peptide slowly becomes inactive. This functional change is proven by mass spectrometry to be triggered by the formation of an intrapeptide disulfide bond between the two cysteine residues on the peptide. Interpeptide cross-linking does not occur. The active and inactive forms of the peptide have almost identical secondary structures as shown by circular dichroism (CD). Zinc ions bind to the active peptide and completely prevents formation of the inactive form. Cobalt(II) ions also bind to the peptide, and the UV-Vis absorption spectrum of the cobalt-peptide complex shows that: (1) a near-UV sulfur-to-metal-ion charge-transfer band had a molar extinction coefficient consistent with two thiolate bonds to Co(II); (2) the lowest-energy visible d-d transition maximum at 659 nm, also, demonstrated that the two cysteine residues are ligands for the metal ion; (3) the d-d molar extinction coefficient showed that the metal ion-ligand complex was in a distorted tetrahedral symmetry. The peptide has two cysteines, and it is speculated that the other two metal ion ligands might be the two histidines. The Zn(II)- and Co(II)-peptide complexes had similar peptide conformations as indicated by their ultraviolet CD spectra, which differed very slightly from that of the free peptide. Surprisingly, the cobalt ions acted in the reverse of the zinc ions in that, instead of stabilizing anti-growth form of the peptide, they catalyzed its loss. Metal ion control of peptide function is a saliently interesting concept. Calcium ions, in the conditions studied, apparently do not bind to the peptide. Trifluoroethanol and temperature (60 degrees C) affected the secondary structure of the peptide, and the peptide was found capable of assuming various conformations in solution. This conformational flexibility may possibly be related to the biological activity of the peptide.

Identification and characterization of mycobacterial proteins differentially expressed under standing and shaking culture conditions, including Rv2623 from a novel class of putative ATP-binding proteins.

The environmental signals that affect gene regulation in Mycobacterium tuberculosis remain largely unknown despite their importance to tuberculosis pathogenesis. Other work has shown that several promoters, including acr (also known as hspX) (alpha-crystallin homolog), are upregulated in shallow standing cultures compared with constantly shaking cultures. Each of these promoters is also induced to a similar extent within macrophages. The present study used two-dimensional gel electrophoresis and mass spectrometry to further characterize differences in mycobacterial protein expression during growth under standing and shaking culture conditions. Metabolic labeling of M. bovis BCG showed that at least 45 proteins were differentially expressed under standing and shaking culture conditions. Rv2623, CysA2-CysA3, Gap, and Acr were identified from each of four spots or gel bands that were specifically increased in bacteria from standing cultures. An additional standing-induced spot contained two comigrating proteins, GlcB and KatG. The greatest induction was observed with Rv2623, a 32-kDa protein of unknown function that was strongly expressed under standing conditions and absent in shaking cultures. Analysis using PROBE, a multiple sequence alignment and database mining tool, classified M. tuberculosis Rv2623 as a member of a novel class of ATP-binding proteins that may be involved in M. tuberculosis's response to environmental signals. These studies demonstrate the power of combined proteomic and computational approaches and demonstrate that subtle differences in bacterial culture conditions may have important implications for the study of gene expression in mycobacteria.

Restless legs syndrome (RLS) and periodic limb movement disorder (PLMD): acute placebo-controlled sleep laboratory studies with clonazepam.

Restless legs syndrome (RLS) - a common sensorimotor disorder - and periodic limb movement disorder (PLMD) are currently treated with substances of four classes: dopaminergic agents, which are considered the drugs of choice, benzodiazepines, opioids and anticonvulsants. As their effects on sleep variables differ considerably, the aim of the present placebo-controlled sleep laboratory study was to measure the acute effects of 1 mg clonazepam on objective and subjective sleep and awakening quality in ten RLS and 16 PLMD patients, utilizing polysomnography (PSG) and psychometry. Descriptive data analysis demonstrated at the confirmatory level concerning three target variables that - as compared with placebo - clonazepam significantly improved objective sleep efficiency and subjective sleep quality in both patient groups, but failed to reduce the index PLM/h of sleep. At the descriptive level, in PLMD clonazepam improved PLM during time in bed, REM and wakefulness and showed more significant changes in various sleep and awakening measures than in RLS patients, though there were no significant inter-group differences. In conclusion, in both PLMD and RLS clonazepam exhibited acute therapeutic efficacy regarding insomnia, which is quite different from the mode of action of dopamine agonists.

Sleep laboratory studies in periodic limb movement disorder (PLMD) patients as compared with normals and acute effects of ropinirole.

Periodic limb movement disorder (PLMD) occurs in a variety of sleep disorders and can cause insomnia as well as hypersomnia with daytime somnolence. The aim of this study was to investigate 12 untreated PLMD patients as compared with 12 normal controls and to measure the acute effects of 0.5 mg ropinirole (Requip((R))) - a non-ergoline dopamine agonist - as compared with placebo. In three nights (adaptation, placebo, ropinirole night) objective and subjective sleep and awakening quality were evaluated. In the target variable 'periodic leg movements per hour of sleep' (PLM/(hTST)) PLMD patients showed an increased value of 42/h (normal 0-5/h) with a greater number of arousals due to periodic leg movements (PLM) in sleep. They further demonstrated an increased number of awakenings, sleep stage S1, S4, stage shifts and decreased S2, but there were no significant differences concerning total sleep time, sleep efficiency (SE), subjective sleep quality and morning measures of mood, drive and drowsiness. However, measures of attention variability, numerical memory, fine motor activity and reaction time performance were impaired. Ropinirole 0.5 mg was shown to significantly improve the index PLM/(hTST) by 64% and arousals due to PLM, increase spontaneous arousals, REM-latency, stage 2 and stage shifts and decrease SREM. In the morning attention variability was attenuated and numerical memory augmented. Thus, ropinirole improved some sleep architecture and early morning measures of performance but specifically all PLM variables, which suggests a dopaminergic pathogenesis in PLMD. Copyright 2001 John Wiley & Sons, Ltd.

Sleep laboratory studies in restless legs syndrome patients as compared with normals and acute effects of ropinirole. 1. Findings on objective and subjective sleep and awakening quality.

Although the restless legs syndrome (RLS) is a disorder with a relatively high prevalence rate (8% in Austria) and leads to insomnia and excessive daytime tiredness, there is a paucity of sleep laboratory data concerning objective and subjective sleep and awakening quality. Thus, the aim of this study was to investigate 12 untreated RLS patients as compared with 12 normal controls and subsequently measure the acute effects of 0.5 mg ropinirole (Requip((R))) - a nonergoline dopamine agonist - as compared with placebo. In 3 nights (adaptation, placebo, ropinirole night) sleep induction, maintenance and architecture were measured objectively by polysomnography, subjective sleep and awakening quality were assessed by self-rating scales and visual-analog scales, and objective awakening quality was evaluated by a psychometric test battery. In polysomnography, RLS patients demonstrated, as compared with normal controls, a decreased total sleep time (TST) and sleep efficacy, increased wakefulness during the total sleep period and frequency of nocturnal awakenings, increased sleep stage S1, decreased S2 and increased stage shifts. Subjective sleep quality tended to decrease, and morning well-being, mood, affectivity and wakefulness were deteriorated. In the noopsyche, fine motor activity and reaction time performance were deteriorated. Ropinirole 0.5 mg induced, as compared with placebo, an increase in TST, sleep efficacy, S2 sleep and stage shifts. In the morning, somatic complaints increased slightly, while fine motor activity and reaction time performance improved. Our findings suggest a key-lock principle in the diagnosis/treatment of RLS and a dopaminergic mechanism in its pathogenesis, which is supported by the data on periodic leg movements during sleep and arousals of the subsequent paper.

Sleep laboratory studies in restless legs syndrome patients as compared with normals and acute effects of ropinirole. 2. Findings on periodic leg movements, arousals and respiratory variables.

The restless legs syndrome (RLS) is a common sensorimotor disorder which leads to severe sleep disturbances and showed a prevalence of 7.9% in our sleep laboratory. The aim of this study was to investigate periodic leg movements (PLM), arousal and respiratory variables in 12 untreated RLS patients and to measure the acute effects of 0.5 mg ropinirole, a nonergoline dopamine agonist, as compared with placebo. In the target variable PLM/h of total sleep time (PLM/h TST), RLS patients showed an increased value of 40/h (normal 0-5/h). Further, we found an increased number of PLM (368), PLM/h of time in bed (49/h), PLM/h of REM sleep (11), PLM/h of non-REM sleep (46) and PLM/h awake (61). The arousal index was also increased (32/h; normal 0-25/h), as were arousals due to PLM. In the confirmatory part of our descriptive data analysis, ropinirole 0.5 mg significantly improved, as compared with placebo, the index PLM/h TST by 75%. In the descriptive part, all the other PLM variables were improved as well. Arousals due to PLM decreased, while spontaneous arousals increased. Respiratory variables, which had a priori been in the normal range, showed a slight but significant improvement after the dopamine agonist. Thus, 0.5 mg ropinirole significantly improved the target variable PLM/h TST, along with objective and subjective sleep quality and morning noopsychic performance, as described in the preceding paper. Our data encourage further sleep studies including all above-mentioned variables in a larger group of RLS/PLM during sleep patients as well as long-term efficacy trials.

[Daytime tiredness correlated with nocturnal respiratory and arousal variables in patients with sleep apnea: polysomnographic and EEG mapping studies]. / Tagesmüdigkeit korreliert mit nächtlichen Atmungs- und Arousal-Variablen bei Schlafapnoepatienten: Polysomnographische und EEG-Mapping-Untersuchungen.

There is evidence that daytime tiredness is caused by apnea/hypopnea with oxygen desaturation and/or by sleep fragmentation due to arousals. The aim of this study was to investigate objective and subjective sleep and awakening quality and daytime vigilance--objectified by midmorning mapping of vigilance-controlled EEG (V-EEG)--in sleep apnea patients (N: 18), as compared with age- and sex-matched normal controls (N: 18) as well as to correlate nocturnal respiratory distress and arousals to daytime brain function. Statistical analyses demonstrated a deterioration in subjective and objective sleep and awakening quality in apnea patients. Midmorning V-EEG mapping in apnea patients exhibited less total power, more delta and theta, less alpha and beta activity, as well as a slower dominant frequency and centroid of the total activity compared to controls, which suggests a vigilance decrement. The Spearman rank correlation between 6 polysomnographically registered respiratory variables and 36 diurnal quantitative EEG measures demonstrated the following: the higher the apnea, apnea-hypopnea, snoring and desaturation indices and the lower the minimum and average low oxygen saturation, the more pronounced was diurnal tiredness. Eleven arousal measures based on ASDA criteria showed the following significant correlations: the higher the nocturnal arousal index and the more arousals due to hypopneas, the greater was daytime tiredness. On the other hand, the greater the average frequency change during arousals and the more spontaneous arousals, the better was daytime vigilance. Our findings show that, in contrast to the lengthy Multiple Sleep Latency (MSLT) and Maintenance of Wakefulness (MWT) tests which evaluate sleep pressure under resting conditions conducive to sleep, V-EEG mapping provides a brief objective measure of a sleep apnea patient's daytime tiredness under conditions of wakefulness more appropriate to reflect the patient's everyday life.

An overall perspective of X-ray damage to a DNA oligomer mediated by reactive oxygen species.

The products produced by X irradiation of an oxygenated aqueous solution containing d(CpApTpG) were analyzed by NMR spectroscopy and mass spectrometry. Thirteen different base modifications were detected, including a novel product formed by the addition of oxygen to guanine. Seven different strand break products were identified, including strands having 5'-phosphoryl groups, 3'-phosphoryl groups and groups having 3'-phosphoglycolates as termini. The products produced in largest yield contained base modifications: Pyrimidine bases degraded to a formamido moiety, the 8-oxo-7,8-dihydroguanine (8-oxoguanine) lesion, and double base lesions in which both the 8-oxo-7,8-dihydroguanine lesion and a formamido remnant are present.

Characterization of recombinant human brain-derived neurotrophic factor variants.

The purpose of this work was the chemical characterization of variants of the recombinant human brain derived neurotrophic factor (rHu-BDNF), expressed in Escherichia coli. This paper also addresses the question of the in vitro activity of these variants. Chemical characterization of the variants employed peptide mapping using Glu-C protease and cyanogen bromide digestion on reduced and alkylated variants followed by the analysis of the digested peptides using mass spectrometry and Edman sequencing. The BDNF variants in this work have been designated by the order of their elution as observed from the high temperature RPLC assay. It was determined that Peaks 1 and 2, which eluted just before the predominant BDNF peak, had methionine sulfoxide instead of methionine at positions 31 and 61, respectively. Peak 4, which is chromatographically a single peak, contained three variants. Two of these variants had norleucine instead of methionine, at positions 61 and 92, respectively, while the third had methionine sulfoxide instead of methionine at position 92. Peak 5 had norleucine at position 31 instead of methionine. All of these variants showed in vitro biological activity consistent with the BDNF standard, suggesting the preservation of the trkB receptor-ligand binding domain of the variants.